PubMed

Related Articles Modelling diabetic nephropathy in mice. Nat Rev Nephrol. 2017 Oct 24;: Authors: Azushima K, Gurley SB, Coffman TM Abstract Diabetic nephropathy (DN) is a leading cause of end-stage renal disease in the developed world. Accordingly, an urgent need exists for new, curative treatments as well as for biomarkers to stratify risk of DN among individuals with diabetes mellitus. A barrier to progress in these areas has been a lack of animal models that faithfully replicate the main features of human DN. Such models could be used to define the pathogenesis, identify drug targets and test new therapies. Owing to their tractability for genetic manipulation, mice are widely used to model human diseases, including DN. Questions have been raised, however, about the general utility of mouse models in human drug discovery. Standard mouse models of diabetes typically manifest only modest kidney abnormalities, whereas accelerated models, induced by superimposing genetic stressors, recapitulate key features of human DN. Incorporation of systems biology approaches and emerging data from genomics and metabolomics studies should enable further model refinement. Here, we discuss the current status of mouse models for DN, their limitations and opportunities for improvement. We emphasize that future efforts should focus on generating robust models that reproduce the major clinical and molecular phenotypes of human DN. PMID: 29062142 [PubMed - as supplied by publisher]

Related Articles Early-onset and classical forms of type 2 diabetes show impaired expression of genes involved in muscle branched-chain amino acids metabolism. Sci Rep. 2017 Oct 23;7(1):13850 Authors: Hernández-Alvarez MI, Díaz-Ramos A, Berdasco M, Cobb J, Planet E, Cooper D, Pazderska A, Wanic K, O'Hanlon D, Gomez A, de la Ballina LR, Esteller M, Palacin M, O'Gorman DJ, Nolan JJ, Zorzano A Abstract The molecular mechanisms responsible for the pathophysiological traits of type 2 diabetes are incompletely understood. Here we have performed transcriptomic analysis in skeletal muscle, and plasma metabolomics from subjects with classical and early-onset forms of type 2 diabetes (T2D). Focused studies were also performed in tissues from ob/ob and db/db mice. We document that T2D, both early and late onset, are characterized by reduced muscle expression of genes involved in branched-chain amino acids (BCAA) metabolism. Weighted Co-expression Networks Analysis provided support to idea that the BCAA genes are relevant in the pathophysiology of type 2 diabetes, and that mitochondrial BCAA management is impaired in skeletal muscle from T2D patients. In diabetic mice model we detected alterations in skeletal muscle proteins involved in BCAA metabolism but not in obese mice. Metabolomic analysis revealed increased levels of branched-chain keto acids (BCKA), and BCAA in plasma of T2D patients, which may result from the disruption of muscle BCAA management. Our data support the view that inhibition of genes involved in BCAA handling in skeletal muscle takes place as part of the pathophysiology of type 2 diabetes, and this occurs both in early-onset and in classical type 2 diabetes. PMID: 29062026 [PubMed - in process]

Related Articles AML-specific cytotoxic antibodies in patients with durable graft versus leukemia responses. Blood. 2017 Oct 23;: Authors: Gillissen MA, Kedde M, de Jong G, Moiset G, Yasuda E, Levie SE, Bakker AQ, Claassen YB, Wagner K, Böhne M, Hensbergen PJ, Speijer D, van Helden PM, Beaumont T, Spits H, Hazenberg MD Abstract Most acute myeloid leukemia (AML) patients can only be cured when an allogeneic hematopoietic stem cell transplantation (HSCT) induces a graft versus leukemia immune response (GvL). While the role of T cells and NK cells in tumor immunology has been established, less is known about the contribution of B cells. From B cells of high-risk AML patients with potent and lasting GvL responses we isolated monoclonal antibodies directed against antigens expressed on the cell surface of AML cells but not on normal hematopoietic and non-hematopoietic cells. A number of these donor-derived antibodies recognized the U5 snRNP200 complex, a component of the spliceosome that in normal cells is found in the cell. In AML however, the U5 snRNP200 complex is exposed on the cell membrane of leukemic blasts. U5 snRNP200 complex-specific antibodies induced death of AML cells in a FcR dependent way in the absence of cytotoxic leukocytes or complement. In an AML mouse model, treatment with U5 snRNP200 complex-specific antibodies led to significant tumor growth inhibition. Thus, donor derived U5 snRNP200 complex-recognizing AML-specific antibodies may contribute to anti-tumor responses. PMID: 29061569 [PubMed - as supplied by publisher]

