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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 18 min 18 sec ago

Integrated proteomics, genomics, metabolomics approaches reveal oxalic acid as pathogenicity factor in Tilletia indica inciting Karnal bunt disease of wheat.

Sun, 20/05/2018 - 12:25
Related Articles Integrated proteomics, genomics, metabolomics approaches reveal oxalic acid as pathogenicity factor in Tilletia indica inciting Karnal bunt disease of wheat. Sci Rep. 2018 May 18;8(1):7826 Authors: Pandey V, Singh M, Pandey D, Kumar A Abstract Tilletia indica incites Karnal bunt (KB) disease in wheat. To date, no KB resistant wheat cultivar could be developed due to non-availability of potential biomarkers related to pathogenicity/virulence for screening of resistant wheat genotypes. The present study was carried out to compare the proteomes of T. indica highly (TiK) and low (TiP) virulent isolates. Twenty one protein spots consistently observed as up-regulated/differential in the TiK proteome were selected for identification by MALDI-TOF/TOF. Identified sequences showed homology with fungal proteins playing essential role in plant infection and pathogen survival, including stress response, adhesion, fungal penetration, invasion, colonization, degradation of host cell wall, signal transduction pathway. These results were integrated with T. indica genome sequence for identification of homologs of candidate pathogenicity/virulence related proteins. Protein identified in TiK isolate as malate dehydrogenase that converts malate to oxaloacetate which is precursor of oxalic acid. Oxalic acid is key pathogenicity factor in phytopathogenic fungi. These results were validated by GC-MS based metabolic profiling of T. indica isolates indicating that oxalic acid was exclusively identified in TiK isolate. Thus, integrated omics approaches leads to identification of pathogenicity/virulence factor(s) that would provide insights into pathogenic mechanisms of fungi and aid in devising effective disease management strategies. PMID: 29777151 [PubMed - in process]

Comparison of the serum metabolic signatures based on 1H NMR between patients and a rat model of deep vein thrombosis.

Sun, 20/05/2018 - 12:25
Related Articles Comparison of the serum metabolic signatures based on 1H NMR between patients and a rat model of deep vein thrombosis. Sci Rep. 2018 May 18;8(1):7837 Authors: Cao J, Jin QQ, Wang GM, Dong HL, Feng YM, Tian JS, Yun KM, Wang YY, Sun JH Abstract Deep vein thrombosis (DVT) and pulmonary embolism (PE) have high morbidity, reduce quality of life, and can cause death. Biomarkers or genetic risk factors have not been identified in patients with DVT. In present study, serum of 61 patients suffering from DVT and a rat DVT model (n = 10) were assayed by a proton nuclear magnetic resonance (1H NMR) metabolomics technique combing with multivariate statistical analysis to identify the metabolites. The MetPA platform was used to identify differences in the metabolic pathways between the rat model and patients. The metabolomics results discovered that 11 different metabolites in rats and 20 different metabolites in DVT patients. Seven metabolites both altered in the rats and patients. Moreover, we observed changes in the metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism that were induced immediately by the thrombosis. Pathway of aminoacyl-tRNA biosynthesis perturbed only in the patients which was associated with the genetic risk factor of DVT. The study demonstrated that serum 1H NMR metabolomics can be used to diagnose DVT in the clinic. The altered pathways related to thrombosis and genetics will provide a foundation and new strategies for understanding the pathological mechanism and pharmacological targets of DVT. PMID: 29777128 [PubMed - in process]

Comparative study on metabolite level in tissue-specific human mesenchymal stem cells by an ultra-performance liquid chromatography quadrupole time of flight mass spectrometry.

