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

Oxalobacter formigenes produces metabolites and lipids undetectable in oxalotrophic Bifidobacterium animalis.

Sun, 22/11/2020 - 12:32
Related Articles Oxalobacter formigenes produces metabolites and lipids undetectable in oxalotrophic Bifidobacterium animalis. Metabolomics. 2020 Nov 21;16(12):122 Authors: Chamberlain CA, Hatch M, Garrett TJ Abstract INTRODUCTION: In the search for new potential therapies for pathologies of oxalate, such as kidney stone disease and primary hyperoxaluria, the intestinal microbiome has generated significant interest. Resident oxalate-degrading bacteria inhabit the gastrointestinal tract and reduce absorption of dietary oxalate, thereby potentially lowering the potency of oxalate as a risk factor for kidney stone formation. Although several species of bacteria have been shown to degrade oxalate, select strains of Oxalobacter formigenes (O. formigenes) have thus far demonstrated the unique ability among oxalotrophs to initiate a net intestinal oxalate secretion into the lumen from the bloodstream, allowing them to feed on both dietary and endogenous metabolic oxalate. There is significant interest in this function as a potential therapeutic application for circulating oxalate reduction, although its mechanism of action is still poorly understood. Since this species-exclusive, oxalate-regulating function is reported to be dependent on the use of a currently unidentified secreted bioactive compound, there is much interest in whether O. formigenes produces unique biochemicals that are not expressed by other oxalotrophs which lack the ability to transport oxalate. Hence, this study sought to analyze and compare the metabolomes of O. formigenes and another oxalate degrader, Bifidobacterium animalis subsp. lactis (B. animalis), to determine whether O. formigenes could produce features undetectable in another oxalotroph, thus supporting the theory of a species-exclusive secretagogue compound. METHODS: A comparative metabolomic analysis of O. formigenes strain HC1 (a human isolate) versus B. animalis, another oxalate-degrading human intestinal microbe, was performed by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). Bacteria were cultured independently in anaerobic conditions, harvested, lysed, and extracted by protein precipitation. Metabolite extracts were chromatographically separated and analyzed by UHPLC-HRMS using reverse phase gradient elution (ACE Excel 2 C18-Pentafluorophenyl column) paired with a Q Exactive™ mass spectrometer. OBJECTIVES: The purpose of this study was to assess whether O. formigenes potentially produces unique biochemicals from other oxalate degraders to better understand its metabolic profile and provide support for the theoretical production of a species-exclusive secretagogue compound responsible for enhancing intestinal oxalate secretion. RESULTS: We report a panel of metabolites and lipids detected in the O. formigenes metabolome which were undetectable in B. animalis, several of which were identified either by mass-to-charge ratio and retention time matching to our method-specific metabolite library or MS/MS fragmentation. Furthermore, re-examination of data from our previous work showed most of these features were also undetected in the metabolomes of Lactobacillus acidophilus and Lactobacillus gasseri, two other intestinal oxalate degraders. CONCLUSIONS: Our observation of O. formigenes metabolites and lipids which were undetectable in other oxalotrophs suggests that this bacterium likely holds the ability to produce biochemicals not expressed by at least a selection of other oxalate degraders. These findings provide support for the hypothesized biosynthesis of a species-exclusive secretagogue responsible for the stimulation of net intestinal oxalate secretion. PMID: 33219444 [PubMed - as supplied by publisher]

Comparative use of aqueous humour 1H NMR metabolomics and potassium concentration for PMI estimation in an animal model.