Related Articles Using MutPred derived mtDNA load scores to evaluate mtDNA variation in hypertension and diabetes in a two-population cohort: The SABPA study. J Genet Genomics. 2017 Mar 20;44(3):139-149 Authors: Venter M, Malan L, van Dyk E, Elson JL, van der Westhuizen FH Abstract Mitochondrial DNA (mtDNA) variation has been implicated in many common complex diseases, but inconsistent and contradicting results are common. Here we introduce a novel mutational load hypothesis, which also considers the collective effect of mainly rare variants, utilising the MutPred Program. We apply this new methodology to investigate the possible role of mtDNA in two cardiovascular disease (CVD) phenotypes (hypertension and hyperglycaemia), within a two-population cohort (n = 363; mean age 45 ± 9 yrs). Very few studies have looked at African mtDNA variation in the context of complex disease, and none using complete sequence data in a well-phenotyped cohort. As such, our study will also extend our knowledge of African mtDNA variation, with complete sequences of Southern Africans being especially under-represented. The cohort showed prevalence rates for hypertension (58.6%) and prediabetes (44.8%). We could not identify a statistically significant role for mtDNA variation in association with hypertension or hyperglycaemia in our cohort. However, we are of the opinion that the method described will find wide application in the field, being especially useful for cohorts from multiple locations or with a variety of mtDNA lineages, where the traditional haplogroup association method has been particularly likely to generate spurious results in the context of association with common complex disease. PMID: 28298255 [PubMed - indexed for MEDLINE]

Related Articles Early Prediction of Developing Type 2 Diabetes by Plasma Acylcarnitines: A Population-Based Study. Diabetes Care. 2016 Sep;39(9):1563-70 Authors: Sun L, Liang L, Gao X, Zhang H, Yao P, Hu Y, Ma Y, Wang F, Jin Q, Li H, Li R, Liu Y, Hu FB, Zeng R, Lin X, Wu J Abstract OBJECTIVE: Acylcarnitines were suggested as early biomarkers even prior to insulin resistance in animal studies, but their roles in predicting type 2 diabetes were unknown. Therefore, we aimed to determine whether acylcarnitines could independently predict type 2 diabetes by using a targeted metabolic profiling approach. RESEARCH DESIGN AND METHODS: A population-based prospective study was conducted among 2,103 community-living Chinese individuals aged 50-70 years from Beijing and Shanghai with a mean follow-up duration of 6 years. Fasting glucose, glycohemoglobin, and insulin were determined at baseline and in a follow-up survey. Baseline plasma acylcarnitines were profiled by liquid chromatography-tandem mass spectrometry. RESULTS: Over the 6-year period, 507 participants developed diabetes. A panel of acylcanitines, especially with long chain, was significantly associated with increased risk of type 2 diabetes. The relative risks of type 2 diabetes per SD increase of the predictive model score were 2.48 (95% CI 2.20-2.78) for the conventional and 9.41 (95% CI 7.62-11.62) for the full model including acylcarnitines, respectively. Moreover, adding selected acylcarnitines substantially improved predictive ability for incident diabetes, as area under the receiver operator characteristic curve improved to 0.89 in the full model compared with 0.73 in the conventional model. Similar associations were obtained when the predictive models were established separately among Beijing or Shanghai residents. CONCLUSIONS: A panel of acylcarnitines, mainly involving mitochondrial lipid dysregulation, significantly improved predictive ability for type 2 diabetes beyond conventional risk factors. These findings need to be replicated in other populations, and the underlying mechanisms should be elucidated. PMID: 27388475 [PubMed - indexed for MEDLINE]

18 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 2017/10/24PubMed 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.