Sun, 20/05/2018 - 12:25
Related Articles Comparative study on metabolite level in tissue-specific human mesenchymal stem cells by an ultra-performance liquid chromatography quadrupole time of flight mass spectrometry. Anal Chim Acta. 2018 Sep 18;1024:112-122 Authors: Lee SJ, Yi T, Ahn SH, Lim DK, Kim SN, Lee HJ, Cho YK, Lim JY, Sung JH, Yun JH, Lim J, Song SU, Kwon SW Abstract Mesenchymal stem cells (MSCs) are a promising therapeutic option for cell-based therapy due to their immunomodulatory and regenerative properties. They can be isolated from various adult tissues, including bone marrow, fat, dental tissue, and glandular tissue. Although they share common characteristics, little is known about the biological differences between MSC populations derived from different tissues. In this study, we used MS to compare the endogenous metabolite level in the human MSCs originating from the bone marrow, adipose tissue, periodontal ligaments, and salivary glands. Using an optimized metabolomics technique, we verified that human MSCs exhibit differences in the endogenous metabolite level depending on their source material, while the multivariate analysis showed that 5 lysophosphatidylcholines and 3 lysophosphatidylethanolamines can serve as markers for the discrimination between MSC sources and may be related to differences in their differentiation capacity. These results may significantly contribute to further mechanistic studies on the MSCs and provide novel insights into the properties and optimal usage of MSCs from different tissues. PMID: 29776537 [PubMed - in process]

Toxicological effects on earthworms (Eisenia fetida) exposed to sub-lethal concentrations of BDE-47 and BDE-209 from a metabolic point.

Sat, 19/05/2018 - 12:07
Toxicological effects on earthworms (Eisenia fetida) exposed to sub-lethal concentrations of BDE-47 and BDE-209 from a metabolic point. Environ Pollut. 2018 May 15;240:653-660 Authors: Liang R, Chen J, Shi Y, Lu Y, Sarvajayakesavalu S, Xu X, Zheng X, Khan K, Su C Abstract Earthworms improve the soil fertility and they are also sensitive to soil contaminants. Earthworms (Eisenia fetida), standard reference species, were usually chosen to culture and handle for toxicity tests. Metabolic responses in earthworms exposed to 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) and decabromodiphenyl ether (BDE-209) were inhibitory and interfered with basal metabolism. In this study, 1H-NMR based metabolomics was used to identify sensitive biomarkers and explore metabolic responses of earthworms under sub-lethal BDE-47 and BDE-209 concentrations for 14 days. The results revealed that lactate was accumulated in earthworms exposed to BDE-47 and BDE-209. Glutamate increased significantly when the concentration of BDE-47 and BDE-209 reached 10 mg/kg. The BDE-47 exposure above 50 mg/kg concentration decreased the content of fumarate significantly, which was noticed different from that of BDE-209. Whereas, the BDE-207 or BDE-209 exposure increased the protein degradation into amino acids in vivo. The increased betaine content indicated that earthworms may maintain the cell osmotic pressure and protected enzyme activity by metabolic regulation. Moreover, the BDE-47 and BDE-209 exposure at 10 mg/kg changed most of the metabolites significantly, indicating that the metabolic responses were more sensitive than growth inhibition and gene expression. The metabolomics results revealed the toxic modes of BDE-47 and BDE-209 act on the osmoregulation, energy metabolism, nerve activities, tricarboxylic acid cycle and amino acids metabolism. Furthermore, our results highlighted that the 1H-NMR based metabolomics is a strong tool for identifying sensitive biomarkers and eco-toxicological assessment. PMID: 29775942 [PubMed - as supplied by publisher]

Metabolomics in breast cancer: A decade in review.

Sat, 19/05/2018 - 12:07
Metabolomics in breast cancer: A decade in review. Cancer Treat Rev. 2018 May 03;67:88-96 Authors: McCartney A, Vignoli A, Biganzoli L, Love R, Tenori L, Luchinat C, Di Leo A Abstract Breast cancer (BC) is a heterogeneous disease which has been characterised and stratified by many platforms such as clinicopathological risk factors, genomic assays, computer generated models, and various "-omic" technologies. Genomic, proteomic and transcriptomic analysis in breast cancer research is well established, and metabolomics, which can be considered a downstream manifestation of the former disciplines, is of growing interest. The past decade has seen significant progress made within the field of clinical metabolomic BC research, with several groups demonstrating results with significant promise in the setting of BC screening and biological characterisation, as well as future potential for prognostic metabolomic biomarkers. PMID: 29775779 [PubMed - as supplied by publisher]

Defining the Osteoarthritis Patient: Back to the Future.

