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22 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 2018/03/13PubMed 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 and its physiological regulation process reveal the salt-tolerant mechanism in Glycine soja seedling roots. Plant Physiol Biochem. 2018 Mar 05;126:187-196 Authors: Jiao Y, Bai Z, Xu J, Zhao M, Khan Y, Hu Y, Shi L Abstract Wild soybean (Glycine soja) is an excellent germplasm resource and has strong resistance and wide adaptability to different environments. Hence, the physiology and metabolomics characteristics of wild soybean under different types of salt stress were determined to improve understanding of salt-tolerant mechanisms of wild soybean in the field. Two types of wild soybean seedlings were exposed to two different types of salt stress for 14 d. The photosynthesis of wild soybean seedling extracts were analyzed using metabolomics based on gas chromatography-mass spectrometry. The wild soybean root extracts used metabolomics to quantify the metabolic changes and ion contents. The assimilative function of photosynthesis in salt-tolerant wild soybean was less inhibited than in common wild soybean, and it regulated accumulation of toxic ions and maintained the accumulation of K+ and Mg2+ to alleviate salt stress. Moreover, in resisting salt stress the salt-tolerant wild soybean has showed improved amino acid and carbohydrate and polyol metabolisms under neutral-salt stress and organic acid, amino acid and tricarboxylic acid metabolisms under alkali-salt stress. Our results provide valuable insights into the response of salt-tolerant wild soybean to two types of salt stress by linking stress-related physiological responses to changes in metabolites. PMID: 29525442 [PubMed - as supplied by publisher]

African horse sickness virus (AHSV) with a deletion of 77 amino acids in NS3/NS3a protein is not virulent and a safe promising AHS Disabled Infectious Single Animal (DISA) vaccine platform. Vaccine. 2018 Mar 07;: Authors: van Rijn PA, Maris-Veldhuis MA, Potgieter CA, van Gennip RGP Abstract African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. Currently, nine serotypes have been defined showing limited cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African Horse Sickness (AHS) in equids with a mortality up to 95% in naïve domestic horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates are competent vectors of closely related bluetongue virus. AHS outbreaks cause huge economic losses in developing countries. In the developed world, outbreaks will result in losses in the equestrian industry and will have an enormous emotional impact on owners of pet horses. Live-attenuated vaccine viruses (LAVs) have been developed, however, safety of these LAVs are questionable due to residual virulence, reversion to virulence, and risk on virulent variants by reassortment between LAVs or with field AHSV. Research aims vaccines with improved profiles. Reverse genetics has recently being developed for AHSV and has opened endless possibilities including development of AHS vaccine candidates, such as Disabled Infectious Single Animal (DISA) vaccine. Here, virulent AHSV5 was recovered and its high virulence was confirmed by experimental infection of ponies. 'Synthetically derived' virulent AHSV5 with an in-frame deletion of 77 amino acids codons in genome segment 10 encoding NS3/NS3a protein resulted in similar in vitro characteristics as published NS3/NS3a knockout mutants of LAV strain AHSV4LP. In contrast to its highly virulent ancestor virus, this deletion AHSV5 mutant (DISA5) was completely safe for ponies. Two vaccinations with DISA5 as well as two vaccinations with DISA vaccine based on LAV strain AHSV4LP showed protection against lethal homologous AHSV. More research is needed to further improve efficacy, to explore the AHS DISA vaccine platform for all nine serotypes, and to study the vaccine profile in more detail. PMID: 29525278 [PubMed - as supplied by publisher]