IgG glycosylation and DNA methylation are interconnected with smoking. Biochim Biophys Acta. 2017 Oct 18;: Authors: Wahl A, Kasela S, Monotoro EC, van Iterson M, Štambuk J, Sharma S, van den Akker E, Klaric L, Benedetti E, Razdorov G, Trbojević-Akmačić I, Vučković F, Ugrina I, Beekman M, Deelen J, van Heemst D, Heijmans BT, Consortium BIOS, Wuhrer M, Plomp R, Keser T, Šimurina M, Pavić T, Gudelj I, Krištić J, Grallert H, Kunze S, Peters A, Bell JT, Spector TD, Milani L, Eline Slagboom P, Lauc G, Gieger C Abstract BACKGROUND: Glycosylation is one of the most common post-translation modifications with large influences on protein structure and function. The effector function of immunoglobulin G (IgG) alters between pro- and anti-inflammatory, based on its glycosylation. IgG glycan synthesis is highly complex and dynamic. METHODS: With the use of two different analytical methods for assessing IgG glycosylation, we aim to elucidate the link between DNA methylation and glycosylation of IgG by means of epigenome-wide association studies. In total, 3000 individuals from 4 cohorts were analyzed. RESULTS: The overlap of the results from the two glycan measurement panels yielded DNA methylation of 7 CpG-sites on 5 genomic locations to be associated with IgG glycosylation: cg25189904 (chr.1, GNG12); cg05951221, cg21566642 and cg01940273 (chr.2, ALPPL2); cg05575921 (chr.5, AHRR); cg06126421 (6p21.33); and cg03636183 (chr.19, F2RL3). Mediation analyses with respect to smoking revealed that the effect of smoking on IgG glycosylation may be at least partially mediated via DNA methylation levels at these 7 CpG-sites. CONCLUSION: Our results suggest the presence of an indirect link between DNA methylation and IgG glycosylation that may in part capture environmental exposures. GENERAL SIGNIFICANCE: An epigenome-wide analysis conducted in four population-based cohorts revealed an association between DNA methylation and IgG glycosylation patterns. Presumably, DNA methylation mediates the effect of smoking on IgG glycosylation. PMID: 29055820 [PubMed - as supplied by publisher]

Proteomics and metabolomics characterizing the pathophysiology of adaptive reactions to the metabolic challenges during the transition from late pregnancy to early lactation in dairy cows. J Proteomics. 2017 Oct 18;: Authors: Ceciliani F, Lecchi C, Urh C, Sauerwein H Abstract The transition from late pregnancy to early lactation is a critical period in a dairy cow's life due to the rapidly increasing drain of nutrients from the maternal organism towards the foetus and into colostrum and milk. In order to cope with the challenges of parturition and lactation, comprehensive adaptive reactions comprising the endocrine and the immune system need to be accomplished. There is high variation in this coping ability and both metabolic and infectious diseases, summarized as "production diseases", such as hypocalcaemia (milk fever), fatty liver syndrome, laminitis and ketosis, may occur and impact welfare, productive lifespan and economic outcomes. Proteomics and metabolomics have emerged as valuable techniques to characterize proteins and metabolite assets from tissue and biological fluids, such as milk, blood and urine. In this review we provide an overview on metabolic status and physiological changes during the transition period and the related production diseases in dairy cows, and summarize the state of art on proteomics and metabolomics of biological fluids and tissues involved in metabolic stress during the peripartum period. We also provide a current and prospective view of the application of the recent achievements generated by omics for biomarker discovery and their potential in diagnosis. BIOLOGICAL SIGNIFICANCE: For high-yielding dairy cows there are several "occupational diseases" that occur mainly during the metabolic challenges related to the transition from pregnancy to lactation. Such diseases and their sequelae form a major concern for dairy production, and often lead to early culling of animals. Beside the economical perspective, metabolic stress may severely influence animal welfare. There is a multitude of studies about the metabolic backgrounds of such so called production diseases like ketosis, fatty liver, or hypocalcaemia, although the investigations aiming to assess the complexity of the pathophysiological reactions are largely focused on gene expression, i.e. transcriptomics. For extending the knowledge towards the proteome and the metabolome, the respective technologies are of increasing importance and can provide an overall view of how dairy cows react to metabolic stress, which is needed for an in-depth understanding of the molecular mechanisms of the related diseases. We herein review the current findings from studies applying proteomics and metabolomics to transition-related diseases, including fatty liver, ketosis, endometritis, hypocalcaemia and laminitis. For each disease, a brief overview of the up to date knowledge about its pathogenesis is provided, followed by an insight into the most recent achievements on the proteome and metabolome of tissues and biological fluids, such as blood serum and urine, highlighting potential biomarkers. We believe that this review would help readers to be become more familiar with the recent progresses of molecular background of transition-related diseases thus encouraging research in this field. PMID: 29055723 [PubMed - as supplied by publisher]