Sat, 19/05/2018 - 12:07
Defining the Osteoarthritis Patient: Back to the Future. Osteoarthritis Cartilage. 2018 May 15;: Authors: Dobson GP, Letson HL, Grant A, McEwen P, Hazratwala K, Wilkinson M, Morris JL Abstract The history of osteoarthritis (OA) is important because it can help broaden our perspective on past and present controversies. The naming of OA, beginning with Heberden's nodes, is itself a fascinating story. According to Albert Hoffa, R. Llewellyn Jones and Archibald Edward Garrod, the name OA was introduced in the mid-19th century by surgeon Richard von Volkmann who distinguished it from rheumatoid arthritis and gout. Others preferred the terms 'chronical rheumatism', 'senile arthritis', 'hypertrophic arthritis' or 'arthritis deformans'. A similar narrative applies to the concept of OA affecting the whole joint vs. the 'wear-and-tear' hypothesis, inflammation and the role of the central nervous system (CNS). In the late 19th and early 20th centuries, the Garrods (father and son) and Hermann Senator argued that OA was a whole joint disease, and that inflammation played a major role in its progression. Garrod Jnr and John Spender also linked OA to a neurogenic lesion 'outside the joint'. The remaining 20th century was no less dynamic, with major advances in basic science, diagnostics, treatments, surgical interventions and technologies. Today, OA is characterized as a multi-disease with inflammation, immune and CNS dysfunction playing central roles in whole joint damage, injury progression, pain and disability. In the current 'omics' era (genomics, proteomics and metabolomics), we owe a great debt to past physicians and surgeons who dared to think 'outside-the-box' to explain and treat OA. Over 130 years later, despite these developments, we still don't fully understand the unravelling complexities of OA, and we still don't have a cure. PMID: 29775734 [PubMed - as supplied by publisher]

Metabolomics Analysis of the Toxic Effects of the Production of Lycopene and Its Precursors.

Sat, 19/05/2018 - 12:07
Related Articles Metabolomics Analysis of the Toxic Effects of the Production of Lycopene and Its Precursors. Front Microbiol. 2018;9:760 Authors: Miguez AM, McNerney MP, Styczynski MP Abstract Using cells as microbial factories enables highly specific production of chemicals with many advantages over chemical syntheses. A number of exciting new applications of this approach are in the area of precision metabolic engineering, which focuses on improving the specificity of target production. In recent work, we have used precision metabolic engineering to design lycopene-producing Escherichia coli for use as a low-cost diagnostic biosensor. To increase precursor availability and thus the rate of lycopene production, we heterologously expressed the mevalonate pathway. We found that simultaneous induction of these pathways increases lycopene production, but induction of the mevalonate pathway before induction of the lycopene pathway decreases both lycopene production and growth rate. Here, we aim to characterize the metabolic changes the cells may be undergoing during expression of either or both of these heterologous pathways. After establishing an improved method for quenching E. coli for metabolomics analysis, we used two-dimensional gas chromatography coupled to mass spectrometry (GCxGC-MS) to characterize the metabolomic profile of our lycopene-producing strains in growth conditions characteristic of our biosensor application. We found that the metabolic impacts of producing low, non-toxic levels of lycopene are of much smaller magnitude than the typical metabolic changes inherent to batch growth. We then used metabolomics to study differences in metabolism caused by the time of mevalonate pathway induction and the presence of the lycopene biosynthesis genes. We found that overnight induction of the mevalonate pathway was toxic to cells, but that the cells could recover if the lycopene pathway was not also heterologously expressed. The two pathways appeared to have an antagonistic metabolic effect that was clearly reflected in the cells' metabolic profiles. The metabolites homocysteine and homoserine exhibited particularly interesting behaviors and may be linked to the growth inhibition seen when the mevalonate pathway is induced overnight, suggesting potential future work that may be useful in engineering increased lycopene biosynthesis. PMID: 29774011 [PubMed]

Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia.