Metabolomics analysis of 'Housui' Japanese pear flower buds during endodormancy reveals metabolic suppression by thermal fluctuation. Plant Physiol Biochem. 2018 Mar 02;126:134-141 Authors: Horikoshi HM, Sekozawa Y, Kobayashi M, Saito K, Kusano M, Sugaya S Abstract Dormancy is a complex phenomenon that allows plants to survive the winter season. Studies of dormancy have recently attracted more attention due to the expansion of temperate fruit production in areas under mild winters and due to climate changes. This study aimed to identify and characterize the metabolic changes induced by chilling temperatures, as well as during thermal fluctuation conditions that simulate mild winter and/or climate change scenarios. To do this, we compared the metabolic profile of Japanese pear flower buds exposed to constant chilling at 6 °C and thermal fluctuations of 6 °C/18 °C (150 h/150 h) during endodormancy. We detected 91 metabolites by gas chromatography paired with time-of-flight mass spectrometry (GC-TOF-MS) that could be classified into eight groups: amino acids, amino acid derivatives, organic acids, sugars and polyols, fatty acids and sterols, phenol lipids, phenylpropanoids, and other compounds. Metabolomics analysis revealed that the level of several amino acids decreased during endodormancy. Sugar and polyol levels increased during endodormancy during constant chilling and might be associated with chilling stress tolerance and providing an energy supply for resuming growth. In contrast, thermal fluctuations produced low levels of metabolites related to the pentose phosphate pathway, energy production, and tricarboxylic acid (TCA) cycle in flower buds, which may be associated with failed endodormancy release. This metabolic profile contributes to our understanding of the biological mechanism of dormancy during chilling accumulation and clarifies the metabolic changes during mild winters and future climate change scenarios. PMID: 29524800 [PubMed - as supplied by publisher]

Metabolomics-assisted metabolite profiling of itraconazole in human liver preparations. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Mar 07;1083:68-74 Authors: Kim JH, Choi WG, Moon JY, Lee JY, Lee S, Lee HS Abstract Itraconazole (ITZ) is a first-generation triazole-containing antifungal agent that effectively treats various fungal infections. As ITZ has a better safety profile than that of ketoconazole (KCZ), ITZ has been used worldwide for over 25 years. However, few reports have explored the metabolic profile of ITZ, and the underlying mechanism of ITZ-induced liver injury is not clearly understood. In the present study, we revisited ITZ metabolism in humans, using a non-targeted metabolomics approach, and identified several novel metabolic pathways including O-dearylation, piperazine oxidation, and piperazine-N,N'-deethylation. Furthermore, we explored the formation of reactive ITZ metabolites using trapping agents as surrogates, to assess the possibility of metabolism-mediated toxicity. We found that ITZ and its metabolites did not form any adducts with nucleophiles including glutathione, potassium cyanide, and semicarbazide. The present study expands our knowledge of ITZ metabolism and supports the suggestion that ITZ has a better safety profile than that of KCZ in terms of metabolism-mediated toxicity. PMID: 29524695 [PubMed - as supplied by publisher]

Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 Mar 07;: Authors: Gong S, Lan T, Zeng L, Luo H, Yang X, Li N, Chen X, Liu Z, Li R, Win S, Liu S, Zhou H, Schnabl B, Jiang Y, Kaplowitz N, Chen P Abstract BACKGROUND & AIMS: Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Here we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. METHODS: Male Balb/C mice were treated with or without antibiotics and orally administrated a single dose of APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period). RESULTS: In agreement with previous findings, hepatic injury was markedly enhanced at ZT12 compared with ZT0. Interestingly, upon antibiotics treatment, ZT12 displayed protection against APAP hepatotoxicity similar to ZT0. Moreover, mice that received the cecal content from ZT12 showed more severe liver damage than mice that received the cecal content from ZT0. 16S sequencing data revealed significant differences in the cecal content between ZT0 and ZT12 in the compositional level. Furthermore, metabolomic analysis showed that the gut microbial metabolites were also different between ZT0 and ZT12. Specifically, the level of 1-phenyl-1,2-propanedione (PPD) was significantly higher at ZT12 than ZT0. Treatment with PPD alone did not cause obvious liver damage. However, PPD synergistically enhanced APAP induced hepatic injury in vivo and in vitro. Finally, we found Saccharomyces cerevisiae, which could reduce intestinal PPD levels, was able to markedly alleviate APAP induced liver damage at ZT12. CONCLUSIONS: The gut microbial metabolite, 1-phenyl-1,2-propanedione was responsible, at least in part, for the diurnal variation of hepatotoxicity induced by APAP by decreasing GSH levels. LAY SUMMARY: Acetaminophen (APAP) induced acute liver failure due to over dose is a leading public health problem. APAP induced liver injury exhibited diurnal variation, in particular, it causes more severe liver damage when taken at night compared with that in the morning. Here we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione (PPD) is involved in the rhythmic hepatotoxicity induced by APAP by depleting hepatic GSH levels. Our data suggest gut microbiota may be a potential target for reducing APAP induced acute liver injury. PMID: 29524531 [PubMed - as supplied by publisher]

