PubMed

Urine metabolomics in neonates with late-onset sepsis in a case-control study. Sci Rep. 2017 Apr 04;7:45506 Authors: Sarafidis K, Chatziioannou AC, Thomaidou A, Gika H, Mikros E, Benaki D, Diamanti E, Agakidis C, Raikos N, Drossou V, Theodoridis G Abstract Although late-onset sepsis (LOS) is a major cause of neonatal morbidity and mortality, biomarkers evaluated in LOS lack high diagnostic accuracy. In this prospective, case-control, pilot study, we aimed to determine the metabolic profile of neonates with LOS. Urine samples were collected at the day of initial LOS evaluation, the 3(rd) and 10(th) day, thereafter, from 16 septic neonates (9 confirmed and 7 possible LOS cases) and 16 non-septic ones (controls) at respective time points. Urine metabolic profiles were assessed using non-targeted nuclear magnetic resonance spectroscopy and targeted liquid chromatography-tandem mass spectrometry analysis. Multivariate statistical models with data from either analytical approach showed clear separation between the metabolic profiles of septic neonates (both possible and confirmed) and the controls. Metabolic changes appeared to be related to disease progression. Overall, neonates with confirmed or possible LOS exhibited comparable metabolic profiles indicating similar metabolic alternations upon the onset of clinical manifestations. This methodology therefore enabled the discrimination of neonates with LOS from non-septic individuals, providing potential for further research toward the discovery of LOS-related biomarkers. PMID: 28374757 [PubMed - in process]

Related Articles Alzheimer's Disease: Biomarkers in the Genome, Blood, and Cerebrospinal Fluid. Front Neurol. 2017;8:102 Authors: Huynh RA, Mohan C Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disorder that slowly destroys memory and thinking skills, resulting in behavioral changes. It is estimated that nearly 36 million are affected globally with numbers reaching 115 million by 2050. AD can only be definitively diagnosed at autopsy since its manifestations of senile plaques and neurofibrillary tangles throughout the brain cannot yet be fully captured with current imaging technologies. Current AD therapeutics have also been suboptimal. Besides identifying markers that distinguish AD from controls, there has been a recent drive to identify better biomarkers that can predict the rates of cognitive decline and neocortical amyloid burden in those who exhibit preclinical, prodromal, or clinical AD. This review covers biomarkers of three main types: genes, cerebrospinal fluid-derived, and blood-derived biomarkers. Looking ahead, cutting-edge OMICs technologies, including proteomics and metabolomics, ought to be fully tapped in order to mine even better biomarkers for AD that are more predictive. PMID: 28373857 [PubMed - in process]

Related Articles Intracellular metabolite β-glucosylceramide is an endogenous Mincle ligand possessing immunostimulatory activity. Proc Natl Acad Sci U S A. 2017 Apr 03;: Authors: Nagata M, Izumi Y, Ishikawa E, Kiyotake R, Doi R, Iwai S, Omahdi Z, Yamaji T, Miyamoto T, Bamba T, Yamasaki S Abstract Sensing and reacting to tissue damage is a fundamental function of immune systems. Macrophage inducible C-type lectin (Mincle) is an activating C-type lectin receptor that senses damaged cells. Notably, Mincle also recognizes glycolipid ligands on pathogens. To elucidate endogenous glycolipids ligands derived from damaged cells, we fractionated supernatants from damaged cells and identified a lipophilic component that activates reporter cells expressing Mincle. Mass spectrometry and NMR spectroscopy identified the component structure as β-glucosylceramide (GlcCer), which is a ubiquitous intracellular metabolite. Synthetic β-GlcCer activated myeloid cells and induced production of inflammatory cytokines; this production was abrogated in Mincle-deficient cells. Sterile inflammation induced by excessive cell death in the thymus was exacerbated by hematopoietic-specific deletion of degrading enzyme of β-GlcCer (β-glucosylceramidase, GBA1). However, this enhanced inflammation was ameliorated in a Mincle-deficient background. GBA1-deficient dendritic cells (DCs) in which β-GlcCer accumulates triggered antigen-specific T-cell responses more efficiently than WT DCs, whereas these responses were compromised in DCs from GBA1 × Mincle double-deficient mice. These results suggest that β-GlcCer is an endogenous ligand for Mincle and possesses immunostimulatory activity. PMID: 28373578 [PubMed - as supplied by publisher]

