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

Stage-specific metabolomic changes in equine oviductal fluid: New insights into the equine fertilization environment.

Sat, 14/12/2019 - 13:09
Stage-specific metabolomic changes in equine oviductal fluid: New insights into the equine fertilization environment. Theriogenology. 2019 Nov 30;143:35-43 Authors: González-Fernández L, Sánchez-Calabuig MJ, Calle-Guisado V, García-Marín LJ, Bragado MJ, Fernández-Hernández P, Gutiérrez-Adán A, Macías-García B Abstract A repeatable protocol for equine in vitro fertilization (IVF) has remained elusive. This is likely, in part, due to suboptimal composition of capacitation or IVF media that are currently in use. Hence, we aimed to analyse the metabolome of equine oviductal fluid (OF) at the pre- (PRE) and immediate post-ovulatory (PST) stages using proton magnetic resonance spectroscopy (1H NMR). Oviductal fluid from eight PRE and six PST mares were used to prepare a total of five samples per group. A total of 18 metabolites were identified. The five metabolites with the highest concentrations in the OF samples were lactate, myoinositol, creatine, alanine and carnitine. Only fumarate and glycine showed significant differences in their concentrations between PRE and PST OF samples, with higher concentrations in the PST samples. In a preliminary study, stallion spermatozoa (n = 3 ejaculates) were incubated with different concentrations of PST OF from one mare (0, 0.0625, 0.125, 0.25, 0.5 or 1%; v:v). After 4 h of sperm incubation, protein tyrosine phosphorylation (PY) by western blotting, sperm motility, and acrosomal status were evaluated. An increase of PY was observed in sperm from two stallions when treated with 0.0625% and 0.125% of OF; however no change in PY was noted in the other stallion. There were no effects of OF on spermatozoa motility or acrosome status. These results provide the first information on the metabolomics of equine OF at different stages of the estrus cycle, and present the possibility that OF may affect PY in stallion spermatozoa. PMID: 31835098 [PubMed - as supplied by publisher]

Cassava Metabolomics and Starch Quality.

Sat, 14/12/2019 - 13:09
Cassava Metabolomics and Starch Quality. Curr Protoc Plant Biol. 2019 Dec;4(4):e20102 Authors: Rosado-Souza L, David LC, Drapal M, Fraser PD, Hofmann J, Klemens PAW, Ludewig F, Neuhaus HE, Obata T, Perez-Fons L, Schlereth A, Sonnewald U, Stitt M, Zeeman SC, Zierer W, Fernie AR Abstract Cassava plays an important role as a staple food for more than 800 million people in the world due to its ability to maintain relatively high productivity even in nutrient-depleted soils. Even though cassava has been the focus of several breeding programs and has become a strong focus of research in the last few years, relatively little is currently known about its metabolism and metabolic composition in different tissues. In this article, the absolute content of sugars, organic acids, amino acids, phosphorylated intermediates, minerals, starch, carotenoids, chlorophylls, tocopherols, and total protein as well as starch quality is described based on multiple analytical techniques, with protocols specifically adjusted for material from different cassava tissues. Moreover, quantification of secondary metabolites relative to internal standards is presented using both non-targeted and targeted metabolomics approaches. The protocols have also been adjusted to apply to freeze-dried material in order to allow processing of field harvest samples that typically will require long-distance transport. © 2019 The Authors. Basic Protocol 1: Metabolic profiling by gas chromatography-mass spectrometry (GC-MS) Support Protocol 1: Preparation of freeze-dried cassava material Support Protocol 2: Preparation of standard compound mixtures for absolute quantification of metabolites by GC-MS Support Protocol 3: Preparation of retention-time standard mixture Basic Protocol 2: Determination of organic acids and phosphorylated intermediates by ion chromatography-mass spectrometry (IC-MS) Support Protocol 4: Preparation of standards and recovery experimental procedure Basic Protocol 3: Determination of soluble sugars, starch, and free amino acids Alternate Protocol: Determination of soluble sugars and starch Basic Protocol 4: Determination of anions Basic Protocol 5: Determination of elements Basic Protocol 6: Determination of total protein Basic Protocol 7: Determination of non-targeted and targeted secondary metabolites Basic Protocol 8: Determination of carotenoids, chlorophylls, and tocopherol Basic Protocol 9: Determination of starch quality. PMID: 31834991 [PubMed - in process]

Metabolomics Horizon Scanning for 2020: Three Actionable Challenges.

