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

PubMed
NCBI: db=pubmed; Term=metabolomics
Updated: 2 hours 20 min ago

Discrimination between Fresh and Frozen-Thawed Fish Involved in Food Safety and Fraud Protection.

Tue, 29/12/2020 - 08:41
Related Articles Discrimination between Fresh and Frozen-Thawed Fish Involved in Food Safety and Fraud Protection. Foods. 2020 Dec 18;9(12): Authors: Chiesa LM, Pavlovic R, Nobile M, Di Cesare F, Malandra R, Pessina D, Panseri S Abstract This study aims to discriminate fresh fish from frozen/thawed by identification of the key metabolites that are altered during the freezing/thawing processing. Atlantic salmon (Salmo salar) and bullet tuna (Auxis rochei) were selected as they are representative of broad consumption, and susceptible to pathogen contamination. Atlantic salmon samples were subjected to the following regimes: -20 °C (24h) and -35 °C (15 h) freezing, then thawed respectively in the blast chiller and in the cold room and analyzed immediately or after 10 days; (2) bullet tuna samples were frozen at -18 °C and thawed after 15, 30 and 90 days. High resolution mass spectrometry based on untargeted metabolomic analyses and statistical data treatment confirmed significant variations in the quantity of certain metabolites: the amount of l-phenylalanine in salmon increased immediately after thawing while that of anserine decreased. The concentration of l-arginine and its metabolites was altered at the 10th day after thawing rendering them promising markers of salmon freezing/thawing. As regards bullet tuna, compounds resulting from lipid degradation (l-α-Glyceryl-phosphoryl-choline and N-methyl-ethanolamine phosphate) increased notably during the storage period. This approach could be used to reveal common fraudulent incidents such as deliberate replacement of fresh fish with frozen/thawed, with food safety risks as the primary implication. PMID: 33353233 [PubMed]

Non-Invasive Human Embryo Metabolic Assessment as a Developmental Criterion.

Tue, 29/12/2020 - 08:41
Related Articles Non-Invasive Human Embryo Metabolic Assessment as a Developmental Criterion. J Clin Med. 2020 Dec 18;9(12): Authors: Motiei M, Vaculikova K, Cela A, Tvrdonova K, Khalili R, Rumpik D, Rumpikova T, Glatz Z, Saha T Abstract The selection of a highly-viable single embryo in assisted reproductive technology requires an acceptable predictive method in order to reduce the multiple pregnancy rate and increase the success rate. In this study, the metabolomic profiling of growing and impaired embryos was assessed on the fifth day of fertilization using capillary electrophoresis in order to find a relationship between the profiling and embryo development, and then to provide a mechanistic insight into the appearance/depletion of the metabolites. This unique qualitative technique exhibited the appearance of most non-essential amino acids and lactate, and depleting the serine, alanyl-glutamine and pyruvate in such a manner that the embryos impaired in their development secreted a considerably higher level of lactate and consumed a significantly higher amount of alanyl-glutamine. The different significant ratios of metabolomic depletion/appearance between the embryos confirm their potential for the improvement of the prospective selection of the developed single embryos, and also suggest the fact that pyruvate and alanyl-glutamine are the most critical ATP suppliers on the fifth day of blastocyst development. PMID: 33353110 [PubMed]

The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy.

Tue, 29/12/2020 - 08:41
Related Articles The Impact of Sample Type on Vitamin D Quantification and Clinical Classification during Pregnancy. Nutrients. 2020 Dec 18;12(12): Authors: Harvey SM, Murphy VE, Gibson PG, Clarke M, Jensen ME Abstract Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2) and Epi-25-hydroxyvitamin D3 (Epi-25(OH)D3)), in plasma and serum samples collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on sample type. Matching samples were collected from n = 114 non-fasting women between 12-25 weeks gestation in a clinical trial in Newcastle, Australia. Samples were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen's Kappa test. Serum total 25(OH)D ranged from 33.8-169.8 nmol/L and plasma ranged from 28.6-211.2 nmol/L. There was a significant difference for total 25(OH)D based on sample type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D3 (7.38 nmol/L; 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D3 (0.39 nmol/L; 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient (<50 nmol/L) or insufficient (<75 nmol/L) based on plasma sample and 36% based on serum sample. Nineteen (16.7%) participants changed vitamin D status category based on sample type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma; this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings. PMID: 33352934 [PubMed - in process]

Metabolic Changes in Serum Metabolome of Beagle Dogs Fed Black Ginseng.