Related Articles Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione. Proc Natl Acad Sci U S A. 2017 Apr 03;: Authors: Peracchi A, Veiga-da-Cunha M, Kuhara T, Ellens KW, Paczia N, Stroobant V, Seliga AK, Marlaire S, Jaisson S, Bommer GT, Sun J, Huebner K, Linster CL, Cooper AJ, Van Schaftingen E Abstract The mammalian gene Nit1 (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known physiological substrate of Nit2), and its actual enzymatic function has so far remained a puzzle. In the present study, we demonstrate that both the mammalian Nit1 and its yeast ortholog are amidases highly active toward deaminated glutathione (dGSH; i.e., a form of glutathione in which the free amino group has been replaced by a carbonyl group). We further show that Nit1-KO mutants of both human and yeast cells accumulate dGSH and the same compound is excreted in large amounts in the urine of Nit1-KO mice. Finally, we show that several mammalian aminotransferases (transaminases), both cytosolic and mitochondrial, can form dGSH via a common (if slow) side-reaction and provide indirect evidence that transaminases are mainly responsible for dGSH formation in cultured mammalian cells. Altogether, these findings delineate a typical instance of metabolite repair, whereby the promiscuous activity of some abundant enzymes of primary metabolism leads to the formation of a useless and potentially harmful compound, which needs a suitable "repair enzyme" to be destroyed or reconverted into a useful metabolite. The need for a dGSH repair reaction does not appear to be limited to eukaryotes: We demonstrate that Nit1 homologs acting as excellent dGSH amidases also occur in Escherichia coli and other glutathione-producing bacteria. PMID: 28373563 [PubMed - as supplied by publisher]

Related Articles Longitudinal analyses of the steroid metabolome in obese PCOS girls with weight loss. Endocr Connect. 2017 Apr 03;: Authors: Reinehr T, Kulle A, Rothermel J, Knop C, Lass N, Bosse C, Holterhus PM Abstract OBJECTIVE: The underlying mechanisms of polycystic ovarian syndrome (PCOS) are not fully understood yet. The aim of the study was to get functional insights into the regulation of steroid hormones in PCOS by steroid metabolomics. DESIGN: This is a longitudinal study of changes of steroid hormones in 40 obese girls aged 13-16 years (50% with PCOS) participating in a 1-year lifestyle intervention. Girls with and without PCOS were matched to age, BMI, and change of weight status. METHODS: We measured progesterone, 17-hydroxyprogesterone, 17-hydroxyprogenolon, 11-deoxycorticosterone, 21-deoxycorticosterone, deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol, cortisone, androstenedione, testosterone, dehydroepiandrostendion-sulfate (DHEA-S), estrone, and estradiol by LC-MS/MS steroid profiling at baseline and one year later. RESULTS: At baseline, obese PCOS girls demonstrated significantly higher androstenedione and testosterone concentrations compared to obese girls without PCOS, while the other steroid hormones including glucocorticoids, mineralocorticoids, estrogens, and precursors of androgens did not differ significantly. Weight loss in obese PCOS girls was associated with a significant decrease of testosterone, androstenedione, DHEA-S, cortisol, and corticosterone concentrations. Weight loss in obese non PCOS girls was associated with a significant decrease of DHEA-S, cortisol, and corticosterone concentrations, while no significant changes of testosterone and androstenedione concentrations could be observed. Without weight loss, no significant changes of steroid hormones were measured except an increase of estradiol in obese PCOS girls without weight loss. CONCLUSIONS: The key steroid hormones in obese adolescents with PCOS are androstenedione and testosterone, while glucocorticoids, mineralocorticoids, estrogens, and precursors of androgens did not differ between obese girls with and without PCOS. PMID: 28373267 [PubMed - as supplied by publisher]

Related Articles Differential expression of novel metabolic and immunological biomarkers in oysters challenged with a virulent strain of OsHV-1. Dev Comp Immunol. 2017 Mar 31;: Authors: Young T, Kesarcodi-Watson A, Alfaro AC, Merien F, Nguyen TV, Mae H, Le DV, Villas-Bôas S Abstract Early lifestages of the Pacific oyster (Crassostrea gigas) are highly susceptible to infection by OsHV-1 μVar, but little information exists regarding metabolic or pathophysiological responses of larval hosts. Using a metabolomics approach, we identified a range of metabolic and immunological responses in oyster larvae exposed to OsHV-1 μVar; some of which have not previously been reported in molluscs. Multivariate analyses of entire metabolite profiles were able to separate infected from non-infected larvae. Correlation analysis revealed the presence of major perturbations in the underlying biochemical networks and secondary pathway analysis of functionally-related metabolites identified a number of prospective pathways differentially regulated in virus-exposed larvae. These results provide new insights into the pathogenic mechanisms of OsHV-1 infection in oyster larvae, which may be applied to develop disease mitigation strategies and/or as new phenotypic information for selective breeding programmes aiming to enhance viral resistance. PMID: 28373065 [PubMed - as supplied by publisher]

