PubMed

Related Articles Quality Control of Preanalytical Handling of Blood Samples for Future Research: A National Survey. J Appl Lab Med. 2019 Dec 06;: Authors: Gils C, Nybo M Abstract BACKGROUND: Assessment and control of preanalytical handling of blood samples for future research are essential to preserve integrity and assure quality of the specimens. However, investigation is limited on how quality control of preanalytical handling of blood samples is performed by biobanks. METHODS: A questionnaire was sent to all Danish departments of clinical biochemistry, all Danish departments of clinical immunology, the Danish Health Surveillance Institution and the Danish Cancer Society. The questionnaire consisted of questions regarding preanalytical handling of samples for future research. The survey was carried out from October 2018 until the end of January 2019. RESULTS: A total of 22 departments (78%) replied, of which 17 (77%) performed preanalytical quality control of the blood samples. This quality control consisted of patient preparation, temperature surveillance of freezers, maintenance of centrifuges, and visual inspection for hemolysis, lipemia, and sample volume. Automated sample check for hemolysis, icterus, and lipemia interferences was performed by 41% of respondents, not performed by 50% of respondents, and 9% did not answer. The majority (55%) of the participants stated that they had no local standard operating procedure for preanalytical handling of samples for research projects. CONCLUSIONS: The preanalytical phase for blood samples obtained and preserved for future research in Denmark is highly heterogeneous, although many aspects (e.g., hemolysis, which also affects DNA analyses, metabolomics, and proteomics) seems highly relevant to document. Our findings emphasize the need to optimize and standardize best practices for the preanalytical phase for blood samples intended for use in future research projects. PMID: 31811074 [PubMed - as supplied by publisher]

Related Articles A global metabolomic insight into the oxidative stress and membrane damage of copper oxide nanoparticles and microparticles on microalga Chlorella vulgaris. Environ Pollut. 2019 Nov 27;:113647 Authors: Wang L, Huang X, Sun W, Too HZ, Laserna AKC, Li SFY Abstract To compare aquatic organisms' responses to the toxicity of copper oxide (CuO) nanoparticles (NPs) with those of CuO microparticles (MPs) and copper (Cu) ions, a global metabolomics approach was employed to investigate the changes of both polar and nonpolar metabolites in microalga Chlorella vulgaris after 5-day exposure to CuO NPs and MPs (1 and 10 mg/L), as well as the corresponding dissolved Cu ions (0.08 and 0.8 mg/L). Unchanged growth, slight reactive oxygen species production, and significant membrane damage (at 10 mg/L CuO particles) in C. vulgaris were demonstrated. A total of 75 differentiated metabolites were identified. Most metabolic pathways perturbed after CuO NPs exposure were shared by those after CuO MPs and Cu ions exposure, including accumulation of chlorophyll intermediates (max. 2.4-5.2 fold), membrane lipids remodeling for membrane protection (decrease of phosphatidylethanolamines (min. 0.6 fold) and phosphatidylcholines (min. 0.2-0.7 fold), as well as increase of phosphatidic acids (max. 1.5-2.9 fold), phosphatidylglycerols (max. 2.2-2.3 fold), monogalactosyldiacylglycerols (max. 1.2-1.4 fold), digalactosylmonoacylglycerols (max. 1.9-3.8 fold), diacylglycerols (max. 1.4 fold), lysophospholipids (max. 1.8-3.0 fold), and fatty acids (max. 3.0-6.2 fold)), perturbation of glutathione metabolism induced by oxidative stress, and accumulation of osmoregulants (max. 1.3-2.6 fold) to counteract osmotic stress. The only difference between metabolic responses to particles and those to ions was the accumulation of fatty acids oxidation products: particles caused higher fold changes (particles/ions ratio 1.9-3.0) at 1 mg/L and lower fold changes (particles/ions ratio 0.4-0.7) at 10 mg/L compared with ions. Compared with microparticles, there was no nanoparticle-specific pathway perturbed. These results confirm the predominant role of dissolved Cu ions on the toxicity of CuO NPs and MPs, and also reveal particle-specific toxicity from a metabolomics perspective. PMID: 31810715 [PubMed - as supplied by publisher]