Sat, 14/12/2019 - 13:09
Metabolomics Horizon Scanning for 2020: Three Actionable Challenges. OMICS. 2019 Dec 13;: Authors: Kilk K PMID: 31834853 [PubMed - as supplied by publisher]

Linking 24-h urines to clinical phenotypes: what alternatives does the future bring?

Sat, 14/12/2019 - 13:09
Linking 24-h urines to clinical phenotypes: what alternatives does the future bring? Curr Opin Urol. 2019 Dec 12;: Authors: Sui W, Hsi RS Abstract PURPOSE OF REVIEW: The 24-h urine test is recommended as part of the metabolic evaluation for patients with nephrolithiasis to guide preventive interventions. However, this test may be challenging to interpret and has limits in its predictive ability. In this review, we summarize and discuss the most recent research on the opportunities and challenges for utilizing urinary biomarkers for kidney stone prevention. RECENT FINDINGS: Contemporary studies utilizing the 24-h urine test have improved our understanding of how to better administer testing and interpret test results. Beyond the standard panel of 24-h urine parameters, recent applications of proteomics and metabolomics have identified protein and metabolic profiles of stone formers. These profiles can be assayed in future studies as potential biomarkers for risk stratification and prediction. Broad collaborative efforts to create large datasets and biobanks from kidney stone formers will be invaluable for kidney stone research. SUMMARY: Recent advances in our understanding of kidney stone risk have opened opportunities to improve metabolic testing for kidney stone formers. These strategies do not appear to be mutually exclusive of 24-h urine testing but instead complementary in their approach. Finally, large clinical datasets hold promise to be leveraged to identify new avenues for stone prevention. PMID: 31834081 [PubMed - as supplied by publisher]

Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections.

Sat, 14/12/2019 - 13:09
Integrated univariate, multivariate and correlation-based network analyses reveal metabolite-specific effects on bacterial growth and biofilm formation in necrotizing soft tissue infections. J Proteome Res. 2019 Dec 13;: Authors: Afzal M, Saccenti E, Madsen M, Hansen MB, Hyldegaard O, Skrede S, Martins Dos Santos V, Norrby Teglund A, Svensson M Abstract Necrotizing soft-tissue infections (NSTIs) have multiple causes, risk factors, anatomical locations, and pathogenic mechanisms. In patients with NSTI, circulating metabolites may serve as substrate having impact on bacterial adaptation at the site of infection. Metabolic signatures associated with NSTI may reveal potential be useful as diagnostic and prognostic markers, as well as novel targets for therapy. This study used untargeted metabolomics analyses of plasma from NSTI patients (n=34) and healthy (non-infected) controls (n=24) to identify the metabolic signatures and connectivity patterns among metabolites associated with NSTI. Metabolite-metabolite association networks were employed to compare the metabolic profiles of NSTI patients and non-infected surgical controls. Out of 97 metabolites detected, the abundance of 33 was significantly altered in NSTI patients. Analysis of metabolite-metabolite association networks showed a more densely connected network: specifically, 20 metabolites differentially connected between NSTI and controls. A selected set of significantly altered metabolites were tested in vitro to investigate potential influence on NSTI group A streptococcal strain growth and biofilm formation. Using chemically defined media supplemented with the selected metabolites, ornithine, ribose, urea and glucuronic acid, revealed metabolite-specific effects on both bacterial growth and biofilm formation. This study identifies for the first time an NSTI specific metabolic signature with implications for optimized diagnostics and therapies. PMID: 31833369 [PubMed - as supplied by publisher]

Berberine combined with stachyose induces better glycometabolism than berberine alone through modulating gut microbiota and fecal metabolomics in diabetic mice.