Tue, 29/12/2020 - 08:41
Related Articles Metabolic Changes in Serum Metabolome of Beagle Dogs Fed Black Ginseng. Metabolites. 2020 Dec 19;10(12): Authors: Yoon D, Kim YJ, Lee WK, Choi BR, Oh SM, Lee YS, Kim JK, Lee DY Abstract The effects of black ginseng, which has many kinds of biological activities, on dogs was investigated. Serum samples of beagle dogs, which were fed with black ginseng for 8 weeks, were measured using high-resolution magic angle spinning (HR-MAS) nuclear magnetic resonance (NMR) spectrometry. Acquired NMR data from the serum of dogs fed for 0, 4, and 8 weeks were analyzed by metabolic profiling and multivariate statistical analysis. In statistical analysis and biomarker analysis results of metabolite profiles, formate, glutamine, histidine, isoleucine, leucine, proline, and valine had variable importance in projection (VIP) scores above 1.0 and excellent area under the curve (AUC) values of receiver operating characteristic (ROC) curves above 0.9. In the result of multivariate statistical analysis, the score plot showed the discrimination between before and after feeding of black ginseng. These differences in metabolic profiles are considered to be due to the involvement of metabolic processes following black ginseng administration, such as enhancing immunity and energy metabolism. Through metabolomics analysis, we confirmed the biological efficacy of black ginseng in dogs and also confirmed that metabolomics can be applied to the pet health industry. PMID: 33352805 [PubMed]

From Proteomics to Personalized Medicine: The Importance of Isoflavone Dose and Estrogen Receptor Status in Breast Cancer Cells.

Tue, 29/12/2020 - 08:41
Related Articles From Proteomics to Personalized Medicine: The Importance of Isoflavone Dose and Estrogen Receptor Status in Breast Cancer Cells. J Pers Med. 2020 Dec 19;10(4): Authors: Ilieș M, Uifălean A, Pașca S, Dhople VM, Lalk M, Iuga CA, Hammer E Abstract Continuing efforts are directed towards finding alternative breast cancer chemotherapeutics, with improved safety and efficacy profiles. Soy isoflavones represent promising agents but, despite extensive research, limited information exists regarding their impact on the breast cancer cell proteome. The purpose of this study was to compare the proteomic profiles of MCF-7 (estrogen responsive) and MDA-MB-231 (estrogen non-responsive) breast cancer cells exposed to different concentrations of genistein, daidzein, and a soy seed extract, using a high throughput LC-UDMSE protein profiling approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay confirmed the dual activity of soy isoflavones on MCF-7 cells and the inhibitory effect on MDA-MB-231 cells. Proteome profiling of paramagnetic beads prepared peptides by nano-LC UDMSE and pathway enrichment analysis revealed that isoflavones affected distinct molecular pathways in MCF-7 and MDA-MB-231 cells, such as tyrosine kinases signaling pathway, cytoskeleton organization, lipid and phospholipid catabolism, extracellular matrix degradation and mRNA splicing. Also, in MCF-7 cells, low and high isoflavone doses induced different changes of the proteome, including cell cycle alterations. Therefore, the expression of estrogen receptors and the isoflavone dose are determinant factors for the molecular impact of isoflavones and must be taken into account when considering adjuvant breast cancer therapy towards personalized medicine. PMID: 33352803 [PubMed]

Exploratory Analysis of Commercial Olive-Based Dietary Supplements Using Untargeted and Targeted Metabolomics.