Related Articles Advancing functional and translational microbiome research using meta-omics approaches. Microbiome. 2019 Dec 06;7(1):154 Authors: Zhang X, Li L, Butcher J, Stintzi A, Figeys D Abstract The gut microbiome has emerged as an important factor affecting human health and disease. The recent development of -omics approaches, including phylogenetic marker-based microbiome profiling, shotgun metagenomics, metatranscriptomics, metaproteomics, and metabolomics, has enabled efficient characterization of microbial communities. These techniques can provide strain-level taxonomic resolution of the taxa present in microbiomes, assess the potential functions encoded by the microbial community and quantify the metabolic activities occurring within a complex microbiome. The application of these meta-omics approaches to clinical samples has identified microbial species, metabolic pathways, and metabolites that are associated with the development and treatment of human diseases. These findings have further facilitated microbiome-targeted drug discovery and efforts to improve human health management. Recent in vitro and in vivo investigations have uncovered the presence of extensive drug-microbiome interactions. These interactions have also been shown to be important contributors to the disparate patient responses to treatment that are often observed during disease therapy. Therefore, developing techniques or frameworks that enable rapid screening, detailed evaluation, and accurate prediction of drug/host-microbiome interactions is critically important in the modern era of microbiome research and precision medicine. Here we review the current status of meta-omics techniques, including integrative multi-omics approaches, for characterizing the microbiome's functionality in the context of health and disease. We also summarize and discuss new frameworks for applying meta-omics approaches and microbiome assays to study drug-microbiome interactions. Lastly, we discuss and exemplify strategies for implementing microbiome-based precision medicines using these meta-omics approaches and high throughput microbiome assays. PMID: 31810497 [PubMed - in process]

Metabolite profiling of onion landraces and the cold storage effect. Plant Physiol Biochem. 2019 Nov 06;146:428-437 Authors: Romo-Pérez ML, Weinert CH, Häußler M, Egert B, Frechen MA, Trierweiler B, Kulling SE, Zörb C Abstract Today, commercial onion breeders focus almost entirely on conventional farming which reduces diversity in the market and leads to loss of desirable traits such as those that impact nutritional and sensory aspects of onions. A way to preserve phenotypic and genetic diversity is to re-evaluate traditional landraces to introduce their benefits to the broader public. Common onion genotypes vary greatly in their storability. In particular, temperature and relative humidity during storage have significant impact on the metabolites in onions after storage. The aim of this study was to assess changes in the metabolite profile of ten onion genotypes after five months of cold storage. In addition, a characterization of onion landraces in their fresh state was also conducted in order to compare their properties against a commercial genotype. Onion genotypes were grown under organic farming conditions. After harvest and curing, bulbs were stored for up to 22 weeks. Before and after storage, bulb samples were analyzed through targeted and untargeted methods. Out of 189 identified metabolites, 128 showed a storage effect. Mainly fructans decreased because of respiration and energy demand, while monosaccharides increased. Further, amino acids were altered in their concentration after storage with an effect on aroma precursors. Eight of the nine landraces had good storability without critical losses. In their fresh state, the onion genotypes clustered into three major groups. For instance, landraces of group III showed consistently and substantially higher levels of amino acids and certain sugars, indicating a high potential of aromatic properties in those onion landraces. PMID: 31810055 [PubMed - as supplied by publisher]

