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

Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms.

Sun, 25/08/2019 - 13:05
Related Articles Blood plasma metabolic profiling of pregnant women with antenatal depressive symptoms. Transl Psychiatry. 2019 Aug 23;9(1):204 Authors: Henriksson HE, Malavaki C, Bränn E, Drainas V, Lager S, Iliadis SI, Papadopoulos FC, Sundström Poromaa I, Chrousos GP, Klapa MI, Skalkidou A Abstract Antenatal depression affects ~9-19% of pregnant women and can exert persistent adverse effects on both mother and child. There is a need for a deeper understanding of antenatal depression mechanisms and the development of tools for reliable diagnosis and early identification of women at high risk. As the use of untargeted blood metabolomics in the investigation of psychiatric and neurological diseases has increased substantially, the main objective of this study was to investigate whether untargeted gas chromatography-mass spectrometry (GC-MS) plasma metabolomics in 45 women in late pregnancy, residing in Uppsala, Sweden, could indicate metabolic differences between women with and without depressive symptoms. Furthermore, seasonal differences in the metabolic profiles were explored. When comparing the profiles of cases with controls, independently of season, no differences were observed. However, seasonal differences were observed in the metabolic profiles of control samples, suggesting a favorable cardiometabolic profile in the summer vs. winter, as indicated by lower glucose and sugar acid concentrations and lactate to pyruvate ratio, and higher abundance of arginine and phosphate. Similar differences were identified between cases and controls among summer pregnancies, indicating an association between a stressed metabolism and depressive symptoms. No depression-specific differences were apparent among depressed and non-depressed women, in the winter pregnancies; this could be attributed to an already stressed metabolism due to the winter living conditions. Our results provide new insights into the pathophysiology of antenatal depression, and warrant further investigation of the use of metabolomics in antenatal depression in larger cohorts. PMID: 31444321 [PubMed - in process]

Supercritical fluid chromatography-mass spectrometry using data independent acquisition for the analysis of polar metabolites in human urine.

Sun, 25/08/2019 - 13:05
Related Articles Supercritical fluid chromatography-mass spectrometry using data independent acquisition for the analysis of polar metabolites in human urine. J Chromatogr A. 2019 Aug 12;:460449 Authors: Akbal L, Hopfgartner G Abstract The application of supercritical fluid chromatography with mass spectrometric (MS) detection (SFC-MS) was compared towards generic reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) for the analysis of urine with regards of ionization performance and analyte identification. The different chromatographic conditions were characterized with a selected set of 51 metabolites from different classes reported in the Human Metabolome DataBase (HMDB) and previously detected in human urine and/or plasma. SFC using a diol column with a gradient of carbon dioxide (CO2) and methanol with 10 mM ammonium hydroxide as modifier was able to retain and separate 20 polar analytes co-eluting in the RPLC eluent front. In the conditions investigated and compared to HILIC where many metabolites were also co-eluting, SFC showed a different ratio between elution domain and analysis time. Similar peak width and symmetry were observed, while retention time variability was slightly lower compared to that of HILIC (0.15% versus 0.24% and 1.26% for RPLC and HILIC, respectively). In SFC-MS, a significant signal enhancement (2-150 times, average of about 10 times) was measured after post-column make-up addition (MeOH/H2O, 95/5, v/v + 25 mM ammonium acetate) for 28 analytes. Nine analytes measured by LC-MS could not be detected in SFC-MS. Applicability of SFC-MS for metabolomics was investigated with the analysis of urine samples using data independent acquisition (DIA) and more specifically Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH/MS). Using a metabolomics library, 74 metabolites from human urine could be identified in positive mode in a single SFC-MS analysis of 15 min. PMID: 31443968 [PubMed - as supplied by publisher]

Untargeted Metabolomic Profile for the Detection of Prostate Carcinoma-Preliminary Results from PARAFAC2 and PLS-DA Models.

Sun, 25/08/2019 - 13:05
Related Articles Untargeted Metabolomic Profile for the Detection of Prostate Carcinoma-Preliminary Results from PARAFAC2 and PLS-DA Models. Molecules. 2019 Aug 22;24(17): Authors: Amante E, Salomone A, Alladio E, Vincenti M, Porpiglia F, Bro R Abstract Prostate-specific antigen (PSA) is the main biomarker for the screening of prostate cancer (PCa), which has a high sensibility (higher than 80%) that is negatively offset by its poor specificity (only 30%, with the European cut-off of 4 ng/mL). This generates a large number of useless biopsies, involving both risks for the patients and costs for the national healthcare systems. Consequently, efforts were recently made to discover new biomarkers useful for PCa screening, including our proposal of interpreting a multi-parametric urinary steroidal profile with multivariate statistics. This approach has been expanded to investigate new alleged biomarkers by the application of untargeted urinary metabolomics. Urine samples from 91 patients (43 affected by PCa; 48 by benign hyperplasia) were deconjugated, extracted in both basic and acidic conditions, derivatized with different reagents, and analyzed with different gas chromatographic columns. Three-dimensional data were obtained from full-scan electron impact mass spectra. The PARADISe software, coupled with NIST libraries, was employed for the computation of PARAFAC2 models, the extraction of the significative components (alleged biomarkers), and the generation of a semiquantitative dataset. After variables selection, a partial least squares-discriminant analysis classification model was built, yielding promising performances. The selected biomarkers need further validation, possibly involving, yet again, a targeted approach. PMID: 31443574 [PubMed - in process]

