PubMed

Related Articles Targeted metabolomic profiling indicates structure-based perturbations in serum phospholipids in children with acetaminophen overdose. Toxicol Rep. 2016;3:747-755 Authors: Bhattacharyya S, Pence L, Yan K, Gill P, Luo C, Letzig LG, Simpson PM, Kearns GL, Beger RD, James LP Abstract Phospholipids are an important class of lipids that act as building blocks of biological cell membranes and participate in a variety of vital cellular functions including cell signaling. Previous studies have reported alterations in phosphatidylcholine (PC) and lysophosphatidylcholine (lysoPC) metabolism in acetaminophen (APAP)-treated animals or cell cultures. However, little is known about phospholipid perturbations in humans with APAP toxicity. In the current study, targeted metabolomic analysis of 180 different metabolites including 14 lysoPCs and 73 PCs was performed in serum samples from children and adolescents hospitalized for APAP overdose. Metabolite profiles in the overdose group were compared to those of healthy controls and hospitalized children receiving low dose APAP for treatment of pain or fever (therapeutic group). PCs and lysoPCs with very long chain fatty acids (VLCFAs) were significantly decreased in the overdose group, while those with comparatively shorter chain lengths were increased in the overdose group compared to the therapeutic and control groups. All ether linked PCs were decreased in the overdose group compared to the controls. LysoPC-C26:1 was highly reduced in the overdose group and could discriminate between the overdose and control groups with 100% sensitivity and specificity. The PCs and lysoPCs with VLCFAs showed significant associations with changes in clinical indicators of drug metabolism (APAP protein adducts) and liver injury (alanine aminotransferase, or ALT). Thus, a structure-dependent reduction in PCs and lysoPCs was observed in the APAP-overdose group, which may suggest a structure-activity relationship in inhibition of enzymes involved in phospholipid metabolism in APAP toxicity. PMID: 28959601 [PubMed]

Related Articles Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop. Regul Toxicol Pharmacol. 2017 Sep 25;: Authors: Buesen R, Chorley BN, da Silva Lima B, Daston G, Deferme L, Ebbels T, Gant TW, Goetz A, Greally J, Gribaldo L, Hackermüller J, Hubesch B, Jennen D, Johnson K, Kanno J, Kauffmann HM, Laffont M, McMullen P, Meehan R, Pemberton M, Perdichizzi S, Piersma AH, Sauer UG, Schmidt K, Seitz H, Sumida K, Tollefsen KE, Tong W, Tralau T, van Ravenzwaay B, Weber RJM, Worth A, Yauk C, Poole A Abstract Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in regulatory toxicology. Against this background, the European Centre for Ecotoxicology and Toxicology of Chemicals (ECETOC) convened a workshop Applying 'omics technologies in chemicals risk assessment that is reported herein. Ahead of the workshop, multi-expert teams drafted frameworks on best practices for (i) a Good-Laboratory Practice-like context for collecting, storing and curating 'omics data; (ii) the processing of 'omics data; and (iii) weight-of-evidence approaches for integrating 'omics data. The workshop participants confirmed the relevance of these Frameworks to facilitate the regulatory applicability and use of 'omics data, and the workshop discussions provided input for their further elaboration. Additionally, the key objective (iv) to establish approaches to connect 'omics perturbations to phenotypic alterations was addressed. Generally, it was considered promising to strive to link gene expression changes and pathway perturbations to the phenotype by mapping them to specific adverse outcome pathways. While further work is necessary before gene expression changes can be used to establish safe levels of substance exposure, the ECETOC workshop provided important incentives towards achieving this goal. PMID: 28958911 [PubMed - as supplied by publisher]

