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

metabolomics; +37 new citations

Tue, 09/02/2021 - 14:11
37 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 2021/02/09PubMed 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.

[Sequential Changes of Serum Biomarkers after Skeletal Muscle Contusion in Rats].

Tue, 09/02/2021 - 08:11
Related Articles [Sequential Changes of Serum Biomarkers after Skeletal Muscle Contusion in Rats]. Fa Yi Xue Za Zhi. 2020 Dec;36(6):755-761 Authors: Zhai HJ, Lin W, Tian T, Liu M Abstract Abstract: Objective To screen serum biomarkers after skeletal muscle contusion in rats based on gas chromatography-mass spectrometry (GC-MS) metabolomics technology, and support vector machine (SVM) regression model was established to estimate skeletal muscle contusion time. Methods The 60 healthy SD rats were randomly divided into experimental group (n=50), control group (n=5) and validation group (n=5). The rats in the experimental group and the validation group were used to establish the model of skeletal muscle contusion through free fall method, the rats in experimental group were executed at 0 h, 2 h, 4 h, 8 h, 12 h, 24 h, 48 h, 96 h, 144 h and 240 h, respectively, and the rats in validation group were executed at 192 h, while the rats in the control group were executed after three days' regular feeding. The skeletal muscles were stained with hematoxylin-eosin (HE). The serum metabolite spectrum was detected by GC-MS, and orthogonal partial least square-discriminant analysis (OPLS-DA) pattern recognition method was used to discriminate the data and select biomarkers. The SVM regression model was established to estimate the contusion time. Results The 31 biomarkers were initially screened by metabolomics method and 6 biomarkers were further selected. There was no regularity in the changes of the relative content of the 6 biomarkers with the contusion time and the SVM regression model can be successfully established according to the data of 6 biomarkers and the 31 biomarkers. Compared with the injury time [(55.344±7.485) h] estimated from the SVM regression model based on the data of 6 biomarkers, the injury time [(195.781±1.629) h] estimated from the SVM regression model based on the data of 31 biomarkers was closer to the actual value. Conclusion The SVM regression model based on metabolites data can be used for the contusion time estimation of skeletal muscles. PMID: 33550722 [PubMed - in process]

[Estimation of Early Postmortem Interval of Asphyxial Death Rats at Different Ambient Temperatures by GC-MS-Based Metabolomics].

Tue, 09/02/2021 - 08:11
Related Articles [Estimation of Early Postmortem Interval of Asphyxial Death Rats at Different Ambient Temperatures by GC-MS-Based Metabolomics]. Fa Yi Xue Za Zhi. 2020 Dec;36(6):741-748 Authors: Fang SY, Dai XH, Xiao L, Zou J, Yang L, Ye Y, Liao LC Abstract Abstract: Objective To establish the orthogonal partial least square (OPLS) model for the estimation of early postmortem interval (PMI) of asphyxial death rats in four ambient temperatures based on gas chromatography-mass spectrometry (GC-MS) metabolomics. Methods The 96 rats were divided into four temperature groups (5 ℃, 15 ℃, 25 ℃ and 35 ℃). Each temperature group was further divided into 3 h, 6 h, 12 h and 24 h after death, and 6 other rats were taken as the control group. The cardiac blood was collected at the set time points for the four temperature groups and 0 h after death for the control group for the metabolomics analysis by GC-MS. By OPLS analysis, the variable importance in projection (VIP)>1 and the result of Kruskal-Wallis test P<0.001 were used to screen out the differential metabolite related to PMIs in the cardiac blood of rats of different temperature groups. Then OPLS regression models of different temperature groups were established with these metabolites. At the same time, a prediction group for investigating the prediction ability of these models was set up. Results Through the analysis of OPLS, 18, 15, 24 and 30 differential metabolites (including organic acids, amino acids, sugars and lipids) were screened out from the rats in groups of 5 ℃, 15 ℃, 25 ℃ and 35 ℃, respectively. The prediction results of the four temperature group models showed that the prediction deviation of 5 ℃ model was larger than that of other groups. The prediction results of other temperature groups were satisfactory. Conclusion There are some differences in the changes of metabolites in cardiac blood of rats at different ambient temperatures. The influence of ambient temperature should be investigated in the study of PMI estimation by metabolomics, which may improve the accuracy of PMI estimation. PMID: 33550720 [PubMed - in process]

Untargeted Metabolomics Reveals Elevated L-Carnitine Metabolism in Pig and Rat Colon Tissue Following Red Versus White Meat Intake.