Related Articles Mung bean (Vigna radiata (L.)) coat extract modulates macrophage functions to enhance antigen presentation: A proteomic study. J Proteomics. 2017 Mar 31;: Authors: Hashiguchi A, Hitachi K, Zhu W, Tian J, Tsuchida K, Komatsu S Abstract The immunomodulatory effect of mung bean is mainly attributed to antioxidant properties of flavonoids; however, the precise machinery for biological effect on animal cells remains uncertain. To understand the physiological change produced by mung bean consumption, proteomic and metabolomic techniques were used. In vitro assay confirmed the importance of synergistic interaction among multiple flavonoids by IL-6 expression. Proteomic analysis detected that the abundance of 190 proteins was changed in lipopolysaccharide-stimulated RAW264.7 cells by treatment with coat extract. Pathway mapping revealed that a range of proteins were regulated including an interferon-responsive antiviral enzyme (2'-5'-oligoadenylate synthetase), antigen processing factors (immunoglobulin heavy chain-binding protein and protein disulfide-isomerase), and proteins related to proteasomal degradation. Major histocompatibility complex pathway was activated. These results suggest that mung bean consumption enhances immune response toward a Th2-promoting polarization. BIOLOGICAL SIGNIFICANCE: This study highlighted the immunomodulation of RAW264.7 cells in response to treatment with mung bean seed coat extract, using gel-free proteomic technique. The mechanism of immunomodulation by mung bean has not been described until today except for a report which identified HMGB1 suppression as a pathway underlying the protective effect against sepsis. This study suggested that the mung bean is involved in the regulation of antigen processing and presentation, and thus shifts immune response from acute febrile illness to specific/systemic and long-lasting immunity to protect the host. PMID: 28373035 [PubMed - as supplied by publisher]

Related Articles Targeting aggression in severe mental illness: The predictive role of genetic, epigenetic, and metabolomic markers. Prog Neuropsychopharmacol Biol Psychiatry. 2017 Mar 31;: Authors: Manchia M, Fanos V Abstract Human aggression is a complex and widespread social behavior that is overrepresented in individuals affected by severe mental illness (SMI), such as schizophrenia (SCZ), bipolar disorder (BD), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD). A substantial proportion of the liability threshold for aggressive behavior is determined by genetic factors, and environmental moderators might facilitate the manifestation of this behavioral phenotype through modification of gene expression via the epigenetic machinery. These specific alterations in the genetic and epigenetic make-up of aggressive individuals might determine specific biochemical modifications detectable through metabolomics. An additional pathophysiological component playing a role in aggressive behavior might be determined by alterations of gut microbiota. Here, we present a selective review of the human data on genetic, epigenetic, and metabolomic markers of aggressive behavior in SMI, discussing also the available evidence on the role of microbiome alterations. Clinical implication of these evidences, as well as future perspectives, will be discussed. PMID: 28372995 [PubMed - as supplied by publisher]

Related Articles Simultaneous metabolomics and lipidomics analysis based on novel heart-cutting two-dimensional liquid chromatography-mass spectrometry. Anal Chim Acta. 2017 May 08;966:34-40 Authors: Wang S, Zhou L, Wang Z, Shi X, Xu G Abstract Increasing metabolite coverage by combining data from different platforms or methods can improve understanding of related metabolic mechanisms and the identification of biomarkers. However, no one method can obtain metabolomic and lipidomic information in a single analysis. In this work, aiming at collecting comprehensive information on metabolome and lipidome in a single analytical run, we developed an on-line heart-cutting two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) method. Complex metabolites from biological samples are divided into two fractions by using a precolumn. The first fraction is directly transferred and subjected to metabolomics analysis. Most lipids are retained on the precolumn until the mobile phases for lipidomics flow through; then they are subjected to lipidomics analysis. Up to 447 and 289 metabolites in plasma, including amino acids, carnitines, bile acids, free fatty acids, lyso-phospholipids, phospholipids, sphingomyelins etc. were identified within 30 min in the positive mode and negative mode, respectively. A comparison of the newly developed method with the conventional metabolomic and lipidomic approaches showed that approximately 99% features obtained by the two conventional methods can be covered with this 2D-LC method. Analytical characteristics evaluation showed the method had a wide linearity range, high sensitivity, satisfactory recovery and repeatability. These results demonstrate that this method is reliable, stable and well qualified in metabolomics analysis, particularly for large-scale metabolomics studies with small amount of samples. PMID: 28372724 [PubMed - in process]