Tue, 29/12/2020 - 08:41
Related Articles Exploratory Analysis of Commercial Olive-Based Dietary Supplements Using Untargeted and Targeted Metabolomics. Metabolites. 2020 Dec 19;10(12): Authors: Garcia-Aloy M, Groff N, Masuero D, Nisi M, Franco A, Battelini F, Vrhovsek U, Mattivi F Abstract The market of olive-based dietary supplements (OBDS) is composed of a broad range of natural extracts claiming different health effects and often sold without a clear statement on their chemical composition. The aim of this survey was to characterize the chemical profiles of 14 commercially available OBDS. As many as 378 compounds were tentatively annotated in the analyzed samples. Although for most of metabolites the annotation at level I was prevented due to the lack of the analytical standard, the spectra obtained from high-resolution tandem mass spectrometry (MS/MS) measurements were very informative, allowing annotation of dozens of metabolites at level II or III. A targeted method allowed the quantification of 26 selected compounds. A large qualitative and quantitative variability was observed. The products obtained from buds by glyceric maceration were those with the lowest concentrations of all the quantified elements. The dose of 5 mg of hydroxytyrosol, corresponding to the European Food Safety Authority (EFSA) health claim, was only reached by four products, all of them originating from the olive fruit or the leaves. If we also take into consideration oleuropein, two additional products provide this daily amount. This work demonstrates the high complexity and diversity in the composition of OBDS. PMID: 33352793 [PubMed]

Evaluation of Saliva Stability for NMR Metabolomics: Collection and Handling Protocols.

Tue, 29/12/2020 - 08:41
Related Articles Evaluation of Saliva Stability for NMR Metabolomics: Collection and Handling Protocols. Metabolites. 2020 Dec 19;10(12): Authors: Duarte D, Castro B, Pereira JL, Marques JF, Costa AL, Gil AM Abstract Maintaining a salivary metabolic profile upon sample collection and preparation is determinant in metabolomics. Nuclear magnetic resonance (NMR) spectroscopy was used to identify metabolite changes during short-term storage, at room temperature (RT)/4 °C/-20 °C, and after sample preparation, at RT/4 °C (mimicking typical clinical/laboratory settings). Interestingly, significant metabolic inter-individual and inter-day variability were noted, probably determining sample stability to some extent. After collection, no changes were noted at -20 °C (at least for 4 weeks). RT storage induced decreases in methylated macromolecules (6 h); lactate (8 h); alanine (12 h); galactose, hypoxanthine, pyruvate (24 h); sarcosine, betaine, choline, N-acetyl-glycoproteins (48 h), while acetate increased (48 h). Less, but different, changes were observed at 4 °C, suggesting different oral and microbial status at different temperatures (with a possible contribution from inter-individual and inter-day variability), and identifying galactose, hypoxanthine, and possibly, choline esters, as potential general stability indicators. After preparation, addition of NaN3 did not impact significantly on saliva stabilization, neither at RT nor at 4 °C, although its absence was accompanied by slight increases in fucose (6.5 h) and proline (8 h) at RT, and in xylose (24 h) at 4 °C. The putative metabolic origins of the above variations are discussed, with basis on the salivary microbiome. In summary, after collection, saliva can be stored at RT/4 °C for up to 6 h and at -20 °C for at least 4 weeks. Upon preparation for NMR analysis, samples are highly stable at 25 °C up to 8 h and at 4 °C up to 48 h, with NaN3 addition preventing possible early changes in fucose, proline (6-8 h), and xylose (24 h) levels. PMID: 33352779 [PubMed]

Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review.

Tue, 29/12/2020 - 08:41
Related Articles Passiflora incarnata in Neuropsychiatric Disorders-A Systematic Review. Nutrients. 2020 Dec 19;12(12): Authors: Janda K, Wojtkowska K, Jakubczyk K, Antoniewicz J, Skonieczna-Żydecka K Abstract BACKGROUND: Stress is a natural response of the body, induced by factors of a physical (hunger, thirst, and infection) and/or psychological (perceived threat, anxiety, or concern) nature. Chronic, long-term stress may cause problems with sleep, concentration, and memory, as well as affective disorders. The passionflower (Passiflora incarnata) is a perennial plant with documented therapeutic properties. The literature data suggest that the passionflower itself, as well as its preparations, helps reduce stress and can therefore be helpful in the treatment of insomnia, anxiety, and depression. The objective of this systematic review was to evaluate Passiflora incarnata in terms of its neuropsychiatric effects. METHODS: The scientific databases PubMed, ClinTrials.gov, and Embase were searched up to 22 October 2019. The search identified randomized clinical trials describing the effects of Passiflora incarnata in neuropsychiatric disorders. RESULTS: The systematic review included nine clinical trials. The duration of the studies included in the analysis varied widely, from one day up to 30 days. Study participants were no less than 18 years old. In each of the papers, the effects of passionflower were measured by using a number of different tests and scales. The majority of studies reported reduced anxiety levels following the administration of Passiflora incarnata preparations, with the effect less evident in people with mild anxiety symptoms. No adverse effects, including memory loss or collapse of psychometric functions, were observed. CONCLUSION: Passiflora incarnata may be helpful in treating some symptoms in neuropsychiatric patients. PMID: 33352740 [PubMed - in process]

Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies.

