PubMed

Related Articles Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome. Lancet Respir Med. 2017 Jun;5(6):512-523 Authors: Meyer NJ, Calfee CS Abstract In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS. PMID: 28664850 [PubMed - indexed for MEDLINE]

Related Articles Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry. Planta Med. 2017 Nov;83(16):1297-1308 Authors: Avula B, Wang YH, Isaac G, Yuk J, Wrona M, Yu K, Khan IA Abstract Ultrahigh-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QToF-MS) profiling was used for the identification of marker compounds and generation of metabolic patterns that could be interrogated using chemometric modeling software. UHPLC-QToF-MS was used to generate comprehensive fingerprints of three botanicals (Hoodia, Terminalia, and chamomile), each having different classes of compounds. Detection of a broad range of ions was carried out in full scan mode in both positive and negative modes over the range m/z 100-1700 using high-resolution mass spectrometry. Multivariate statistical analysis was used to extract relevant chemical information from the data to easily differentiate between Terminalia species, chamomile varieties, and quality control of Hoodia products. Using nontargeted analysis, identification of 37 compounds contributed to the differences between Terminalia species, 26 flavonoids were identified to show the differences between German and Roman chamomile, and 43 pregnane glycosides were identified from Hoodia gordonii samples. The UHPLC-QToF-MS-based chemical fingerprinting with principal component analysis was able to correctly distinguish botanicals and their commercial products. This work can be used as a basis to assure the quality of botanicals and commercial products. PMID: 28454188 [PubMed - indexed for MEDLINE]

Related Articles Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer. Sci Rep. 2016 10 14;6:35110 Authors: Ho YS, Yip LY, Basri N, Chong VS, Teo CC, Tan E, Lim KL, Tan GS, Yang X, Yeo SY, Koh MS, Devanand A, Takano A, Tan EH, Tan DS, Lim TK Abstract Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC. PMID: 27739449 [PubMed - indexed for MEDLINE]

21 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 2018/04/11PubMed 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.

Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 02;1085:54-62 Authors: Chen R, Han S, Liu X, Wang K, Zhou Y, Yang C, Zhang X Abstract Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. PMID: 29631251 [PubMed - as supplied by publisher]

Activation of choline kinase drives aberrant choline metabolism in esophageal squamous cell carcinomas. J Pharm Biomed Anal. 2018 Mar 31;155:148-156 Authors: Ma W, Wang S, Zhang T, Zhang EY, Zhou L, Hu C, Yu JJ, Xu G Abstract Esophageal squamous cell carcinoma (ESCC) is a major health threat worldwide. Research focused on molecular events associated with ESCC carcinogenesis for diagnosis, treatment and prevention is needed. Our goal is to discover novel biomarkers and investigate the underlying molecular mechanisms of ESCC progression by employing a global metabolomic approach. Sera from 34 ESCC patients and 32 age and sex matched healthy controls were profiled using two-dimensional liquid chromatography-mass spectrometry (2D LC-MS). We identified 120 differential metabolites in ESCC patient serums compared to healthy controls. Several amino acids, serine, arginine, lysine and histidine were significantly changed in ESCC patients. Most importantly, we found dysregulated lipid metabolism as an important characteristic in ESCC patients. Several free fat acids (FFA) and carnitines were found down-regulated in ESCC patients. Choline was significantly increased and phosphatidylcholines (PC) were significantly decreased in ESCC serum. The high expression of choline and low expression of total PC in patient serum were associated with the high expression of choline kinase (Chok) and activated Kennedy pathway in ESCC cells. Chok expression can serve as a significant biomarker for ESCC prognosis. In conclusion, metabolite profiles in the ESCC patient serum were significantly different from those in the healthy controls. Phosphatidylcholines and Chok, the key enzyme in the PC metabolism pathway, may serve as novel biomarkers for ESCC. PMID: 29631075 [PubMed - as supplied by publisher]

Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis. Chem Biol Interact. 2018 Apr 06;: Authors: Guo C, Chen L, Huang J, Wang Y, Shi C, Gao J, Hong Y, Chen T, Qiu L Abstract Alcoholic liver injury results in morbidity and mortality worldwide, but there are currently no effective and safe therapeutics. Previously we demonstrated that aldose reductase (AR) inhibitor ameliorated alcoholic hepatic steatosis. To clarify the mechanism whereby AR inhibitor improves alcoholic hepatic steatosis, herein we investigated the effect of AR inhibitor on hepatic metabolism in mice fed a Lieber-DeCarli liquid diet with 5% ethanol. Nontargeted metabolomics showed carbohydrates and lipids were characteristic categories in ethanol diet-fed mice with or without AR inhibitor treatment, whereas AR inhibitor mainly affected carbohydrates and amino acids. Ethanol-induced galactose metabolism and fatty acid biosynthesis are important for the induction of hepatic steatosis, while AR inhibitor impaired galactose metabolism without perturbing fatty acid biosynthesis. In parallel with successful treatment of steatosis, AR inhibitor suppressed ethanol-activated galactose metabolism and saturated fatty acid biosynthesis. Sorbitol in galactose metabolism and stearic acid in saturated fatty acid biosynthesis were potential biomarkers responsible for ethanol or ethanol plus AR inhibitor treatment. In vitro analysis confirmed that exogenous addition of sorbitol augmented ethanol-induced steatosis and stearic acid. These findings not only reveal metabolic patterns associated with disease and treatment, but also shed light on functional biomarkers contribute to AR inhibition therapy. PMID: 29630881 [PubMed - as supplied by publisher]

Human epididymis protein 4 in endometrial cancer: A meta-analysis. Clin Chim Acta. 2018 Apr 06;: Authors: Li LM, Zhu YX, Zhong Y, Su T, Fan XM, Xi Q, Li MY, Fu J, Tan H, Liu S Abstract BACKGROUND: Serum human epididymis protein 4 (HE4) is a potential marker for endometrial cancer (EC), however, the diagnostic value of HE4 for EC remains controversial. In this study, we performed a meta-analysis to estimate the diagnostic accuracy of serum HE4 for EC. METHODS: Literature reports of the diagnostic accuracy of serum HE4 for EC were systematically identified using online data-bases. The meta-analysis was performed using STATA 12.0, Meta-Disc 1.4, and Review Manager 5.2. RESULTS: A total of 4182 participants and 23 studies were included in our meta-analysis. The pooled sensitivity (SEC), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.65 (95% CI: 0.56-0.73), 0.91 (95% CI: 0.84-0.95), (95% CI: 4.38-12.64), 0.38 (95% CI: 0.31-0.47), 19.46 (95% CI: 11.61-32.62) and 0.84 (95% CI: 0.81 to 0.87), respectively. Our overall analysis suggested that HE4 is a useful diagnostic marker for EC. Subgroup analysis indicated that studies with benign disease controls showed higher diagnostic accuracies than those with healthy controls. CONCLUSION: Serum HE4 may serve as a potential biomarker for EC diagnosis. Due to certain limitations, this conclusion should to be cautiously interpreted. PMID: 29630870 [PubMed - as supplied by publisher]