Development of an on-line solid phase extraction ultra performance liquid chromatography technique coupled to tandem mass spectrometry for quantification of bisphenol S and bisphenol S glucuronide: Applicability to toxicokinetic investigations. J Chromatogr A. 2017 Oct 12;: Authors: Grandin F, Picard-Hagen N, Gayrard V, Puel S, Viguié C, Toutain PL, Debrauwer L, Lacroix MZ Abstract Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by structural analogues, such as Bisphenol S (BPS), in consumer products. At present, no toxicokinetic investigations have been conducted to assess the factors determining human internal exposure to BPS for subsequent risk assessment. Toxicokinetic studies require reliable analytical methods to measure the plasma concentrations of BPS and its main conjugated metabolite, BPS-glucuronide (BPS-G). An efficient on-line SPE-UPLC-MS/MS method for the simultaneous quantification of BPS and BPS-G in ovine plasma was therefore developed and validated in accordance with the European Medicines Agency guidelines for bioanalytical method validation. This method has a limit of quantification of 3ngmL(-1) for BPS and 10ngmL(-1) for BPS-G, an analytical capacity of 200 samples per day, and is particularly well suited to toxicokinetic studies. Use of this method in toxicokinetic studies in sheep showed that BPS, like BPA, is efficiently metabolized into its glucuronide form. However, the clearances and distributions of BPS and BPS-G were lower than those of the corresponding unconjugated and glucuroconjugated forms of BPA. PMID: 29055528 [PubMed - as supplied by publisher]

Related Articles The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell death in cultured melanoma cells. Biochimie. 2017 Oct 17;: Authors: Lewies A, Wentzel JF, van Dyk H, Du Plessis LH Abstract Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells present with altered energy metabolism which is associated with elevated reactive oxygen species (ROS) generation. This is also evident for melanoma, the leading cause of skin cancer related deaths. Altered mechanisms affecting mitochondrial bioenergetics pose attractive targets for novel anti-cancer therapies. Antimicrobial peptides have been shown to exhibit selective anti-cancer activities. In this study, the anti-melanoma potential of the antimicrobial peptide, nisin Z, was evaluated in vitro. Nisin Z was shown to induce selective toxicity in melanoma cells compared to non-malignant keratinocytes. Furthermore, nisin Z was shown to negatively affect the energy metabolism (glycolysis and mitochondrial respiration) of melanoma cells, increase reactive oxygen species generation and cause apoptosis. Results also indicate that nisin Z can decrease the invasion and proliferation of melanoma cells demonstrating its potential use against metastasis associated with melanoma. As nisin Z seems to place a considerable extra burden on the energy metabolism of melanoma cells, combination therapies with known anti-melanoma agents may be effective treatment options. PMID: 29054798 [PubMed - as supplied by publisher]

