PubMed

Related Articles Probabilistic identification of saccharide moieties in biomolecules and their protein complexes. Sci Data. 2020 Jul 03;7(1):210 Authors: Dashti H, Westler WM, Wedell JR, Demler OV, Eghbalnia HR, Markley JL, Mora S Abstract The chemical composition of saccharide complexes underlies their biomedical activities as biomarkers for cardiometabolic disease, various types of cancer, and other conditions. However, because these molecules may undergo major structural modifications, distinguishing between compounds of saccharide and non-saccharide origin becomes a challenging computational problem that hinders the aggregation of information about their bioactive moieties. We have developed an algorithm and software package called "Cheminformatics Tool for Probabilistic Identification of Carbohydrates" (CTPIC) that analyzes the covalent structure of a compound to yield a probabilistic measure for distinguishing saccharides and saccharide-derivatives from non-saccharides. CTPIC analysis of the RCSB Ligand Expo (database of small molecules found to bind proteins in the Protein Data Bank) led to a substantial increase in the number of ligands characterized as saccharides. CTPIC analysis of Protein Data Bank identified 7.7% of the proteins as saccharide-binding. CTPIC is freely available as a webservice at (http://ctpic.nmrfam.wisc.edu). PMID: 32620933 [PubMed - as supplied by publisher]

Related Articles Metabolome of Mammary Tumors Differs from Normal Mammary Glands But Is Not Altered by Time-restricted Feeding Under Obesogenic Conditions. Anticancer Res. 2020 Jul;40(7):3697-3705 Authors: Yan L, Sundaram S, Rust BM, Picklo MJ, Bukowski MR Abstract BACKGROUND/AIM: Time restricted feeding (TRF) mitigates the high-fat diet-enhanced mammary tumorigenesis in a MMTV-PyMT breast cancer model. MATERIALS AND METHODS: We performed untargeted metabolomic and targeted transcriptomic analyses on mammary tumors from MMTV-PyMT mice fed a standard AIN93G diet, a high-fat diet (HFD), or HFD with TRF (12 h, dark phase) and mammary glands from wild-type mice fed the AIN93G diet. RESULTS: The metabolic profile of mammary tumors differed from that of mammary glands; there was no impact of TRF upon tumor metabolome. TRF did reduce elevated expression of Hmgcr, Srebp1, Fads2, and Ppard in mammary tumors, indicating a down-regulation of lipid metabolism. CONCLUSION: The null effect of TRF on the metabolomic profile does not rule out changes in more refined intracellular signaling pathways. It suggests that the protection of TRF against mammary tumorigenesis may rely upon its action on the host rather than a direct effect on tumor metabolism. PMID: 32620608 [PubMed - as supplied by publisher]

Related Articles A novel urinary biomarker protein panel to identify children with ureteropelvic junction obstruction - A pilot study. J Pediatr Urol. 2020 Jun 11;: Authors: Devarakonda CKV, Shearier ER, Hu C, Grady J, Balsbaugh JL, Makari JH, Ferrer FA, Shapiro LH Abstract INTRODUCTION AND OBJECTIVE: Reliable urinary biomarker proteins would be invaluable in identifying children with ureteropelvic junction obstruction (UPJO) as the existing biomarker proteins are inconsistent in their predictive ability. Therefore, the aim of this study was to identify consistent and reliable urinary biomarker proteins in children with UPJO. METHODS: To identify candidate biomarker proteins, total protein from age-restricted (<2 years) and sex-matched (males) control (n = 22) and UPJO (n = 21) urine samples was analyzed by mass spectrometry. Proteins that were preferentially identified in UPJO samples were selected (2-step process) and ranked according to their diagnostic odds ratio value. The top ten proteins with highest odds ratio values were selected and tested individually by ELISA. The total amount of each protein was normalized to urine creatinine and the median with interquartile ranges for control and UPJO samples was determined. Additionally, fold change (UPJO/Control) of medians of the final panel of 5 proteins was also determined. Finally, we calculated the average + 3(SD) and average + 4(SD) values of each of the 5 proteins in the control samples and used it as an arbitrary cutoff to classify individual control and UPJO samples. RESULTS: In the first step of our selection process, we identified 171 proteins in UPJO samples that were not detected in the majority of the control samples (16/22 samples, or 72.7%). Of the 171 proteins, only 50 proteins were detected in at least 11/21 (52.4%) of the UPJO samples and hence were selected in the second step. Subsequently, these 50 proteins were ranked according to the odds ratio value and the top 10 ranked proteins were validated by ELISA. Five of the 10 proteins - prostaglandin-reductase-1, ficolin-2, nicotinate-nucleotide pyrophosphorylase [carboxylating], immunoglobulin superfamily-containing leucine-rich-repeat-protein and vascular cell adhesion molecule-1 were present at higher levels in the UPJO samples (fold-change of the median protein concentrations ranging from 2.9 to 9.4) and emerged as a panel of biomarkers to identify obstructive uropathy. Finally, the order of prevalence of the 5 proteins in UPJO samples is PTGR1>FCN2>QPRT>ISLR>VCAM1. CONCLUSION: In summary, this unique screening strategy led to the identification of previously unknown biomarker proteins that when screened collectively, may reliably distinguish between obstructed vs. non-obstructed infants and may prove useful in identifying informative biomarker panels for biological samples from many diseases. PMID: 32620509 [PubMed - as supplied by publisher]