Related Articles A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of unprocessed Angelica sinensis and its 4 kinds of processed products. J Ethnopharmacol. 2017 Sep 25;: Authors: Ji P, Wei Y, Hua Y, Zhang X, Yao W, Ma Q, Yuan Z, Wen Y, Yang C Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (AS), root of Angelica sinensis (Oliv.) Diels, an important kind of Chinese traditional herbal medicine, has been used for women to enrich the blood for thousands of years. It is mainly distributed in Gansu province of China. According to Traditional Chinese medicine usage, unprocessed AS (UAS) and its 4 kinds of processed products (ASs) are all used to treat different diseases or syndromes. The difference among the enriching-blood effects of ASs is unclear. And their exact mechanisms of enriching the blood are not fully understood. AIM OF THE STUDY: In this study, our aim is to compare the enriching-blood effect and explain the related mechanism of ASs, to lay the foundation for the blood deficiency diagnosis and the rational use of ASs in the clinic. MATERIALS AND METHODS: ASs were used to intervene the blood deficiency syndrome model mice induced by acetyl phenylhydrazine (APH) and cyclophosphamide (CTX). A novel approach using metabolomics coupled with hematological and biochemical parameters to explain the enriching-blood effect and mechanism of ASs was established. The blood routine examination, ATPase, glucose-6-phosphate dehydrogenase, methemoglobin, glutathion peroxidase, glutathione reductase, and erythropoietin were measured. Two biofluids (plasma and urine) obtained from mice were analyzed with GC-MS. Distinct changes in metabolite patterns of the two biofluids after mice were induced by APH and CTX, and mice were intervened with ASs were analyzed using partial least squares-discriminant analysis. Potential biomarkers were found using a novel method including variable importance in the projection (VIP) >1.0, volcano plot analysis, and significance analysis of microarray. RESULTS: The results of hematological, biochemical parameters and the integrated metabolomics all showed the blood deficiency syndrome model was built successfully, ASs exhibited different degree of enriching-blood effect, and AS pached with alcohol (AAS) exhibited the best enriching-blood effect. 16 metabolites in the plasma and 8 metabolites in the urine were considered as the potential biomarkers. These metabolites were involved in 7 metabolic pathways which were concerned with the different enriching-blood effect mechanisms of ASs. The correlation analysis results confirmed L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine) and Cholesterol (urine) were strong positive or negative associated with biochemical indicators. CONCLUSIONS: The enriching-blood effects of ASs are different. The pathological mechanisms of blood deficiency syndrome and the enriching-blood effect mechanism of ASs are involved in 7 metabolic pathways. L-Valine (plasma), Linoleic acid (urine), L-Aspartic acid (urine), Cholesterol (urine) are four important biomarkers being related to the enriching-blood effect of ASs. The combination of VIP, volcano plot analysis and significance analysis of microarray is suitable for screening biomarkers in metabolomics study. They can lay the foundation for clinical practice. PMID: 28958590 [PubMed - as supplied by publisher]

Related Articles Modulation of kanamycin B and kanamycin A biosynthesis in Streptomyces kanamyceticus via metabolic engineering. PLoS One. 2017;12(7):e0181971 Authors: Gao W, Wu Z, Sun J, Ni X, Xia H Abstract Both kanamycin A and kanamycin B, antibiotic components produced by Streptomyces kanamyceticus, have medical value. Two different pathways for kanamycin biosynthesis have been reported by two research groups. In this study, to obtain an optimal kanamycin A-producing strain and a kanamycin B-high-yield strain, we first examined the native kanamycin biosynthetic pathway in vivo. Based on the proposed parallel biosynthetic pathway, kanN disruption should lead to kanamycin A accumulation; however, the kanN-disruption strain produced neither kanamycin A nor kanamycin B. We then tested the function of kanJ and kanK. The main metabolite of the kanJ-disruption strain was identified as kanamycin B. These results clarified that kanamycin biosynthesis does not proceed through the parallel pathway and that synthesis of kanamycin A from kanamycin B is catalyzed by KanJ and KanK in S. kanamyceticus. As expected, the kanamycin B yield of the kanJ-disruption strain was 3268±255 μg/mL, 12-fold higher than that of the original strain. To improve the purity of kanamycin A and reduce the yield of kanamycin B in the fermentation broth, four different kanJ- and kanK-overexpressing strains were constructed through either homologous recombination or site-specific integration. The overexpressing strain containing three copies of kanJ and kanK in its genome exhibited the lowest kanamycin B yield (128±20 μg/mL), which was 54% lower than that of the original strain. Our experimental results demonstrate that kanamycin A is derived from KanJ-and-KanK-catalyzed conversion of kanamycin B in S. kanamyceticus. Moreover, based on the clarified biosynthetic pathway, we obtained a kanamycin B-high-yield strain and an optimized kanamycin A-producing strain with minimal byproduct. PMID: 28753625 [PubMed - indexed for MEDLINE]