Sun, 22/11/2020 - 12:32
Related Articles Comparative use of aqueous humour 1H NMR metabolomics and potassium concentration for PMI estimation in an animal model. Int J Legal Med. 2020 Nov 20;: Authors: Locci E, Stocchero M, Gottardo R, De-Giorgio F, Demontis R, Nioi M, Chighine A, Tagliaro F, d'Aloja E Abstract Estimation of the post-mortem interval (PMI) remains a matter of concern in the forensic scenario. Traditional and novel approaches are not yet able to fully address this issue, which relies on complex biological phenomena triggered by death. For this purpose, eye compartments may be chosen for experimental studies because they are more resistant to post-mortem modifications. Vitreous humour, in particular, has been extensively investigated, with potassium concentration ([K+]) being the marker that is better correlated with PMI estimation. Recently, a 1H nuclear magnetic resonance (NMR) metabolomic approach based on aqueous humour (AH) from an animal model was proposed for PMI estimation, resulting in a robust and validated regression model. Here we studied the variation in [K+] in the same experimental setup. [K+] was determined through capillary ion analysis (CIA) and a regression analysis was performed. Moreover, it was investigated whether the PMI information related to potassium could improve the metabolome predictive power in estimating the PMI. Interestingly, we found that a part of the metabolomic profile is able to explain most of the information carried by potassium, suggesting that the rise in both potassium and metabolite concentrations relies on a similar biological mechanism. In the first 24-h PMI window, the AH metabolomic profile shows greater predictive power than [K+] behaviour, suggesting its potential use as an additional tool for estimating the time since death. PMID: 33219398 [PubMed - as supplied by publisher]

Plasma lipidomic profiles after a low and high glycemic load dietary pattern in a randomized controlled crossover feeding study.

Sun, 22/11/2020 - 12:32
Related Articles Plasma lipidomic profiles after a low and high glycemic load dietary pattern in a randomized controlled crossover feeding study. Metabolomics. 2020 Nov 20;16(12):121 Authors: Dibay Moghadam S, Navarro SL, Shojaie A, Randolph TW, Bettcher LF, Le CB, Hullar MA, Kratz M, Neuhouser ML, Lampe PD, Raftery D, Lampe JW Abstract BACKGROUND: Dietary patterns low in glycemic load are associated with reduced risk of cardiometabolic diseases. Improvements in serum lipid concentrations may play a role in these observed associations. OBJECTIVE: We investigated how dietary patterns differing in glycemic load affect clinical lipid panel measures and plasma lipidomics profiles. METHODS: In a crossover, controlled feeding study, 80 healthy participants (n = 40 men, n = 40 women), 18-45 y were randomized to receive low-glycemic load (LGL) or high glycemic load (HGL) diets for 28 days each with at least a 28-day washout period between controlled diets. Fasting plasma samples were collected at baseline and end of each diet period. Lipids on a clinical panel including total-, VLDL-, LDL-, and HDL-cholesterol and triglycerides were measured using an auto-analyzer. Lipidomics analysis using mass-spectrometry provided the concentrations of 863 species. Linear mixed models and lipid ontology enrichment analysis were implemented. RESULTS: Lipids from the clinical panel were not significantly different between diets. Univariate analysis showed that 67 species on the lipidomics panel, predominantly in the triacylglycerol class, were higher after the LGL diet compared to the HGL (FDR < 0.05). Three species with FA 17:0 were lower after LGL diet with enrichment analysis (FDR < 0.05). CONCLUSION: In the context of controlled eucaloric diets with similar macronutrient distribution, these results suggest that there are relative shifts in lipid species, but the overall pool does not change. Further studies are needed to better understand in which compartment the different lipid species are transported in blood, and how these shifts are related to health outcomes. This trial was registered at clinicaltrials.gov as NCT00622661. PMID: 33219392 [PubMed - as supplied by publisher]

Identification and quantification of target metabolites combined with transcriptome of two rheum species focused on anthraquinone and flavonoids biosynthesis.

