Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Pharmacogenomic assessment of herbal drugs in affective disorders.

Sun, 16/12/2018 - 13:48
Related Articles Pharmacogenomic assessment of herbal drugs in affective disorders. Biomed Pharmacother. 2019 Jan;109:1148-1162 Authors: Sahoo S, S B Abstract Anxiety and depression, the most prevalent psychiatric disorders are co-morbid in nature affecting several people across the world. There is an increase in demand for complementary and alternative medicines, specifically herbal botanicals due to various side effects exhibited by conventional drugs. Herbal drugs mentioned in traditional medicines, face acceptance issues by the medical community due to lack of scientific data regarding their neurochemical pathways. Hence, there has been an increased interest in the quest to unravel the mechanisms of action of herbal psychotropics. With the advancements in "omic technologies" such as genomics, proteomics and metabolomics, research in the field of herbal psychopharmacology has gained momentum, providing a faster and informative platform for thorough evaluation of herbal drugs and formulations. In this article, we have reviewed several medicinal plants and their formulations that have shown potential anxiolytic and anti-depressant activities and have been screened for their biological mechanisms either at the gene, protein or metabolic level. PMID: 30551365 [PubMed - in process]

Targeted and untargeted LC-MS polyphenolic profiling and chemometric analysis of propolis from different regions of Croatia.

Sat, 15/12/2018 - 13:32
Targeted and untargeted LC-MS polyphenolic profiling and chemometric analysis of propolis from different regions of Croatia. J Pharm Biomed Anal. 2018 Dec 04;165:162-172 Authors: Saftić L, Peršurić Ž, Fornal E, Pavlešić T, Kraljević Pavelić S Abstract Propolis is a complex biological matrix consisting mostly of plant resins and waxes, and in a small proportion of the herbal secondary metabolites, phenols. Phenols are components that are responsible for biological activities of propolis, however, their qualitative and quantitative composition is strongly influenced by climate and vegetation. Although studies on profiling of propolis samples from different countries have been carried out for some time propolis from Croatia is still not characterized till now. Targeted liquid chromatography coupled to triple quadrupole (LC-QQQ), untargeted liquid chromatography coupled to quadrupole time-of-flight (LC-QTOF) and direct injection QTOF methods were developed and 56 propolis samples from different geographical regions of Croatia were analyzed. Results revealed that there is not only one expected type of propolis in the territory of Croatia; i.e. beside expected European "poplar" propolis another type can be distinguished. Principal component analysis (PCA) and Partial least squares Discriminant Analysis (PLS-DA) indicated that the phenolic content of propolis samples significantly changes under the influence of the Mediterranean, so the "European" propolis type mixes with the Mediterranean type on the Croatian coast, especially on the islands. For fast screening of propolis type, direct injection QTOF analysis demonstrated to be fast and reliable method, but for unambiguous identification of phenolic compounds, chromatographic separation is indispensable. This paper presents the findings from the first research on phenolic profiling of propolis from Croatia. PMID: 30551071 [PubMed - as supplied by publisher]

A review of lifestyle, metabolic risk factors and blood-based biomarkers for early diagnosis of pancreatic ductal adenocarcinoma.

Sat, 15/12/2018 - 13:32
A review of lifestyle, metabolic risk factors and blood-based biomarkers for early diagnosis of pancreatic ductal adenocarcinoma. J Gastroenterol Hepatol. 2018 Dec 14;: Authors: Pang Y, Holmes MV, Chen Z, Kartsonaki C Abstract We aimed to review the epidemiologic literature examining lifestyle, metabolic risk factors, and blood-based biomarkers including multi-omics (genomics, proteomics, and metabolomics) and to discuss how these predictive markers can inform early diagnosis of pancreatic ductal adenocarcinoma (PDAC). A search of the PubMed database was conducted in June 2018 to review epidemiologic studies of (1) lifestyle and metabolic risk factors for PDAC, genome-wide association studies (GWAS), and risk prediction models incorporating these factors and (2) blood-based biomarkers for PDAC (conventional diagnostic markers, metabolomics, and proteomics). Prospective cohort studies have reported at least twenty possible risk factors for PDAC, including smoking, heavy alcohol drinking, adiposity, diabetes, and pancreatitis, but the relative risks (RR) and population attributable fractions of individual risk factors are small (mostly <10%). High-throughput technologies have continued to yield promising genetic, metabolic, and protein biomarkers in addition to conventional biomarkers such as carbohydrate antigen 19-9 (CA 19-9). Nonetheless, most studies have utilised a hospital-based case-control design, and the diagnostic accuracy is low in studies that collected pre-diagnostic samples. Risk prediction models incorporating lifestyle and metabolic factors as well as other clinical parameters have shown good discrimination and calibration. Combination of traditional risk factors, genomics and blood-based biomarkers can help identify high-risk populations and inform clinical decisions. Multi-omics investigations can provide valuable insights into disease aetiology, but prospective cohort studies that collect pre-diagnostic samples and validation in independent studies are warranted. PMID: 30550622 [PubMed - as supplied by publisher]