Tue, 29/12/2020 - 08:41
Related Articles Fourier-Transform Infrared Spectroscopy of Skeletal Muscle Tissue: Expanding Biomarkers in Primary Mitochondrial Myopathies. Genes (Basel). 2020 Dec 19;11(12): Authors: Gervasoni J, Primiano A, Marini F, Sabino A, Biancolillo A, Calvani R, Picca A, Marzetti E, Persichilli S, Urbani A, Servidei S, Primiano G Abstract Primary mitochondrial myopathies (PMM) are a group of mitochondrial disorders characterized by a predominant skeletal muscle involvement. The aim of this study was to evaluate whether the biochemical profile determined by Fourier-transform infrared (FTIR) spectroscopic technique would allow to distinguish among patients affected by progressive external ophthalmoplegia (PEO), the most common PMM presentation, oculopharyngeal muscular dystrophy (OPMD), and healthy controls. Thirty-four participants were enrolled in the study. FTIR spectroscopy was found to be a sensitive and specific diagnostic marker for PEO. In particular, FTIR spectroscopy was able to distinguish PEO patients from those affected by OPMD, even in the presence of histological findings similar to mitochondrial myopathy. At the same time, FTIR spectroscopy differentiated single mtDNA deletion and mutations in POLG, the most common nuclear gene associated with mitochondrial diseases, with high sensitivity and specificity. In conclusion, our data suggest that FTIR spectroscopy is a valuable biodiagnostic tool for the differential diagnosis of PEO with a high ability to also distinguish between single mtDNA deletion and mutations in POLG gene based on specific metabolic transitions. PMID: 33352713 [PubMed - in process]

Shed Light in the DaRk LineagES of the Fungal Tree of Life-STRES.

Tue, 29/12/2020 - 08:41
Related Articles Shed Light in the DaRk LineagES of the Fungal Tree of Life-STRES. Life (Basel). 2020 Dec 19;10(12): Authors: Selbmann L, Benkő Z, Coleine C, de Hoog S, Donati C, Druzhinina I, Emri T, Ettinger CL, Gladfelter AS, Gorbushina AA, Grigoriev IV, Grube M, Gunde-Cimerman N, Karányi ZÁ, Kocsis B, Kubressoian T, Miklós I, Miskei M, Muggia L, Northen T, Novak-Babič M, Pennacchio C, Pfliegler WP, Pòcsi I, Prigione V, Riquelme M, Segata N, Schumacher J, Shelest E, Sterflinger K, Tesei D, U'Ren JM, Varese GC, Vázquez-Campos X, Vicente VA, Souza EM, Zalar P, Walker AK, Stajich JE Abstract The polyphyletic group of black fungi within the Ascomycota (Arthoniomycetes, Dothideomycetes, and Eurotiomycetes) is ubiquitous in natural and anthropogenic habitats. Partly because of their dark, melanin-based pigmentation, black fungi are resistant to stresses including UV- and ionizing-radiation, heat and desiccation, toxic metals, and organic pollutants. Consequently, they are amongst the most stunning extremophiles and poly-extreme-tolerant organisms on Earth. Even though ca. 60 black fungal genomes have been sequenced to date, [mostly in the family Herpotrichiellaceae (Eurotiomycetes)], the class Dothideomycetes that hosts the largest majority of extremophiles has only been sparsely sampled. By sequencing up to 92 species that will become reference genomes, the "Shed light in The daRk lineagES of the fungal tree of life" (STRES) project will cover a broad collection of black fungal diversity spread throughout the Fungal Tree of Life. Interestingly, the STRES project will focus on mostly unsampled genera that display different ecologies and life-styles (e.g., ant- and lichen-associated fungi, rock-inhabiting fungi, etc.). With a resequencing strategy of 10- to 15-fold depth coverage of up to ~550 strains, numerous new reference genomes will be established. To identify metabolites and functional processes, these new genomic resources will be enriched with metabolomics analyses coupled with transcriptomics experiments on selected species under various stress conditions (salinity, dryness, UV radiation, oligotrophy). The data acquired will serve as a reference and foundation for establishing an encyclopedic database for fungal metagenomics as well as the biology, evolution, and ecology of the fungi in extreme environments. PMID: 33352712 [PubMed]