Related Articles Analysis of metabolomic profile of fermented Orostachys japonicus A. Berger by capillary electrophoresis time of flight mass spectrometry. PLoS One. 2017;12(7):e0181280 Authors: Das G, Patra JK, Lee SY, Kim C, Park JG, Baek KH Abstract Microbial cell performance in food biotechnological processes has become an important concern for improving human health worldwide. Lactobacillus plantarum, which is widely distributed in nature, is a lactic acid bacterium with many industrial applications for fermented foods or functional foods (e.g., probiotics). In the present study, using capillary electrophoresis time of flight mass spectrometry, the metabolomic profile of dried Orostachys japonicus A. Berger, a perennial medicinal herb with L. plantarum was compared with that of O. japonicus fermented with L. plantarum to elucidate the metabolomic changes induced by the fermentation process. The levels of several metabolites were changed by the fermentation process, indicating their involvement in microbial performance. For example, glycolysis, the pentose phosphate pathway, the TCA cycle, the urea cycle-related metabolism, nucleotide metabolism, and lipid and amino acid metabolism were altered significantly by the fermentation process. Although the fermented metabolites were not tested using in vivo studies to increase human health benefits, our findings provide an insight into the alteration of metabolites induced by fermentation, and indicated that the metabolomic analysis for the process should be accompanied by fermenting strains and conditions. PMID: 28704842 [PubMed - indexed for MEDLINE]

Related Articles [Autophagy, fitness and longevity]. Med Sci (Paris). 2017 Mar;33(3):246-251 Authors: Galluzzi L, Bravo-San Pedro JM, Kroemer G Abstract Autophagy is a key mechanism for the maintenance of intracellular and organismal homeostasis. Accordingly, defects in core components of the autophagic machinery are etiologically associated with a variety of human pathologies, including infectious disorders, cardiovascular diseases, neurodegenerative conditions, and cancer. Intriguingly, several maneuvers that increase the lifespan of model organisms in the laboratory, like caloric restriction, do so in an autophagy-dependent manner. Here, we briefly discuss the intimate relationship between the autophagic preservation of intracellular and organismal fitness and healthy aging. PMID: 28367810 [PubMed - indexed for MEDLINE]

Related Articles Measurement of Metabolome Samples Using Liquid Chromatography-Mass Spectrometry, Data Acquisition, and Processing. Cold Spring Harb Protoc. 2016 Dec 01;2016(12):pdb.prot091561 Authors: Pluskal T, Yanagida M Abstract We present a protocol for metabolomic sample measurement using hydrophilic interaction chromatography (HILIC) combined with high-resolution Orbitrap mass spectrometry (MS). We also introduce a raw data processing method using MZmine 2 software, and include a list of 111 metabolite peaks (with their m/z values and retention times) previously identified in metabolome samples using this method. PMID: 27934688 [PubMed - indexed for MEDLINE]

Related Articles Preparation of Intracellular Metabolite Extracts from Liquid Schizosaccharomyces pombe Cultures. Cold Spring Harb Protoc. 2016 Dec 01;2016(12):pdb.prot091553 Authors: Pluskal T, Nakamura T, Yanagida M Abstract The success of metabolomic analysis relies heavily on the sample preparation protocol. Here we present a protocol for intracellular metabolite extraction from liquid fission yeast cultures based on rapid quenching in pure methanol at -40°C, bead-beating in 50% methanol for cell disruption, and 10 kDa cutoff ultrafiltration for removal of proteins. Samples are concentrated by vacuum evaporation and resuspended in 50% acetonitrile for mass spectrometric analysis. This protocol is optimal for extraction of polar metabolites such as amino acids, organic acids, nucleotides, sugars, or sugar-phosphates. Its implementation requires <6 h and allows preparation of multiple samples in parallel. PMID: 27934687 [PubMed - indexed for MEDLINE]