Metabolomics study of serum and urine samples reveals metabolic pathways and biomarkers associated with pelvic organ prolapse. J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Nov 14;1136:121882 Authors: Deng W, Rao J, Chen X, Li D, Zhang Z, Liu D, Liu J, Wang Y, Huang O Abstract Pelvic organ prolapse (POP) is a common medical condition among women and involves complicated diagnostics and controversial surgical management. The exact molecular mechanism underlying POP is poorly understood, especially at the metabolism level. To explore the metabolic mechanism underlying POP and discover potential biomarkers for POP diagnosis, we applied a non-targeted metabolomics approach using ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). Metabolomics study of serum samples from patients with POP (n = 24) and controls (n = 22) revealed a total of 59 metabolites that are significantly different (VIP ≥ 1 and p ≤ 0.05) between the two groups. Between urine samples from POP patients (n = 45) and controls (n = 59), 33 metabolites differed significantly (VIP ≥ 1 and p ≤ 0.05). Metabolic pathways affected by these differentially expressed metabolites were analyzed. In both serum and urine samples, three pathways including arginine biosynthesis and purine metabolism were found to be significantly related to POP. Six metabolites including GPC, 1-methyladenosine, maleic acid, L-pyroglutamic acid, inosine, and citrate are significantly changed (VIP ≥ 1 and p ≤ 0.05) in both serum and urine samples from patients with POP. Receiver operating characteristics (ROC) curve analysis showed that using these six metabolites as a biomarker could distinguish patients with POP from controls with good accuracy in both serum (AUC = 1) and urine samples (AUC = 0.854). Collectively, these results further extended our understanding of key regulatory metabolic pathways involved in the pathophysiology of POP, as well as provided some promising biomarkers for effective POP diagnosis. PMID: 31809960 [PubMed - as supplied by publisher]

The comparative metabolic response of Bactrocera dorsalis larvae to azadirachtin, pyriproxyfen and tebufenozide. Ecotoxicol Environ Saf. 2019 Dec 03;189:110020 Authors: Zhou Y, Qin DQ, Zhang PW, Liu BJ, Chen XT, Zhang ZX Abstract Azadirachtin, as the most promising and effective botanical insecticide, exhibits significant growth inhibition activity against agricultural and forestry pests. However, its biochemical effects at the metabolic level compared with those of other insect growth regulators have not been studied. Therefore, in this study, a GC-MS based untargeted metabolomics approach was applied to compare azadirachtin with pyriproxyfen (a juvenile hormone analog) and tebufenozide (a molting hormone analog) in terms of their metabolic effects on Bactrocera dorsalis larvae. The bioactivity of azadirachtin against B. dorsalis larvae was significantly different than those of pyriproxyfen and tebufenozide. A total of 693 mass features were recognized, and 112 metabolites were identified in this study. The results showed that a total of 16, 13 and 10 differentially regulated metabolites corresponding to 12, 5 and 8 pathways occur in Aza versus CK, Pyr versus CK and Teb versus CK group, respectively. Further analysis showed that 6 differentially regulated metabolites corresponding to 5 key pathways could be the primary differential metabolic response of B. dorsalis larvae to the three insect growth regulators. The pathways were myo-inositol corresponding to ascorbate and aldarate metabolism as the specific response of B. dorsalis larvae to azadirachtin; xylitol, xylulose and 3-aminopropionitrile corresponding to pentose and glucuronate interconversions, and cyanoamino acid metabolism as the common responses to azadirachtin and pyriproxyfen; and 3-hydroxypropionic acid and beta-alanine corresponding to propanoate metabolism and beta-alanine metabolism as the specific responses to tebufenozide. The results showed that the metabolic response of B. dorsalis larvae to azadirachitin is closer to that of pyriproxyfen than tebufenozide. The differentially regulated metabolites and pathways responsible for this difference are discussed. PMID: 31809954 [PubMed - as supplied by publisher]

The intestinal microbiome potentially affects thrombin generation in human subjects. J Thromb Haemost. 2019 Dec 06;: Authors: Mohammed Y, Kootte RS, Kopatz WF, Borchers CH, Büller HR, Versteeg HH, Nieuwdorp M, van Mens TE Abstract BACKGROUND: The intestinal microbiome plays a versatile role in the etiology of arterial thrombosis. In venous thrombosis, driven chiefly by plasma coagulation, no such role has yet been established. We hypothesized that the intestinal microbiome composition affects coagulation in humans. METHODS: We used healthy donor fecal microbiota transplant (FMT) to experimentally change the microbiome composition in metabolic syndrome patients. 35 subjects were randomized in a blinded fashion to healthy donor FMT or autologous FMT as a control in a 2:1 ratio. We measured thrombin generation at baseline and after 6 weeks using automated calibrated thrombinography, and we determined plasma abundance of 32 coagulation related proteins using a targeted mass spectrometry-based quantitative proteomics assay with heavy labeled internal standards. RESULTS: Healthy donor FMT prolonged the thrombinography lag time (median delta 0.0 vs. 0.25 minutes, p=0.039). The other thrombinography parameters showed no significant difference. Unsupervised cluster analysis suggested overall downregulation of coagulation related plasma proteins in subject clusters containing predominantly subjects that had a metabolic response to healthy donor FMT. FMT treatment status itself showed no clear clustering pattern with up- or downregulation however, and proteins did not cluster according to an apparent biological grouping. DISCUSSION: A single healthy donor FMT tends to modestly suppress the onset thrombin generation in metabolic syndrome patients, representing initial proof-of-principle that the intestinal microbiota composition might affect the coagulation system in humans. The findings merit external validation as a role for intestinal microbiota in coagulation can have clinically important implications. PMID: 31808596 [PubMed - as supplied by publisher]