Metabololipidomic profiling of functional immunoresolvent clusters and eicosanoids in mammalian tissues. Biochem Biophys Res Commun. 2018 Mar 07;: Authors: Norris PC, Serhan CN Abstract Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels. Here, we review novel approaches to understand the relationship(s) between coagulation and resolution of inflammation and infection. To determine whether coagulation is involved in host-protective actions by lipid mediators, we used a metabololipidomic-based profiling approach with human whole blood (WB) during coagulation. We identified recently temporal clusters of endogenously produced pro-thrombotic and proinflammatory lipid mediators (eicosanoids), as well as specialized proresolving mediators (SPMs) in this vital process. In addition to the classic eicosanoids (prostaglandins, thromboxanes and leukotrienes), a specific SPM cluster was identified that consists of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B4, and maresin 1, each of which present at bioactive concentrations (0.1-1 nM). The removal of adenosine from coagulating blood samples significantly enhances SPM amounts and unleashes the biosynthesis of RvD3, RvD4, and RvD6 evident following rapid snap freezing with centrifugation before extraction and LC-MS-MS. The classic cyclooxygenase inhibitors, celecoxib and indomethacin, that block thromboxanes and prostanoids do not block production of the clot-driven SPM cluster. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targets leukocytes at the single-cell level, directly activating extracellular signaling in human neutrophils and monocytes. Human whole blood treated with the components of this SPM cluster enhanced both phagocytosis and killing of Escherichia coli by leukocytes. Thus, we identified a pro-resolving lipid mediator circuit and specific SPM cluster that promotes host defense. This new lipid mediator (LM)-SPM metabololipidomic approach now provides accessible metabolomic profiles in healthy and diseased human tissues, including cancer, for precision and personalized medicine. PMID: 29524409 [PubMed - as supplied by publisher]

Related Articles Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders. J Inherit Metab Dis. 2018 Mar 09;: Authors: Mocking RJT, Assies J, Ruhé HG, Schene AH Abstract Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an up-to-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease. PMID: 29524021 [PubMed - as supplied by publisher]

Related Articles In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis. Arch Toxicol. 2018 Mar 09;: Authors: Wang D, Yan J, Teng M, Yan S, Zhou Z, Zhu W Abstract In this study, we investigated the effects of in utero and lactational exposure to BDE-47 on the progression of obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were treated via oral gavage with low doses of BDE-47 (0, 0.002, and 0.2 mg/kg body weight) from gestational day 6 to postnatal day 21. After weaning, male offspring were fed an AIN93-based normal diet (ND) or high-fat diet (HFD: 60% calories from fat) for 14 weeks. We examined body weight, liver weight, histopathology, blood biochemistry, gene expression, and serum metabolic changes. A combination of 16S rRNA gene sequencing and 1H NMR-based metabolomics was conducted to examine the effects of BDE-47 on the gut microbiome. Results showed that in utero and lactational exposure to BDE-47 caused a worsening of HFD-induced obesity, hepatic steatosis, and injury; impaired glucose homeostasis and metabolic dysfunction, and mRNA levels of genes involved in lipid metabolism were significantly altered in the BDE-47-treated HFD group. The gut microbiome were perturbed by BDE-47, causing diversity reduction, compositional alteration, and metabolic changes. These changes were more pronounced for BDE-47-treated HFD mice. All these results indicate that early life exposure to low doses of BDE-47 can promote obesity and the development of metabolic dysfunction. PMID: 29523931 [PubMed - as supplied by publisher]