Related Articles The Tumor Suppressor Hace1 Is a Critical Regulator of TNFR1-Mediated Cell Fate. Cell Rep. 2016 May 17;15(7):1481-1492 Authors: Tortola L, Nitsch R, Bertrand MJM, Kogler M, Redouane Y, Kozieradzki I, Uribesalgo I, Fennell LM, Daugaard M, Klug H, Wirnsberger G, Wimmer R, Perlot T, Sarao R, Rao S, Hanada T, Takahashi N, Kernbauer E, Demiröz D, Lang M, Superti-Furga G, Decker T, Pichler A, Ikeda F, Kroemer G, Vandenabeele P, Sorensen PH, Penninger JM Abstract The HECT domain E3 ligase HACE1 has been identified as a tumor suppressor in multiple cancers. Here, we report that HACE1 is a central gatekeeper of TNFR1-induced cell fate. Genetic inactivation of HACE1 inhibits TNF-stimulated NF-κB activation and TNFR1-NF-κB-dependent pathogen clearance in vivo. Moreover, TNF-induced apoptosis was impaired in hace1 mutant cells and knockout mice in vivo. Mechanistically, HACE1 is essential for the ubiquitylation of the adaptor protein TRAF2 and formation of the apoptotic caspase-8 effector complex. Intriguingly, loss of HACE1 does not impair TNFR1-mediated necroptotic cell fate via RIP1 and RIP3 kinases. Loss of HACE1 predisposes animals to colonic inflammation and carcinogenesis in vivo, which is markedly alleviated by genetic inactivation of RIP3 kinase and TNFR1. Thus, HACE1 controls TNF-elicited cell fate decisions and exerts tumor suppressor and anti-inflammatory activities via a TNFR1-RIP3 kinase-necroptosis pathway. PMID: 27160902 [PubMed - indexed for MEDLINE]

Existence of life-time stable proteins in mature rats-Dating of proteins' age by repeated short-term exposure to labeled amino acids throughout age. PLoS One. 2017;12(9):e0185605 Authors: Bechshøft CL, Schjerling P, Bornø A, Holm L Abstract In vivo turnover rates of proteins covering the processes of protein synthesis and breakdown rates have been measured in many tissues and protein pools using various techniques. Connective tissue and collagen protein turnover is of specific interest since existing results are rather diverging. The aim of this study is to investigate whether we can verify the presence of protein pools within the same tissue with very distinct turnover rates over the life-span of rats with special focus on connective tissue. Male and female Lewis rats (n = 35) were injected with five different isotopically labeled amino acids tracers. The tracers were injected during fetal development (Day -10 to -2), after birth (Day 5-9), at weaning (Day 25-32) at puberty (Day 54-58) and at adulthood (Day 447-445). Subgroups of rats were euthanized three days after every injection period, at different time point between injection periods and lastly at day 472. Tissue (liver, muscle, eye lens and patellar tendon) and blood samples were collected after euthanization. The enrichment of the labeled amino acids in the tissue or blood samples was measured using GC-MS-MS. In muscle and liver we demonstrated a rapid decrease of tracer enrichments throughout the rat's life, indicating that myofibrillar and cytoskeleton proteins have a high turnover. In contrast, the connective tissue protein in the eye lens and patellar tendon of the mature rat showed detainment of tracer enrichment injected during fetal development and first living days, indicating very slow turnover. The data support the hypothesis that some proteins synthesized during the early development and growth still exist much later in life of animals and hence has a very slow turnover rate. PMID: 28957442 [PubMed - in process]

Translational Aspects of Diet and Non-Alcoholic Fatty Liver Disease. Nutrients. 2017 Sep 28;9(10): Authors: Goossens N, Jornayvaz FR Abstract Non-alcoholic fatty liver disease (NAFLD) is a spectrum of diseases ranging from simple steatosis without inflammation or fibrosis to nonalcoholic steatohepatitis (NASH). Despite the strong association between dietary factors and NAFLD, no dietary animal model of NAFLD fully recapitulates the complex metabolic and histological phenotype of the disease, although recent models show promise. Although animal models have significantly contributed to our understanding of human diseases, they have been less successful in accurate translation to predict effective treatment strategies. We discuss strategies to overcome this challenge, in particular the adoption of big data approaches combining clinical phenotype, genomic heterogeneity, transcriptomics, and metabolomics changes to identify the ideal NAFLD animal model for a given scientific question or to test a given drug. We conclude by noting that novel big data approaches may help to bridge the translational gap for selecting dietary models of NAFLD. PMID: 28956824 [PubMed - in process]