Sun, 22/11/2020 - 12:32
Related Articles Identification and quantification of target metabolites combined with transcriptome of two rheum species focused on anthraquinone and flavonoids biosynthesis. Sci Rep. 2020 Nov 20;10(1):20241 Authors: Liu J, Leng L, Liu Y, Gao H, Yang W, Chen S, Liu A Abstract Rheum emodi is a perennial herb and an important medicinal plant, with anthraquinones and flavonoids as its main bioactive compounds. However, there is little knowledge about the biosynthetic pathway of anthraquinones in rhubarbs. In this study, we qualitatively and quantitatively assessed 62 pharmacological metabolites in rhubarb using dynamic multiple reaction monitoring (dMRM) of triple-quadrupole mass spectrometry (QqQ-MS), including 21 anthraquinones, 17 flavonoids, 6 stilbenes, 12 gallate esters, 3 tannins, and 3 others. Besides, the metabolomics results showed significant differences among all the 60 metabolites, except for gallic acid and piceatannol-O-β-glucoside. The combined transcriptome data of R. palmatum L. (RPL) and R. officinale Baill. (ROB) showed that 21,691 unigenes were annotated in the metabolic pathways. Taken together, 17 differentially expressed genes (DEGs) were associated with the anthraquinone biosynthetic pathway. Additionally, a significant correlation between anthraquinone peak intensity and DEG expression level existed, validating that DEGs contribute to the anthraquinone biosynthetic pathway. RT-qPCR results showed that the cluster-14354.38156 gene may catalyze the O-methylation of emodin to produce physcion. This study provides a useful resource for further studies on secondary metabolism in rhubarb and the combination analysis of transcriptome and metabolome, which can help with the discovery of enzyme genes involved in metabolite biosynthesis. PMID: 33219248 [PubMed - as supplied by publisher]

Crayfish tissue metabolomes effectively distinguish impacts of wastewater and agriculture in aquatic ecosystems.

Sun, 22/11/2020 - 12:32
Related Articles Crayfish tissue metabolomes effectively distinguish impacts of wastewater and agriculture in aquatic ecosystems. Sci Total Environ. 2020 Nov 04;:143322 Authors: Izral NM, Brua RB, Culp JM, Yates AG Abstract Environmental metabolomics has been proposed as a tool for biomonitoring because organisms regulate production or consumption of metabolites in response to environmental conditions. We evaluated the efficacy of the metabolome of three tissues (hepatopancreas, gill, and tail muscle) from the northern crayfish (Faxonius virilis) to detect and differentiate between impacts of human activities (i.e., reference, municipal wastewater, and agriculture). We conducted a reciprocal transfer study exposing crayfish for 1 or 2 weeks in three streams with different amounts and types of human activities in southern Manitoba, Canada. Tissue samples were analyzed using nuclear magnetic resonance spectroscopy to generate a metabolic profile. Findings indicated the gill tissue metabolome best detected and differentiated between human activities. In particular, the gill metabolome was able to rapidly integrate abrupt changes in environmental conditions associated with municipal wastewater activity. In contrast, the tail metabolome best differentiated between crayfish collected at the reference site from those collected at the two impacted sites. Metabolites extracted from hepatopancreas tissue showed limited and inconsistent detection of among site differences. Based on our findings, we conclude that the metabolome of the northern crayfish can be an effective biomonitoring tool, but monitoring purpose will dictate tissue selection. Indeed, we recommend the gill metabolome be used for short-term assays aimed at detecting acute effects, whereas the tail be applied for survey monitoring aimed at detecting deviations in ecological condition at test sites from reference site conditions. PMID: 33218799 [PubMed - as supplied by publisher]

Pentachlorophenol and ciprofloxacin present dissimilar joint toxicities with carbon nanotubes to Bacillus subtilis.

Sun, 22/11/2020 - 12:32
Related Articles Pentachlorophenol and ciprofloxacin present dissimilar joint toxicities with carbon nanotubes to Bacillus subtilis. Environ Pollut. 2020 Nov 11;:116071 Authors: Deng R, Yang K, Lin D Abstract Discharged carbon nanotubes (CNTs) likely interact with co-existing organic contaminants (OCs) and pose joint toxicity to environmental microbes. Herein, hydrophobic pentachlorophenol (PCP) and hydrophilic ciprofloxacin (CIP) were used as representative OCs and their joint toxicities with CNTs to Bacillus subtilis were systematically investigated at cellular, biochemical, and omics levels. The 3-h bacterial growth half inhibitory concentrations of CNTs, PCP, and CIP were 12.5 ± 2.6, 3.5 ± 0.5, and 0.46 ± 0.03 mg/L, respectively, and they all could damage cell membrane, increase intracellular oxidative stress, and alter bacterial metabolomics and transcriptomics; while CNTs-PCP and CNTs-CIP binary exposures exhibited distinct additive and synergistic toxicities, respectively. CNTs increased bacterial bioaccumulation of PCP and CIP via destabilizing and damaging cell membrane. PCP reduced the bioaccumulation of CNTs, while CIP had no significant effect; this difference could be owing to the different effects of the two OCs on cell-surface hydrophobicity and CNTs electronegativity. The additive toxicity outcome upon CNTs-PCP co-exposure could be a result of the balance between the increased toxicity from increased PCP bioaccumulation and the decreased toxicity from decreased CNTs bioaccumulation. The increased bioaccumulation of CIP contributed to the synergistic toxicity upon CNTs-CIP co-exposure, as confirmed by the increased inhibition of topoisomerase Ⅳ activity and interference in gene expressions regulating ABC transporters and lysine biosynthesis. The findings provide novel insights into environmental risks of CNTs. PMID: 33218776 [PubMed - as supplied by publisher]