Tue, 09/02/2021 - 08:11
Related Articles Untargeted Metabolomics Reveals Elevated L-Carnitine Metabolism in Pig and Rat Colon Tissue Following Red Versus White Meat Intake. Mol Nutr Food Res. 2021 Feb 07;:e2000463 Authors: Rombouts C, Van Meulebroek L, De Spiegeleer M, Goethals S, Van Hecke T, De Smet S, De Vos WH, Vanhaecke L Abstract SCOPE: The consumption of red and processed meat, and not white meat, has been associated with the development of various Western diseases such as colorectal cancer and type 2 diabetes. This work aimed at unravelling novel meat-associated mechanisms that are involved in disease development. METHODS AND RESULTS: A non-hypothesis driven strategy of untargeted metabolomics was applied to assess colon tissue from rats (fed a high dose of beef versus white meat) and from pigs (fed red/processed meat versus white meat), receiving a realistic human background diet. An increased carnitine metabolism was observed, which was reflected by higher levels of acylcarnitines and 3-dehydroxycarnitine (rats and pigs) and trimethylamine-N-oxide (rats). While 3-dehydroxycarnitine was higher in HT29 cells, incubated with colonic beef digests, acylcarnitine levels were reduced. This suggested an altered response from colon cancer cell line towards meat-induced oxidative stress. Moreover, metabolic differences between rat and pigs were observed in N-glycolylneuraminic acid incorporation, prostaglandin and fatty acid synthesis. CONCLUSION: This study demonstrated elevated (acyl)carnitine metabolism in colon tissue of animals that followed a red meat-based diet, providing mechanistic insights that may aid in explaining the nutritional-physiological correlation between red/processed meat and Western diseases. This article is protected by copyright. All rights reserved. PMID: 33550692 [PubMed - as supplied by publisher]

Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus.

Tue, 09/02/2021 - 08:11
Related Articles Global metabolomic profiling reveals hepatic biosignatures that reflect the unique metabolic needs of late-term mother and fetus. Metabolomics. 2021 02 07;17(2):23 Authors: Saini N, Virdee M, Helfrich KK, Kwan STC, Smith SM Abstract OBJECTIVE: Gestational disorders including preeclampsia, growth restriction and diabetes are characterized, in part, by altered metabolic interactions between mother and fetus. Understanding their functional relevance requires metabolic characterization under normotypic conditions. METHODS: We performed untargeted metabolomics on livers of pregnant, late-term C57Bl/6J mice (N = 9 dams) and their fetuses (pooling 4 fetuses/litter), using UPLC-MS/MS. RESULTS: Multivariate analysis of 730 hepatic metabolites revealed that maternal and fetal metabolite profiles were highly compartmentalized, and were significantly more similar within fetuses (ρaverage = 0.81), or within dams (ρaverage = 0.79), than within each maternal-fetal dyad (ρaverage = - 0.76), suggesting that fetal hepatic metabolism is under distinct and equally tight metabolic control compared with its respective dam. The metabolite profiles were consistent with known differences in maternal-fetal metabolism. The reduced fetal glucose reflected its limited capacity for gluconeogenesis and dependence upon maternal plasma glucose pools. The fetal decreases in essential amino acids and elevations in their alpha-keto acid carnitine conjugates reflects their importance as secondary fuel sources to meet fetal energy demands. Whereas, contrasting elevations in fetal serine, glycine, aspartate, and glutamate reflects their contributions to endogenous nucleotide synthesis and fetal growth. Finally, the elevated maternal hepatic lipids and glycerol were consistent with a catabolic state that spares glucose to meet competing maternal-fetal energy demands. CONCLUSIONS: The metabolite profile of the late-term mouse dam and fetus is consistent with prior, non-rodent analyses utilizing plasma and urine. These data position mouse as a suitable model for mechanistic investigation into how maternal-fetal metabolism adapts (or not) to gestational stressors. PMID: 33550560 [PubMed - in process]

Untargeted metabolomic profiling of serum in dogs with hypothyroidism.