Related Articles Reduced Arogenate Dehydratase Expression: Ramifications for Photosynthesis and Metabolism. Plant Physiol. 2018 Mar 09;: Authors: Höhner R, Marques JV, Ito T, Amakura Y, Budgeon AD, Weitz K, Hixson KK, Davin LB, Kirchhoff H, Lewis NG Abstract Arogenate dehydratase (ADT) catalyzes the final step of phenylalanine (Phe) biosynthesis. Previous work showed that ADT-deficient Arabidopsis thaliana mutants had significantly reduced lignin contents, with stronger reductions in lines that had deficiencies in more ADT isoforms. Here, by analyzing Arabidopsis ADT mutants using our phenomics facility and UPLC-MS based metabolomics, we describe the effects of modulation of ADT on photosynthetic parameters and secondary metabolism. Our data indicate that a reduced carbon flux into Phe biosynthesis in ADT mutants impairs the consumption of photosynthetically produced ATP leading to an increased ATP/ADP ratio, the over-accumulation of transitory starch, and lower electron transport rates. The effect on electron transport rates is caused by an increase in proton motive force across the thylakoid membrane that down-regulates Photosystem II activity by the high energy quenching mechanism. Furthermore, quantitation of secondary metabolites in ADT mutants revealed reduced flavonoid, phenylpropanoid, lignan, and glucosinolate contents, including glucosinolates that are not derived from aromatic amino acids, and significantly increased contents of putative galactolipids and apocarotenoids. Additionally, we used real-time atmospheric monitoring mass spectrometry to compare respiration and carbon fixation rates between wild-type and adt3/4/5/6, our most extreme ADT knock-out mutant, which revealed no significant difference in both night- and day-adapted plants. Overall, these data reveal the profound effects of altered ADT activity and Phe metabolism on secondary metabolites and photosynthesis with implications for plant improvement. PMID: 29523714 [PubMed - as supplied by publisher]

Related Articles Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells. J Biol Chem. 2018 Mar 09;: Authors: Crooks DR, Maio N, Lane AN, Jarnik M, Higashi RM, Haller RG, Yang Y, Fan TWM, Linehan M, Rouault TA Abstract Iron-sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant-negative variants of the primary Fe-S biogenesis scaffold protein iron-sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-S-containing proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a ~12-fold increase in intracellular citrate content in Fe-S-deficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-S-deficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-S-deficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in non-adipose tissues. PMID: 29523684 [PubMed - as supplied by publisher]

19 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 2018/03/10PubMed 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.

19 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 2018/03/10PubMed 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.

Potential biomarkers of Parkinson's disease revealed by plasma metabolic profiling. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Feb 02;1081-1082:101-108 Authors: Zhao H, Wang C, Zhao N, Li W, Yang Z, Liu X, Le W, Zhang X Abstract The plasma of Parkinson's disease (PD) patients may contain various altered metabolites associated with the risk or progression of the disease. Characterization of the abnormal metabolic pattern in PD plasma is therefore critical for the search for potential PD biomarkers. We collected blood plasma samples from PD patients and used an LC-MS based metabolomics approach to identify 17 metabolites with significantly altered levels. Metabolic network analysis was performed to place the metabolites linked to different pathways. The metabolic pathways involved were associated with tyrosine biosynthesis, glycerol phospholipid metabolism, carnitine metabolism and bile acid biosynthesis, within which carnitine and bile acid metabolites as potential biomarkers are first time reported. These abnormal metabolic changes in the plasma of patients with PD were mainly related to lipid metabolism and mitochondrial function. PMID: 29518718 [PubMed - as supplied by publisher]

1H-nuclear magnetic resonance metabolomics revealing the intrinsic relationships between neurochemical alterations and neurobehavioral and neuropathological abnormalities in rats exposed to tris(2-chloroethyl)phosphate. Chemosphere. 2018 Feb 09;200:649-659 Authors: Yang W, Zhao F, Fang Y, Li L, Li C, Ta N Abstract Tris(2-chloroethyl)phosphate (TCEP) is a widely used environmental organic pollutant. Studies have revealed the presence of both TCEP and its metabolites in environmental media. The neurotoxicity of TCEP has been investigated in vitro but rarely in mammals. This study aimed to determine the neurotoxic effects of TCEP on rats and to explore the possible intrinsic relationships between neurochemical alterations and the neurotoxic effects. For this, 6-week-old female SD rats were administered 50, 100, or 250 mg/kg/d TCEP daily by oral gavage for 60 days. TCEP exposure produced neurotoxicity in the female SD rats. The Morris water maze results revealed a dose-dependent decline in spatial learning and memory functions of exposed rats. In addition, pathological examination of the brain showed apoptotic and necrotic lesions in the CA1 field pyramidal cells of the hippocampus; further, rats treated with the highest TCEP dose showed inflammatory cells and calcified/ossified foci in the cortex areas. Furthermore, 1H-nuclear magnetic resonance metabolomics results revealed that TCEP exposure interfered with normal biological processes, including amino acid and neurotransmitter metabolism, energy metabolism, and cell membrane function integrity by changing the concentrations of glutamate, γ-aminobutyric acid, N-acetyl-d-aspartate, creatine, and lactic acid metabolites in the brain of treated rats. However, the changes in the concentrations of taurine, myo-inositol, creatine, and choline metabolites, which are associated with antioxidant physiological processes, might be a neuroprotective mechanism to prevent the neurotoxicity induced by TCEP. Thus, metabolomics combined with neuropathology and neurobehavioral analyses provided critical insights to investigate the TCEP-induced neurotoxic effects and mechanisms. PMID: 29518649 [PubMed - as supplied by publisher]