In vitro long-term culture of isolated ovine preantral follicles: Influence of ethanol on steroid production, oocyte meiotic resumption, and metabolomic profile.

Sun, 22/11/2020 - 12:32
Related Articles In vitro long-term culture of isolated ovine preantral follicles: Influence of ethanol on steroid production, oocyte meiotic resumption, and metabolomic profile. Res Vet Sci. 2020 Nov 02;: Authors: Silva RF, Lima LF, Rocha RMP, Brito IR, Silva GM, Correia HHV, Rodrigues GQ, Ferreira ACA, Nunes-Pinheiro DCS, Moura AAAN, Silveira LBR, Lo Turco EG, Wheeler MB, Rodrigues APR, Campello CC, Figueiredo JR Abstract Ethanol is used routinely to dilute cell culture media supplements with little or no water solubility. This study evaluates the effect of low concentration of ethanol on the follicular development, oocyte maturation, hormone production, gene expression, and metabolomics profile of spent culture medium after long-term culture of isolated ovine preantral follicles. For this, follicles were cultured for 18 days in α-Minimum Essential Medium+ alone (control treatment) or supplemented with 100 ng/mL recombinant bovine FSH (rbFSH treatment) or with 0.2%-v/v ethanol (ethanol treatment). Ethanol treatment increased the percentage of degenerated follicles and oocytes significantly, however, it showed the highest estradiol secretion. Also, the rate of meiosis resumption was higher in ethanol treatment than Control treatment. Ethanol treatment decreased the mRNA levels of B-cell lymphoma 2 (BCL2), BCL2 associated X, Aquaporin 3, Connexin 43, Inhibin Subunit Beta A, kit ligand, Heat Shock Protein (HSP A1A) significantly when compared to the Control treatment. However, mRNA levels of cytochrome P450 family 19, and FSH receptors were significantly higher in ethanol treatment than in the Control treatment. The levels of some metabolites, which are likely amino acids, lipids, an analog of Cyclic guanosine monophosphate, and a derivative of phosphoinositol phosphate metabolism, had higher relative concentrations in ethanol and rbFSH treatments than the Control treatment. In conclusion, ethanol addition augmented the follicular and oocyte degeneration rates but increased the estradiol production and the meiotic resumption. Furthermore, the follicular metabolomic profile was similar between ethanol and rbFSH treatments being both treatments; however, different from the Control treatment. PMID: 33218694 [PubMed - as supplied by publisher]

Metabolomics strategy assisted by transcriptomics analysis to identify biomarkers associated with schizophrenia.

