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1.
Ray O. Bahado-Singh Stewart F. Graham BeomSoo Han Onur Turkoglu James Ziadeh Rupasri Mandal Anil Er David S. Wishart Philip L. Stahel 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):100
Introduction
Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.Objectives
Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.Methods
A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.Results
Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.Conclusion
Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.2.
Kazuyuki Abe Yutaka Nakamura Kohei Yamauchi Makoto Maemondo 《Clinical and molecular allergy : CMA》2018,16(1):9
Background
Single nucleotide polymorphisms (SNPs) in chitinase 3-like 1 (CHI3L1) are associated with bronchial severity and pulmonary function. CHI3L1 proteins are involved in both innate and adaptive immune responses; however, to date, the correlation of these SNPs and their age of onset of bronchial asthma has not been demonstrated.Methods
To address the role of these genetic variations, 390 patients with well-controlled bronchial asthma and living in Japan were recruited, genotyped, and had a pulmonary function test performed on them in this study. To analyze the concentration levels of CHI3L1 protein, bronchial lavage fluids were examined.Results
Forced expiratory volume in one second, %predicted (%FEV1), was significantly decreased in homozygotes of rs1214194 compared to heterozygotes and wild type. The age of onset of adult bronchial asthma was significantly younger in GG homozygotes of rs4950928 and AA homozygotes of rs1214194 than in the other two genotypes. The concentration of CHI3L1 protein in bronchial lavage fluid increased in both homozygotes of rs4950928 and rs1214194.Conclusions
Our study demonstrated that the homozygotes of rs4950928 and rs1214194 of CHI3L1 might predict an early onset of bronchial asthma and have the propensity to promote airway remodeling.Trial registration JMA-IIA00045 remodeling-ICS3.
Background
Children receiving Total Body Irradiation (TBI) in preparation for Hematopoietic Stem Cell Transplantation (HSCT) are at risk for Growth Hormone Deficiency (GHD), which sometimes severely compromises their Final Height (FH). To better represent the impact of such therapies on growth we apply a mathematical model, which accounts both for the gompertzian-like growth trend and the hormone-related ‘spurts’, and evaluate how the parameter values estimated on the children undergoing TBI differ from those of the matched normal population.Methods
25 patients long-term childhood lymphoblastic and myeloid acute leukaemia survivors followed at Pediatric Onco-Hematology, Stem Cell Transplantation and Cellular Therapy Division, Regina Margherita Children’s Hospital (Turin, Italy) were retrospectively analysed for assessing the influence of TBI on their longitudinal growth and for validating a new method to estimate the GH therapy effects. Six were treated with GH therapy after a GHD diagnosis.Results
We show that when TBI was performed before puberty overall growth and pubertal duration were significantly impaired, but such growth limitations were completely reverted in the small sample (6 over 25) of children who underwent GH replacement therapies.Conclusion
Since in principle the model could account for any additional growth ‘spurt’ induced by therapy, it may become a useful ‘simulation’ tool for paediatricians for comparing the predicted therapy effectiveness depending on its timing and dosage.4.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.5.
Manuela Capone Laura Maggi Veronica Santarlasci Maria Caterina Rossi Alessio Mazzoni Gianni Montaini Rolando Cimaz Matteo Ramazzotti Marie Pierre Piccinni Giusi Barra Raffaele De Palma Francesco Liotta Enrico Maggi Sergio Romagnani Francesco Annunziato Lorenzo Cosmi 《Clinical and molecular allergy : CMA》2016,14(1):16
Background
CHI3L1 is a chitinase-like protein without enzymatic activity, produced by activated macrophages, chondrocytes, neutrophils. Recent studies on arthritis, asthma, and inflammatory bowel diseases suggest that chitinases are important in inflammatory processes and tissue remodeling, but their production by human T cells, has never been reported.Methods
A microarray analysis of gene expression profile was performed on Th17 and classic Th1 cell clones and CHI3L1 was found among the up-regulated genes on Th17 cells. Different types of helper T cell clones (TCCs) were then evaluated by Real Time PCR (RT-PCR) for CHI3L1 mRNA expression; protein expression was investigated in cell lysates by western blotting and in cultures supernatants by ELISA. ELISA was also used to measure CHI3L1 in the serum and in the synovial fluid (SF) of juvenile idiopathic arthritis (JIA) patients.Results
At mRNA level CHI3L1 was highly expressed by Th17, Th17/Th1, non classic Th1 and even in Th17/Th2 cell clones, whereas it was virtually absent in CD161? classic Th1 and Th2 TCCs. CHI3L1 was also detected in cell culture supernatants of Th17 and Th17-derived cells but not of classic Th1. Moreover CHI3L1 was higher in the SF than in serum of JIA patients, and it positively correlated with the frequency of Th17 and non-classic Th1 cells in SF. CHI3L1 in SF also positively correlated with the C reactive protein (CRP) serum levels, and with the levels of some proinflammatory cytokines, such as IL-6 and p40, which is the common subunit of IL12 and IL23.Conclusions
Here we describe for the first time CHI3L1 production by T cells owing the Th17 family. Moreover the positive correlation found between the frequency of Th17 and Th17-derived cell subsets and CHI3L1 levels in SF of JIA patients, in agreement with the suggested role of these cells in inflammatory process, candidates CHI3L1 as a possible biological target in JIA treatment.6.