Related Articles Ion Mobility Spectrometry-Mass Spectrometry Coupled with Gas-Phase Hydrogen/Deuterium Exchange for Metabolomics Analyses. J Am Soc Mass Spectrom. 2017 Sep 27;: Authors: Maleki H, Karanji AK, Majuta S, Maurer MM, Valentine SJ Abstract Ion mobility spectrometry-mass spectrometry (IMS-MS) in combination with gas-phase hydrogen/deuterium exchange (HDX) and collision-induced dissociation (CID) is evaluated as an analytical method for small-molecule standard and mixture characterization. Experiments show that compound ions exhibit unique HDX reactivities that can be used to distinguish different species. Additionally, it is shown that gas-phase HDX kinetics can be exploited to provide even further distinguishing capabilities by using different partial pressures of reagent gas. The relative HDX reactivity of a wide variety of molecules is discussed in light of the various molecular structures. Additionally, hydrogen accessibility scoring (HAS) and HDX kinetics modeling of candidate (in silico) ion structures is utilized to estimate the relative ion conformer populations giving rise to specific HDX behavior. These data interpretation methods are discussed with a focus on developing predictive tools for HDX behavior. Finally, an example is provided in which ion mobility information is supplemented with HDX reactivity data to aid identification efforts of compounds in a metabolite extract. Graphical Abstract ᅟ. PMID: 28956290 [PubMed - as supplied by publisher]

Related Articles Direct detection of surface localized specialized metabolites from Glycyrrhiza lepidota (American licorice) by leaf spray mass spectrometry. Planta. 2017 Sep 27;: Authors: Freund DM, Martin AC, Cohen JD, Hegeman AD Abstract MAIN CONCLUSION: Leaf spray-MS minimizes tissue manipulation by effectively and quickly assessing in vivo specialized metabolites from intact plant tissue surfaces, including trichome metabolites. Intact leaves of Glycyrrhiza lepidota Pursh. (American licorice) were analyzed by direct electrospray leaf spray-MS, an ambient ionization technique. Comparison of metabolites detected by leaf spray-MS to those from LC-MS of bulk tissue and trichome enriched extracts showed dramatic differences. Leaf spray-MS results suggest that in specific situations this approach could complement traditional LC-MS analysis of bulk extracts. Leaf spray-MS as a metabolomics technique eliminates sample pretreatment and preparation allowing for rapid sampling in real time of living intact tissues. Specialized metabolites on the surface of tissues such as glandular trichomes metabolites are detected by leaf spray-MS. PMID: 28956161 [PubMed - as supplied by publisher]

Related Articles Metabolomics reveal mitochondrial and fatty acid metabolism disorders that contribute to the development of DKD in T2DM patients. Mol Biosyst. 2017 Sep 28;: Authors: Li L, Wang C, Yang H, Liu S, Lu Y, Fu P, Liu J Abstract Diabetic kidney disease (DKD) is the leading cause of ESRD; however, early intervention can greatly prevent the progression of DKD; thus, sensitive biomarkers for DKD are still required. This study was aimed at the identification of potential biomarkers and revelation of underlying pathways in DKD patients by non-targeted metabolomics. Gas chromatography-mass spectrometry was used to analyze urine obtained from the control and type 2 diabetes mellitus (T2DM) and DKD patients, and the renal histological changes in DKD patients were assessed. The DKD group showed increased level of uric acid, 1,5-anhydroglucitol, hippuric acid, stearic acid, and palmitic acid and reduced level of uracil, glycine, aconitic acid, isocitric acid, 4-hydroxybutyrate, 2-deoxyerythritol, and glycolic acid as compared to the control and T2DM groups. Further analysis indicated that many of the changed metabolites were involved in mitochondrial and fatty acid (FA) metabolism, and combined mitochondrial and FA metabolites showed better diagnosis values for DKD. Histological results confirmed that renal expression of key proteins was reduced in DKD patients with respect to mitochondrial biogenesis (PGC-1α, p-AMPK) and FA oxidation (PPAR-α, CPT-1) as compared to that in the control and T2DM groups. This study highlighted that both mitochondrial and FA metabolism were disturbed in DKD, and thus, they could serve as combined biomarkers for the prediction of DKD. PMID: 28956034 [PubMed - as supplied by publisher]