Related Articles Machine learning distilled metabolite biomarkers for early stage renal injury. Metabolomics. 2019 Dec 05;16(1):4 Authors: Guo Y, Yu H, Chen D, Zhao YY Abstract INTRODUCTION: With chronic kidney disease (CKD), kidney becomes damaged overtime and fails to clean blood. Around 15% of US adults have CKD and nine in ten adults with CKD do not know they have it. OBJECTIVE: Early prediction and accurate monitoring of CKD may improve care and decrease the frequent progression to end-stage renal disease. There is an urgent demand to discover specific biomarkers that allow for monitoring of early-stage CKD, and response to treatment. METHOD: To discover such biomarkers, shotgun high throughput was applied to the detection of serum metabolites biomarker discovery for early stages of CKD from 703 participants. Ultra performance liquid chromatography coupled with high-definition mass spectrometry (UPLC-HDMS)-based metabolomics was used for the determination of 703 fasting serum samples from five stages of CKD patients and age-matched healthy controls. RESULTS AND CONCLUSION: We discovered a set of metabolite biomarkers using a series of classic and neural network based machine learning techniques. This set of metabolites can separate early CKD stage patents from normal subjects with high accuracy. Our study illustrates the power of machine learning methods in metabolite biomarker study. PMID: 31807893 [PubMed - in process]

Related Articles The Natural Products Atlas: An Open Access Knowledge Base for Microbial Natural Products Discovery. ACS Cent Sci. 2019 Nov 27;5(11):1824-1833 Authors: van Santen JA, Jacob G, Singh AL, Aniebok V, Balunas MJ, Bunsko D, Neto FC, Castaño-Espriu L, Chang C, Clark TN, Cleary Little JL, Delgadillo DA, Dorrestein PC, Duncan KR, Egan JM, Galey MM, Haeckl FPJ, Hua A, Hughes AH, Iskakova D, Khadilkar A, Lee JH, Lee S, LeGrow N, Liu DY, Macho JM, McCaughey CS, Medema MH, Neupane RP, O'Donnell TJ, Paula JS, Sanchez LM, Shaikh AF, Soldatou S, Terlouw BR, Tran TA, Valentine M, van der Hooft JJJ, Vo DA, Wang M, Wilson D, Zink KE, Linington RG Abstract Despite rapid evolution in the area of microbial natural products chemistry, there is currently no open access database containing all microbially produced natural product structures. Lack of availability of these data is preventing the implementation of new technologies in natural products science. Specifically, development of new computational strategies for compound characterization and identification are being hampered by the lack of a comprehensive database of known compounds against which to compare experimental data. The creation of an open access, community-maintained database of microbial natural product structures would enable the development of new technologies in natural products discovery and improve the interoperability of existing natural products data resources. However, these data are spread unevenly throughout the historical scientific literature, including both journal articles and international patents. These documents have no standard format, are often not digitized as machine readable text, and are not publicly available. Further, none of these documents have associated structure files (e.g., MOL, InChI, or SMILES), instead containing images of structures. This makes extraction and formatting of relevant natural products data a formidable challenge. Using a combination of manual curation and automated data mining approaches we have created a database of microbial natural products (The Natural Products Atlas, www.npatlas.org) that includes 24 594 compounds and contains referenced data for structure, compound names, source organisms, isolation references, total syntheses, and instances of structural reassignment. This database is accompanied by an interactive web portal that permits searching by structure, substructure, and physical properties. The Web site also provides mechanisms for visualizing natural products chemical space and dashboards for displaying author and discovery timeline data. These interactive tools offer a powerful knowledge base for natural products discovery with a central interface for structure and property-based searching and presents new viewpoints on structural diversity in natural products. The Natural Products Atlas has been developed under FAIR principles (Findable, Accessible, Interoperable, and Reusable) and is integrated with other emerging natural product databases, including the Minimum Information About a Biosynthetic Gene Cluster (MIBiG) repository, and the Global Natural Products Social Molecular Networking (GNPS) platform. It is designed as a community-supported resource to provide a central repository for known natural product structures from microorganisms and is the first comprehensive, open access resource of this type. It is expected that the Natural Products Atlas will enable the development of new natural products discovery modalities and accelerate the process of structural characterization for complex natural products libraries. PMID: 31807684 [PubMed]