metabolomics; +25 new citations

Wed, 23/12/2020 - 14:10
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 2020/12/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

metabolomics; +36 new citations

Tue, 22/12/2020 - 14:03
36 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 2020/12/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI.

Mon, 21/12/2020 - 13:57
Related Articles Supervised machine learning enables non-invasive lesion characterization in primary prostate cancer with [68Ga]Ga-PSMA-11 PET/MRI. Eur J Nucl Med Mol Imaging. 2020 Dec 19;: Authors: Papp L, Spielvogel CP, Grubmüller B, Grahovac M, Krajnc D, Ecsedi B, Sareshgi RAM, Mohamad D, Hamboeck M, Rausch I, Mitterhauser M, Wadsak W, Haug AR, Kenner L, Mazal P, Susani M, Hartenbach S, Baltzer P, Helbich TH, Kramer G, Shariat SF, Beyer T, Hartenbach M, Hacker M Abstract PURPOSE: Risk classification of primary prostate cancer in clinical routine is mainly based on prostate-specific antigen (PSA) levels, Gleason scores from biopsy samples, and tumor-nodes-metastasis (TNM) staging. This study aimed to investigate the diagnostic performance of positron emission tomography/magnetic resonance imaging (PET/MRI) in vivo models for predicting low-vs-high lesion risk (LH) as well as biochemical recurrence (BCR) and overall patient risk (OPR) with machine learning. METHODS: Fifty-two patients who underwent multi-parametric dual-tracer [18F]FMC and [68Ga]Ga-PSMA-11 PET/MRI as well as radical prostatectomy between 2014 and 2015 were included as part of a single-center pilot to a randomized prospective trial (NCT02659527). Radiomics in combination with ensemble machine learning was applied including the [68Ga]Ga-PSMA-11 PET, the apparent diffusion coefficient, and the transverse relaxation time-weighted MRI scans of each patient to establish a low-vs-high risk lesion prediction model (MLH). Furthermore, MBCR and MOPR predictive model schemes were built by combining MLH, PSA, and clinical stage values of patients. Performance evaluation of the established models was performed with 1000-fold Monte Carlo (MC) cross-validation. Results were additionally compared to conventional [68Ga]Ga-PSMA-11 standardized uptake value (SUV) analyses. RESULTS: The area under the receiver operator characteristic curve (AUC) of the MLH model (0.86) was higher than the AUC of the [68Ga]Ga-PSMA-11 SUVmax analysis (0.80). MC cross-validation revealed 89% and 91% accuracies with 0.90 and 0.94 AUCs for the MBCR and MOPR models respectively, while standard routine analysis based on PSA, biopsy Gleason score, and TNM staging resulted in 69% and 70% accuracies to predict BCR and OPR respectively. CONCLUSION: Our results demonstrate the potential to enhance risk classification in primary prostate cancer patients built on PET/MRI radiomics and machine learning without biopsy sampling. PMID: 33341915 [PubMed - as supplied by publisher]

UPLC-MS based plasma metabolomics and lipidomics reveal alterations associated with IgG4-related disease.