Perineuronal Nets and Their Role in Synaptic Homeostasis.

Sun, 25/08/2019 - 13:05
Related Articles Perineuronal Nets and Their Role in Synaptic Homeostasis. Int J Mol Sci. 2019 Aug 22;20(17): Authors: Bosiacki M, Gąssowska-Dobrowolska M, Kojder K, Fabiańska M, Jeżewski D, Gutowska I, Lubkowska A Abstract Extracellular matrix (ECM) molecules that are released by neurons and glial cells form perineuronal nets (PNNs) and modulate many neuronal and glial functions. PNNs, whose structure is still not known in detail, surround cell bodies and dendrites, which leaves free space for synapses to come into contact. A reduction in the expression of many neuronal ECM components adversely affects processes that are associated with synaptic plasticity, learning, and memory. At the same time, increased ECM activity, e.g., as a result of astrogliosis following brain damage or in neuroinflammation, can also have harmful consequences. The therapeutic use of enzymes to attenuate elevated neuronal ECM expression after injury or in Alzheimer's disease has proven to be beneficial by promoting axon growth and increasing synaptic plasticity. Yet, severe impairment of ECM function can also lead to neurodegeneration. Thus, it appears that to ensure healthy neuronal function a delicate balance of ECM components must be maintained. In this paper we review the structure of PNNs and their components, such as hyaluronan, proteoglycans, core proteins, chondroitin sulphate proteoglycans, tenascins, and Hapln proteins. We also characterize the role of ECM in the functioning of the blood-brain barrier, neuronal communication, as well as the participation of PNNs in synaptic plasticity and some clinical aspects of perineuronal net impairment. Furthermore, we discuss the participation of PNNs in brain signaling. Understanding the molecular foundations of the ways that PNNs participate in brain signaling and synaptic plasticity, as well as how they change in physiological and pathological conditions, may help in the development of new therapies for many degenerative and inflammatory diseases of the brain. PMID: 31443560 [PubMed - in process]

Advances of Metabolomics in Fungal Pathogen-Plant Interactions.

Sun, 25/08/2019 - 13:05
Related Articles Advances of Metabolomics in Fungal Pathogen-Plant Interactions. Metabolites. 2019 Aug 15;9(8): Authors: Chen F, Ma R, Chen XL Abstract Plant disease caused by fungus is one of the major threats to global food security, and understanding fungus-plant interactions is important for plant disease control. Research devoted to revealing the mechanisms of fungal pathogen-plant interactions has been conducted using genomics, transcriptomics, proteomics, and metabolomics. Metabolomics research based on mass spectrometric techniques is an important part of systems biology. In the past decade, the emerging field of metabolomics in plant pathogenic fungi has received wide attention. It not only provides a qualitative and quantitative approach for determining the pathogenesis of pathogenic fungi but also helps to elucidate the defense mechanisms of their host plants. This review focuses on the methods and progress of metabolomics research in fungal pathogen-plant interactions. In addition, the prospects and challenges of metabolomics research in plant pathogenic fungi and their hosts are addressed. PMID: 31443304 [PubMed]

metabolomics; +20 new citations

Sat, 24/08/2019 - 15:52
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/24PubMed 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; +20 new citations

Sat, 24/08/2019 - 12:51
20 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/24PubMed 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; +38 new citations

Fri, 23/08/2019 - 15:46
38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/23PubMed 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; +38 new citations

Fri, 23/08/2019 - 12:45
38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/23PubMed 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

Thu, 22/08/2019 - 15:36
18 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/22PubMed 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; +25 new citations

Wed, 21/08/2019 - 15:29
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/21PubMed 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; +25 new citations

Wed, 21/08/2019 - 12:25
25 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/21PubMed 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; +38 new citations

Tue, 20/08/2019 - 15:10
38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/20PubMed 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; +38 new citations

Tue, 20/08/2019 - 12:09
38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/08/20PubMed 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

Sat, 17/08/2019 - 14:43
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 2019/08/17PubMed 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.