Related Articles Metabolomic Profiling of Human Urine as a Screen for Multiple Inborn Errors of Metabolism. Genet Test Mol Biomarkers. 2016 Sep;20(9):485-95 Authors: Kennedy AD, Miller MJ, Beebe K, Wulff JE, Evans AM, Miller LA, Sutton VR, Sun Q, Elsea SH Abstract AIMS: We wished to determine the efficacy of using urine as an analyte to screen for a broad range of metabolic products associated with multiple different types of inborn errors of metabolism (IEMs), using an automated mass spectrometry-based assay. Urine was compared with plasma samples from a similar cohort analyzed using the same assay. Specimens were analyzed using two different commonly utilized urine normalization methods based on creatinine and osmolality, respectively. METHODS: Biochemical profiles for each sample (from both affected and unaffected subjects) were obtained using a mass spectrometry-based platform and population-based statistical analyses. RESULTS: We identified over 1200 biochemicals from among 100 clinical urine samples and identified clear biochemical signatures for 16 of 18 IEM diseases tested. The two diseases that did not result in clear signatures, X-linked creatine transporter deficiency and ornithine transcarbamylase deficiency, were from individuals under treatment, which masked biomarker signatures. Overall the process variability and coefficient of variation for isolating and identifying biochemicals by running technical replicates of each urine sample was 10%. CONCLUSIONS: A single urine sample analyzed with our integrated metabolomic platform can identify signatures of IEMs that are traditionally identified using many different assays and multiple sample types. Creatinine and osmolality-normalized data were robust to the detection of the disorders and samples tested here. PMID: 27448163 [PubMed - indexed for MEDLINE]

Related Articles DNA hypomethylation upregulates expression of the MGAT3 gene in HepG2 cells and leads to changes in N-glycosylation of secreted glycoproteins. Sci Rep. 2016 Apr 13;6:24363 Authors: Klasić M, Krištić J, Korać P, Horvat T, Markulin D, Vojta A, Reiding KR, Wuhrer M, Lauc G, Zoldoš V Abstract Changes in N-glycosylation of plasma proteins are observed in many types of cancer, nevertheless, few studies suggest the exact mechanism involved in aberrant protein glycosylation. Here we studied the impact of DNA methylation on the N-glycome in the secretome of the HepG2 cell line derived from hepatocellular carcinoma (HCC). Since the majority of plasma glycoproteins originate from the liver, the HepG2 cells represent a good model for glycosylation changes in HCC that are detectable in blood, which is an easily accessible analytic material in a clinical setting. Two different concentrations of 5-aza-2'-deoxycytidine (5-aza-2dC) differentially affected global genome methylation and induced different glycan changes. Around twenty percent of 84 glyco-genes analysed changed expression level after the 5-aza-2dC treatment as a result of global genome hypomethylation. A correlation study between the changes in glyco-gene expression and the HepG2 glycosylation profile suggests that the MGAT3 gene might be responsible for the glycan changes consistently induced by both doses of 5-aza-2dC. Core-fucosylated tetra-antennary structures were decreased in quantity likely as a result of hypomethylated MGAT3 gene promoter followed by increased expression of this gene. PMID: 27073020 [PubMed - indexed for MEDLINE]