Mon, 21/12/2020 - 13:57
Related Articles UPLC-MS based plasma metabolomics and lipidomics reveal alterations associated with IgG4-related disease. Rheumatology (Oxford). 2020 Dec 20;: Authors: Gong Y, Zhang P, Liu Z, Li J, Lu H, Wang Y, Qiu B, Wang M, Fei Y, Chen H, Peng L, Li J, Zhou J, Shi Q, Zhang X, Shen M, Zeng X, Zhang F, Zhang W Abstract OBJECTIVE: The pathogenesis of IgG4-related disease (IgG4-RD) remains unclear. Metabolomic profiling of IgG4-RD patients offers an opportunity to identify novel pathophysiological targets and biomarkers. This study aims to identify potential plasma biomarkers associated with IgG4-RD. METHODS: Thirty newly diagnosed IgG4-RD patients, age-matched healthy controls and post-treated IgG4-RD patients were enrolled. Patients' clinical data, laboratory parameters and plasma were collected. Plasma was measured for ultraperformance liquid chromatography-tandem mass spectrometry based metabolomics and lipidomics profiling. Multivariate and univariate statistical analyses were conducted to identify potential biomarkers. The receiver operating characteristic and the correlations between biomarkers and clinical parameters were investigated. RESULTS: The plasma metabolites are altered among healthy controls, newly diagnosed IgG4-RD and post-treated IgG4-RD groups. Of the identified features, eight metabolites were significantly perturbed in the IgG4-RD group, including glyceric acid 1,3-biphosphate (1,3-BPG), uridine triphosphate (UTP), uridine diphosphate glucose (UDP-Glc) or uridine diphosphate galactose (UDP-Gal), lysophospholipids, linoleic acid derivatives and ceramides. Receiver operating characteristic analysis indicated that UTP, UDP-Glc/UDP-Gal and LysoPC (18:1) had high sensitivity and specificity in diagnosis of IgG4-RD. A Pearson correlation analysis showed that 1,3-BPG and UTP were strongly correlated with clinical parameters. CONCLUSION: IgG4-RD patients have a unique plasma metabolomic profile compared with healthy controls. Our study suggested that metabolomic profiling may provide important insights into pathophysiology and testable biomarkers for diagnosis of IgG4-RD. PMID: 33341881 [PubMed - as supplied by publisher]

Lindera aggregata intervents adenine-induced chronic kidney disease by mediating metabolism and TGF-β/Smad signaling pathway.

Sun, 20/12/2020 - 13:41
Related Articles Lindera aggregata intervents adenine-induced chronic kidney disease by mediating metabolism and TGF-β/Smad signaling pathway. Biomed Pharmacother. 2020 Dec 16;134:111098 Authors: Cai H, Wang J, Luo Y, Wang F, He G, Zhou G, Peng X Abstract INTRODUCTION: Lindera aggregata is a main Chinese herb of ancient prescriptions Suoquan pill applied for treating the chronic kidney disease (CKD). A large number of application histories of Lindera aggregata in the treatment of CKD have been recorded in Chinese traditional medical literature. The previous reports revealed that Lindera aggregata can treat CKD. METHODS: Rats were randomly divided into control, model, Huangkui,Lindera aggregata ethanol extract (LEE) and Lindera aggregata water extract (LWE) groups. hematoxylin-eosin (HE) staining was used to detect the pathology of kidney. The levels of serum creatinine (Scr), serum Neutrophil gelatinase-associated lipocalin (NGAL), blood urea nitrogen (BUN), urine protein (UP), kidney index(KI) were evaluated. The UPLC - QTOF/MS were applied to probe the metabolic profile. Furthermore, Indoxyl sulfate-induced human renal tubular epithelial (HK-2) cell model was built to determine the expression levels of pathogenesis-related proteins. RESULTS: The results demonstrated that LEE and LWE significantly inhibited the rebound in Scr, BUN, NGAL, UP and KI in models, except for the effect of LWE at low dose (LWE-L) and LEE at low dose (LEE-L) on KI and the effect of LWE-H at high dose (LWE-H) and LEE-L on BUN and NGAL. Moreover,Lindera aggregata extracts alleviated renal tubular dilatation, interstitial fibrosis and interstitial inflammation. By analysis, twenty-eight metabolites were related to CKD. After intervention of Lindera aggregata extracts, some metabolites approach to a normal-like level, such as Indoxyl sulfate. These metabolites are mainly involved in tryptophan, fatty acid, glycerophospholipid, tyrosine and arachidonic acid metabolic pathways. Furthermore, Lindera aggregata extracts mediate the expression of smad2, smad3, smad7 and TGF-β in Indoxyl sulfate-induced HK-2 cell. CONCLUSIONS: Lindera aggregata extracts can mitigate adenine-induced CKD by modulating the metabolic profile and TGF-β/Smad signaling pathway, providing important supports for developing protective agent of Lindera aggregata for CKD. PMID: 33341058 [PubMed - as supplied by publisher]

Recent development of nanoparticle-assisted metabolites analysis with mass spectrometry.