Related Articles (1)H NMR and MVA metabolomic profiles of urines from piglets fed with boluses contaminated with a mixture of five mycotoxins. Biochem Biophys Rep. 2017 Sep;11:9-18 Authors: De Pascali SA, Gambacorta L, Oswald IP, Del Coco L, Solfrizzo M, Fanizzi FP Abstract Metabolic profile of urine from piglets administered with single boluses contaminated with mycotoxin mixture (deoxynivalenol, aflatoxin B1, fumonisin B1, zearalenone, and ochratoxin A) were studied by (1)H NMR spectroscopy and chemometrics (PCA, PLS-DA, and OPLS-DA). The mycotoxin levels were close to the established maximum and guidance levels for animal feed (2003/100/EC and 2006/576/EC). Urine samples were obtained from four groups of four piglets before (control, C) or within 24 h (treated, T) after receiving a contaminated boluses with increasing doses of mycotoxins (boluses 1-4). For the two highest dose groups, the urines were collected also after one week of wash out (W). For the two lowest doses groups no significant differences between the C and T samples were observed. By contrast, for the two highest doses groups the T urines separated from the controls for a higher relative content of creatinine, p-cresol glucuronide and phenyl acetyl glycine and lower concentration of betaine and TMAO. Interestingly, a similar profile was found for both W and T urines suggesting, at least for the highest doses used, serious alteration after a single bolus of mycotoxin mixture. PMID: 28955762 [PubMed]

Related Articles Hypoglycemic Potential of Aqueous Extract of Moringa oleifera Leaf and In Vivo GC-MS Metabolomics. Front Pharmacol. 2017;8:577 Authors: Khan W, Parveen R, Chester K, Parveen S, Ahmad S Abstract Moringa oleifera Lam. (family; Moringaceae), commonly known as drumstick, have been used for centuries as a part of the Ayurvedic system for several diseases without having any scientific data. Demineralized water was used to prepare aqueous extract by maceration for 24 h and complete metabolic profiling was performed using GC-MS and HPLC. Hypoglycemic properties of extract have been tested on carbohydrate digesting enzyme activity, yeast cell uptake, muscle glucose uptake, and intestinal glucose absorption. Type 2 diabetes was induced by feeding high-fat diet (HFD) for 8 weeks and a single injection of streptozotocin (STZ, 45 mg/kg body weight, intraperitoneally) was used for the induction of type 1 diabetes. Aqueous extract of M. oleifera leaf was given orally at a dose of 100 mg/kg to STZ-induced rats and 200 mg/kg in HFD mice for 3 weeks after diabetes induction. Aqueous extract remarkably inhibited the activity of α-amylase and α-glucosidase and it displayed improved antioxidant capacity, glucose tolerance and rate of glucose uptake in yeast cell. In STZ-induced diabetic rats, it produces a maximum fall up to 47.86% in acute effect whereas, in chronic effect, it was 44.5% as compared to control. The fasting blood glucose, lipid profile, liver marker enzyme level were significantly (p < 0.05) restored in both HFD and STZ experimental model. Multivariate principal component analysis on polar and lipophilic metabolites revealed clear distinctions in the metabolite pattern in extract and in blood after its oral administration. Thus, the aqueous extract can be used as phytopharmaceuticals for the management of diabetes by using as adjuvants or alone. PMID: 28955221 [PubMed]

Related Articles Hydrogen Inhalation Protects against Ototoxicity Induced by Intravenous Cisplatin in the Guinea Pig. Front Cell Neurosci. 2017;11:280 Authors: Fransson AE, Kisiel M, Pirttilä K, Pettersson C, Videhult Pierre P, Laurell GFE Abstract Introduction: Permanent hearing loss and tinnitus as side-effects from treatment with the anticancer drug cisplatin is a clinical problem. Ototoxicity may be reduced by co-administration of an otoprotective agent, but the results in humans have so far been modest. Aim: The present preclinical in vivo study aimed to explore the protective efficacy of hydrogen (H2) inhalation on ototoxicity induced by intravenous cisplatin. Materials and Methods: Albino guinea pigs were divided into four groups. The Cispt (n = 11) and Cispt+H2 (n = 11) groups were given intravenous cisplatin (8 mg/kg b.w., injection rate 0.2 ml/min). Immediately after, the Cispt+H2 group also received gaseous H2 (2% in air, 60 min). The H2 group (n = 5) received only H2 and the Control group (n = 7) received neither cisplatin nor H2. Ototoxicity was assessed by measuring frequency specific ABR thresholds before and 96 h after treatment, loss of inner (IHCs) and outer (OHCs) hair cells, and by performing densitometry-based immunohistochemistry analysis of cochlear synaptophysin, organic transporter 2 (OCT2), and copper transporter 1 (CTR1) at 12 and 7 mm from the round window. By utilizing metabolomics analysis of perilymph the change of metabolites in the perilymph was assessed. Results: Cisplatin induced electrophysiological threshold shifts, hair cell loss, and reduced synaptophysin immunoreactivity in the synapse area around the IHCs and OHCs. H2 inhalation mitigated all these effects. Cisplatin also reduced the OCT2 intensity in the inner and outer pillar cells and in the stria vascularis as well as the CTR1 intensity in the synapse area around the IHCs, the Deiters' cells, and the stria vascularis. H2 prevented the majority of these effects. Conclusion: H2 inhalation can reduce cisplatin-induced ototoxicity on functional, cellular, and subcellular levels. It is proposed that synaptopathy may serve as a marker for cisplatin ototoxicity. The effect of H2 on the antineoplastic activity of cisplatin needs to be further explored. PMID: 28955207 [PubMed]