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Related Articles Metabolomics analysis of anaphylactoid reaction reveals its mechanism in a rat model. Asian Pac J Allergy Immunol. 2017 Apr 01;: Authors: Xu Y, Guo N, Dou D, Ran X, Liu C Abstract BACKGROUND: Anaphylactoid reactions, accounting for more than 77% of all immune-mediated immediate hypersensitivity reactions, have become a serious threat to public health, but their effect mechanism is not clear and diagnostic tests are limited. Comprehensive metabolite analysis may reveal the anaphylactoid effect mechanism systematically and provide reference for future diagnostic purposes. METHODS: Plasma from Brown Norway rats given intravenous injection of saline, compound 48/80 (2.5 mL/kg) or ovalbumin (20 mL/kg) in 20 s for the first time was used to study the effect mechanism of anaphylactoid reactions through metabolomics (UPLC-qTOF-MS/MS). Metabolomics integrated with proteomics data were used to analyze the anaphylactoid pathways by MetaboAnalyst followed by integrated pathway analysis. RESULTS: Thirty metabolites were identified through the METLIN database by MS/MS and 18 of them were confirmed by authentic standards. The results showed that adenosine, histamine, N-acetylhistamine, N(α)-γ-glutamylhistamine, malate and xanthine are important indices for anaphylactoid reactions. It could be concluded that the effect mechanism is mainly composed of histidine metabolism, arachidonic acid metabolism, energy metabolism, purine metabolism and other small molecules through 30 metabolites. Multiple linear regression analysis indicated that not only histamine but also N(α)-γ-glutamylhistamine and arachidonic acid could be used to evaluate anaphylactoid symptoms of animals. Furthermore, the citrate cycle, histidine metabolism and arachidonic acid metabolism could be the main pathways of anaphylactoid reactions as determined by MetaboAnalyst. CONCLUSION: The results may provide a reference to improve diagnostic accuracy and predict and monitor treatment efficacy in anaphylactoid reactions in the clinical setting. PMID: 28364409 [PubMed - as supplied by publisher]

Related Articles Comparison of Ambient and Atmospheric Pressure Ion Sources for Cystic Fibrosis Exhaled Breath Condensate Ion Mobility-Mass Spectrometry Metabolomics. J Am Soc Mass Spectrom. 2017 Mar 31;: Authors: Zang X, Pérez JJ, Jones CM, Monge ME, McCarty NA, Stecenko AA, Fernández FM Abstract Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the gene that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The vast majority of the mortality is due to progressive lung disease. Targeted and untargeted CF breath metabolomics investigations via exhaled breath condensate (EBC) analyses have the potential to expose metabolic alterations associated with CF pathology and aid in assessing the effectiveness of CF therapies. Here, transmission-mode direct analysis in real time traveling wave ion mobility spectrometry time-of-flight mass spectrometry (TM-DART-TWIMS-TOF MS) was tested as a high-throughput alternative to conventional direct infusion (DI) electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) methods, and a critical comparison of the three ionization methods was conducted. EBC was chosen as the noninvasive surrogate for airway sampling over expectorated sputum as EBC can be collected in all CF subjects regardless of age and lung disease severity. When using pooled EBC collected from a healthy control, ESI detected the most metabolites, APCI a log order less, and TM-DART the least. TM-DART-TWIMS-TOF MS was used to profile metabolites in EBC samples from five healthy controls and four CF patients, finding that a panel of three discriminant EBC metabolites, some of which had been previously detected by other methods, differentiated these two classes with excellent cross-validated accuracy. Graphical Abstract ᅟ. PMID: 28364225 [PubMed - as supplied by publisher]