A rapid and concise setup for the fast screening of FRET pairs using bioorthogonalized fluorescent dyes. Org Biomol Chem. 2018 Apr 09;: Authors: Petrovics R, Söveges B, Egyed A, Knorr G, Kormos A, Imre T, Török G, Zeke A, Kocsmár É, Lotz G, Kele P, Németh K Abstract One of the most popular means to follow interactions between bio(macro)molecules is Förster resonance energy transfer (FRET). There is large interest in widening the selection of fluorescent FRET pairs especially in the region of the red/far red range, where minimal autofluorescence is encountered. A set of bioorthogonally applicable fluorescent dyes, synthesized recently in our lab, were paired (Cy3T/Cy5T; Cy1A/Cy3T and Cy1A/CBRD1A) based on their spectral characteristics in order to test their potential in FRET applications. For fast elaboration of the selected pairs we have created a bioorthogonalized platform based on complementary 17-mer DNA oligomers. The cyclooctynylated strands were modified nearly quantitatively with the fluorophores via bioorthogonal chemistry steps, using azide- (Cy1; CBRD1) or tetrazine-modified (Cy3; Cy5) dyes. Reactions were followed by capillary electrophoresis using a method specifically developed for this project. FRET efficiencies of the fluorescent dye pairs were compared both in close proximity (5' and 3' matched) and at larger distance (5' and 5' matched). The specificity of FRET signals was further elaborated by denaturation and competition studies. Cy1A/Cy3T and Cy1A/CBRD1A introduced here as novel FRET pairs are highly recommended for FRET applications based on the significant changes in fluorescence intensities of the donor and acceptor peaks. Application of one of the FRET pairs was demonstrated in live cells, transfected with labeled oligos. Furthermore, the concise installation of the dyes allows for efficient fluorescence modification of any selected DNA strands as was demonstrated in the construction of Cy3T labeled oligomers, which were used in the FISH-based detection of Helicobacter pylori. PMID: 29629719 [PubMed - as supplied by publisher]

Related Articles Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites? mSystems. 2018 Mar-Apr;3(2): Authors: Lyu Q, Hsu CC Abstract The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases. Chemical compounds in diet also shape the gut flora. In order to understand which and how the gut microbe-derived specialized metabolites affect human health, the "gut microbiome-metabolomic-human health axis" is thus proposed. In our laboratory, a strategy combining genomic, chemical, phenotypical analyses has been implemented to mine the treasures of bioactive molecules found in our gut and stool. We believe that the cutting edge metabolomics will bridge microbiology and human health. PMID: 29629422 [PubMed]

Related Articles Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses. Metabolomics. 2018;14(5):59 Authors: Pan D, Lindau C, Lagies S, Wiedemann N, Kammerer B Abstract Introduction: Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations. Objectives: To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker's yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling. Methods: Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography-mass spectrometry (GC-MS) based metabolic profiling. Results: Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the FOF1-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others. Conclusion: By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism. PMID: 29628813 [PubMed]

Related Articles LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study. Int J Cardiol. 2018 Mar 29;: Authors: Pichler G, Amigo N, Tellez-Plaza M, Pardo-Cea MA, Dominguez-Lucas A, Marrachelli VG, Monleon D, Martin-Escudero JC, Ascaso JF, Chaves FJ, Carmena R, Redon J Abstract BACKGROUND: The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. METHODS: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. RESULTS: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. CONCLUSIONS: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD. PMID: 29628276 [PubMed - as supplied by publisher]

Related Articles Metabolism, Metabolomics, and Inflammation in Posttraumatic Stress Disorder. Biol Psychiatry. 2018 Feb 22;: Authors: Mellon SH, Gautam A, Hammamieh R, Jett M, Wolkowitz OM Abstract Posttraumatic stress disorder (PTSD) is defined by classic psychological manifestations, although among the characteristics are significantly increased rates of serious somatic comorbidities, such as cardiovascular disease, immune dysfunction, and metabolic syndrome. In this review, we assess the evidence for disturbances that may contribute to somatic pathology in inflammation, metabolic syndrome, and circulating metabolites (implicating mitochondrial dysfunction) in individuals with PTSD and in animal models simulating features of PTSD. The clinical and preclinical data highlight probable interrelated features of PTSD pathophysiology, including a proinflammatory milieu, metabolomic changes (implicating mitochondrial and other processes), and metabolic dysregulation. These data suggest that PTSD may be a systemic illness, or that it at least has systemic manifestations, and the behavioral manifestations are those most easily discerned. Whether somatic pathology precedes the development of PTSD (and thus may be a risk factor) or follows the development of PTSD (as a result of either shared pathophysiologies or lifestyle adaptations), comorbid PTSD and somatic illness is a potent combination placing affected individuals at increased physical as well as mental health risk. We conclude with directions for future research and novel treatment approaches based on these abnormalities. PMID: 29628193 [PubMed - as supplied by publisher]