Sun, 20/12/2020 - 13:41
Related Articles Recent development of nanoparticle-assisted metabolites analysis with mass spectrometry. J Chromatogr A. 2020 Dec 05;1636:461785 Authors: Li H, Li T, Shi X, Xu G Abstract Metabolomics systematically studies the changes of metabolites in biological systems in the temporal or spatial dimensions. It is a challenging task for comprehensive analysis of metabolomics because of diverse physicochemical properties and wide concentration distribution of metabolites. Used as enrichment sorbents, chemoselective probes, chromatographic stationary phases, MS ionization matrix, nanomaterials play excellent roles in improving the selectivity, separation performance, detection sensitivity and identification efficiency of metabolites when mass spectrometry is employed as the detection technique. This review summarized the recent development of nanoparticle-assisted metabolites analysis in terms of assisting the pretreatment of biological samples, improving the separation performance and enhancing the MALDI-MS detection. PMID: 33340742 [PubMed - as supplied by publisher]

Dominant optic atrophy: Culprit mitochondria in the optic nerve.

Sun, 20/12/2020 - 13:41
Related Articles Dominant optic atrophy: Culprit mitochondria in the optic nerve. Prog Retin Eye Res. 2020 Dec 16;:100935 Authors: Lenaers G, Neutzner A, Le Dantec Y, Jüschke C, Xiao T, Decembrini S, Swirski S, Kieninger S, Agca C, Kim US, Reynier P, Yu-Wai-Man P, Neidhardt J, Wissinger B Abstract Dominant optic atrophy (DOA) is an inherited mitochondrial disease leading to specific degeneration of retinal ganglion cells (RGCs), thus compromising transmission of visual information from the retina to the brain. Usually, DOA starts during childhood and evolves to poor vision or legal blindness, affecting the central vision, whilst sparing the peripheral visual field. In 20% of cases, DOA presents as syndromic disorder, with secondary symptoms affecting neuronal and muscular functions. Twenty years ago, we demonstrated that heterozygous mutations in OPA1 are the most frequent molecular cause of DOA. Since then, variants in additional genes, which functions in many instances converge to OPA1 functions, were identified by next generation sequencing. OPA1 encodes a dynamin-related GTPase imported into mitochondria and located to inner membrane and intermembrane space. The many OPA1 isoforms, resulting from alternative splicing of three exons, form complex homopolymers that structure mitochondrial cristae, and contribute to fusion of the outer membrane, thus shaping the whole mitochondrial network. Moreover, OPA1 is required for oxidative phosphorylation, maintenance of mitochondrial genome, calcium homeostasis and regulation of apoptosis, thus making OPA1 the Swiss army-knife of mitochondria. Understanding DOA pathophysiology requires the understanding of RGC peculiarities with respect to OPA1 functions. Besides the tremendous energy requirements of RGCs to relay visual information from the eye to the brain, these neurons present unique features related to their differential environments in the retina, and to the anatomical transition occurring at the lamina cribrosa, which parallel major adaptations of mitochondrial physiology and shape, in the pre- and post-laminar segments of the optic nerve. Three DOA mouse models, with different Opa1 mutations, have been generated to study intrinsic mechanisms responsible for RGC degeneration, and these have further revealed secondary symptoms related to mitochondrial dysfunctions, mirroring the more severe syndromic phenotypes seen in a subgroup of patients. Metabolomics analyses of cells, mouse organs and patient plasma mutated for OPA1 revealed new unexpected pathophysiological mechanisms related to mitochondrial dysfunction, and biomarkers correlated quantitatively to the severity of the disease. Here, we review and synthesize these data, and propose different approaches for embracing possible therapies to fulfil the unmet clinical needs of this disease, and provide hope to affected DOA patients. PMID: 33340656 [PubMed - as supplied by publisher]

Hallmarks of Health.