Related Articles X-Linked Cobalamin Disorder (HCFC1) Mimicking Nonketotic Hyperglycinemia With Increased Both Cerebrospinal Fluid Glycine and Methylmalonic Acid. Pediatr Neurol. 2017 Jan 07;: Authors: Scalais E, Osterheld E, Weitzel C, De Meirleir L, Mataigne F, Martens G, Shaikh TH, Coughlin CR, Yu HC, Swanson M, Friederich MW, Scharer G, Helbling D, Wendt-Andrae J, Van Hove JL Abstract BACKGROUND: Autosomal recessive or X-linked inborn errors of intracellular cobalamin metabolism can lead to methylmalonic aciduria and homocystinuria. In neonates, both increased cerebrospinal fluid glycine and cerebrospinal fluid/plasma glycine ratio are biochemical features of nonketotic hyperglycinemia. METHODS: We describe a boy presenting in the neonatal period with hypotonia, tonic, clonic, and later myoclonic seizures, subsequently evolving into refractory epilepsy and severe neurocognitive impairment. RESULTS: Increased cerebrospinal fluid glycine and cerebrospinal fluid to plasma glycine ratio were indicative of nonketotic hyperglycinemia. Early magnetic resonance imaging showed restricted diffusion and decreased apparent diffusion coefficient values in posterior limb of internal capsules and later in entire internal capsules and posterior white matter. Sequencing did not show a mutation in AMT, GLDC, or GCSH. Biochemical analysis identified persistently increased cerebrospinal fluid levels of glycine and methylmalonic acid and increased urinary methylmalonic acid and plasma homocysteine levels, which improved on higher parenteral hydroxocobalamin dose. Exome sequencing identified a known pathogenic sequence variant in X-linked cobalamin (HCFC1), c.344C>T, p. Ala115Val. In addition, a hemizygous mutation was found in the ATRX (c. 2728A>G, p. Lys910Glu). Retrospective review of two other patients with X-linked cobalamin deficiency also identified increased cerebrospinal fluid glycine levels. CONCLUSIONS: This boy had X-linked cobalamin deficiency (HCFC1) with increased cerebrospinal fluid glycine and methylmalonic acid and increased cerebrospinal fluid to plasma glycine ratio suggesting a brain hyperglycinemia. Putative binding sites for HCFC1 and its binding partner THAP11 were identified near genes of the glycine cleavage enzyme, providing a potential mechanistic link between HCFC1 mutations and increased glycine. PMID: 28363510 [PubMed - as supplied by publisher]

Effect of Major Royal Jelly Proteins on Spatial Memory in Aged Rats: Metabolomics Analysis in Urine. J Agric Food Chem. 2017 Mar 31;: Authors: Chen D, Liu F, Wan JB, Lai CQ, Shen L Abstract Royal jelly (RJ) produced by worker honeybees is the sole food for the queen bee throughout her life as well as the larvae of worker bees for the first three days after hatching. Supplementation of RJ in the diet has been shown to increase spatial memory in rodents. However, the key constituents in RJ responsible for improvement of cognitive function are unknown. Our objective was to find out if the major royal-jelly proteins (MRJPs) extracted from RJ can improve the spatial memory of aged rats. The spatial memory assay using the Morris Water Maze test was administrated once to all the rats after 14-week feeding. Metabolomics analysis based on quadrupole time-of-flight mass spectrometry was conducted to examine the differences in compounds from urine. Aged male rats fed MRJPs were improved for spatial memory up to 48.5% when compared to the control male aged rats fed with distilled water. Metabolite pattern of the MRJPs-fed aged rats was regressed to that of the young rats. Compounds altered by MRJPs were mapped to nicotinate and nicotinamide metabolism, cysteine taurine metabolism and energy metabolism pathways. In summary, MRJPs may improve spatial memory and possess the potential for prevention of cognitive impairment via the cysteine and taurine metabolism and energy metabolism pathways in aged rats. PMID: 28362493 [PubMed - as supplied by publisher]

The genetic basis of obesity complications. Acta Sci Pol Technol Aliment. 2017 Jan-Mar;16(1):83-91 Authors: Skrypnik K, Suliburska J, Skrypnik D, Pilarski Ł, Reguła J, Bogdański P Abstract Intensive research is currently being performed into the genetic background of excess body mass compli- cations such as diabetes, cardiovascular disorders, especially atherosclerosis and coronary heart disease. Chronic inflammation is an important process in the pathogenesis of obesity, wherein there is an aberrant ex- pression of genes encoding adipokines. Visceral tissue is characterized by a higher expression and secretion of interleukin-8, interleukin-1ß and plasminogen activator inhibitor 1 in the subcutaneous tissue secretion of leptin prevails. An important complication of obesity is obstructive sleep apnea, often observed in Prader- Willi syndrome. The genetic background of sleep apnea may be a polymorphism of the SREBF1 gene. The consequence of excess body mass is metabolic syndrome, which may be related to the occurrence of the rs926198 variant of gene encoding caveolin-1. The genes of transcription factor TCF7L2 and PPAR-γ2 take part in the pathogenesis of diabetes development. It has been demonstrated that oncogenes FOS, FOSB, and JUN may be co-responsible not only for obesity but also for osteoporosis and colorectal cancer. It has been shown that weight loss causes a modification in the expression of about 100 genes involvedt in the production of substances such as cytokines and other responsible for chronic inflammation in obesity. In future studies on the complications of obesity, such scientific disciplines as proteomics, peptidomics, metabolomics and transcriptomics should be used. The aim of this study is to present the current state of knowledge about the genetic basis of obesity complications. PMID: 28362475 [PubMed - in process]