Related Articles Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease. Trends Mol Med. 2020 Jun 30;: Authors: Bourgonje AR, Feelisch M, Faber KN, Pasch A, Dijkstra G, van Goor H Abstract Inflammatory bowel disease (IBD) is associated with the production of reactive species that target cysteine redox switches in proteins, thereby affecting gene regulation, DNA damage, ion transport, intermediary metabolism, and mitochondrial function. Precursors of reactive species are derived from organic and inorganic compounds and their cofactors, including amino acids, vitamins, oxygen, nitrite, and sulfate. Nutrition and the gut microbiome fuel this process to a significant extent. The production of reactive species in IBD is reflected by a reduction in systemic free thiols, the major components of the antioxidant machinery. Systemic free thiols are amenable to nutritional or therapeutic intervention. This opens up future avenues for therapeutic modulation of redox status in IBD. PMID: 32620502 [PubMed - as supplied by publisher]

Related Articles Plasma high-resolution metabolomics identifies linoleic acid and linked metabolic pathways associated with bone mineral density. Clin Nutr. 2020 Jun 04;: Authors: Bellissimo MP, Ziegler TR, Jones DP, Liu KH, Fernandes J, Roberts JL, Weitzmann MN, Pacifici R, Alvarez JA Abstract BACKGROUND & AIMS: There is a considerable degree of variation in bone mineral density (BMD) within populations. Use of plasma metabolomics may provide insight into established and novel determinants of BMD variance, such as nutrition and gut microbiome composition, to inform future prevention and treatment strategies for loss of BMD. Using high-resolution metabolomics (HRM), we examined low-molecular weight plasma metabolites and nutrition-related metabolic pathways associated with BMD. METHODS: This cross-sectional study included 179 adults (mean age 49.5 ± 10.3 yr, 64% female). Fasting plasma was analyzed using ultra-high-resolution mass spectrometry with liquid chromatography. Whole body and spine BMD were assessed by dual energy X-ray absorptiometry and expressed as BMD (g/cm2) or Z-scores. Multiple linear regression, pathway enrichment, and module analyses were used to determine key plasma metabolic features associated with bone density. RESULTS: Of 10,210 total detected metabolic features, whole body BMD Z-score was associated with 710 metabolites, which were significantly enriched in seven metabolic pathways, including linoleic acid, fatty acid activation and biosynthesis, and glycerophospholipid metabolism. Spine BMD was associated with 970 metabolites, significantly enriched in pro-inflammatory pathways involved in prostaglandin formation and linoleic acid metabolism. In module analyses, tryptophan- and polyamine-derived metabolites formed a network that was significantly associated with spine BMD, supporting a link with the gut microbiome. CONCLUSIONS: Plasma HRM provides comprehensive information relevant to nutrition and components of the microbiome that influence bone health. This data supports pro-inflammatory fatty acids and the gut microbiome as novel regulators of postnatal bone remodeling. PMID: 32620447 [PubMed - as supplied by publisher]