Sat, 19/05/2018 - 12:07
Related Articles Metabolic perturbations of post-load hyperglycemia vs. fasting hyperglycemia. Acta Pharmacol Sin. 2018 May 17;: Authors: Lu JY, Peng JH, Ma XJ, Zhang YN, Zhu W, He XX, Ying LW, Bao YQ, Zhou J, Jia WP Abstract There is evidence that post-load/post-meal hyperglycemia is a stronger risk factor for cardiovascular disease than fasting hyperglycemia. The underlying mechanism remains to be elucidated. The current study aimed to compare the metabolic profiles of post-load hyperglycemia and fasting hyperglycemia. All subjects received an oral glucose tolerance test (OGTT) and were stratified into fasting hyperglycemia (FH) or post-load hyperglycemia (PH). Forty-six (FH, n = 23; PH, n = 23) and 40 patients (FH, n = 20; PH, n = 20) were recruited as the exploratory and the validation set, respectively, and underwent metabolic profiling. Eighty-seven subjects including normal controls (NC: n = 36; FH: n = 22; PH: n = 29) were additionally enrolled and assayed with enzyme-linked immunosorbent assay (ELISA). In the exploratory set, 10 metabolites were selected as differential metabolites of PH (vs. FH). Of them, mannose and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were confirmed in the validation set to be significantly higher in FH than in PH. In the 87 subjects measured with ELISA, FH had numerically higher mannose (466.0 ± 179.3 vs. 390.1 ± 140.2 pg/ml) and AICAR (523.5 ± 164.8 vs. 512.1 ± 186.0 pg/ml) than did PH. In the pooled dataset comprising 173 subjects, mannose was independently associated with FPG (β = 0.151, P = 0.035) and HOMA-IR (β = 0.160, P = 0.026), respectively. The associations of AICAR with biochemical parameters did not reach statistical significance. FH and PH exhibited distinct metabolic profiles. The perturbation of mannose may be involved in the pathophysiologic disturbances in diabetes. PMID: 29773885 [PubMed - as supplied by publisher]

When fed foods with similar palatability, healthy adult dogs and cats choose different macronutrient compositions.

Sat, 19/05/2018 - 12:07
Related Articles When fed foods with similar palatability, healthy adult dogs and cats choose different macronutrient compositions. J Exp Biol. 2018 May 17;: Authors: Hall JA, Vondran JC, Vanchina MA, Jewell DE Abstract Dogs and cats make short-term food choices based on palatability. We hypothesized that if palatability were masked, long-term food choices would be based on physiologic requirements, and circulating metabolite concentrations would reflect those choices. Four experimental foods with similar palatability, but varying in macronutrient composition, were prepared for healthy adult dogs (n=17) and cats (n=27). Food 1 was high protein; Food 2 was high fat; Food 3 was high carbohydrates; and Food 4 was balanced for macronutrients. By choosing any combination of foods, dogs and cats could individually set their macronutrient intake. Plasma metabolomic profiles were determined at baseline and after animals had consumed their food intake of choice for 28 days. Based on food intake calculations over 28 days, dogs on average chose to consume most of their calories from fat (41.1±4.3%) and then carbohydrate (35.8±3.7%), whereas cats on average chose to consume most of their calories from carbohydrate (43.1±4.0%) and then protein (30.3±3.9%; all P<0.001). Age and lean or fat body mass also influenced protein intake. Younger, leaner cats consumed more protein compared with older cats, whereas younger leaner dogs consumed less protein compared with dogs having more fat body mass. Older cats with moderate protein intake had lower circulating docosahexaenoic acid (DHA) concentrations as well as higher concentrations of sulfated microbial catabolic products compared with younger, leaner cats. In summary, when fed foods with similar palatability, dogs and cats consume different macronutrient compositions, and concentrations of circulating metabolites in cats reflect food choices. PMID: 29773684 [PubMed - as supplied by publisher]

Relations of gut liver axis components and gut microbiota in obese children with fatty liver: A pilot study.

Sat, 19/05/2018 - 12:07
Related Articles Relations of gut liver axis components and gut microbiota in obese children with fatty liver: A pilot study. Clin Res Hepatol Gastroenterol. 2018 May 14;: Authors: Pierri L, Saggese P, Guercio Nuzio S, Troisi J, Di Stasi M, Poeta M, Savastano R, Marchese G, Tarallo R, Massa G, Ciccone V, Ziegenhardt D, Cavallo P, Bergheim I, Weisz A, Vajro P PMID: 29773420 [PubMed - as supplied by publisher]

Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats.