Tue, 09/02/2021 - 08:11
Related Articles Untargeted metabolomic profiling of serum in dogs with hypothyroidism. Res Vet Sci. 2021 Jan 30;136:6-10 Authors: Muñoz-Prieto A, González-Arostegui LG, Rubić I, Cerón JJ, Tvarijonaviciute A, Horvatić A, Mrljak V Abstract Hypothyroidism is one of the most commonly diagnosed endocrine disease in dogs. The clinical signs are caused by a deficiency of the active thyroid hormones triiodothyronine (T3) and thyroxine (T4) and have a negative impact on dog's quality of life. We hypothesized that serum metabolic profile varies between healthy dogs and dogs with hypothyroidism. Twenty serum samples from dogs with hypothyroidism and 20 from healthy dogs were used for untargeted metabolomics analysis performed by LC/MS analysis. Fifteen metabolites showed significant changes between hypothyroid and healthy dogs, being the pentose phosphate pathway (PPP), aminoacyl-tRNA biosynthesis and pyrimidine metabolism the principal pathways altered in hypothyroidism. Specifically, metabolites such as D-gluconic acid and L-Isoleucine may potentially act as biomarkers of disease. PMID: 33550147 [PubMed - as supplied by publisher]

An 'omics approach to investigate the growth effects of environmentally relevant concentrations of guanylurea exposure on Japanese medaka (Oryzias latipes).

Tue, 09/02/2021 - 08:11
Related Articles An 'omics approach to investigate the growth effects of environmentally relevant concentrations of guanylurea exposure on Japanese medaka (Oryzias latipes). Aquat Toxicol. 2021 Jan 29;232:105761 Authors: Ussery EJ, Nielsen KM, Simmons D, Pandelides Z, Mansfield C, Holdway D Abstract Metformin is a widely prescribed pharmaceutical used in the treatment of numerous human health disorders, including Type 2 Diabetes, and as a results of its widespread use, metformin is thought to be the most prevalent pharmaceutical in the aquatic environment by weight. The removal of metformin during the water treatment process is directly related to the formation of its primary degradation product, guanylurea, generally present at higher concentrations in surface waters relative to metformin. Growth effects observed in 28-day early life stage (ELS) Japanese medaka exposed to guanylurea were found to be similar to growth effects in 28-day ELS medaka exposed to metformin; however, effect concentrations were orders of magnitude below those of metformin. The present study uses a multi-omics approach to investigate potential mechanisms by which low-level, 1 ng · L-1 nominal, guanylurea exposure may lead to altered growth in 28-day post hatch medaka via shotgun metabolomics and proteomics and qPCR. Specifically, analyses show 6 altered metabolites, 66 altered proteins and 2 altered genes. Collectively, metabolomics, proteomics, and gene expression data (using qPCR) indicate that developmental exposure to guanylurea exposure alters a number of important pathways related to the overall health of ELS fish, including biomolecule metabolism, cellular energetics, nervous system function/development, cellular communication and structure, and detoxification of reactive oxygen species, among others. To our knowledge, this is the first study to both report the molecular level effects of guanylurea on non-target aquatic organisms, and to relate molecular-level changes to whole organism effects. PMID: 33550114 [PubMed - as supplied by publisher]

Biochemical mechanisms of rhizospheric Bacillus subtilis-facilitated phytoextraction by alfalfa under cadmium stress - Microbial diversity and metabolomics analyses.