Related Articles Rewiring carbohydrate catabolism differentially affects survival of pancreatic cancer cell lines with diverse metabolic profiles. Oncotarget. 2017 Jun 20;8(25):41265-41281 Authors: Tataranni T, Agriesti F, Ruggieri V, Mazzoccoli C, Simeon V, Laurenzana I, Scrima R, Pazienza V, Capitanio N, Piccoli C Abstract An increasing body of evidence suggests that targeting cellular metabolism represents a promising effective approach to treat pancreatic cancer, overcome chemoresistance and ameliorate patient's prognosis and survival. In this study, following whole-genome expression analysis, we selected two pancreatic cancer cell lines, PANC-1 and BXPC-3, hallmarked by distinct metabolic profiles with specific concern to carbohydrate metabolism. Functional comparative analysis showed that BXPC-3 displayed a marked deficit of the mitochondrial respiratory and oxidative phosphorylation activity and a higher production of reactive oxygen species and a reduced NAD+/NADH ratio, indicating their bioenergetic reliance on glycolysis and a different redox homeostasis as compared to PANC-1. Both cell lines were challenged to rewire their metabolism by substituting glucose with galactose as carbon source, a condition inhibiting the glycolytic flux and fostering full oxidation of the sugar carbons. The obtained data strikingly show that the mitochondrial respiration-impaired-BXPC-3 cell line was unable to sustain the metabolic adaptation required by glucose deprivation/substitution, thereby resulting in a G2\M cell cycle shift, unbalance of the redox homeostasis, apoptosis induction. Conversely, the mitochondrial respiration-competent-PANC-1 cell line did not show clear evidence of cell sufferance. Our findings provide a strong rationale to candidate metabolism as a promising target for cancer therapy. Defining the metabolic features at time of pancreatic cancer diagnosis and likely of other tumors, appears to be crucial to predict the responsiveness to therapeutic approaches or coadjuvant interventions affecting metabolism. PMID: 28476035 [PubMed - indexed for MEDLINE]

Sorting cells alters their redox state and cellular metabolome. Redox Biol. 2018 Mar 09;16:381-387 Authors: Llufrio EM, Wang L, Naser FJ, Patti GJ Abstract A growing appreciation of the metabolic artifacts of cell culture has generated heightened enthusiasm for performing metabolomics on populations of cells purified from tissues and biofluids. Fluorescence activated cell sorting, or FACS, is a widely used experimental approach to purify specific cell types from complex heterogeneous samples. Here we show that FACS introduces oxidative stress and alters the metabolic state of cells. Compared to unsorted controls, astrocytes subjected to FACS prior to metabolomic analysis showed altered ratios of GSSG to GSH, NADPH to NADP+, and NAD+ to NADH. Additionally, a 50% increase in reactive oxygen species was observed in astrocytes subjected to FACS relative to unsorted controls. At a more comprehensive scale, nearly half of the metabolomic features that we profiled by liquid chromatography/mass spectrometry were changed by at least 1.5-fold in intensity due to cell sorting. Some specific metabolites identified to have significantly altered levels as a result of cell sorting included glycogen, nucleosides, amino acids, central carbon metabolites, and acylcarnitines. Although the addition of fetal bovine serum to the cell-sorting buffer decreased oxidative stress and attenuated changes in metabolite concentrations, fetal bovine serum did not preserve the metabolic state of the cells during FACS. We conclude that, irrespective of buffer components and data-normalization strategies we examined, metabolomic results from sorted cells do not accurately reflect physiological conditions prior to sorting. PMID: 29627745 [PubMed - as supplied by publisher]

Biomedical analysis of formalin-fixed, paraffin-embedded tissue samples: The Holy Grail for molecular diagnostics. J Pharm Biomed Anal. 2018 Apr 02;155:125-134 Authors: Donczo B, Guttman A Abstract More than a century ago in 1893, a revolutionary idea about fixing biological tissue specimens was introduced by Ferdinand Blum, a German physician. Since then, a plethora of fixation methods have been investigated and used. Formalin fixation with paraffin embedment became the most widely used types of fixation and preservation method, due to its proper architectural conservation of tissue structures and cellular shape. The huge collection of formalin-fixed, paraffin-embedded (FFPE) sample archives worldwide holds a large amount of unearthed information about diseases that could be the Holy Grail in contemporary biomarker research utilizing analytical omics based molecular diagnostics. The aim of this review is to critically evaluate the omics options for FFPE tissue sample analysis in the molecular diagnostics field. PMID: 29627729 [PubMed - as supplied by publisher]