Metabolic Profiling of High Egg Consumption and the Associated Lower Risk of Type 2 Diabetes in Middle-Aged Finnish Men.

Sat, 15/12/2018 - 13:32
Metabolic Profiling of High Egg Consumption and the Associated Lower Risk of Type 2 Diabetes in Middle-Aged Finnish Men. Mol Nutr Food Res. 2018 Dec 12;:e1800605 Authors: Noerman S, Kärkkäinen O, Mattsson A, Paananen J, Lehtonen M, Nurmi T, Tuomainen TP, Voutilainen S, Hanhineva K, Virtanen JK Abstract SCOPE: Higher egg intake was previously associated with a lower risk of developing type 2 diabetes (T2D) in the prospective, population-based Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) in eastern Finland. We explored potential compounds that could explain this association using non-targeted LC-MS-based metabolic profiling. METHODS AND RESULTS: We analyzed 239 baseline serum samples from the KIHD in 4 groups: subjects with higher (mean intake 1 egg/d) or lower (mean intake 2 eggs/wk) egg intake who developed T2D (cases) or remained heatlhy (controls) during the mean follow-up of 19.3 years. We observed different serum profiles of subjects who had either higher or lower egg intakes, and of those who developed type 2 diabetes or remained healthy. The higher baseline tyrosine level predicted higher odds of T2D (OR 1.94; 95% CI 1.45, 2.60; P<0.001; FDR 0.023) along with an unknown hexose-containing compound (OR 2.13; 95% CI 1.57, 2.88; P<0.001; FDR 0.005). Certain predominant metabolites in T2D cases were correlated positively with ones in lower-egg-intake group and negatively with ones in higher-egg-intake group. CONCLUSION: Our current findings may underline some potential metabolites that could explain how egg intake was associated with a lower risk of T2D. This article is protected by copyright. All rights reserved. PMID: 30548819 [PubMed - as supplied by publisher]

Comparative proteomics of Helicobacter pylori strains reveals geographical features rather than genomic variations.

Sat, 15/12/2018 - 13:32
Comparative proteomics of Helicobacter pylori strains reveals geographical features rather than genomic variations. Genes Cells. 2018 Dec 12;: Authors: Sugiyama N, Miyake S, Lin MH, Wakabayashi M, Marusawa H, Nishiumi S, Yoshida M, Ishihama Y Abstract Helicobacter pylori, a pathogen of various gastric diseases, has many genome sequence variants. Thus, the pathogenesis and infection mechanisms of the H. pylori-driven gastric diseases have not been elucidated. Here, we performed a large-scale proteome analysis to profile the heterogeneity of the proteome expression of 7 H. pylori strains by using an LC/MS/MS-based proteomics approach combined with a customized database consisting of nonredundant tryptic peptide sequences derived from full genome sequences of 52 H. pylori strains. The nonredundant peptide database enabled us to identify more peptides in the database search of MS/MS data compared with a simply merged protein database. Using this approach, we performed proteome analysis of genome-unknown strains of H. pylori at as large a scale as genome-known ones. Clustering of the H. pylori strains using proteome profiling slightly differed from the genome profiling and more clearly divided the strains into two groups based on the isolated area. Furthermore, we identified phosphorylated proteins and sites of the H. pylori strains and obtained the phosphorylation motifs located in the N-terminus that are commonly observed in bacteria. This article is protected by copyright. All rights reserved. PMID: 30548729 [PubMed - as supplied by publisher]

Molecular signatures of increased freezing tolerance due to low temperature memory in Arabidopsis.