Sun, 22/11/2020 - 12:32
Related Articles Metabolomics strategy assisted by transcriptomics analysis to identify biomarkers associated with schizophrenia. Anal Chim Acta. 2020 Dec 15;1140:18-29 Authors: Liu L, Zhao J, Chen Y, Feng R Abstract BACKGROUND: Metabolomics strategy was perform to identify the novel serum biomarkers linked to schizophrenia with the assistance of transcriptomics analysis. METHODS: Two analytical platforms, UPLC-Q-TOF MS/MS and 1H NMR, were used to acquire the serum fingerprinting profiles from a total of 112 participants (57 healthy controls and 55 schizophrenia patients). The differential metabolites were primarily selected after statistical analyses. Meanwhile, GSE17612 dataset downloaded from GEO database was implemented WGCNA analysis to discover crucial genes and corresponding biological processes. Based on metabolomics analysis, the metabolic distinctions were explored under the aid of transcriptomics. Then using Boruta algorithm identified the biomarkers, and LASSO regression analysis and Random Forest algorithm were used to evaluate the performance of the diagnostic model constructed by biomarkers selected. RESULTS: A total of four metabolites (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) were selected as the biomarkers to establish diagnosis model. The performance of this model showed a higher accuracy rate to distinguish schizophrenia patients from healthy controls (area under the receive operating characteristic curve, 0.992; precision recall curve, 1.000, the mean accuracy of random forest algorithm, 95.00%). CONCLUSIONS: A four-biomarker model (α-CEHC, neuraminic acid, glyceraldehyde and asparagine) seems to be a good model for diagnosing schizophrenia patients. It might be helpful to guide the future studies on permitting early intervention designed to prevent disease progression. PMID: 33218480 [PubMed - as supplied by publisher]

DNA-Based Authentication and Metabolomics Analysis of Medicinal Plants Samples by DNA Barcoding and Ultra-High-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry (UHPLC-MS).

Sun, 22/11/2020 - 12:32
Related Articles DNA-Based Authentication and Metabolomics Analysis of Medicinal Plants Samples by DNA Barcoding and Ultra-High-Performance Liquid Chromatography/Triple Quadrupole Mass Spectrometry (UHPLC-MS). Plants (Basel). 2020 Nov 18;9(11): Authors: Sánchez M, González-Burgos E, Divakar PK, Gómez-Serranillos MP Abstract There is growing interest for medicinal plants in the world drug market. Particularly, Matricaria recutita L., Valeriana officinalis L., Tilia spp., and Camellia sinensis (L.) Kuntze are some of the most consumed medicinal plants for treatment of minor health problems. Medicinal plants are seen as natural and safe; however, they can cause interactions and produce adverse reactions. Moreover, there is lack of consensus in medicinal plants regulation worldwide. DNA barcoding and UHPLC-MS technique are increasingly used to correctly identify medicinal plants and guarantee their quality and therapeutic safety. We analyzed 33 samples of valerian, linden, tea, and chamomile acquired in pharmacies, supermarkets, and herbal shops by DNA barcoding and UHPLC-MS. DNA barcoding, using matk as a barcode marker, revealed that CH1 sold as Camellia sinensis was Blepharocalyx tweediei, and sample TS2 sold as linden belong to Malvales. On the other hand, UHPLC-MS analysis revealed the presence of bioactive compounds (apigenin-7-glucoside, acetoxy valerenic acid, valerenic acid, epigallocatechin, and tiliroside). However, none of samples met minimum content of these active principles (except for valerenic acid in VF3) according to the European Medicines Agency (EMA) and Real Spanish Pharmacopeia. In conclusion, this study revealed the need to incorporate DNA barcoding and HPLC-MS techniques in quality controls of medicinal plants. PMID: 33218119 [PubMed - as supplied by publisher]

metabolomics; +34 new citations

Sat, 21/11/2020 - 15:20
34 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 2020/11/21PubMed 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; +34 new citations

Sat, 21/11/2020 - 12:19
34 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 2020/11/21PubMed 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; +31 new citations

Fri, 20/11/2020 - 15:06
31 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 2020/11/20PubMed 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; +20 new citations

Fri, 20/11/2020 - 09:05
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 2020/11/20PubMed 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; +34 new citations

Wed, 18/11/2020 - 14:54
34 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 2020/11/18PubMed 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; +31 new citations

Tue, 17/11/2020 - 23:48
31 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 2020/11/17PubMed 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.

metabolomics; +34 new citations

Tue, 17/11/2020 - 02:41
34 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 2020/11/16PubMed 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; +33 new citations

Fri, 13/11/2020 - 14:07
33 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 2020/11/13PubMed 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; +34 new citations

Thu, 12/11/2020 - 20:01
34 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 2020/11/12PubMed 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; +49 new citations

Wed, 11/11/2020 - 13:50
49 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 2020/11/11PubMed 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; +52 new citations

Tue, 10/11/2020 - 19:48
52 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 2020/11/10PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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