Related Articles Sparse reduced-rank regression for integrating omics data. BMC Bioinformatics. 2020 Jul 03;21(1):283 Authors: Hilafu H, Safo SE, Haine L Abstract BACKGROUND: The problem of assessing associations between multiple omics data including genomics and metabolomics data to identify biomarkers potentially predictive of complex diseases has garnered considerable research interest nowadays. A popular epidemiology approach is to consider an association of each of the predictors with each of the response using a univariate linear regression model, and to select predictors that meet a priori specified significance level. Although this approach is simple and intuitive, it tends to require larger sample size which is costly. It also assumes variables for each data type are independent, and thus ignores correlations that exist between variables both within each data type and across the data types. RESULTS: We consider a multivariate linear regression model that relates multiple predictors with multiple responses, and to identify multiple relevant predictors that are simultaneously associated with the responses. We assume the coefficient matrix of the responses on the predictors is both row-sparse and of low-rank, and propose a group Dantzig type formulation to estimate the coefficient matrix. CONCLUSION: Extensive simulations demonstrate the competitive performance of our proposed method when compared to existing methods in terms of estimation, prediction, and variable selection. We use the proposed method to integrate genomics and metabolomics data to identify genetic variants that are potentially predictive of atherosclerosis cardiovascular disease (ASCVD) beyond well-established risk factors. Our analysis shows some genetic variants that increase prediction of ASCVD beyond some well-established factors of ASCVD, and also suggest a potential utility of the identified genetic variants in explaining possible association between certain metabolites and ASCVD. PMID: 32620072 [PubMed - as supplied by publisher]

24 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 2020/07/05PubMed 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.

24 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 2020/07/04PubMed 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.

23 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 2020/07/03PubMed 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.

29 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 2020/07/02PubMed 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.

29 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 2020/07/02PubMed 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.

53 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 2020/07/01PubMed 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.

53 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 2020/07/01PubMed 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.

Obligatory Metabolomic Profiling of Gene-edited Crops is Risk Disproportionate. Plant J. 2020 Jun 27;: Authors: Fedorova M, Herman RA Abstract It has been argued that the application of metabolomics to gene-edited crops would present value in three areas: 1) detection of gene-edited crops, 2) characterization of unexpected changes that might affect safety, and 3) building on the track record of rigorous government regulation in supporting consumer acceptance of GMOs. Here, we offer a different perspective relative to each of these areas. 1) Metabolomics is unable to differentiate if a mutation has resulted from gene editing or traditional breeding techniques. 2) It is risk-disproportionate to apply metabolomics for regulatory purposes to search for possible compositional differences within crops developed using the least likely technique to generate unexpected compositional changes. 3) Onerous regulations for genetically engineered crops have only contributed to unwarranted public fears, and repeating this approach for gene-edited crops is unlikely to result in a different outcome. It is also suggested that manuscripts proposing the utility of specific analytical techniques to support risk assessment would benefit from input from scientists with risk assessment subject-matter expertise. PMID: 32593232 [PubMed - as supplied by publisher]

Plasma metabolomic fingerprint of advanced cirrhosis stages among HIV/HCV-coinfected and HCV-monoinfected patients. Liver Int. 2020 Jun 27;: Authors: Salgüero S, Rojo D, Berenguer J, González-García J, Fernández-Rodríguez A, Brochado-Kith O, Díez C, Hontañon V, Virseda-Berdices A, Martínez J, Ibañez-Samaniego L, Llop-Herrera E, Barbas C, Resino S, Jiménez-Sousa MA, ESCORIAL Study Group Abstract BACKGROUND & AIMS: Hepatitis C virus (HCV), human immunodeficiency virus (HIV), and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with Child-Turcotte-Pugh (CTP) score and hepatic decompensation in HIV/HCV-coinfected and HCV-monoinfected patients with advanced cirrhosis. METHODS: Observational study in 62 HIV/HCV-coinfected and 28 HCV-monoinfected patients. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS-DA) and generalized linear model (GLM) with binomial distribution (to analyze HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyze different stages of cirrhosis (CTP score). RESULTS: The statistical analysis identified plasma metabolites associated to HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulfur amino acids, butyrate derivatives, oxidized phospholipids, energy-related metabolites, and bacterial fermentation-related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched-chain amino acids (BCAA), and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV and HCV infected patients. Glycolic acid, LPC(16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥7). CONCLUSION: Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV-coinfected and HCV-monoinfected patients. PMID: 32593189 [PubMed - as supplied by publisher]