Sat, 19/05/2018 - 12:07
Related Articles Protective effects of ethanolic peel and pulp extracts of Citrus macroptera fruit against isoproterenol-induced myocardial infarction in rats. Biomed Pharmacother. 2017 Oct;94:256-264 Authors: Paul S, Das S, Tanvir EM, Hossen MS, Saha M, Afroz R, Islam MA, Hossain MS, Gan SH, Ibrahim Khalil M Abstract Increases in the incidence of cardiovascular disease (CVD) have aroused strong interest in identifying antioxidants from natural sources for use in preventive medicine. Citrus macroptera (C. macroptera), commonly known as "Satkara", is an important herbal and medicinal plant reputed for its antioxidant, nutritious and therapeutic uses. The aim of the present study was to investigate the cardio-protective effects of ethanol extracts of C. macroptera peel and pulp against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats (n=36) were pre-treated with peel and pulp extracts (500mg/kg) for 45days. They received a challenge with ISO (85mg/kg) on the 44th and 45th days. Our findings indicated that subcutaneous injection of ISO induced severe myocardial injuries associated with oxidative stress, as confirmed by elevated lipid peroxidation (LPO) and decreased cellular reduced glutathione (GSH) and anti-peroxidative enzymes, including glutathione peroxidase, glutathione reductase and glutathione-S-transferase, compared with levels observed in control animals. Pre-treatment with C. macroptera peel and pulp extracts prior to ISO administration however, significantly improved many of the investigated biochemical parameters, i.e., cardiac troponin I, cardiac marker enzymes, lipid profile and oxidative stress markers. The fruit peel extract showed stronger cardio-protective effects than the pulp extract. The biochemical findings were further confirmed by histopathological examinations. Overall, the increased endogenous antioxidant enzyme activity against heightened oxidative stress in the myocardium is strongly suggestive of the cardio-protective potential of C. macroptera. PMID: 28763749 [PubMed - indexed for MEDLINE]

RIP3 attenuates the pancreatic damage induced by deletion of ATG7.

Sat, 19/05/2018 - 12:07
Related Articles RIP3 attenuates the pancreatic damage induced by deletion of ATG7. Cell Death Dis. 2017 Jul 13;8(7):e2918 Authors: Zhou X, Xie L, Xia L, Bergmann F, Büchler MW, Kroemer G, Hackert T, Fortunato F Abstract Invalidation of pancreatic autophagy entails pancreatic atrophy, endocrine and exocrine insufficiency and pancreatitis. The aim of this study was to investigate whether depletion of Rip3, which is involved in necroptotic signaling, may attenuate the pancreatic atrophy and pancreatitis resulting from autophagy inhibition. Autophagy and necroptosis signaling were evaluated in mice lacking expression of Rip3 in all organs and Atg7 in the pancreas. Acinar cell death, inflammation and fibrosis were evaluated by using of a compendium of immunofluorescence methods and immunoblots. Mice deficient for pancreatic Atg7 developed acute pancreatitis, which progressed to chronic pancreatitis. This phenotype reduces autophagy, increase apoptosis and necroptosis, inflammation and fibrosis, as well as premature death of the animals. Knockout of Rip3 exacerbated the apoptotic death of acinar cells, increased tissue damage, reduced macrophage infiltration and further accelerated the death of the mice with Atg7-deficient pancreas. The pancreatic degeneration induced by autophagy inhibition was exacerbated by Rip3 deletion. PMID: 28703808 [PubMed - indexed for MEDLINE]

Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children.

Sat, 19/05/2018 - 12:07
Related Articles Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children. World J Gastroenterol. 2017 May 28;23(20):3643-3654 Authors: Martin FP, Su MM, Xie GX, Guiraud SP, Kussmann M, Godin JP, Jia W, Nydegger A Abstract AIM: To identify metabolic signatures in urine samples from healthy and inflammatory bowel disease (IBD) children. METHODS: We applied liquid chromatography and gas chromatography coupled to targeted mass spectrometry (MS)-based metabolite profiling to identify and quantify bile acids and host-gut microbial metabolites in urine samples collected from 21 pediatric IBD patients monitored three times over one year (baseline, 6 and 12 mo), and 27 age- and gender-matched healthy children. RESULTS: urinary metabolic profiles of IBD children differ significantly from healthy controls. Such metabolic differences encompass central energy metabolism, amino acids, bile acids and gut microbial metabolites. In particular, levels of pyroglutamic acid, glutamic acid, glycine and cysteine, were significantly higher in IBD children in the course of the study. This suggests that glutathione cannot be optimally synthesized and replenished. Whilst alterations of the enterohepatic circulation of bile acids in pediatric IBD patients is known, we show here that non-invasive urinary bile acid profiling can assess those altered hepatic and intestinal barrier dysfunctions. CONCLUSION: The present study shows how non-invasive sampling of urine followed by targeted MS-based metabonomic analysis can elucidate and monitor the metabolic status of children with different GI health/disease status. PMID: 28611517 [PubMed - indexed for MEDLINE]

Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease.