Sat, 15/12/2018 - 13:32
Molecular signatures of increased freezing tolerance due to low temperature memory in Arabidopsis. Plant Cell Environ. 2018 Dec 12;: Authors: Zuther E, Schaarschmidt S, Fischer A, Erban A, Pagter M, Mubeen U, Giavalisco P, Kopka J, Sprenger H, Hincha DK Abstract Alternating temperatures require fast and coordinated adaptation responses of plants. Cold acclimation has been extensively investigated and results in increased freezing tolerance in Arabidopsis thaliana. Here we show that the two Arabidopsis accessions Col-0 and N14 that differ in their freezing tolerance, showed memory of cold acclimation, i.e. cold priming. Freezing tolerance was higher in plants exposed to cold priming at 4°C, a lag phase at 20°C and a second triggering cold stress (4°C) than in plants that were only cold primed. To our knowledge this is the first report on cold memory improving plant freezing tolerance. The triggering response was distinguishable from the priming response at the levels of gene expression (RNA-Seq), lipid (UPLC/MS) and metabolite composition (GC-MS). Transcriptomic responses pointed to induced lipid, secondary and stress metabolism in Col-0 and growth-related functions in N14. Specific accumulation of lipids included arabidopsides with possible functions as signaling molecules or precursors of jasmonic acid. While cold induced metabolites such as raffinose and its precursors were maintained in N14 during the lag phase, they were strongly accumulated in Col-0 after the cold trigger. This indicates genetic differences in the metabolic regulation of cold memory. PMID: 30548618 [PubMed - as supplied by publisher]

Identification of new urinary gamma-hydroxybutyric acid (GHB) markers applying untargeted metabolomics analysis following placebo-controlled administration to humans.

Sat, 15/12/2018 - 13:32
Identification of new urinary gamma-hydroxybutyric acid (GHB) markers applying untargeted metabolomics analysis following placebo-controlled administration to humans. Drug Test Anal. 2018 Dec 12;: Authors: Steuer AE, Raeber J, Steuer C, Boxler MI, Dornbierer DA, Bosch OG, Quednow BB, Seifritz E, Kraemer T Abstract Gamma-hydroxybutyrate (GHB) is a short-chain fatty acid that occurs naturally in the mammalian brain and that is prescribed as a medication against narcolepsy or used as a drug of abuse. Particularly, its use as a knock-out drug in cases of drug facilitated crimes is of major importance in forensic toxicology. Because of its rapid metabolism and resulting narrow detection windows (<12 h in urine), detection of GHB remains challenging. Thus, there is an urgent call for new markers to improve the reliable detection of GHB use. In the framework of a randomized, placebo-controlled, crossover study in 20 healthy male volunteers, urine samples obtained 4.5 hours post-administration were submitted to untargeted mass spectrometry (MS, QTOF) analysis to identify possible new markers of GHB intake. MS data from four different analytical methods (reversed phase and hydrophilic interaction liquid chromatography; positive and negative electrospray ionization) were filtered for significantly changed features applying uni- and multivariate statistics. From the resulting 42 compounds of interest, eight were finally identified including conjugates of GHB with carnitine, glutamate, and glycine as well as the endogenous compounds glycolate and succinylcarnitine. While GHB conjugates were only detectable in the GHB, but not in the placebo group, glycolate and succinylcarnitine were present in both groups albeit significantly increased through GHB intake. Untargeted metabolomics proved as a suitable tool for the non-hypothesis driven identification of new GHB markers. However, more studies on actual concentrations, detection windows, and stability will be necessary to assess the suitability of these markers for routine application. PMID: 30548573 [PubMed - as supplied by publisher]

Clinical implementation of gene panel testing for lysosomal storage diseases.