Cold acclimation and freezing tolerance in three Eucalyptus species: A metabolomic and proteomic approach. Plant Physiol Biochem. 2020 May 26;154:316-327 Authors: Oberschelp GPJ, Guarnaschelli AB, Teson N, Harrand L, Podestá FE, Margarit E Abstract The ability of plants to cope with frost events relies on the physiological and molecular responses triggered by cold temperatures. This process, named acclimation, involves reprogramming gene expression in order to adjust metabolism. Planted Eucalyptus species are highly productive but most of them are frost sensitive. However, acclimation process varies among species and environmental conditions, promoting more or less frost damage in young plantations of frost-prone areas. To identify metabolites and proteins responsible for these differences, two acclimation regimes were imposed to seedling of Eucalyptus grandis Hill ex Maiden (Eg), Eucalyptus dunnii Maiden (Ed) and Eucalyptus benthamii Maiden Cambage (Eb), and leaves submitted to biochemical and molecular analyses. Further, seedlings were used for simulated frosts in order to test the acclimation status effect on frost tolerance. Eb showed higher frost tolerance than Ed and Eg under control and acclimation scenarios, possibly due to its higher accumulation of phenolics, anthocyanins and soluble sugars as well as lower levels of photosynthetic pigments and related proteins. Also, a rise in frost tolerance and in osmoprotectants and antioxidants was observed for all the species due to cold acclimation treatment. Interestingly, metabolic profiles differed among species, suggesting different mechanisms to endure frosts and, probably, different requirements for cold acclimation. Shotgun proteomics reinforced differences and commonalities and supported metabolome observations. An in depth understanding of these responses could help to safeguard planted forests productivity through breeding of tolerant genetic material. PMID: 32593088 [PubMed - as supplied by publisher]

Loss of CLN3, the gene mutated in juvenile neuronal ceroid lipofuscinosis, leads to metabolic impairment and autophagy induction in retina pigment epithelium. Biochim Biophys Acta Mol Basis Dis. 2020 Jun 24;:165883 Authors: Zhong Y, Mohan K, Liu J, Al-Attar A, Lin P, Flight RM, Sun Q, Warmoes MO, Deshpande RR, Liu H, Jung KS, Mitov MI, Lin N, Butterfield DA, Lu S, Liu J, Moseley HNB, Fan TWM, Kleinman ME, Wang QJ Abstract Juvenile neuronal ceroid lipofuscinosis (JNCL, aka. juvenile Batten disease or CLN3 disease) is a lysosomal storage disease characterized by progressive blindness, seizures, cognitive and motor failures, and premature death. JNCL is caused by mutations in the Ceroid Lipofuscinosis, Neuronal 3 (CLN3) gene, whose function is unclear. Although traditionally considered a neurodegenerative disease, CLN3 disease displays eye-specific effects: JNCL often first presents as vision loss; and vision loss has also been reported in non-syndromic CLN3 disease. Here we described the roles of CLN3 protein in maintaining healthy retinal pigment epithelium (RPE) and normal vision. Using electroretinogram, fundoscopy and microscopy, we showed impaired visual function, retinal autofluorescent lesions, and RPE disintegration and metaplasia/hyperplasia in a Cln3 ~ 1 kb-deletion mouse model [1] on C57BL/6J backgroun. Utilizing a combination of biochemical analyses, RNA-Seq, Seahorse XF bioenergetic analysis, and Stable Isotope Resolved Metabolomics (SIRM), we further demonstrated that loss of CLN3 increased autophagic flux, suppressed mTORC1 and Akt activities, enhanced AMPK activity, and up-regulated gene expression of the autophagy-lysosomal system in RPE-1 cells, suggesting autophagy induction. This CLN3 deficiency induced autophagy induction coincided with decreased mitochondrial oxygen consumption, glycolysis, the tricarboxylic acid (TCA) cycle, and ATP production. We also report for the first time that loss of CLN3 led to glycogen accumulation despite of impaired glycogen synthesis. Our comprehensive analyses shed light on how loss of CLN3 affect autophagy and metabolism. This work suggests possible links among metabolic impairment, autophagy induction and lysosomal storage, as well as between RPE atrophy/degeneration and vision loss in JNCL. PMID: 32592935 [PubMed - as supplied by publisher]