The environmental distribution and toxicity of short-chain chlorinated paraffins and underlying mechanisms: Implications for further toxicological investigation.

Fri, 16/08/2019 - 14:31
Related Articles The environmental distribution and toxicity of short-chain chlorinated paraffins and underlying mechanisms: Implications for further toxicological investigation. Sci Total Environ. 2019 Aug 07;695:133834 Authors: Wang X, Zhu J, Xue Z, Jin X, Jin Y, Fu Z Abstract Short-chain chlorinated paraffin (SCCP) pollution has become a global threat. Much attention has been paid to their environmental occurrence and toxicity. In this review, we summarized the wide distribution of SCCPs in various environmental matrices and biota, including human beings. Toxicokinetics and the toxicities of SCCPs, including lethality, hepatotoxicity, developmental toxicity, carcinogenicity, endocrine- and metabolism-disrupting effects, and immunomodulatory effects have been considered. The mechanisms of SCCP toxicity are mainly related to oxidative stress, metabolic disturbance, endocrine disruption and binding to biomacromolecules. In the future, further studies of SCCPs should focus on searching for their novel toxicity targets, and uncovering their toxic effects using transcriptomics, proteomics, metabolomics, and mutigenerational toxicity. PMID: 31416033 [PubMed - as supplied by publisher]

Comparative metabolomics of Tilia platyphyllos Scop. bracts during phenological development.

Fri, 16/08/2019 - 14:31
Related Articles Comparative metabolomics of Tilia platyphyllos Scop. bracts during phenological development. Phytochemistry. 2019 Aug 12;167:112084 Authors: Szűcs Z, Cziáky Z, Kiss-Szikszai A, Sinka L, Vasas G, Gonda S Abstract The medicinal plant drug "Tiliae flos" consists of the botanical flowers and bracts of Tilia sp., gathered almost exclusively during flowering. In this study, we examined the changes in the metabolome of specialized products in the bracts of Tilia platyphyllos from the appearance of the organ till the onset of senescence by LC-ESI-MS and data mining. A set of 504 natural products were detected, 241 of which showed significant seasonal variation (p < 9.92E-5). Seven compounds were quantified and an additional 45 were putatively identified. These included flavonoid glycosides, catechins, procyanidins, quinic acid derivatives (including chlorogenic acid) and coumarins. Compared to bracts during flowering, young tissues were characterized by a relatively high diversity of polyphenolic substances. Higher amounts of flavonol glycosides (quercetin, kaempferol), catechins and derivatives have been observed. Deoxyhexosides were almost exclusive to this phenological stage. Changes of about one order of magnitude were not uncommon. For some substances, 5-fold differences were observed (calibration with authentic standards). Some compounds (e.g. the coumarin fraxin) were more prominent at the late fruit growth stage. It was shown that bracts gathered before or after flowering could potentially be therapeutically useful. Changes are rapid during the early phase of bract development: three different groups of compounds presented their maxima during the first 32 days. Considering seasonal variation is of extreme importance during bioactivity tests and screening candidate sources for bioactive natural products. In the case of T. platyphyllos, young and old bracts can be of interest because of their high diversity of distinct specialized metabolites. PMID: 31415913 [PubMed - as supplied by publisher]

Antibacterial mechanism of polysaccharide from Tetrastigma hemsleyanum Diels et Gilg's polysaccharides by metabolomics based on HPLC/MS.

Fri, 16/08/2019 - 14:31
Related Articles Antibacterial mechanism of polysaccharide from Tetrastigma hemsleyanum Diels et Gilg's polysaccharides by metabolomics based on HPLC/MS. Int J Biol Macromol. 2019 Aug 12;: Authors: Chen X, Tao L, Ru Y, Weng S, Chen Z, Wang J, Guo L, Lin Z, Pan W, Qiu B Abstract Tetrastigma hemsleyanum Diels et Gilg (THDG) is used as a Chinese traditional anti-inflammatory medicine for about thousands of years. In this work, Tetrastigma hemsleyanum Diels et Gilg's polysaccharide (TP) can inhibit E. coli's growth in initial dosing period. Compared with the antibacterial effect of Achyranthe's polysaccharide (AP) from their metabolic profile, it's obviously that their metabolic sites for E. coli were inconsistent. Moreover, TP could not only increase the level of fructose-6-phosphate (F6P), decrease the level of fructose-1,6-diphosphate (FBP), but also charge the amount of the two 0- = differential metabolic with the change of the concentration and the dosing time. Actually, F6P could transform into FBP by catalyze of 6-phosphofructokinase-1(6-PFK-1), which is an important process in glycolysis. Furthermore, FBP was considered have positively correlated with E. coli's growth rate. Therefore, TP can inhibit the E. coli's proliferation by interfering with the process for glycolysis and gluconeogenesis. Based on the experimental result, we proposed a new mouthwash method to evaluate the anti-bacterial activity. Compared with AP, TP can inhibit the E. coli's growth within 2 h with a low concentration (0.5%) and a short dosing time (5 min). This study extends the applications of THDG and establishes a new assessment method for the pharmacology activity of Chinese herbal medicine. PMID: 31415856 [PubMed - as supplied by publisher]