Identification of ethanol tolerant outer membrane proteome reveals OmpC-dependent mechanism in a manner of EnvZ/OmpR regulation in Escherichia coli. J Proteomics. 2018 Mar 05;: Authors: Zhang DF, Ye JZ, Dai HH, Lin XM, Li H, Peng XX Abstract Ethanol is an efficient disinfectant, but long-term and wide usage of ethanol leads to microbial tolerance. Bacteria with the tolerance are widely identified. However, mechanisms of the tolerance are not elucidated. To explore the mechanisms of outer membrane (OM) proteins underlying ethanol tolerance in bacteria, functional proteomic methodologies were utilized to characterize OM proteins of E. coli suddenly exposed to 3.125% ethanol. Of eleven proteins altered significantly, seven were OM proteins, in which LamB, FadL and OmpC were up-regulated, and OmpT, OmpF, Tsx and OmpA were down-regulated. The alterations were validated using Western blot. Then, functional characterization of the altered abundance of OM proteins was investigated in gene-deleted and gene-complemented mutants cultured in 1.56-6.25% ethanol. Higher inhibiting rate was detected in ΔompC than ΔlamB and ΔompA, but no difference was found between Δtsx, ΔompF, ΔfadL or ΔompT and control. Furthermore, EnvZ/OmpR two-component signal transduction system, which regulates OmpC and OmpF expression, was determined to participate in the tolerance. Finally, our results show that absence of envZ, ompR or ompC and ompA led to elevated and reduced intracellular ethanol, respectively. These findings indicate EnvZ-dependent phosphotransfer signaling pathway of the OmpR-mediated expression of OmpC plays a crucial role in ethanol tolerance. BIOLOGICAL SIGNIFICANCE: Ethanol tolerance is an adaptation strategy of bacteria. In the present study, we used the proteomic approaches involving 2-DE and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) to determined outer membrane (OM) protein changes in E. coli K-12 after 2 h of 1/2 MIC of ethanol exposure. Under ethanol stress, seven differential OM proteins were found, which were validated by Western blot. Functions of these seven OM proteins were compared using their genetically modified strains. Furthermore, the role of EnvZ/OmpR two-component signal transduction system was identified in ethanol tolerance of E. coli. Finally, Loss of ompC, envZ or ompR increases intracellular ethanol, while absence of ompA reduces reversal effect. This is the first report of OM proteomics in E. coli exposed to ethanol. Our findings reveal an unknown OmpC-dependent mechanism of ethanol tolerance in a manner of EnvZ/OmpR regulation. PMID: 29518576 [PubMed - as supplied by publisher]

Predictive biomarkers for type 2 of diabetes mellitus: bridging the gap between systems research and personalized medicine. J Proteomics. 2018 Mar 05;: Authors: Kraniotou C, Karadima V, Bellos G, Tsangaris GT Abstract The global incidence of metabolic disorders like type 2 diabetes mellitus (DM2) has assumed epidemic proportions, leading to adverse health and socio-economic impacts. It is therefore of critical importance the early diagnosis of DM2 patients and the detection of those at increased risk of disease. In this respect, Precision Medicine (PM) is an emerging approach that includes practices, tests, decisions and treatments adapted to the characteristics of each patient. With regard to DM2, PM manages a wealth of "omics" data (genomic, metabolic, proteomic, environmental, clinical and paraclinical) to increase the number of clinically validated biomarkers in order to identify patients in early stage even before the prediabetic phase. SIGNIFICANCE: In this paper, we discuss the epidemic dimension of metabolic disorders like type 2 diabetes mellitus (DM2) and the urgent demand for novel biomarkers to reduce the incidence or even delay the onset of DM2. Recent research data produced by "multi-omics" technologies (genomics/epigenomics, transcriptomics, proteomics and metabolomics), suggest that many potential biomarkers might be helpful in the prediction and early diagnosis of DM2. Predictive, Preventive and Personalized Medicine (PPPM) manages and integrates these data to apply personalized, preventive, and therapeutic approaches. This is significant because there is an emerging need for establishing channels for communication and personalized consultation between systems research and precision medicine, as the medicine of the future. PMID: 29518575 [PubMed - as supplied by publisher]