The depressed central carbon and energy metabolisms is associated to the acquisition of levofloxacin resistance in Vibrio alginolyticus. J Proteomics. 2018 Apr 05;: Authors: Cheng ZX, Yang MJ, Peng B, Peng XX, Lin XM, Li H Abstract The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. It is especially required to understand for the mechanism of antibiotic resistance to control antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus with the most advanced iTRAQ quantitative proteomics technology. A total of 160 proteins of differential abundance were identified, where 70 were decreased and 90 were increased. Further analysis demonstrated that crucial metabolic pathways like TCA cycle were significantly down-regulated. qRT-PCR analysis demonstrated the decreased gene expression of glycolysis/gluconeogenesis, the TCA cycle, and fatty acid biosynthesis. Moreover, Na(+)-NQR complex gene expression, membrane potential and the adenylate energy charge ratio were decreased, indicating that the decreased central carbon metabolism is associated to the acquisition of levofloxacin resistance. Therefore, the reduced central carbon and energy metabolisms form a characteristic feature as fitness costs of V. alginolyticus in resistance to levofloxacin. BIOLOGICAL SIGNIFICANCE: The overuse and misuse of antibiotics lead to bacterial antibiotic resistance, challenging human health and intensive cultivation. Understanding for the antibiotic resistance mechanisms is especially required to control these antibiotic-resistant pathogens. The present study characterized the differential proteome of levofloxacin-resistant Vibrio alginolyticus using the most advanced iTRAQ quantitative proteomics technology. A total of 160 differential abundance of proteins were identified with 70 decreases and 90 increases by liquid chromatography matrix assisted laser desorption ionization mass spectrometry. Most interestingly, crucial metabolic pathways such as the TCA cycle sharply fluctuated. This is the first report that the reduced central carbon and energy metabolisms form a characteristic feature as a mechanism of V. alginolyticus in resistance to levofloxacin. PMID: 29627625 [PubMed - as supplied by publisher]

Evaluation of Bisphenol A influence on endocannabinoid system in pregnant women. Chemosphere. 2018 Mar 30;203:387-392 Authors: Zbucka-Kretowska M, Zbucki R, Parfieniuk E, Maslyk M, Lazarek U, Miltyk W, Czerniecki J, Wolczynski S, Kretowski A, Ciborowski M Abstract Bisphenol A (BPA) is a synthetic chemical widely used in the industry, which may potentially evoke negative effects on human health, especially on reproductive processes and fetal development. BPA has been reported to act on estrogen, estrogen-related, androgen, thyroid hormone, pregnane X, peroxisome proliferation-activated, and aryl hydrocarbon receptors. However, other potential mechanisms of BPA action on pregnancy cannot be excluded. Comprehensive evaluation of BPA effect on pregnant women can be performed by use of metabolomics. In the present study LC-MS-based plasma metabolomics was performed in the group of pregnant women with known concentrations of free, conjugated and total BPA. Significant positive correlations were observed between several endocannabinoids (fatty acid amides) and free (r = 0.307-0.557, p-value = 0.05-0.00002) and total (r = 0.413-0.519, p-value = 0.008-0.00006) BPA concentrations. Palmitoleamide was positively correlated with conjugated (r = 0.348, p-value = 0.05) while lysophosphatidylethanolamine 18:0 with free (r = 0.519, p-value = 0.00006) BPA concentration. The docking calculations of BPA and fatty acid amide hydrolase (enzyme degrading endocannabinoids, FAAH) indicated that it can act as a competitive inhibitor by blocking FAAH catalytic residues. In vitro study showed that BPA moderately inhibits FAAH activity (15% decrease for 200 ng mL-1 and almost 50% for 200 μg mL-1 of BPA). In the present study for the first time inhibitory potential of BPA on FAAH hydrolase is reported. Inhibition of FAAH may lead to a rise of plasma endocannabinoids level. BPA exposure and increased level of endocannabinoids are miscarriage risk factors. Based on obtained results it can be hypothesized that BPA may induce adverse pregnancy outcomes by acting on endocannabinoid system. PMID: 29627605 [PubMed - as supplied by publisher]