Sat, 14/12/2019 - 13:09
Related Articles Berberine combined with stachyose induces better glycometabolism than berberine alone through modulating gut microbiota and fecal metabolomics in diabetic mice. Phytother Res. 2019 Dec 13;: Authors: Li CN, Wang X, Lei L, Liu MZ, Li RC, Sun SJ, Liu SN, Huan Y, Zhou T, Liu Q, Cao H, Bai GL, Han YW, Shen ZF Abstract Berberine (BBR), a small alkaloid, is used as a hypoglycemic agent in China. Stachyose (Sta), a Rehmannia glutinosa oligosaccharide, acts as a prebiotic. This study aimed to evaluate whether BBR combined with Sta produced better glycometabolism than BBR alone, and explored the effects on gut microbiota and metabolomics. Type-2 diabetic db/db mice were administered BBR (100 mg/kg), Sta (200 mg/kg), or both by gavage once daily. Glucose metabolism, the balance of α- and β-cells, and mucin-2 expression were ameliorated by combined treatment of BBR and Sta, with stronger effects than upon treatment with BBR alone. The microbial diversity and richness were altered after combined treatment and after treatment with BBR alone. The abundance of Akkermansia muciniphila was increased by combined treatment compared to treatment with BBR alone, while the levels of the metabolite all-trans-heptaprenyl diphosphate were decreased and the levels of fumaric acid were increased, which both showed a strong correlation with A. muciniphila. In summary, BBR combined with Sta produced better glycometabolism than BBR alone through modulating gut microbiota and fecal metabolomics, and may aid in the development of a novel pharmaceutical strategy for treating Type 2 diabetes mellitus. PMID: 31833107 [PubMed - as supplied by publisher]

A Review on MS-Based Blood Biomarkers for Alzheimer's Disease.

Sat, 14/12/2019 - 13:09
Related Articles A Review on MS-Based Blood Biomarkers for Alzheimer's Disease. Neurol Ther. 2019 Dec;8(Suppl 2):113-127 Authors: Oeckl P, Otto M Abstract Alzheimer's disease (AD) is the most common form of neurodegenerative dementia and there is no cure to date. Biomarkers in cerebrospinal fluid (CSF) are already included in the diagnostic work-up of symptomatic patients but markers for preclinical diagnosis and disease progression are not available. Furthermore, blood biomarkers are highly appreciated because they are minimally invasive and more accessible in primary care and in clinical studies. Mass spectrometry (MS) is an established tool for the measurement of various analytes in biological fluids such as blood. Its major strength is the high selectivity which is why it is also preferred as a reference method for immunoassays. MS has been used in several studies in the past for blood biomarker discovery and validation in AD using targeted MS such as multiple/selected reaction monitoring (MRM/SRM) or unbiased approaches (proteomics, metabolomics). In this short review, we give an overview on the status of current MS-based biomarker candidates for AD in blood plasma and serum.Plain Language Summary: Plain language summary available for this article. PMID: 31833028 [PubMed]

Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status.

Sat, 14/12/2019 - 13:09
Related Articles Cerebrospinal fluid lipidomics: effects of an intravenous triglyceride infusion and apoE status. Metabolomics. 2019 Dec 12;16(1):6 Authors: Hanson AJ, Banks WA, Bettcher LF, Pepin R, Raftery D, Craft S Abstract INTRODUCTION: High-fat diets increase risk for Alzheimer's disease, but individuals with the risk gene APOE ε4 (E4) paradoxically have improved memory soon after high fat feeding. Little is known about how dietary lipids affect CNS lipids, especially in older adults. OBJECTIVES: We analyzed the lipidomic signature of cerebrospinal fluid (CSF) in older adults who underwent both a saline and TG infusion. We further analyzed these data by E4 carrier status. METHODS: Older adults (n = 21, age 67.7 ± 8.6) underwent a 5-h TG and saline infusion on different days in random crossover design; lumbar CSF was collected at the end of the infusion. Lipids were extracted using dichloromethane/methanol and 13 classes of lipids analyzed using the Lipidyzer platform consisting of an AB Sciex 5500 MS/MS QTraps system equipped with a SelexION for differential mobility spectrometry (DMS). Multiple reaction monitoring was used to target and quantify 1070 lipids in positive and negative ionization modes with and without DMS. RESULTS: The TG infusion increased total lipids in the CSF, including the appearance of more lipids at the detection limit in the TG samples compared to saline (Chi square p < 0.0001). The infusion increased the total level of diacylglycerols and lysophosphatidylcholines and reduced dihydroceramides. Of the possible 1070 lipids detectable, we found 348 after saline and 365 after TG infusion. Analysis using MetaboAnalyst revealed 11 specific lipids that changed; five of these lipids decreased after TG infusion, and four of them differed by E4 status, but none differed by cognitive diagnosis or sex. CONCLUSION: These results in older adults show that blood lipids affect lipid profiles in CSF and such profiles are modified by APOE status. This suggests that how the CNS handles lipids may be important in the AD phenotype. PMID: 31832778 [PubMed - in process]

Urinary metabolites and risk of coronary heart disease: A prospective investigation among urban Chinese adults.