Related Articles Fluvial biofilms exposed to desiccation and pharmaceutical pollution: New insights using metabolomics. Sci Total Environ. 2017 Oct 17;: Authors: Serra-Compte A, Corcoll N, Huerta B, Rodríguez-Mozaz S, Sabater S, Barceló D, Álvarez-Muñoz D Abstract In many arid and semi-arid systems, biological communities in river ecosystems are submitted to flow interruption and desiccation, as well as to the impact of urban wastewaters. In this work, we studied (using a LC-LTQ-Orbitrap) the metabolomic response of biofilm communities exposed to both hydrological and chemical stressors. Fluvial biofilms were exposed to a mixture of 9 pharmaceuticals at a total concentration of 5000ng/L (mimicking concentrations and compounds found in polluted aquatic environments) and/or to seven days of desiccation, under laboratory conditions. The biosynthesis of fatty acids was the main metabolic pathway disrupted in biofilms. Endogenous biofilm's metabolites (metabolome) altered due to these stressors were identified. The metabolites that significantly changed only due to one of the stressors could be proposed as potential specific biomarkers. A biomarker of pharmaceutical exposure was the lysophosphatidic acid, which decreased a 160%, while for desiccation stearidonic acid (increased 160%), 16-Oxohexadecanoic acid (increased 340%) and palmitoleic acid (decreased 290%) were the biomarkers proposed. Besides, other metabolites showed different responses depending on the treatment, such as palmitic acid, linolenic acid, behenic acid, lignoceric acid and azelaic acid. The Carbon:Phosphorus (C:P) molar ratio increased due to all stress factors, whereas the algal community composition changed mainly due to desiccation. A possible relationship between those changes observed in structural parameters and the metabolome of biofilms was explored. Overall, our findings support the use of metabolomics to unravel at molecular level the effects from chemical and physical stressors on complex microbial communities, such as biofilms, and pinpoint biomarkers of exposure. PMID: 29054673 [PubMed - as supplied by publisher]

Related Articles Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted metabolomics by target-directed data dependent acquisition with time-staggered precursor ion list. Anal Chim Acta. 2017 Nov 01;992:67-75 Authors: Wang Y, Feng R, Wang R, Yang F, Li P, Wan JB Abstract Metabolite identification is one of the major bottlenecks in liquid chromatography-mass spectrometry (LC-MS)-based untargeted metabolomics owing to the difficulty of acquiring MS/MS information of most metabolites detected. Data dependent acquisition (DDA) has been currently used to acquire MS/MS data in untargeted metabolomics. When dealing with the complex biological samples, top-n-based DDA method selects only a small fraction of the ions for fragmentation, leading to low MS/MS coverage of metabolites in untargeted metabolomics. In this study, we proposed a novel DDA method to improve the performance of MS/MS acquisition in LC-MS-based untargeted metabolomics using target-directed DDA (t-DDA) with time-staggered precursor ion lists (ts-DDA). Full scan-based untargeted analysis was applied to extract the target ions. After peak alignment, ion filtration, and ion fusion, the target precursor ion list was generated for subsequent t-DDA and ts-DDA. Compared to the conventional DDA, the ts-DDA exhibits the better MS/MS coverage of metabolomes in a plasma sample, especially for the low abundant metabolites. Even in high co-elution zones, the ts-DDA also showed the superiority in acquiring MS/MS information of co-eluting ions, as evidenced by better MS/MS coverage and MS/MS efficiency, which was mainly attributed to the pre-selection of precursor ion and the reduced number of concurrent ions. The newly developed method might provide more informative MS/MS data of metabolites, which will be helpful to increase the confidence of metabolite identification in untargeted metabolomics. PMID: 29054151 [PubMed - in process]

Subacute oral toxicity assessment of benalaxyl in mice based on metabolomics methods. Chemosphere. 2017 Oct 15;191:373-380 Authors: Wang X, Wang D, Zhou Z, Zhu W Abstract In this study, the metabolic responses of mice after 30 days of exposure to benalaxyl were assessed using NMR-based untargeted metabolomics and LC-MS-based targeted profiling of 20 amino acids. Urinary (1)H NMR analyses revealed alterations in energy metabolism, lipid metabolism, vitamin B metabolism, the urea cycle and amino acid metabolism, and targeted analyses indicated that the serum levels of asparagine, histidine, lysine and aspartic acid were significantly altered. Additionally, significant oxidative stress was observed in the liver and kidney, although no apparent histopathological injury was observed. The tissue distribution indicated a significant stereoselectivity in the brain, where (-)-R-benalaxyl was enriched. These data provide a comprehensive picture of the subacute toxic effects of benalaxyl in mice. The results of this study suggested that, for a toxicity evaluation, metabolomics analysis is much more sensitive than traditional toxicological methods. The results also highlight the combined use of untargeted and targeted metabolomics approaches in evaluating the health risks of xenobiotics. PMID: 29054078 [PubMed - as supplied by publisher]