Tue, 09/02/2021 - 08:11
Related Articles Biochemical mechanisms of rhizospheric Bacillus subtilis-facilitated phytoextraction by alfalfa under cadmium stress - Microbial diversity and metabolomics analyses. Ecotoxicol Environ Saf. 2021 Feb 04;212:112016 Authors: Li Q, Xing Y, Fu X, Ji L, Li T, Wang J, Chen G, Qi Z, Zhang Q Abstract The effects of Bacillus subtilis inoculation on the growth and Cd uptake of alfalfa were evaluated in this research using pot experiments, and the relevant biochemical mechanisms were first investigated by combined microbial diversity and nontarget metabolomics analyses. The results indicated that inoculation with alfalfa significantly decreased the amount of plant malondialdehyde (MDA) and improved the activities of plant antioxidant enzymes and soil nutrient cycling-involved enzymes, thereby promoting biomass by 29.4%. Inoculation also increased Cd bioavailability in rhizosphere soil by 12.0% and Cd removal efficiency by 139.3%. The biochemical mechanisms included enhanced bacterial diversity, transformed microbial community composition, regulated amounts of amino acids, fatty acids, carbohydrates, flavonoids and phenols in rhizosphere soil metabolites, and modulations of the corresponding Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. These responses were beneficial to microbial activity, nutrient cycling, and Cd mobilization, detoxification, and decontamination by alfalfa in soil. This study, especially the newly identified differential metabolites and metabolic pathways, provides new insights into mechanism revelation and strategy development in microbe-assisted phytomanagement of heavy metal-contaminated soils. PMID: 33550079 [PubMed - as supplied by publisher]

Measurement of melanin metabolism in live cells by [U-13C]-tyrosine fate tracing using LC-MS.

Tue, 09/02/2021 - 08:11
Related Articles Measurement of melanin metabolism in live cells by [U-13C]-tyrosine fate tracing using LC-MS. J Invest Dermatol. 2021 Feb 04;: Authors: Chen Q, Zhou D, Abdel-Malek Z, Zhang F, Goff PS, Sviderskaya EV, Wakamatsu K, Ito S, Gross SS, Zippin JH Abstract Melanin synthesis occurs within a specialized organelle called the melanosome. Traditional methods for measuring melanin levels rely on the detection of chemical degradation products of melanin by high-performance liquid chromatography (HPLC). Although these methods are robust, they are unable to distinguish between melanin synthesis and degradation, and are best suited to measure melanin changes over long periods of time. We developed a method that actively measures both eumelanin and pheomelanin synthesis by fate tracing [U-13C] tyrosine using liquid chromatography-mass spectrometry (LC-MS). Using this method, we confirmed previous reports of melanin synthesis differences between melanocytes derived from individuals with different skin color or MC1R genotype, and uncovered new information regarding the differential de novo synthesis of eumelanin and pheomelanin, also called mixed melanogenesis. We also revealed that distinct mechanisms that alter melanosomal pH differentially induce new eumelanin and pheomelanin synthesis. Finally, we revealed that the synthesis of L-DOPA, an important metabolite of tyrosine, is differentially controlled by multiple factors. Because tyrosine fate tracing is compatible with untargeted LC-MS based metabolomics, this approach enables the broad measurement of cellular metabolism in combination with melanin metabolism, and we anticipate that this approach will shed new light on multiple mechanisms of melanogenesis. PMID: 33549605 [PubMed - as supplied by publisher]

Investigation of the effects of actinorhodin biosynthetic gene cluster expression and a rpoB point mutation on the metabolome of Streptomyces coelicolor M1146.

Tue, 09/02/2021 - 08:11
Related Articles Investigation of the effects of actinorhodin biosynthetic gene cluster expression and a rpoB point mutation on the metabolome of Streptomyces coelicolor M1146. J Biosci Bioeng. 2021 Feb 03;: Authors: Nitta K, Breitling R, Takano E, Putri SP, Fukusaki E Abstract The previously reported Streptomyces coelicolor M1146 is commonly used as a host strain for engineering of secondary metabolite production. In this study, absolute quantification of intracellular and extracellular metabolites of M1146 was performed in mid-log phase and stationary phase to observe major metabolites and the changes that occurred during growth. Decreased levels of central carbon metabolites (glycolysis, TCA cycle, and pentose phosphate pathway) and increased levels of amino acids were observed in stationary phase compared to mid-log phase. Furthermore, comparative metabolome analyses of M1146 upon expression of the actinorhodin biosynthetic gene cluster (M1146+ACT), a point mutation on the rpoB gene encoding RNA polymerase beta-subunit (M1152), and both expression of actinorhodin biosynthetic gene cluster and a rpoB point mutation (M1152+ACT) were performed. M1146+ACT showed higher levels of important cofactors, such as ATP, NADPH, and FMN while M1152 led to higher levels of intracellular S-adenosyl-methionine, acyl-CoAs, and extracellular nucleosides compared to M1146. M1152+ACT exhibited the highest levels of actinorhodin with elevated bases, nucleosides, and nucleotides, such as intracellular PRPP (phosphoribosyl phosphate), ATP, along with extracellular inosine, uridine, and guanine compared to the other three strains, which were considered to be combined effects of actinorhodin gene cluster expression and a rpoB point mutation. Metabolites analysis by means of absolute quantification demonstrated changes in precursors of secondary metabolites before and after phosphate depletion in M1146. Comparative metabolome analysis provided further insights into the effects of actinorhodin gene cluster expression along with a rpoB point mutation on the metabolome of S. coelicolor. PMID: 33549493 [PubMed - as supplied by publisher]