Related Articles Profiling glucose-induced selective inhibition of disaccharide catabolism in Bacillus megaterium QM B1551 by stable isotope labelling. Microbiology. 2017 Sep 28;: Authors: Youngster T, Wushensky JA, Aristilde L Abstract We investigated the co-catabolism of carbohydrate mixtures in Bacillus megaterium QM B1551 using a (13)C-assisted metabolomics profiling approach. Specifically, we monitored the ability of B. megaterium to achieve the simultaneous catabolism of glucose and a common disaccharide - cellobiose, maltose, or sucrose. Growth experiments indicated that each disaccharide alone can serve as a sole carbon source for B. megaterium, in accordance with the genetic analysis of this bacterium, which predicted diverse metabolic capabilities. However, following growth on (13)C-labelled glucose and each unlabelled disaccharide, the labelling patterns of the intracellular metabolites in glycolysis and the pentose phosphate pathway revealed a hierarchy in disaccharide catabolism: (i) complete inhibition of cellobiose catabolism, (ii) minimal catabolism of maltose and (iii) unbiased catabolism of sucrose. The labelling of amino acids confirmed this selective assimilation of each substrate in biomass precursors. This study highlights the fact that B. megaterium exhibits a mixed-carbohydrate utilization that is different from that of B. subtilis, the most studied model Bacillus species. PMID: 28954687 [PubMed - as supplied by publisher]

Related Articles Molecular Biological Methods in Environmental Engineering. Water Environ Res. 2017 Oct 01;89(10):942-959 Authors: Li C, Xia F, Zhang Y, Chang CC, Wei D, Wei L Abstract Microorganisms can respond fast to the environmental changes, and well suited for environmental assessment. DNA and RNA are generally extracted by extraction kits. After extraction, molecular biological methods including genomics, transcriptomics, proteomics and metabolomics are applied to characterize the genetic and functional diversity of microorganisms. Quantitative PCR, FISH and mass sequence of amplicons are also described. This review provides environmental engineers and microbiologists an overview of important advancements in molecular techniques and highlights the application of these methods in diverse environments. PMID: 28954649 [PubMed - in process]

Related Articles Metabolomic profiling to characterize acute intestinal ischemia/reperfusion injury. PLoS One. 2017;12(6):e0179326 Authors: Khadaroo RG, Churchill TA, Tso V, Madsen KL, Lukowski C, Salim SY Abstract Sepsis and septic shock are the leading causes of death in critically ill patients. Acute intestinal ischemia/reperfusion (AII/R) is an adaptive response to shock. The high mortality rate from AII/R is due to the severity of the disease and, more importantly, the failure of timely diagnosis. The objective of this investigation is to use nuclear magnetic resonance (NMR) analysis to characterize urine metabolomic profile of AII/R injury in a mouse model. Animals were exposed to sham, early (30 min) or late (60 min) acute intestinal ischemia by complete occlusion of the superior mesenteric artery, followed by 2 hrs of reperfusion. Urine was collected and analyzed by NMR spectroscopy. Urinary metabolite concentrations demonstrated that different profiles could be delineated based on the duration of the intestinal ischemia. Metabolites such as allantoin, creatinine, proline, and methylamine could be predictive of AII/R injury. Lactate, currently used for clinical diagnosis, was found not to significantly contribute to the classification model for either early or late ischemia. This study demonstrates that patterns of changes in urinary metabolites are effective at distinguishing AII/R progression in an animal model. This is a proof-of-concept study to further support examination of metabolites in the clinical diagnosis of intestinal ischemia reperfusion injury in patients. The discovery of a fingerprint metabolite profile of AII/R will be a major advancement in the diagnosis, treatment, and prevention of systemic injury in critically ill patients. PMID: 28662085 [PubMed - indexed for MEDLINE]