Sat, 15/12/2018 - 13:32
Clinical implementation of gene panel testing for lysosomal storage diseases. Mol Genet Genomic Med. 2018 Dec 11;: Authors: Gheldof A, Seneca S, Stouffs K, Lissens W, Jansen A, Laeremans H, Verloo P, Schoonjans AS, Meuwissen M, Barca D, Martens G, De Meirleir L Abstract BACKGROUND: The diagnostic workup in patients with a clinical suspicion of lysosomal storage diseases (LSD) is often difficult due to the variability in the clinical phenotype. The gold standard for diagnosis of LSDs consists of enzymatic testing. However, due to the sequential nature of this methodology and inconsistent genotype-phenotype correlations of certain LSDs, finding a diagnosis can be challenging. METHOD: We developed and clinically implemented a gene panel covering 50 genes known to cause LSDs when mutated. Over a period of 18 months, we analyzed 150 patients who were referred for LSD testing and compared these results with the data of patients who were previously enrolled in a scheme of classical biochemical testing. RESULTS: Our panel was able to determine the molecular cause of the disease in 22 cases (15%), representing an increase in diagnostic yield compared to biochemical tests developed for 21 LSDs (4.6%). We were furthermore able to redirect the diagnosis of a mucolipidosis patient who was initially suspected to be affected with galactosialidosis. Several patients were identified as being affected with neuronal ceroid lipofuscinosis, which cannot readily be detected by enzyme testing. Finally, several carriers of pathogenic mutations in LSD genes related to the disease phenotype were identified as well, thus potentially increasing the diagnostic yield of the panel as heterozygous deletions cannot be detected. CONCLUSION: We show that the implementation of a gene panel for LSD diagnostics results in an increased yield in comparison to classical biochemical testing. As the panel is able to cover a wider range of diseases, we propose to implement this methodology as a first-tier test in cases of an aspecific LSD presentation, while enzymatic testing remains the first choice in patients with a more distinctive clinical presentation. Positive panel results should however still be enzymatically confirmed whenever possible. PMID: 30548430 [PubMed - as supplied by publisher]

figHigh Spatial Resolution MALDI-MS Imaging in the Study of Membranous Nephropathy.

Sat, 15/12/2018 - 13:32
figHigh Spatial Resolution MALDI-MS Imaging in the Study of Membranous Nephropathy. Proteomics Clin Appl. 2018 Dec 07;:e1800016 Authors: Smith A, L'Imperio V, Denti V, Mazza M, Ivanova M, Stella M, Piga I, Chinello C, Ajello E, Pieruzzi F, Pagni F, Magni F Abstract MALDI-MSI technology has advanced rapidly during recent years with the development of instruments equipped with low-diameter lasers that are suitable for high spatial resolution imaging. This may provide significant advantages in certain fields of molecular pathology where more specific protein fingerprints of individual cell types are required, such as renal pathology. Here we performed MALDI-MSI analysis of a cohort of MN patients among which patients either responded favourably (R; n = 6), or unfavourably (NR; n = 4), to immunosuppressive treatment (Ponticelli Regimen), employing a 10μm laser spot diameter. Specific tryptic peptide profiles of the different cellular regions within the glomerulus could be generated, similarly for the epithelial cells belonging to the proximal and distal tubules. Conversely, specific glomerular and sub-glomerular profiles could not be obtained whilst using the pixel size performed in previous studies (50μm). Furthermore, we highlight two proteins, Sonic Hedgehog (SHH) and α-smooth muscle actin (α-SMA), whose signal intensity and spatial localisation within the sub-glomerular and tubulointerstitial compartments differed between treatment responders and non-responders. The current study exemplifies the advantage of using high spatial resolution MALDI-MSI for the study of MN and highlights that such findings have the potential to provide complimentary support in the routine prognostic assessment of MN patients. This article is protected by copyright. All rights reserved. PMID: 30548219 [PubMed - as supplied by publisher]

Serum metabolic signatures in patients with overt hepatic encephalopathy.

Sat, 15/12/2018 - 13:32
Related Articles Serum metabolic signatures in patients with overt hepatic encephalopathy. J Hepatol. 2017 11;67(5):1114-1115 Authors: Stengel S, Stallmach A, Richter K, Landrock A, Hampe J, Bruns T PMID: 28690175 [PubMed - indexed for MEDLINE]

metabolomics; +42 new citations

Fri, 14/12/2018 - 22:16
42 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 2018/12/14PubMed 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.

Assessing the potential of sputtered gold nanolayers in mass spectrometry imaging for metabolomics applications.

Thu, 13/12/2018 - 12:41
Assessing the potential of sputtered gold nanolayers in mass spectrometry imaging for metabolomics applications. PLoS One. 2018;13(12):e0208908 Authors: Ràfols P, Vilalta D, Torres S, Calavia R, Heijs B, McDonnell LA, Brezmes J, Del Castillo E, Yanes O, Ramírez N, Correig X Abstract Mass spectrometry imaging (MSI) is a molecular imaging technique that maps the distribution of molecules in biological tissues with high spatial resolution. The most widely used MSI modality is matrix-assisted laser desorption/ionization (MALDI), mainly due to the large variety of analyte classes amenable for MALDI analysis. However, the organic matrices used in classical MALDI may impact the quality of the molecular images due to limited lateral resolution and strong background noise in the low mass range, hindering its use in metabolomics. Here we present a matrix-free laser desorption/ionization (LDI) technique based on the deposition of gold nanolayers on tissue sections by means of sputter-coating. This gold coating method is quick, fully automated, reproducible, and allows growing highly controlled gold nanolayers, necessary for high quality and high resolution MS image acquisition. The performance of the developed method has been tested through the acquisition of MS images of brain tissues. The obtained spectra showed a high number of MS peaks in the low mass region (m/z below 1000 Da) with few background peaks, demonstrating the ability of the sputtered gold nanolayers of promoting the desorption/ionization of a wide range of metabolites. These results, together with the reliable MS spectrum calibration using gold peaks, make the developed method a valuable alternative for MSI applications. PMID: 30540827 [PubMed - in process]