Sun, 20/12/2020 - 13:41
Related Articles Hallmarks of Health. Cell. 2020 Dec 15;: Authors: López-Otín C, Kroemer G Abstract Health is usually defined as the absence of pathology. Here, we endeavor to define health as a compendium of organizational and dynamic features that maintain physiology. The biological causes or hallmarks of health include features of spatial compartmentalization (integrity of barriers and containment of local perturbations), maintenance of homeostasis over time (recycling and turnover, integration of circuitries, and rhythmic oscillations), and an array of adequate responses to stress (homeostatic resilience, hormetic regulation, and repair and regeneration). Disruption of any of these interlocked features is broadly pathogenic, causing an acute or progressive derailment of the system coupled to the loss of numerous stigmata of health. PMID: 33340459 [PubMed - as supplied by publisher]

Overexpression and inhibition of 3-hydroxy-3-methylglutaryl-CoA synthase affect central metabolic pathways in tobacco.

Sun, 20/12/2020 - 13:41
Related Articles Overexpression and inhibition of 3-hydroxy-3-methylglutaryl-CoA synthase affect central metabolic pathways in tobacco. Plant Cell Physiol. 2020 Dec 19;: Authors: Liao P, Lung SC, Chan WL, Hu M, Kong GK, Bach TJ, Hao Q, Lo C, Chye ML Abstract Little has been established on the relationship between the mevalonate (MVA) pathway and other metabolic pathways except for the sterol and glucosinolate biosynthesis pathways. In the MVA pathway, 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the condensation of acetoacetyl-CoA and acetyl-CoA to form HMG-CoA. Our previous studies had shown that while the recombinant Brassica juncea HMGS1 (BjHMGS1) mutant S359A displayed 10-fold higher enzyme activity than wild-type (wt) BjHMGS1, transgenic tobacco overexpressing S359A (OE-S359A) exhibited higher sterol content, growth rate and seed yield than OE-wtBjHMGS1. Herein, untargeted proteomics and targeted metabolomics were employed to understand the phenotypic effects of HMGS overexpression in tobacco by examining which other metabolic pathways were affected. SWATH-MS quantitative proteomics analysis on OE-wtBjHMGS1 and OE-S359A identified the misregulation of proteins in primary metabolism and cell wall modification, while some proteins related to photosynthesis and the tricarboxylic acid cycle were upregulated in OE-S359A. Metabolomic analysis indicated corresponding changes in carbohydrate, amino acid and fatty acid contents in HMGS-OEs, and F-244, a specific inhibitor of HMGS, was applied successfully on tobacco to confirm these observations. Finally, the crystal structure of acetyl-CoA-liganded S359A revealed that improved activity of S359A likely resulted from a loss in hydrogen bonding between Ser359 and acyl-CoA which is evident in wtBjHMGS1. This work suggests that regulation of plant growth by HMGS can influence the central metabolic pathways. Furthermore, this study demonstrates that the application of the HMGS-specific inhibitor (F-244) in tobacco represents an effective approach for studying the HMGS/MVA pathway. PMID: 33340324 [PubMed - as supplied by publisher]

Systems biology in cardiovascular disease: a multiomics approach.

Sun, 20/12/2020 - 13:41
Related Articles Systems biology in cardiovascular disease: a multiomics approach. Nat Rev Cardiol. 2020 Dec 18;: Authors: Joshi A, Rienks M, Theofilatos K, Mayr M Abstract Omics techniques generate large, multidimensional data that are amenable to analysis by new informatics approaches alongside conventional statistical methods. Systems theories, including network analysis and machine learning, are well placed for analysing these data but must be applied with an understanding of the relevant biological and computational theories. Through applying these techniques to omics data, systems biology addresses the problems posed by the complex organization of biological processes. In this Review, we describe the techniques and sources of omics data, outline network theory, and highlight exemplars of novel approaches that combine gene regulatory and co-expression networks, proteomics, metabolomics, lipidomics and phenomics with informatics techniques to provide new insights into cardiovascular disease. The use of systems approaches will become necessary to integrate data from more than one omic technique. Although understanding the interactions between different omics data requires increasingly complex concepts and methods, we argue that hypothesis-driven investigations and independent validation must still accompany these novel systems biology approaches to realize their full potential. PMID: 33340009 [PubMed - as supplied by publisher]

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