Related Articles Metabolomics analysis of the saliva in patients with chronic hepatitis B using nuclear magnetic resonance: a pilot study. Iran J Basic Med Sci. 2019 Sep;22(9):1044-1049 Authors: Gilany K, Mohamadkhani A, Chashmniam S, Shahnazari P, Amini M, Arjmand B, Malekzadeh R, Nobakht Motlagh Ghoochani BF Abstract Objectives: Hepatitis B virus infection causes chronic disease such as cirrhosis and hepatocellular carcinoma. The metabolomics investigations have been demonstrated to be related to pathophysiologic mechanisms in many disorders such as hepatitis B infection. The aim of this study was to investigate the saliva metabolic profile of patients with chronic hepatitis B infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Materials and Methods: Saliva from 16 healthy subjects and 20 patients with chronic hepatitis B virus were analyzed by nuclear magnetic resonance (NMR). Then, multivariate statistical analysis was performed to identify discriminative metabolites between two groups. Results: A set of metabolites were detected, including propionic acid, putrescine, acetic acid, succinic acid, tyrosine, lactic acid, butyric acid, pyruvic acid, 4-pyridoxic acid and 4-hydroxybenzoic acid, which in combination with one another could accurately distinguish patients from healthy controls. Our results clearly demonstrated altered metabolites are involved in nine metabolic pathways. Conclusion: Metabolomics has the potential to be considered as a novel clinical tool for hepatitis B diagnosis while contributing to a comprehensive understanding of disease mechanisms. PMID: 31807248 [PubMed]

Related Articles Altered cellular metabolism in gliomas - an emerging landscape of actionable co-dependency targets. Nat Rev Cancer. 2019 Dec 05;: Authors: Bi J, Chowdhry S, Wu S, Zhang W, Masui K, Mischel PS Abstract Altered cellular metabolism is a hallmark of gliomas. Propelled by a set of recent technological advances, new insights into the molecular mechanisms underlying glioma metabolism are rapidly emerging. In this Review, we focus on the dynamic nature of glioma metabolism and how it is shaped by the interaction between tumour genotype and brain microenvironment. Recent advances integrating metabolomics with genomics are discussed, yielding new insight into the mechanisms that drive glioma pathogenesis. Studies that shed light on interactions between the tumour microenvironment and tumour genotype are highlighted, providing important clues as to how gliomas respond to and adapt to their changing tissue and biochemical contexts. Finally, a road map for the discovery of potential new glioma drug targets is suggested, with the goal of translating these new insights about glioma metabolism into clinical benefits for patients. PMID: 31806884 [PubMed - as supplied by publisher]

Related Articles Lipokine 5-PAHSA is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for de novo Lipogenesis in Mice. Diabetes. 2019 Dec 05;: Authors: Paluchova V, Oseeva M, Brezinova M, Cajka T, Bardova K, Adamcova K, Zacek P, Brejchova K, Balas L, Chodounska H, Kudova E, Schreiber R, Zechner R, Durand T, Rossmeisl M, Abumrad NA, Kopecky J, Kuda O Abstract Branched esters of palmitic acid and hydroxy-stearic acid (PAHSA) are anti-inflammatory and anti-diabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the crosstalk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using 2H2O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol/fatty acid (TAG/FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG-estolides) in WAT. Utilization of 13C isotope tracers and dynamic metabolomics documented that 5-PAHSA primed adipocytes for glucose metabolism in a different way from insulin, promoting DNL, and impeding TAG synthesis. In summary, our data revealed new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA, its relation to insulin action in adipocytes, and independently confirmed a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis. PMID: 31806624 [PubMed - as supplied by publisher]