Activation of glycogenolysis and glycolysis in breast cancer stem cell models. Biochim Biophys Acta Mol Basis Dis. 2020 Jun 24;:165886 Authors: Abad E, Samino S, Yanes O, Potesil D, Zdrahal Z, Lyakhovich A PMID: 32592934 [PubMed - as supplied by publisher]

Global Metabolomics in Allogeneic Hematopoietic Cell Transplant Recipients Discordant for Chronic Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2020 Jun 24;: Authors: Kelly DL, Farharfar N, Starkweather A, Garrett TJ, Yao Y, Wingard JR, Mahmud I, Menzies V, Patel P, Alabasi KM, Lyon D Abstract BACKGROUND: Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation survivors contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Due to lack of early diagnostic tests and pathophysiology ambiguity, there remain limited targeted treatments. Biomarkers for prediction, control response or prognostication are not yet identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD however not known in this population. This study examined global metabolites of stored plasma to examine differentially expressed metabolites of individuals discordant for cGVHD following allogeneic HCT. METHODS: A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from two parent studies approved by the Institutional Review Board. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed using R statistical software version 3.4.3 by a PhD prepared, trained bioinformatics statistician. RESULTS: There were 10 differentially expressed metabolites between those with and without cGVHD. Differential metabolites included those related to energy metabolism (n=3), amino acid metabolism (n=3), lipid metabolism (n=2), caffeine metabolism (n=1), and neurotransmission (n=1). Serotonin had the greatest fold change (FC) (FC = 21.01). CONCLUSION: This study suggests cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that need to be further explored as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomics risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD. PMID: 32592859 [PubMed - as supplied by publisher]

Related Articles Rationale and design of "Hearts & Parks": study protocol for a pragmatic randomized clinical trial of an integrated clinic-community intervention to treat pediatric obesity. BMC Pediatr. 2020 Jun 26;20(1):308 Authors: Armstrong SC, Windom M, Bihlmeyer NA, Li JS, Shah SH, Story M, Zucker N, Kraus WE, Pagidipati N, Peterson E, Wong C, Wiedemeier M, Sibley L, Berchuck SI, Merrill P, Zizzi A, Sarria C, Dressman HK, Rawls JF, Skinner AC Abstract BACKGROUND: The prevalence of child and adolescent obesity and severe obesity continues to increase despite decades of policy and research aimed at prevention. Obesity strongly predicts cardiovascular and metabolic disease risk; both begin in childhood. Children who receive intensive behavioral interventions can reduce body mass index (BMI) and reverse disease risk. However, delivering these interventions with fidelity at scale remains a challenge. Clinic-community partnerships offer a promising strategy to provide high-quality clinical care and deliver behavioral treatment in local park and recreation settings. The Hearts & Parks study has three broad objectives: (1) evaluate the effectiveness of the clinic-community model for the treatment of child obesity, (2) define microbiome and metabolomic signatures of obesity and response to lifestyle change, and (3) inform the implementation of similar models in clinical systems. METHODS: Methods are designed for a pragmatic randomized, controlled clinical trial (n = 270) to test the effectiveness of an integrated clinic-community child obesity intervention as compared with usual care. We are powered to detect a difference in body mass index (BMI) between groups at 6 months, with follow up to 12 months. Secondary outcomes include changes in biomarkers for cardiovascular disease, psychosocial risk, and quality of life. Through collection of biospecimens (serum and stool), additional exploratory outcomes include microbiome and metabolomics biomarkers of response to lifestyle modification. DISCUSSION: We present the study design, enrollment strategy, and intervention details for a randomized clinical trial to measure the effectiveness of a clinic-community child obesity treatment intervention. This study will inform a critical area in child obesity and cardiovascular risk research-defining outcomes, implementation feasibility, and identifying potential molecular mechanisms of treatment response. CLINICAL TRIAL REGISTRATION: NCT03339440 . PMID: 32590958 [PubMed - as supplied by publisher]