Sat, 19/05/2018 - 12:07
Related Articles Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease. World J Gastroenterol. 2017 May 28;23(20):3607-3614 Authors: Lv K, Fan YH, Xu L, Xu MS Abstract Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis. PMID: 28611513 [PubMed - indexed for MEDLINE]

Metabolic profiling identification of metabolites formed in Mediterranean mussels (Mytilus galloprovincialis) after diclofenac exposure.

Sat, 19/05/2018 - 12:07
Related Articles Metabolic profiling identification of metabolites formed in Mediterranean mussels (Mytilus galloprovincialis) after diclofenac exposure. Sci Total Environ. 2017 Apr 01;583:257-268 Authors: Bonnefille B, Arpin-Pont L, Gomez E, Fenet H, Courant F Abstract Despite the growing concern on the presence of pharmaceutically active compounds in the environment, few studies have been conducted on their metabolism in marine organisms. In this study, a non-targeted strategy based on the generation of chemical profiles generated by liquid chromatography combined with high resolution mass spectrometry was used to highlight metabolite production by the Mediterranean mussel (Mytilus galloprovincialis) after diclofenac exposure. This method allowed revealing the production of 13 metabolites in mussel tissues. Three of them were phase I metabolites, including 4'-hydroxy-diclofenac and 5-hydroxy-diclofenac. The remaining 10 were phase II metabolites, including sulfate and amino acids conjugates. Among all of the metabolites highlighted, 5 were reported for the first time in an aquatic organism exposed to diclofenac. PMID: 28108094 [PubMed - indexed for MEDLINE]

Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription.

Sat, 19/05/2018 - 12:07
Related Articles Differential integrative omic analysis for mechanism insights and biomarker discovery of abnormal Savda syndrome and its unique Munziq prescription. Sci Rep. 2016 06 14;6:27831 Authors: Guo X, Bakri I, Abudula A, Arken K, Mijit M, Mamtimin B, Upur H Abstract Research has shown that many cancers have acommon pathophysiological origin and often present with similar symptoms. In terms of Traditional Uighur Medicine (TUM) Hilit (body fluid) theory, abnormal Savda syndrome (ASS) formed by abnormal Hilit is the common phenotype of complex diseases and in particular tumours. Abnormal Savda Munziq (ASMq), one representative of TUM, has been effective in the treatment of cancer since ancient times. Despite the physiopathology of ASS, the relationship between causative factors and the molecular mechanism of ASMq are not fully understood. The current study expanded upon earlier work by integrating traditional diagnostic approaches with others utilizing systems biology technology for the analysis of proteomic (iTRAQ) and metabolomic ((1)H-NMR) profiles of Uighur Medicine target organ lesion (liver) tumours. The candidate proteins were analyzed by enrichment analysis of the biological process and biomarker filters. Subsequently, 3Omics web-based tools were used to determine the relationships between proteins and appropriate metabolites. ELISA assay and IHC methods were used to verify the proteomic result; the protein von Willebrand factor (vWF) may be the "therapeutic window" of ASMq and biomarkers of ASS. This study is likely to be of great significance for the standardization and modernization of TUM. PMID: 27296761 [PubMed - indexed for MEDLINE]

[¹H-NMR-based metabonomics on chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet].

Sat, 19/05/2018 - 12:07
Related Articles [¹H-NMR-based metabonomics on chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet]. Zhongguo Zhong Yao Za Zhi. 2016 Jun;41(12):2228-2234 Authors: Xu WF, Pei YH Abstract To study the chemical component groups with toxicity alleviation effect to Realgar in Niuhuang Jiedu tablet based on ¹H-NMR metabonomics. Twenty-four male Wistar rats were divided into four groups: control group, R group (treated with Realgar), RRSPG group (treated with Realgar, the root and rhizoma of Rheum palmatum, the root of Scutellaria baicalensis, the root of Platycodon grandiflorum and the root and rhizoma of Glycyrrhiza uralensis) and RC group (treated with total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis). Based on ¹H-NMR spectra of urine and serum from rats, PLS-DA was performed to identify different metabolic profiles.The metabolic profiles of R group were different from that of control group, while the metabolic profiles of RC group were almost similar to control group.Total anthraquinones from the root and rhizoma of R. palmatum, total flavonoids from the root of S. baicalensis, total saponins from the root of P. grandiflorum, total flavonoids and saponins from the root and rhizoma of G. uralensis regulated energy, choline and amino acid metabolism and gut flora disorder affected by realgar's toxicity. PMID: 28901065 [PubMed - indexed for MEDLINE]

LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.).