Sports Injuries: Diagnosis, Prevention, Stem Cell Therapy, and Medical Sport Strategy.

Thu, 13/12/2018 - 12:41
Related Articles Sports Injuries: Diagnosis, Prevention, Stem Cell Therapy, and Medical Sport Strategy. Adv Exp Med Biol. 2018 Dec 12;: Authors: Rahim S, Rahim F, Shirbandi K, Haghighi BB, Arjmand B Abstract Sports injuries diagnosis, prevention, and treatment are the most important issues of sports medicine. Fortunately, sports injuries are often treated effectively, and people with damage recover and return to the sport in a satisfactory condition. Meanwhile, many sports injuries and complications can be prevented. In general, sports injuries include acute or chronic injuries. Given increasing in popularity, sports medicine doctors use stem cells to treat a wide variety of sports injuries, including damage to tendons, ligaments, muscles, and cartilage. Stem cell therapy to an injured area could be done through direct surgical application, stem-cell-bearing sutures, and injection. Stem cell therapy holds potential for repair and functional plasticity following sports injuries compared to traditional methods; however, the mechanism of stem cell therapy for sports injuries remains largely unknown. Medical imaging technologies provide the hope to ample the knowledge concerning basic stem cell biology in real time when transplanted into sport-induced damaged organs. Using stem cell treatment might restore continuity and regeneration and promote growth back the organ targets. Besides, using a noninvasive medical imaging method would have the long-time monitoring advantage to the stem cells transplanting individual. The multimodality imaging technique allows for studying acute pathological events following sports injuries; therefore, the use of imaging techniques in medicine permits the straight examination of dynamic regenerative events of specific stem cells following a sports injury in people. PMID: 30539427 [PubMed - as supplied by publisher]

International Space Station conditions alter genomics, proteomics, and metabolomics in Aspergillus nidulans.

Thu, 13/12/2018 - 12:41
Related Articles International Space Station conditions alter genomics, proteomics, and metabolomics in Aspergillus nidulans. Appl Microbiol Biotechnol. 2018 Dec 12;: Authors: Romsdahl J, Blachowicz A, Chiang AJ, Chiang YM, Masonjones S, Yaegashi J, Countryman S, Karouia F, Kalkum M, Stajich JE, Venkateswaran K, Wang CCC Abstract The first global genomic, proteomic, and secondary metabolomic characterization of the filamentous fungus Aspergillus nidulans following growth onboard the International Space Station (ISS) is reported. The investigation included the A. nidulans wild-type and three mutant strains, two of which were genetically engineered to enhance secondary metabolite production. Whole genome sequencing revealed that ISS conditions altered the A. nidulans genome in specific regions. In strain CW12001, which features overexpression of the secondary metabolite global regulator laeA, ISS conditions induced the loss of the laeA stop codon. Differential expression of proteins involved in stress response, carbohydrate metabolic processes, and secondary metabolite biosynthesis was also observed. ISS conditions significantly decreased prenyl xanthone production in the wild-type strain and increased asperthecin production in LO1362 and CW12001, which are deficient in a major DNA repair mechanism. These data provide valuable insights into the adaptation mechanism of A. nidulans to spacecraft environments. PMID: 30539259 [PubMed - as supplied by publisher]

Occurrence and Dynamism of Lactic Acid Bacteria in Distinct Ecological Niches: A Multifaceted Functional Health Perspective.