Marine Omega-3 Fatty Acids and Cardiovascular Disease Prevention: Seeking Clearer Water.

Tue, 09/02/2021 - 08:11
Related Articles Marine Omega-3 Fatty Acids and Cardiovascular Disease Prevention: Seeking Clearer Water. Mayo Clin Proc. 2021 Feb;96(2):277-279 Authors: Farukhi ZM, Mora S, Manson JE PMID: 33549246 [PubMed - in process]

New insights into the role of MADS-box transcription factor gene CmANR1 on root and shoot development in chrysanthemum (Chrysanthemum morifolium).

Tue, 09/02/2021 - 08:11
Related Articles New insights into the role of MADS-box transcription factor gene CmANR1 on root and shoot development in chrysanthemum (Chrysanthemum morifolium). BMC Plant Biol. 2021 Feb 06;21(1):79 Authors: Sun CH, Wang JH, Gu KD, Zhang P, Zhang XY, Zheng CS, Hu DG, Ma F Abstract BACKGROUND: MADS-box transcription factors (TFs) are the key regulators of multiple developmental processes in plants; among them, a chrysanthemum MADS-box TF CmANR1 has been isolated and described as functioning in root development in response to high nitrate concentration signals. However, how CmANR1 affects root and shoot development remains unclear. RESULTS: We report that CmANR1 plays a positive role in root system development in chrysanthemum throughout the developmental stages of in vitro tissue cultures. Metabolomics combined with transcriptomics assays show that CmANR1 promotes robust root system development by facilitating nitrate assimilation, and influencing the metabolic pathways of amino acid, glycolysis, and the tricarboxylic acid cycle (TCA) cycle. Also, we found that the expression levels of TFs associated with the nitrate signaling pathways, such as AGL8, AGL21, and LBD29, are significantly up-regulated in CmANR1-transgenic plants relative to the wild-type (WT) control; by contrast, the expression levels of RHD3-LIKE, LBD37, and GATA23 were significantly down-regulated. These results suggest that these nitrate signaling associated TFs are involved in CmANR1-modulated control of root development. In addition, CmANR1 also acts as a positive regulator to control shoot growth and development. CONCLUSIONS: These findings provide potential mechanisms of MADS-box TF CmANR1 modulation of root and shoot development, which occurs by regulating a series of nitrate signaling associated TFs, and influencing the metabolic pathways of amino acid and glycolysis, as well as TCA cycle and nitrate assimilation. PMID: 33549046 [PubMed - in process]

metabolomics; +16 new citations

Sun, 07/02/2021 - 14:00
16 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 2021/02/07PubMed 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

Sat, 06/02/2021 - 19:55
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 2021/02/06PubMed 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; +27 new citations

Fri, 05/02/2021 - 13:47
27 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 2021/02/05PubMed 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.

Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype.