Related Articles A Multi-Cohort Metabolomics Analysis Discloses Sphingomyelin (32:1) Levels to be Inversely Related to Incident Ischemic Stroke. J Stroke Cerebrovasc Dis. 2019 Dec 02;:104476 Authors: Lind L, Salihovic S, Ganna A, Sundström J, Broeckling CD, Magnusson PK, Pedersen NL, Siegbahn A, Prenni J, Fall T, Ingelsson E, Ärnlöv J Abstract BACKGROUND AND PURPOSE: To search for novel pathophysiological pathways related to ischemic stroke using a metabolomics approach. METHODS: We identified 204 metabolites in plasma by liquid chromatography mass spectrometry in 3 independent population-based samples (TwinGene, Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) and Uppsala Longitudinal Study of Adult Men). TwinGene was used for discovery and the other 2 samples were meta-analyzed as replication. In PIVUS, traditional cardiovascular (CV) risk factors, multiple markers of subclinical CV disease, markers of coagulation/fibrinolysis were measured and analyzed in relation to top metabolites. RESULTS: In TwinGene (177 incident cases, median follow-up 4.3 years), levels of 28 metabolites were associated with incident ischemic stroke at a false discover rate (FDR) of 5%. In the replication (together 194 incident cases, follow-up 10 and 12 years, respectively), only sphingomyelin (32:1) was significantly associated (HR .69 per SD change, 95% CI .57-0.83, P value = .00014; FDR <5%) when adjusted for systolic blood pressure, diabetes, smoking, low density lipoportein (LDL)- and high density lipoprotein (HDL), body mass index (BMI) and atrial fibrillation. In PIVUS, sphingomyelin (32:1) levels were significantly related to both LDL- and HDL-cholesterol in a positive fashion, and to serum triglycerides, BMI and diabetes in a negative fashion. Furthermore, sphingomyelin (32:1) levels were related to vasodilation in the forearm resistance vessels, and inversely to leukocyte count (P < .0069 and .0026, respectively). CONCLUSIONS: An inverse relationship between sphingomyelin (32:1) and incident ischemic stroke was identified, replicated, and characterized. A possible protective role for sphingomyelins in stroke development has to be further investigated in additional experimental and clinical studies. PMID: 31806450 [PubMed - as supplied by publisher]

Related Articles UPLC-MS based urine untargeted metabolomic analyses to differentiate bladder cancer from renal cell carcinoma. BMC Cancer. 2019 Dec 05;19(1):1195 Authors: Wang Z, Liu X, Liu X, Sun H, Guo Z, Zheng G, Zhang Y, Sun W Abstract BACKGROUND: To discover biomarker panels that could distinguish cancers (BC and RCC) from healthy controls (HCs) and bladder cancers (BC) from renal cell carcinoma (RCC), regardless of whether the patients have haematuria. In addition, we also explored the altered metabolomic pathways of BC and RCC. METHODS: In total, 403 participants were enrolled in our study, which included 146 BC patients (77 without haematuria and 69 with haematuria), 115 RCC patients (94 without haematuria and 21 with haematuria) and 142 sex- and age-matched HCs. Their midstream urine samples were collected and analysed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarker panels and altered metabolic pathways. RESULTS: The panel of α-CEHC, β-cortolone, deoxyinosine, flunisolide, 11b,17a,21-trihydroxypreg-nenolone and glycerol tripropanoate could distinguish the patients with cancer from the HCs (the AUC was 0.950) and the external validation also displayed a good predictive ability (the AUC was 0.867). The panel of 4-ethoxymethylphenol, prostaglandin F2b, thromboxane B3, hydroxybutyrylcarnitine, 3-hydroxyphloretin and N'-formylkynurenine could differentiate BC from RCC without haematuria. The AUC was 0.829 in the discovering group and 0.76 in the external validation. The metabolite panel comprising 1-hydroxy-2-oxopropyl tetrahydropterin, 1-acetoxy-2-hydroxy-16-heptadecyn-4-one, 1,2-dehydrosalsolinol and L-tyrosine could significantly discriminate BC from RCC with haematuria (AUC was 0.913). Pathway analyses revealed altered lipid and purine metabolisms between cancer patients and HCs, together with disordered amino acid and purine metabolisms between BC and RCC with haematuria. CONCLUSIONS: UPLC-MS urine metabolomic analyses could not only differentiate cancers from HCs but also discriminate BC from RCC. In addition, pathway analyses demonstrated a deeper metabolic mechanism of BC and RCC. PMID: 31805976 [PubMed - in process]