Production of Amphidinols and Other Bioproducts of Interest by the Marine Microalga Amphidinium carterae Unraveled by Nuclear Magnetic Resonance Metabolomics Approach Coupled to Multivariate Data Analysis.

Fri, 16/08/2019 - 14:31
Related Articles Production of Amphidinols and Other Bioproducts of Interest by the Marine Microalga Amphidinium carterae Unraveled by Nuclear Magnetic Resonance Metabolomics Approach Coupled to Multivariate Data Analysis. J Agric Food Chem. 2019 Aug 15;: Authors: Abreu AC, Molina-Miras A, Aguilera-Sáez LM, López-Rosales L, Cerón-García MDC, Sánchez-Mirón A, Olmo-García L, Carrasco-Pancorbo A, García-Camacho F, Molina-Grima E, Fernández I Abstract This study assessed the feasibility of an NMR metabolomics approach coupled to multivariate data analysis to monitor the naturally present or stresses-elicited metabolites from a long-term (>170 days) culture of the dinoflagellate marine microalgae Amphidinium carterae grown in a fiberglass paddlewheel-driven raceway photobioreactor. Metabolic contents, in particular, in two members of the amphidinol family, amphidinol A and its 7-sulfate derivative amphidinol B (referred as APDs), and other compounds of interest (fatty acids, carotenoids, oxylipins, etc.) were evaluated by altering concentration levels of the f/2 medium nutrients and daily mean irradiance. Operating with a 24 h sinusoidal light cycle allowed a 3-fold increase in APD production, which was also detected by an increase in hemolytic activity of the methanolic extract of A. carterae biomass. The presence of APDs was consistent with the antitumoral activity measured in the methanolic extracts of the biomass. Increased daily irradiance was accompanied by a general decrease in pigments and an increase in SFAs (saturated fatty acids), MUFAs (monounsaturated fatty acids), and DHA (docosahexaenoic acid), while increased nutrient availability lead to an increase in sugar, amino acid, and PUFA ω-3 contents and pigments and a decrease in SFAs and MUFAs. NMR-based metabolomics is shown to be a fast and suitable method to accompany the production of APD and bioactive compounds without the need of tedious isolation methods and bioassays. The two APD compounds were chemically identified by spectroscopic NMR and spectrometric ESI-IT MS (electrospray ionization ion trap mass spectrometry) and ESI-TOF MS (ESI time-of-flight mass spectrometry) methods. PMID: 31415166 [PubMed - as supplied by publisher]

The applications of metabolomics in the molecular diagnostics of cancer.

Fri, 16/08/2019 - 14:31
Related Articles The applications of metabolomics in the molecular diagnostics of cancer. Expert Rev Mol Diagn. 2019 Aug 15;: Authors: Cheung PK, Ma MH, Tse HF, Yeung KF, Tsang HF, Chu MKM, Kan CM, Cho WCS, Ng LBW, Chan LWC, Wong SCC Abstract Introduction: Metabolomics, the study of metabolites, is a promising research field for cancers. The metabolic pathway in a tumor cell is different from a normal tissue cell. There are two approaches to study the metabolism, targeted and untargeted. The general approach is that metabolomic data are interpreted by bioinformatics tools correlating with metabolomic databases to obtain significant findings. With the use of specific analysis tools, such as nuclear magnetic resonance (NMR) and mass spectrometer (MS) combined with chromatography, metabolic profile or metabolic fingerprint of various biological specimens could be obtained. The applications of metabolomics are used to discover potential cancer biomarkers and monitor the metastatic state, therapeutic and drug response for better patient management. Areas covered: In this review, the author introduce metabolomics and discuss the use of metabolomics approaches in different cancers, including the study of colorectal cancer, prostate cancer, liver cancer, pancreatic cancer and breast cancer using NMR and MS. Expert opinion: Knowledge on the molecular basis of cancer metabolism and its potential clinical applications has been improving recently. However, there are still many challenges for the technological development and integration of metabolomics with other omics spaces such as genomics. In the near future, it is expected that metabolomics will play an important role in cancer molecular diagnostics. PMID: 31414918 [PubMed - as supplied by publisher]

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