Resolution of inflammation and sepsis survival are improved by dietary Ω-3 fatty acids. Cell Death Differ. 2017 Oct 20;: Authors: Körner A, Schlegel M, Theurer J, Frohnmeyer H, Adolph M, Heijink M, Giera M, Rosenberger P, Mirakaj V Abstract Critical conditions such as sepsis following infection or traumatic injury disturb the complex state of homeostasis that may lead to uncontrolled inflammation resulting in organ failure, shock and death. They are associated with endogenous mediators that control the onset of acute inflammatory response, but the central problem remains the complete resolution of inflammation. Omega-3 enriched lipid emulsions (Ω-3(+) LEs) were used in experimental studies and clinical trials to establish homeostasis, yet with little understanding about their role on the resolution of inflammation and tissue regeneration. Here, we demonstrate that Ω-3 lipid emulsions (LEs) orchestrate inflammation-resolution/regeneration mechanism during sterile peritonitis and murine polymicrobial sepsis. Ω-3(+) LEs recessed neutrophil infiltration, reduced pro-inflammatory mediators, reduced the classical monocyte and enhanced the non-classical monocytes/macrophages recruitment and finally increased the efferocytosis in sepsis. The actions of Ω-3(+) LE were 5-lipoxygenase (5-LOX) and 12/15-lipoxygenase (12/15-LOX) dependent. Ω-3(+) LEs shortened the resolution interval by 56%, stimulated the endogenous biosynthesis of resolution mediators lipoxin A4, protectin DX and maresin 1 and contributed to tissue regeneration. Ω-3(+) LEs protected against hypothermia and weight loss and enhanced survival in murine polymicrobial sepsis. We highlighted a role of Ω-3(+) LEs in regulating key mechanisms within the resolution terrain during murine sepsis. This might form the basis for a rational design of sepsis specific clinical nutrition.Cell Death and Differentiation advance online publication, 20 October 2017; doi:10.1038/cdd.2017.177. PMID: 29053142 [PubMed - as supplied by publisher]

Metabolic shift in density-dependent stem cell differentiation. Cell Commun Signal. 2017 Oct 20;15(1):44 Authors: Singh SJ, Turner W, Glaser DE, McCloskey KE, Filipp FV Abstract BACKGROUND: Vascular progenitor cells (VPCs) derived from embryonic stem cells (ESCs) are a valuable source for cell- and tissue-based therapeutic strategies. During the optimization of endothelial cell (EC) inductions from mouse ESCs using our staged and chemically-defined induction methods, we found that cell seeding density but not VEGF treatment between 10 ng/mL and 40 ng/mL was a significant variable directing ESCs into FLK1(+) VPCs during stage 1 induction. Here, we examine potential contributions from cell-to-cell signaling or cellular metabolism in the production of VPCs from ESCs seeded at different cell densities. METHODS: Using 1D (1)H-NMR spectroscopy, transcriptomic arrays, and flow cytometry, we observed that the density-dependent differentiation of ESCs into FLK1(+) VPCs positively correlated with a shift in metabolism and cellular growth. RESULTS: Specifically, cell differentiation correlated with an earlier plateauing of exhaustive glycolysis, decreased lactate production, lower metabolite consumption, decreased cellular proliferation and an increase in cell size. In contrast, cells seeded at a lower density of 1,000 cells/cm(2) exhibited increased rates of glycolysis, lactate secretion, metabolite utilization, and proliferation over the same induction period. Gene expression analysis indicated that high cell seeding density correlated with up-regulation of several genes including cell adhesion molecules of the notch family (NOTCH1 and NOTCH4) and cadherin family (CDH5) related to vascular development. CONCLUSIONS: These results confirm that a distinct metabolic phenotype correlates with cell differentiation of VPCs. PMID: 29052507 [PubMed - in process]