Mitochondrial oxodicarboxylate carrier deficiency is associated with mitochondrial DNA depletion and spinal muscular atrophy-like disease. Genet Med. 2018 Mar 08;: Authors: Boczonadi V, King MS, Smith AC, Olahova M, Bansagi B, Roos A, Eyassu F, Borchers C, Ramesh V, Lochmüller H, Polvikoski T, Whittaker RG, Pyle A, Griffin H, Taylor RW, Chinnery PF, Robinson AJ, Kunji ERS, Horvath R Abstract PurposeTo understand the role of the mitochondrial oxodicarboxylate carrier (SLC25A21) in the development of spinal muscular atrophy-like disease.MethodsWe identified a novel pathogenic variant in a patient by whole-exome sequencing. The pathogenicity of the mutation was studied by transport assays, computer modeling, followed by targeted metabolic testing and in vitro studies in human fibroblasts and neurons.ResultsThe patient carries a homozygous pathogenic variant c.695A>G; p.(Lys232Arg) in the SLC25A21 gene, encoding the mitochondrial oxodicarboxylate carrier, and developed spinal muscular atrophy and mitochondrial myopathy. Transport assays show that the mutation renders SLC25A21 dysfunctional and 2-oxoadipate cannot be imported into the mitochondrial matrix. Computer models of central metabolism predicted that impaired transport of oxodicarboxylate disrupts the pathways of lysine and tryptophan degradation, and causes accumulation of 2-oxoadipate, pipecolic acid, and quinolinic acid, which was confirmed in the patient's urine by targeted metabolomics. Exposure to 2-oxoadipate and quinolinic acid decreased the level of mitochondrial complexes in neuronal cells (SH-SY5Y) and induced apoptosis.ConclusionMitochondrial oxodicarboxylate carrier deficiency leads to mitochondrial dysfunction and the accumulation of oxoadipate and quinolinic acid, which in turn cause toxicity in spinal motor neurons leading to spinal muscular atrophy-like disease.GENETICS in MEDICINE advance online publication, 8 March 2018; doi:10.1038/gim.2017.251. PMID: 29517768 [PubMed - as supplied by publisher]

Related Articles The crucial role of multiomic approach in cancer research and clinically relevant outcomes. EPMA J. 2018 Mar;9(1):77-102 Authors: Lu M, Zhan X Abstract Cancer with heavily economic and social burden is the hot point in the field of medical research. Some remarkable achievements have been made; however, the exact mechanisms of tumor initiation and development remain unclear. Cancer is a complex, whole-body disease that involves multiple abnormalities in the levels of DNA, RNA, protein, metabolite and medical imaging. Biological omics including genomics, transcriptomics, proteomics, metabolomics and radiomics aims to systematically understand carcinogenesis in different biological levels, which is driving the shift of cancer research paradigm from single parameter model to multi-parameter systematical model. The rapid development of various omics technologies is driving one to conveniently get multi-omics data, which accelerates predictive, preventive and personalized medicine (PPPM) practice allowing prediction of response with substantially increased accuracy, stratification of particular patients and eventual personalization of medicine. This review article describes the methodology, advances, and clinically relevant outcomes of different "omics" technologies in cancer research, and especially emphasizes the importance and scientific merit of integrating multi-omics in cancer research and clinically relevant outcomes. PMID: 29515689 [PubMed]

Related Articles Growth of Malignant Non-CNS Tumors Alters Brain Metabolome. Front Genet. 2018;9:41 Authors: Kovalchuk A, Nersisyan L, Mandal R, Wishart D, Mancini M, Sidransky D, Kolb B, Kovalchuk O Abstract Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as "tumor brain." Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID: 29515623 [PubMed]