Lipidomic profiling of plasma samples from patients with mitochondrial disease. Biochem Biophys Res Commun. 2018 Apr 05;: Authors: Ren C, Liu J, Zhou J, Liang H, Zhu Y, Wang Q, Leng Y, Zhang Z, Yuan Y, Wang Z, Yin Y Abstract Mitochondrial disease (MD) is a rare mitochondrial respiratory chain disorder with a high mortality and extremely challenging to treat. Although genomic, transcriptomic, and proteomic analyses have been performed to investigate the pathogenesis of MD, the role of metabolomics in MD, particularly of lipidomics remains unclear. This study was undertaken to identify potential lipid biomarkers of MD. An untargeted lipidomic approach was used to compare the plasma lipid metabolites in 20 MD patients and 20 controls through Liquid Chromatography coupled to Mass Spectrometry. Volcano plot analysis was performed to identify the different metabolites. Receiver operating characteristic (ROC) curves were constructed and the area under the ROC curves (AUC) was calculated to determine the potentially sensitive and specific biomarkers. A total of 41 lipids were significantly different in MD patients and controls. ROC curve analysis showed the top 5 AUC values of lipids (phosphatidylinositols 38:6, lysoPC 20:0, 19:0, 18:0, 17:0) are more than 0.99. Multivariate ROC curve based exploratory analysis showed the AUC of combination of top 5 lipids is 1, indicating they may be potentially sensitive and specific biomarkers for MD. We propose combination of these lipid species may be more valuable in predicting the development and progression of MD, and this will have important implications for the diagnosis and treatment of MD. PMID: 29627572 [PubMed - as supplied by publisher]

Metabolite changes in risk of type 2 diabetes mellitus in cohort studies: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2018 Apr 04;: Authors: Park JE, Lim H, Woo Kim J, Shin KH Abstract AIMS: Fasting plasma glucose, oral glucose tolerance test, and glycated hemoglobin are diagnostic markers for type 2 diabetes mellitus (T2DM). However, it is necessary to detect physiological changes in T2DM rapidly and stratify diabetic stage using other biomarkers. We performed a systematic review and meta-analysis to contribute to the development of objective and sensitive diagnostic indicators by integrating metabolite biomarkers derived from large-scale cohort studies. METHODS: We searched for metabolomics studies of T2DM cohort in PubMed, Scopus, and Web of Science for studies published within the last 10 years from January 2008 to February 2017. The concentrations of metabolites and odds ratios (ORs) were integrated and risk ratio (RR) values were estimated to distinguish subjects with T2DM and normal participants. RESULTS: Fourteen cohort studies were investigated in this meta-analysis. There were 4,592 patients in the case group and 11,492 participants in the control group. We noted a 1.89-, 1.63-, and 1.87-fold higher risk of T2DM associated with leucine (RR 1.89 [95% CI 1.57-2.29]), alanine (RR 1.63 [95% CI 1.48-1.79]), and oleic acid (RR 1.87 [95% CI 1.62-2.17]), respectively. Lysophosphatidylcholine C18:0 (RR 0.80 [95% CI 0.72-0.90]) and creatinine (RR 0.63 [95% CI 0.53-0.74]) were associated with 20% and 37% decreased T2DM risks, respectively. CONCLUSIONS: Most amino acids in patients were positively related to diabetes, while creatinine and some lysophosphatidylcholines showed a negative relationship. This suggests that diabetic risk prediction using metabolites that sensitively reflect changes in the body will improve individual diagnosis and personalize medicine. PMID: 29626587 [PubMed - as supplied by publisher]