Related Articles [Serum metabonomics in mice infected with mycoplasma pneumoniae by UPLC-Q-TOF-MS]. Zhongguo Zhong Yao Za Zhi. 2017 Apr;42(7):1382-1389 Authors: Wei WF, Chu YT, Liu Y, Huo JH, Wang WM Abstract Ultra high performance liquid chromatography coupled with tandem quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) was applied to metabonomics study in BALB/c mice infected with mycoplasma pneumoniae(MP) to analyze the changes in serum endogenous metabolites, identify potential biomarkers associated with mycoplasma pneumoniae pneumonia(MPP), analyze the metabolic pathway and explore the pathogenic mechanism of MPP. The BALB/c mice were inoculated with MP by repeated intranasal infectious routes to establish MPP models, and the results of the lung tissue biopsy, IgM and mycoplasma nucleic acid content determination showed that the models of MP in BALB/c mice were successfully established. UPLC-Q-TOF-MS was used to analyze the serum metabolic profiling of BALB/c mice infected with MP, and then principal component analysis(PCA) was combined with orthogonal partial least squares discriminant analysis(OPLS-DA) for data processing. The results showed that there were significant differences in serum metabolic profile between the MP infected mice and the normal mice. Forty-seven potential biomarkers such as ornithine, cortisol, vitamin A and tryptophan were screened out by database searching and MS information matching. These potential biomarkers related to 17 metabolic pathways including retinol metabolism, arginine and proline metabolism, steroid hormone synthesis and so on. The metabonomic research method for serum of mice infected with mycoplasma pneumoniae based on UPLC-Q-TOF-MS was established in this study. The metabolic changes of endogenous small molecules in mice infected with MP were reflected in the overall level, laying the foundation for the selection and evaluation of MPP drugs. PMID: 29052403 [PubMed - in process]

Related Articles [Research progress of serum pharmacochemistry of traditional Chinese medicine]. Zhongguo Zhong Yao Za Zhi. 2017 Apr;42(7):1265-1270 Authors: Ma FX, Xue PF, Wang YY, Wang YN, Xue SY Abstract Serum pharmacochemistry of traditional Chinese medicine(TCM) is an effective method to rapidly screen the effective substances and reveal the compatibility law of compound by identification and analysis of constituents migrating to blood after oral administration. In the last two decades, it has been universally accepted and widely applied in the field. With the cross-fusion with other disciplines, such as serum pharmacology, pharmacokinetics, metabolomics, network pharmacology and systems biology, serum pharmacochemistry shows comprehensive superiority in explaining drug changes in vivo and in vitro, interactions between drugs, interactions between drug and body, which coincides with the complexity of TCM compatibility, multi-components, multi-targets and multi-mechanisms. Based on the references related with the serum pharmacochemistry from CNKI scholar and Pubmed in 2013-2016, the research results of serum pharmacochemistry were statistically analyzed, and the key technical problems during the study of serum pharmacochemistry, for example, preparation of test sample, selection of experimental animal, determination of drug delivery scheme, method and time of the adoption blood, preparation and pretreatment of blood sample, as well as analysis of constituents migrating to blood, and the solving ways were empirically introduced. In addition, the development and comprehensive application of serum pharmacochemistry in TCM were summarized in this paper, hoping to lay a foundation for the further application of this method in TCM research. PMID: 29052384 [PubMed - in process]

Related Articles Control of biotin biosynthesis in mycobacteria by a pyruvate carboxylase dependent metabolic signal. Mol Microbiol. 2017 Oct 20;: Authors: Lazar N, Fay A, Nandakumar M, Boyle KE, Xavier J, Rhee K, Glickman MS Abstract Biotin is an essential cofactor utilized by all domains of life, but only synthesized by bacteria, fungi and plants, making biotin biosynthesis a target for antimicrobial development. To understand biotin biosynthesis in mycobacteria, we executed a genetic screen in Mycobacterium smegmatis for biotin auxotrophs and identified pyruvate carboxylase (Pyc) as required for biotin biosynthesis. The biotin auxotrophy of the pyc::tn strain is due to failure to transcriptionally induce late stage biotin biosynthetic genes in low biotin conditions. Loss of bioQ, the repressor of biotin biosynthesis, in the pyc::tn strain reverted biotin auxotrophy, as did reconstituting the last step of the pathway through heterologous expression of BioB and provision of its substrate DTB. The role of Pyc in biotin regulation required its catalytic activities and could be supported by M. tuberculosis Pyc. Quantitation of the kinetics of depletion of biotinylated proteins after biotin withdrawal revealed that Pyc is the most rapidly depleted biotinylated protein and metabolomics revealed a broad metabolic shift in wild type cells upon biotin withdrawal which was blunted in cell lacking Pyc. Our data indicate that mycobacterial cells monitor biotin sufficiency through a metabolic signal generated by dysfunction of a biotinylated protein of central metabolism. This article is protected by copyright. All rights reserved. PMID: 29052269 [PubMed - as supplied by publisher]