Related Articles Immunological Effects of Epigenetic Modifiers. Cancers (Basel). 2019 Dec 01;11(12): Authors: Bezu L, Chuang AW, Liu P, Kroemer G, Kepp O Abstract Epigenetic alterations are associated with major pathologies including cancer. Epigenetic dysregulation, such as aberrant histone acetylation, altered DNA methylation, or modified chromatin organization, contribute to oncogenesis by inactivating tumor suppressor genes and activating oncogenic pathways. Targeting epigenetic cancer hallmarks can be harnessed as an immunotherapeutic strategy, exemplified by the use of pharmacological inhibitors of DNA methyltransferases (DNMT) and histone deacetylases (HDAC) that can result in the release from the tumor of danger-associated molecular patterns (DAMPs) on one hand and can (re-)activate the expression of tumor-associated antigens on the other hand. This finding suggests that epigenetic modifiers and more specifically the DNA methylation status may change the interaction of chromatin with chaperon proteins including HMGB1, thereby contributing to the antitumor immune response. In this review, we detail how epigenetic modifiers can be used for stimulating therapeutically relevant anticancer immunity when used as stand-alone treatments or in combination with established immunotherapies. PMID: 31805711 [PubMed]

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/06PubMed 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.

17 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/06PubMed 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.

28 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/05PubMed 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.

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2019/12/04PubMed 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.

Related Articles Analysis of brain metabolites by gas chromatography-mass spectrometry reveals the risk-benefit concerns of prednisone in MRL/lpr lupus mice. Inflammopharmacology. 2019 Nov 30;: Authors: Zhou J, Lu F, Li S, Xie M, Lu H, Xie Z, Wu D, Wang S, Wen C, Xu ZH Abstract OBJECTIVE: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a common cause of disability in systemic lupus erythematosus (SLE). This study aims to investigate the metabolic changes in the hypothalamus and frontal cortex in lupus-prone MRL/lpr mice. METHODS: Metabolic changes were analyzed using gas chromatography-mass spectrometry (GC-MS). RESULTS: According to the principal component analysis (PCA), the metabolic profiles were different between the frontal cortex and hypothalamus, but they were comparable between MRL/lpr and MRL/MpJ mice (16 weeks of age). By OPLS-DA, eight cortical and six hypothalamic differential metabolites were identified in MRL/lpr as compared to MRL/MpJ mice. Among these differential metabolites, we found a decrease of N-acetyl-L-aspartate (NAA, a potential marker of neuronal integrity), an increase of pyruvate and a decrease of glutamate in the frontal cortex but not in the hypothalamus. Prednisone treatment (3 mg/kg from 8 weeks of age) relieved the decrease of NAA but further increased the accumulation of pyruvate in the frontal cortex, additionally affected eight enriched pathways in the hypothalamus, and led to significant imbalances between the excitation and inhibition in both the frontal cortex and hypothalamus. CONCLUSION: These results suggest that the frontal cortex may be more preferentially affected than the hypothalamus in SLE. Prednisone disrupted rather than relieved metabolic abnormalities in the brain, especially in the hypothalamus, indicating that the risk-benefit balance of prednisone for SLE or NPSLE remains to be further evaluated. PMID: 31786803 [PubMed - as supplied by publisher]