Thu, 13/12/2018 - 12:41
Related Articles Occurrence and Dynamism of Lactic Acid Bacteria in Distinct Ecological Niches: A Multifaceted Functional Health Perspective. Front Microbiol. 2018;9:2899 Authors: George F, Daniel C, Thomas M, Singer E, Guilbaud A, Tessier FJ, Revol-Junelles AM, Borges F, Foligné B Abstract Lactic acid bacteria (LAB) are representative members of multiple ecosystems on earth, displaying dynamic interactions within animal and plant kingdoms in respect with other microbes. This highly heterogeneous phylogenetic group has coevolved with plants, invertebrates, and vertebrates, establishing either mutualism, symbiosis, commensalism, or even parasitism-like behavior with their hosts. Depending on their location and environment conditions, LAB can be dominant or sometimes in minority within ecosystems. Whatever their origins and relative abundance in specific anatomic sites, LAB exhibit multifaceted ecological and functional properties. While some resident LAB permanently inhabit distinct animal mucosal cavities, others are provided by food and may transiently occupy the gastrointestinal tract. It is admitted that the overall gut microbiome has a deep impact on health and diseases. Here, we examined the presence and the physiological role of LAB in the healthy human and several animal microbiome. Moreover, we also highlighted some dysbiotic states and related consequences for health, considering both the resident and the so-called "transionts" microorganisms. Whether LAB-related health effects act collectively or follow a strain-specificity dogma is also addressed. Besides the highly suggested contribution of LAB to interplay with immune, metabolic, and even brain-axis regulation, the possible involvement of LAB in xenobiotic detoxification processes and metal equilibrium is also tackled. Recent technological developments such as functional metagenomics, metabolomics, high-content screening and design in vitro and in vivo experimental models now open new horizons for LAB as markers applied for disease diagnosis, susceptibility, and follow-up. Moreover, identification of general and more specific molecular mechanisms based on antioxidant, antimicrobial, anti-inflammatory, and detoxifying properties of LAB currently extends their selection and promising use, either as probiotics, in traditional and functional foods, for dedicated treatments and mostly for maintenance of normobiosis and homeostasis. PMID: 30538693 [PubMed]

Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma.

Thu, 13/12/2018 - 12:41
Related Articles Integrated multi-omics characterization reveals a distinctive metabolic signature and the role of NDUFA4L2 in promoting angiogenesis, chemoresistance, and mitochondrial dysfunction in clear cell renal cell carcinoma. Aging (Albany NY). 2018 Dec 11;: Authors: Lucarelli G, Rutigliano M, Sallustio F, Ribatti D, Giglio A, Signorile ML, Grossi V, Sanese P, Napoli A, Maiorano E, Bianchi C, Perego RA, Ferro M, Ranieri E, Serino G, Bell LN, Ditonno P, Simone C, Battaglia M Abstract An altered metabolism is involved in the development of clear cell - renal cell carcinoma (ccRCC), and in this tumor many altered genes play a fundamental role in controlling cell metabolic activities. We delineated a large-scale metabolomic profile of human ccRCC, and integrated it with transcriptomic data to connect the variations in cancer metabolism with gene expression changes. Moreover, to better analyze the specific contribution of metabolic gene alterations potentially associated with tumorigenesis and tumor progression, we evaluated the transcription profile of primary renal tumor cells. Untargeted metabolomic analysis revealed a signature of an increased glucose uptake and utilization in ccRCC. In addition, metabolites related to pentose phosphate pathway were also altered in the tumor samples in association with changes in Krebs cycle intermediates and related metabolites. We identified NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) as the most highly expressed gene in renal cancer cells and evaluated its role in sustaining angiogenesis, chemoresistance, and mitochondrial dysfunction. Finally, we showed that silencing of NDUFA4L2 affects cell viability, increases mitochondrial mass, and induces ROS generation in hypoxia. PMID: 30538212 [PubMed - as supplied by publisher]

Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis.