Thu, 04/02/2021 - 13:41
Related Articles Characteristics and Mechanisms of a Sphingolipid-associated Childhood Asthma Endotype. Am J Respir Crit Care Med. 2021 Feb 03;: Authors: Rago D, Pedersen CT, Huang M, Kelly RS, Gürdeniz G, Brustad N, Knihtil H, Lee-Sarwar KA, Morin A, Rasmussen MA, Stokholm J, Bønnelykke K, Litonjua AA, Wheelock CE, Weiss ST, Lasky-Su J, Bisgaard H, Chawes BL Abstract RATIONALE: A link between sphingolipids, 17q21 genetic variants and childhood asthma has been suggested, but the underlying mechanisms and characteristics of such asthma endotype remain to be elucidated. OBJECTIVE: To study the sphingolipid-associated childhood asthma endotype using multi-omics data. METHODS: We used untargeted LC-MS plasma metabolomics profiles at age 6 months and 6 years from >500 children in the COPSAC2010 birth cohort focusing on sphingolipids, and integrated 17q21 genotype and nasal gene expression of serine palmitoyl-CoA transferase (SPT), i.e. the rate-limiting enzyme in the de novo sphingolipid synthesis, in relation to asthma development and lung function traits from infancy till age 6 years. Replication was sought in the independent VDAART cohort. MEASUREMENTS AND MAIN RESULTS: Lower levels of ceramides and sphingomyelins at age 6 months were associated with increased risk of developing asthma before age 3, which was also observed in VDAART. At age 6 years, lower levels of key phosphosphingolipids, e.g. sphinganine-1-phosphate were associated with increased airway resistance. This relationship was dependent on 17q21 genotype and nasal SPT gene expression with significant interaction between genotype and phosphosphingolipids levels and between genotype and SPT expression, showing lower phosphosphingolipids and reduced SPT expression with increasing number of at-risk alleles. However, the findings did not pass FDR<0.05. CONCLUSIONS: This exploratory study suggests the existence of a childhood asthma endotype with early onset and increased airway resistance that is characterized by reduced sphingolipid levels that is associated with 17q21 genetic variants and expression of the SPT enzyme. PMID: 33535020 [PubMed - as supplied by publisher]

Plasma metabolomic profile associated with fatigue in cancer patients.

Thu, 04/02/2021 - 13:41
Related Articles Plasma metabolomic profile associated with fatigue in cancer patients. Cancer Med. 2021 Feb 03;: Authors: Feng LR, Barb JJ, Regan J, Saligan LN Abstract BACKGROUND: Metabolomics is the newest -omics methodology and allows for a functional snapshot of the biochemical activity and cellular state. The goal of this study is to characterize metabolomic profiles associated with cancer-related fatigue, a debilitating symptom commonly reported by oncology patients. METHODS: Untargeted ultrahigh performance liquid chromatography/mass spectrometry metabolomics approach was used to identify metabolites in plasma samples collected from a total of 197 participants with or without cancer. Partial least squares-discriminant analysis (PLS-DA) was used to identify discriminant metabolite features, and diagnostic performance of selected classifiers was quantified using area under the receiver operating characteristics (AUROC) curve analysis. Pathway enrichment analysis was performed using Fisher's exact test and the Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway database. FINDINGS: The global metabolomics approach yielded a total of 1120 compounds of known identity. Significant metabolic pathways unique to fatigued cancer versus control groups included sphingolipid metabolism, histidine metabolism, and cysteine and methionine metabolism. Significant pathways unique to non-fatigued cancer versus control groups included inositol phosphate metabolism, primary bile acid biosynthesis, ascorbate and aldarate metabolism, starch and sucrose metabolism, and pentose and glucuronate interconversions. Pathways shared between the two comparisons included caffeine metabolism, tyrosine metabolism, steroid hormone biosynthesis, sulfur metabolism, and phenylalanine metabolism. CONCLUSIONS: We found significant metabolomic profile differences associated with cancer-related fatigue. By comparing metabolic signatures unique to fatigued cancer patients with metabolites associated with, but not unique to, fatigued cancer individuals (overlap pathways) and metabolites associated with cancer but not fatigue, we provided a broad view of the metabolic phenotype of cancer-related fatigue. PMID: 33534943 [PubMed - as supplied by publisher]

Metabolic dysfunction in pregnancy: Fingerprinting the maternal metabolome using proton nuclear magnetic resonance spectroscopy.