Fri, 18/05/2018 - 14:46
Related Articles LCM-seq reveals the crucial role of LsSOC1 in heat-promoted bolting of lettuce (Lactuca sativa L.). Plant J. 2018 May 17;: Authors: Chen Z, Zhao W, Ge D, Han Y, Ning K, Luo C, Wang S, Liu R, Zhang X, Wang Q Abstract Lettuce (Lactuca sativa L.) is one of the most economically important vegetables. The floral transition in lettuce is accelerated under high temperatures, which can significantly decrease yields. However, the molecular mechanism underlying the floral tranition in lettuce is poorly known. Using laser capture microdissection coupled with RNA sequencing, we isolated shoot apical meristem cells from the bolting-sensitive lettuce line S39 at four critical stages of development. Subsequently, we screened specifically for the flowering-related gene LsSOC1 during the floral transition through comparative transcriptomic analysis. Molecular biology, developmental biology, and biochemical tools were combined to investigate the biological function of LsSOC1 in lettuce. LsSOC1 knockdown by RNA interference resulted in a significant delay in the timing of bolting and insensitivity to high temperature, which indicated that LsSOC1 functions as an activator during heat-promoted bolting in lettuce. We determined that two heat-shock transcription factors, HsfA1e and HsfA4c, bound to the promoter of LsSOC1 to confirm that LsSOC1 played an important role in heat-promoted bolting. This study indicates that LsSOC1 plays a crucial role in the heat-promoted bolting process in lettuce. Further investigation of LsSOC1 may be useful for clarification of the bolting mechanism in lettuce. This article is protected by copyright. All rights reserved. PMID: 29772090 [PubMed - as supplied by publisher]

Detection of novel metabolite for roxadustat doping by global metabolomics.

Fri, 18/05/2018 - 14:46
Related Articles Detection of novel metabolite for roxadustat doping by global metabolomics. J Biochem. 2018 Jun 01;163(6):e1 Authors: Saigusa D, Suzuki N, Matsumoto Y, Umeda K, Tomioka Y, Koshiba S, Yamamoto M PMID: 29771375 [PubMed - in process]

The influence of juicing on the appearance of blueberry metabolites 2 h after consumption: a metabolite profiling approach.

Fri, 18/05/2018 - 14:46
Related Articles The influence of juicing on the appearance of blueberry metabolites 2 h after consumption: a metabolite profiling approach. Br J Nutr. 2018 Jun;119(11):1233-1244 Authors: Langer S, Kennel A, Lodge JK Abstract The consumption of berries has been linked to decreased risk of degenerative disease. Berries are regularly processed into juices. It is largely unknown how the juicing process affects the bioavailability of metabolites. As metabolomics has shown to be a valuable nutritional tool to study global metabolite differences, the aim of this study was to investigate the effect of juicing on the relative appearance of blueberry metabolites in humans using metabolomics. Nine healthy subjects consumed 250 g of fresh blueberries either as the whole fruit or after juicing, and provided blood and urine samples before and 2 h after intake in a cross-over design. Samples underwent metabolite profiling using LCMS, and data were mined with multivariate analysis. Overall, <12 % of all ions detected were significantly influenced by blueberry treatment (P<0·05). Partial least-squared discriminant analysis models of post-treatment samples revealed good discrimination. In urinary samples, whole blueberry treatment resulted in 108 ions that were significantly higher compared with juiced treatment (positive and negative mode combined), whereas only eight were significantly higher after juiced treatment. Examples of putative annotations included metabolites of ferulic and caffeic acids, several phenolic metabolites conjugated to sulphate, glycoside or glucuronide and fatty acyl derivatives, which were of higher intensity after whole blueberry treatment. In conclusion, consumption of whole blueberries resulted in a higher range of phenolic and other metabolites in plasma and urine samples 2 h after consumption. Both whole and juiced blueberries resulted in very similar metabolite profiles at 2 h, although this was the only time point measured. PMID: 29770756 [PubMed - in process]

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