Thu, 13/12/2018 - 12:41
Related Articles Mutant ASXL1 cooperates with BAP1 to promote myeloid leukaemogenesis. Nat Commun. 2018 07 16;9(1):2733 Authors: Asada S, Goyama S, Inoue D, Shikata S, Takeda R, Fukushima T, Yonezawa T, Fujino T, Hayashi Y, Kawabata KC, Fukuyama T, Tanaka Y, Yokoyama A, Yamazaki S, Kozuka-Hata H, Oyama M, Kojima S, Kawazu M, Mano H, Kitamura T Abstract ASXL1 mutations occur frequently in myeloid neoplasms and are associated with poor prognosis. However, the mechanisms by which mutant ASXL1 induces leukaemogenesis remain unclear. In this study, we report mutually reinforcing effects between a C-terminally truncated form of mutant ASXL1 (ASXL1-MT) and BAP1 in promoting myeloid leukaemogenesis. BAP1 expression results in increased monoubiquitination of ASXL1-MT, which in turn increases the catalytic function of BAP1. This hyperactive ASXL1-MT/BAP1 complex promotes aberrant myeloid differentiation of haematopoietic progenitor cells and accelerates RUNX1-ETO-driven leukaemogenesis. Mechanistically, this complex induces upregulation of posterior HOXA genes and IRF8 through removal of H2AK119 ubiquitination. Importantly, BAP1 depletion inhibits posterior HOXA gene expression and leukaemogenicity of ASXL1-MT-expressing myeloid leukemia cells. Furthermore, BAP1 is also required for the growth of MLL-fusion leukemia cells with posterior HOXA gene dysregulation. These data indicate that BAP1, which has long been considered a tumor suppressor, in fact plays tumor-promoting roles in myeloid neoplasms. PMID: 30013160 [PubMed - indexed for MEDLINE]

The gut microbiota and its potential role in obesity.

Thu, 13/12/2018 - 12:41
Related Articles The gut microbiota and its potential role in obesity. Future Microbiol. 2018 04;13:589-603 Authors: Shabana, Shahid SU, Irfan U Abstract The human GI tract harbors a diverse and dynamic microbial community comprising bacteria, archaea, viruses and eukaryotic microbes, which varies in composition from individual to individual. A healthy microbiota metabolizes various indigestible dietary components of the host, maintains host immune homeostasis and nutrient intake, but, an imbalanced microbiota has been reported to be associated with many diseases, including obesity. Rodent studies have produced evidence in support of the causal role of the gut microbiota in the development of obesity, however, such causal relationship is lacking in humans. The objective of this review is to critically analyze the vast information available on the composition, function and alterations of the gut microbiota in obesity and explore the future prospects of this research area. PMID: 29533087 [PubMed - indexed for MEDLINE]

Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy.

Thu, 13/12/2018 - 12:41
Related Articles Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy. Eur J Nucl Med Mol Imaging. 2018 05;45(5):727-734 Authors: Su TP, Lin G, Huang YT, Liu FY, Wang CC, Chao A, Chou HH, Yen TC, Lai CH Abstract PURPOSE: Our purpose was to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) and pelvic/abdominal magnetic resonance imaging (MRI) after concurrent chemoradiotherapy (CCRT) for posttherapy evaluation in patients with advanced cervical cancer. METHODS: Patients with cervical squamous cell carcinoma, either with advanced FIGO stage or with positive pelvic or para-aortic lymph node (PALN), received PET/CT using [18F]fluorodeoxyglucose and MRI including diffusion-weighted imaging between 2 and 3 months after CCRT completion. PET/CT were interpreted independently by two nuclear medicine physicians and MRI by two radiologists using the same scoring system. Active residual tumor was proven by pathological confirmation or disease progression on imaging studies within one year after CCRT and the disease regions were classified as local, regional, PALN, or distant. Patient-based and region-based comparison was performed using the receiver operating characteristic curve analysis. RESULTS: The study included 55 patients and 15 (27%) patients had active residual tumor. The diagnostic performance of PET/CT is significantly superior to that of MRI in patient-based analysis (P = 0.025) and in the detection of local (P = 0.045) and regional (P = 0.014) disease. The patient-based sensitivity, specificity, and accuracy of PET/CT are 60%, 100%, and 89% while those of MRI are 27%, 100%, and 80%. CONCLUSIONS: PET/CT is superior to MRI for posttherapy evaluation in patients with advanced cervical cancer 2-3 months after definitive CCRT, mainly for the detection of residual local and regional disease. Patients with negative or equivocal results should be followed up regularly due to suboptimal sensitivities of imaging. PMID: 29159572 [PubMed - indexed for MEDLINE]

Editorial:Combination of Mass Spectrometry and Omics/Chemometrics Approaches to Unravel Bioactives in Natural Products Mixtures.

Thu, 13/12/2018 - 12:41
Related Articles Editorial:Combination of Mass Spectrometry and Omics/Chemometrics Approaches to Unravel Bioactives in Natural Products Mixtures. Comb Chem High Throughput Screen. 2017;20(4):278 Authors: Calderon AI PMID: 28917074 [PubMed - indexed for MEDLINE]

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