Discrimination of Four Marine Biofilm-Forming Bacteria by LC-MS Metabolomics and Influence of Culture Parameters. J Proteome Res. 2017 Mar 31;: Authors: Favre L, Ortalo-Magné A, Greff S, Pérez T, Thomas OP, Martin JC, Culioli G Abstract Most of the marine bacteria can form biofilms and they are the main components of biofilms observed on marine surfaces. Biofilms constitute a widespread life strategy, as growing in such structures offers many important biological benefits. The molecular compounds expressed in biofilms and, more generally, the metabolomes of marine bacteria remain poorly studied. In this context, a non-targeted LC-MS metabolomics approach of marine biofilm-forming bacterial strains was developed. Four marine bacteria, Persicivirga (Nonlabens) mediterranea TC4 and TC7, Pseudoalteromonas lipolytica TC8 and Shewanella sp. TC11, were used as model organisms. The main objective was to search for some strain-specific bacterial metabolites and to determine how culture parameters (culture medium, phase growth and mode of culture) may affect the cellular metabolism of each strain and thus the global inter-strain metabolic discrimination. LC-MS profiling and statistical partial least-square discriminant analyses showed that the four strains could be differentiated at the species level whatever the medium, the growth phase or the mode of culture (planktonic vs biofilm). A MS/MS molecular network was subsequently built and allowed the identification of putative bacterial biomarkers. TC8 was discriminated by a series of ornithine lipids while the P. mediterranea strains produced hydroxylated ornithine and glycine lipids. Among the P. mediterranea strains, TC7 extracts were distinguished by the occurrence of diamine derivatives, such as putrescine amides. PMID: 28362105 [PubMed - as supplied by publisher]

Spontaneous DNA damage propels tumorigenicity. Cell Res. 2017 Mar 31;: Authors: Vitale I, Kroemer G Abstract High levels of endogenously generated DNA damage drive oncogenesis, sustain malignant progression and increase therapy resistance. In a paper recently published in Cell Research, Liu and colleagues added additional insights into this topic by uncovering a novel intrinsic source of double-strand breaks that fosters the aggressiveness and stemness of malignant cells. PMID: 28361897 [PubMed - as supplied by publisher]

Related Articles A molecular analysis of the GBA gene in Caucasian South Africans with Parkinson's disease. Mol Genet Genomic Med. 2017 Mar;5(2):147-156 Authors: Barkhuizen M, Anderson DG, van der Westhuizen FH, Grobler AF Abstract BACKGROUND: The molecular basis of Parkinson's disease in South African population groups remains elusive. To date, substitutions in the GBA gene are the most common large-effect genetic risk factor for Parkinson's disease. The primary objective of this study was to determine the prevalence of GBA substitutions in South Africans with idiopathic Parkinson's disease. METHODS: Participants were recruited from tertiary hospitals in the Gauteng Province in South Africa. All participants were screened for substitutions in GBA exon 8-11 and the full coding region was analysed in 20 participants. Peripheral β-glucocerebrosidase enzymatic activity of GBA-carriers was measured in mixed leukocytes. RESULTS: Of 105 Caucasian Parkinson's disease participants (82.7% Afrikaner) with an average age of disease onset of 61.9 ± 12.2 years and 40 controls (age 73.4 ± 12.4 years) were included. Heterozygous GBA substitutions were identified in 12.38% of affected participants (p.G35A, p.E326K, p.I368T, p.T369M, p.N370S, p.P387L and p.K441N) and 5.00% of controls (p.E326K and p.T369M). The substitutions ranged from predicted benign to moderately damaging; with p.E326K and p.T369M most prevalent, followed by the Afrikaner Gaucher disease substitution p.P387L. Severe Gaucher disease mutations, like p.L444P, were absent in this cohort. Enzyme activity analysis revealed a nonsignificant reduction in the GBA-Parkinson's disease individuals (14.49 ± 2.30 nmol/h/mg protein vs. 15.98 ± 3.06 nmol/h/mg in control samples). GBA substitutions occur in both young-onset and late-onset Parkinson's cases in the cohort. CONCLUSION: Mild GBA substitutions that may not cause Gaucher disease were a common risk factor for Parkinson's disease in the participant group. PMID: 28361101 [PubMed - in process]