Thu, 04/02/2021 - 13:41
Related Articles Metabolic dysfunction in pregnancy: Fingerprinting the maternal metabolome using proton nuclear magnetic resonance spectroscopy. Endocrinol Diabetes Metab. 2021 Jan;4(1):e00201 Authors: Scott HD, Buchan M, Chadwick C, Field CJ, Letourneau N, Montina T, Leung BMY, Metz GAS Abstract Aims: Maternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long-term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre-GDM), compared to controls. Methods and Materials: Second trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with 1H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation. Results: Obesity and pre-GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre-GDM. The three most impacted metabolites for the comparison of obesity versus pre-GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM. Conclusion: These findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk. PMID: 33532625 [PubMed]

Capsule endoscopy transit-related indicators in choosing the insertion route for double-balloon enteroscopy: a systematic review.

Thu, 04/02/2021 - 13:41
Related Articles Capsule endoscopy transit-related indicators in choosing the insertion route for double-balloon enteroscopy: a systematic review. Endosc Int Open. 2021 Feb;9(2):E163-E170 Authors: Cortegoso Valdivia P, Skonieczna-Żydecka K, Pennazio M, Rondonotti E, Marlicz W, Toth E, Koulaouzidis A Abstract Background and study aims  When capsule endoscopy (CE) detects a small bowel (SB) target lesion that may be manageable with enteroscopy, the selection of the insertion route is critical. Time- and progression-based CE indices have been proposed for localization of SB lesions. This systematic review analysed the role of CE transit indicators in choosing the insertion route for double-balloon enteroscopy (DBE). Methods  A comprehensive literature search identified papers assessing the role of CE on the choice of the route selection for DBE. Data on CE, criteria for route selection, and DBE success parameters were retrieved and analyzed according to the PRISMA statement. Risk of bias was assessed through the STROBE assessment. The primary outcome evaluated was DBE success rate in reaching a SB lesion, measured as the ratio of positive initial DBE to the number of total DBE. Results  Seven studies including 262 CEs requiring subsequent DBE were selected. Six studies used time-based indices and one used the PillCam Progress indicator. SB lesions were identified and insertion route was selected according to a specific cut-off, using fixed landmarks for defining SB transit except for one study in which the mouth-cecum transit was considered. DBE success rate was high in all studies, ranging from 78.3 % to 100 %. Six of seven studies were high quality. Conclusions  The precise localization of SB lesions remains an open issue, and larger studies are required to determine the most accurate index for selecting the DBE insertion route. In the future, 3 D localization technologies and tracking systems will be essential to accomplish this tricky task. PMID: 33532554 [PubMed]

Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions.

Thu, 04/02/2021 - 13:41
Related Articles Metabolomics study reveals the potential evidence of metabolic reprogramming towards the Warburg effect in precancerous lesions. J Cancer. 2021;12(5):1563-1574 Authors: Chen X, Yi C, Yang MJ, Sun X, Liu X, Ma H, Li Y, Li H, Wang C, He Y, Chen G, Chen S, Yu L, Yu D Abstract Background: Most tumors have an enhanced glycolysis flux, even when oxygen is available, called the aerobic glycolysis or the Warburg effect. Metabolic reprogramming promotes cancer progression, and is even related to the tumorigenesis. However, it is not clear whether the observed metabolic changes act as a driver or a bystander in cancer development. Methods: In this study, the metabolic characteristics of oral precancerous cells and cervical precancerous lesions were analyzed by metabolomics, and the expression of glycolytic enzymes in cervical precancerous lesions was evaluated by RT-PCR and Western blot analysis. Results: In total, 115 and 23 metabolites with reliable signals were identified in oral cells and cervical tissues, respectively. Based on the metabolome, oral precancerous cell DOK could be clearly separated from normal human oral epithelial cells (HOEC) and oral cancer cells. Four critical differential metabolites (pyruvate, glutamine, methionine and lysine) were identified between DOK and HOEC. Metabolic profiles could clearly distinguish cervical precancerous lesions from normal cervical epithelium and cervical cancer. Compared with normal cervical epithelium, the glucose consumption and lactate production increased in cervical precancerous lesions. The expression of glycolytic enzymes LDHA, HK II and PKM2 showed an increased tendency in cervical precancerous lesions compared with normal cervical epithelium. Conclusions: Our findings suggest that cell metabolism may be reprogrammed at the early stage of tumorigenesis, implying the contribution of metabolic reprogramming to the development of tumor. PMID: 33532002 [PubMed]

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