Sat, 14/12/2019 - 13:09
Related Articles Urinary metabolites and risk of coronary heart disease: A prospective investigation among urban Chinese adults. Nutr Metab Cardiovasc Dis. 2019 Nov 05;: Authors: Yoon HS, Jeong Yang J, Rivera ES, Shu XO, Xiang YB, Calcutt MW, Cai Q, Zhang X, Li H, Gao YT, Zheng W, Yu D Abstract BACKGROUND AND AIMS: Studies have linked several metabolites to the risk of coronary heart disease (CHD) among Western populations, but prospective studies among Asian populations on the metabolite-CHD association remain limited. METHODS AND RESULTS: We evaluated the association of urinary metabolites with CHD risk among Chinese adults in a nested case-control study of 275 incident cases and 275 matched controls (127 pairs of men and 148 pairs of women). Fifty metabolites were measured by a predefined metabolomics panel and adjusted using urinary creatinine. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After adjusting for traditional CHD risk factors, urinary tryptophan showed a positive association with incident CHD: OR (95% CI) for the highest vs. lowest quartiles was 2.02 (1.15-3.56) among all study participants (p-trend = 0.02). The tryptophan-CHD association was more evident among individuals with dyslipidemia than among those without the condition (OR [95% CI] for the highest vs. lowest quartiles = 3.90 [1.86-8.19] and 0.74 [0.26-2.06], respectively; p-interaction<0.01). Other metabolites did not show significant associations with CHD risk among all study participants. However, a positive association of methionine with CHD risk was observed only among women (OR [95% CI] for the highest vs. lowest quartiles = 2.77 [1.17-6.58]; p-interaction = 0.03), and an inverse association of inosine with CHD risk was observed only among men (OR [95% CI] for the highest vs. lowest quartiles = 0.29 [0.11-0.81]; p-interaction = 0.04). CONCLUSION: Elevated urinary tryptophan may be related to CHD risk among Chinese adults, especially for those with dyslipidemia. PMID: 31831367 [PubMed - as supplied by publisher]

Systematic analysis of the metabolites of Angelol B by UPLC-Q-TOF-MS after oral administration to rats.

Sat, 14/12/2019 - 13:09
Related Articles Systematic analysis of the metabolites of Angelol B by UPLC-Q-TOF-MS after oral administration to rats. Chin J Nat Med. 2019 Nov;17(11):822-834 Authors: Wan MQ, Zhang YB, Liu XY, Li KM, Jia LY, Yang XW Abstract Angelicae Pubescentis Radix (APR), a widely used traditional Chinese medicine (TCM), is mainly used to treat rheumatism and headache diseases. Angelol B is one of the bioactive constituents of APR with significant anti-inflammatory activity. This paper is aimed to illustrate the metabolites of angelol B in vivo. To achieve this objective, a metabolomics approach based on a rapid and accurate UPLC-Q-TOF-MS method was used to detect the metabolites of Angelol B in rat. A gradient elution system (ACN and 0.1% formic acid water) equipped with an Agilent SB-C18 column (1.8 μm, 2.1 mm × 50 mm) to complete the separation. Scanning area at m/z 100.800 operated on an electrospray ionization (ESI). The data were collected in both positive and negative ion mode and analyzed by the Masslynx 4.1 and SIMCA 13.0 software. A total of 31 metabolites including 20 phase I and 11 phase II. metabolites were identified. Their structure and fragmentation process were deduced based on the MS and MS/MS data. All of thirty-one metabolites are new compounds based on the search of SCI-Finder database. PMID: 31831129 [PubMed - in process]

metabolomics; +21 new citations

Fri, 13/12/2019 - 16:01
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 2019/12/13PubMed 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; +21 new citations