Related Articles The Impacts of Genistein and Daidzein on Estrogen Conjugations in Human Breast Cancer Cells: A Targeted Metabolomics Approach. Front Pharmacol. 2017;8:699 Authors: Poschner S, Maier-Salamon A, Zehl M, Wackerlig J, Dobusch D, Pachmann B, Sterlini KL, Jäger W Abstract The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as in vitro data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells at low concentrations. As genistein and daidzein are known to inhibit key enzymes in the steroid metabolism pathway, and thus may influence levels of active estrogens, we investigated the impacts of genistein and daidzein on the formation of estrogen metabolites, namely 17β-estradiol (E2), 17β-estradiol-3-(β-D-glucuronide) (E2-G), 17β-estradiol-3-sulfate (E2-S) and estrone-3-sulfate (E1-S) in estrogen-dependent ERα+ MCF-7 cells. We found that both isoflavones were potent inhibitors of E1 and E2 sulfation (85-95% inhibition at 10 μM), but impeded E2 glucuronidation to a lesser extent (55-60% inhibition at 10 μM). The stronger inhibition of E1 and E2 sulfation compared with E2 glucuronidation was more evident for genistein, as indicated by significantly lower inhibition constants for genistein [Kis: E2-S (0.32 μM) < E1-S (0.76 μM) < E2-G (6.01 μM)] when compared with those for daidzein [Kis: E2-S (0.48 μM) < E1-S (1.64 μM) < E2-G (7.31 μM)]. Concomitant with the suppression of E1 and E2 conjugation, we observed a minor but statistically significant increase in E2 concentration of approximately 20%. As the content of genistein and daidzein in soy food is relatively low, an increased risk of breast cancer development and progression in women may only be observed following consumption of high-dose isoflavone supplements. Further long-term human studies monitoring free estrogens and their conjugates are therefore highly warranted to evaluate the potential side effects of high-dose genistein and daidzein, especially in patients diagnosed with ERα+ breast cancer. PMID: 29051735 [PubMed]

Related Articles Myocardial metabolic alterations in mice with diet-induced atherosclerosis: linking sulfur amino acid and lipid metabolism. Sci Rep. 2017 Oct 19;7(1):13597 Authors: Lee J, Jung S, Kim N, Shin MJ, Ryu DH, Hwang GS Abstract Atherosclerosis is a leading cause of cardiovascular disease (CVD), but the effect of diet on the atherosclerotic heart's metabolism is unclear. We used an integrated metabolomics and lipidomics approach to evaluate metabolic perturbations in heart and serum from mice fed an atherogenic diet (AD) for 8, 16, and 25 weeks. Nuclear magnetic resonance (NMR)-based metabolomics revealed significant changes in sulfur amino acid (SAA) and lipid metabolism in heart from AD mice compared with heart from normal diet mice. Higher SAA levels in AD mice were quantitatively verified using liquid chromatography-mass spectrometry (LC/MS). Lipidomic profiling revealed that fatty acid and triglyceride (TG) levels in the AD group were altered depending on the degree of unsaturation. Additionally, levels of SCD1, SREBP-1, and PPARγ were reduced in AD mice after 25 weeks, while levels of reactive oxygen species were elevated. The results suggest that a long-term AD leads to SAA metabolism dysregulation and increased oxidative stress in the heart, causing SCD1 activity suppression and accumulation of toxic TGs with a low degree of unsaturation. These findings demonstrate that the SAA metabolic pathway is a promising therapeutic target for CVD treatment and that metabolomics can be used to investigate the metabolic signature of atherosclerosis. PMID: 29051579 [PubMed - in process]