Fri, 13/12/2019 - 13:01
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 2019/12/13PubMed 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; +28 new citations

Thu, 12/12/2019 - 15:52
28 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 2019/12/12PubMed 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; +28 new citations

Thu, 12/12/2019 - 12:52
28 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 2019/12/12PubMed 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; +25 new citations

Wed, 11/12/2019 - 15:46
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 2019/12/11PubMed 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; +25 new citations

Wed, 11/12/2019 - 12:45
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 2019/12/11PubMed 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; +22 new citations

Tue, 10/12/2019 - 15:36
22 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 2019/12/10PubMed 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.

metabolomics; +22 new citations

Tue, 10/12/2019 - 12:35
22 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 2019/12/10PubMed 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.

Correction of Dyssynergic Defecation, but not Fiber Supplementation, Reduces Symptoms of Functional Dyspepsia in Patients With Constipation in a Randomized Trial.

Sun, 08/12/2019 - 12:22
Correction of Dyssynergic Defecation, but not Fiber Supplementation, Reduces Symptoms of Functional Dyspepsia in Patients With Constipation in a Randomized Trial. Clin Gastroenterol Hepatol. 2019 Dec 04;: Authors: Huaman JW, Mego M, Bendezú A, Monrroy H, Samino S, Accarino A, Saperas E, Azpiroz F Abstract BACKGROUND & AIMS: Patients with functional dyspepsia are believed to have increased sensitivity of the gastrointestinal tract, and some also have functional constipation. We investigated whether in patients with functional dyspepsia, correction of dyssynergic defecation can reduce postprandial fullness. METHODS: We performed a parallel trial at 2 referral centers in Spain, from June 2016 through January 2018 of 50 patients who fulfilled the Rome IV criteria for functional dyspepsia with postprandial distress syndrome and functional constipation and dyssynergic defecation. After a 2-week pretreatment phase, the patients were randomly assigned to groups that learned to correct dyssynergic defecation (2-3 sessions of biofeedback combined with instructions for daily exercise; n=25) or received dietary fiber supplementation (3.5 g plantago ovata per day; n=25) for 4 weeks. The primary outcome was change in postprandial abdominal fullness, measured daily on a scale of 0-10, during the last 7 days treatment phase vs the last 7 days of the pretreatment phase. Anal gas evacuations were measured (by an event marker) during the last 2 days of the pretreatment vs treatment phases. RESULTS: Biofeedback treatment corrected dyssynergic defecation in 19/25 patients; corrected dyssynergic defection reduced postprandial fullness by 22%±1% in these patients (P<.001), and reduced the number of anal evacuations by 21%±8% (P=.009). Fiber supplementation did not reduce postprandial fullness or anal evacuations (P≤.023 between groups for both parameters in the intent to treat analysis). CONCLUSIONS: Diagnosis and correction of dyssynergic defecation reduces dyspeptic symptoms by more than 20% in patients with functional dyspepsia and associated constipation. Dietary fiber supplementation does not reduce symptoms in these patients. ClinicalTrials.gov no: NCT02956187. PMID: 31811952 [PubMed - as supplied by publisher]

Harnessing microbial metabolomics for industrial applications.

Sun, 08/12/2019 - 12:22
Related Articles Harnessing microbial metabolomics for industrial applications. World J Microbiol Biotechnol. 2019 Dec 06;36(1):1 Authors: Zhao J, Wang G, Chu J, Zhuang Y Abstract Metabolome defines a set of metabolites present in a biological sample, which provides an immediate and dynamic recording of microbes in response to genetic and/or environmental perturbations. In recent years, metabolomics in combination with other omics diagnostic tools such as genomics, transcriptomics and proteomics is focused on addressing open biological questions that accelerate our understanding of the system as a whole and boost the use of systems metabolic engineering tools in industrial settings. In this review article, we summarize the applications of metabolomics to industrial microbial fermentations with respect to the bulk production of organic acids, amino acids, enzymes, antibiotics and therapeutic proteins. In addition, future prospects regarding metabolomics-assisted research are provided. PMID: 31811524 [PubMed - in process]

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