Background
Traumatic brain injury (TBI) represents a critical health problem of which timely diagnosis and treatment remain challenging. TBI is a result of an external force damaging brain tissue, accompanied by delayed pathogenic events which aggravate the injury. Molecular responses to different mild TBI subtypes have not been well characterized. TBI subtype classification is an important step towards the development and application of novel treatments. The computational systems biology approach is proved to be a promising tool in biomarker discovery for central nervous system injury.Results
In this study, we have performed a network-based analysis on gene expression profiles to identify functional gene subnetworks. The gene expression profiles were obtained from two experimental models of injury in rats: the controlled cortical impact and the fluid percussion injury. Our method integrates protein interaction information with gene expression profiles to identify subnetworks of genes as biomarkers. We have demonstrated that the selected gene subnetworks are more accurate to classify the heterogeneous responses to different injury models, compared to conventional analysis using individual marker genes selected without network information.Conclusions
The systems approach can lead to a better understanding of the underlying complexities of the molecular responses after TBI and the identified subnetworks will have important prognostic functions for patients who sustain mild TBIs.7.
Background
In recent years the visualization of biomagnetic measurement data by so-called pseudo current density maps or Hosaka-Cohen (HC) transformations became popular.Methods
The physical basis of these intuitive maps is clarified by means of analytically solvable problems.Results
Examples in magnetocardiography, magnetoencephalography and magnetoneurography demonstrate the usefulness of this method.Conclusion
Hardware realizations of the HC-transformation and some similar transformations are discussed which could advantageously support cross-platform comparability of biomagnetic measurements.8.
Rachel A. Spicer Christoph Steinbeck 《Metabolomics : Official journal of the Metabolomic Society》2018,14(1):16
Introduction
Data sharing is being increasingly required by journals and has been heralded as a solution to the ‘replication crisis’.Objectives
(i) Review data sharing policies of journals publishing the most metabolomics papers associated with open data and (ii) compare these journals’ policies to those that publish the most metabolomics papers.Methods
A PubMed search was used to identify metabolomics papers. Metabolomics data repositories were manually searched for linked publications.Results
Journals that support data sharing are not necessarily those with the most papers associated to open metabolomics data.Conclusion
Further efforts are required to improve data sharing in metabolomics.9.
Jamie V. de Seymour Stephanie Tu Xiaoling He Hua Zhang Ting-Li Han Philip N. Baker Karolina Sulek 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):79
Introduction
Intrahepatic cholestasis of pregnancy (ICP) is a common maternal liver disease; development can result in devastating consequences, including sudden fetal death and stillbirth. Currently, recognition of ICP only occurs following onset of clinical symptoms.Objective
Investigate the maternal hair metabolome for predictive biomarkers of ICP.Methods
The maternal hair metabolome (gestational age of sampling between 17 and 41 weeks) of 38 Chinese women with ICP and 46 pregnant controls was analysed using gas chromatography–mass spectrometry.Results
Of 105 metabolites detected in hair, none were significantly associated with ICP.Conclusion
Hair samples represent accumulative environmental exposure over time. Samples collected at the onset of ICP did not reveal any metabolic shifts, suggesting rapid development of the disease.10.
Introduction
Untargeted metabolomics is a powerful tool for biological discoveries. To analyze the complex raw data, significant advances in computational approaches have been made, yet it is not clear how exhaustive and reliable the data analysis results are.Objectives
Assessment of the quality of raw data processing in untargeted metabolomics.Methods
Five published untargeted metabolomics studies, were reanalyzed.Results
Omissions of at least 50 relevant compounds from the original results as well as examples of representative mistakes were reported for each study.Conclusion
Incomplete raw data processing shows unexplored potential of current and legacy data.11.
Renato de Souza Pinto Lemgruber Kaspar Valgepea Mark P. Hodson Ryan Tappel Sean D. Simpson Michael Köpke Lars K. Nielsen Esteban Marcellin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(3):35
Introduction
Quantification of tetrahydrofolates (THFs), important metabolites in the Wood–Ljungdahl pathway (WLP) of acetogens, is challenging given their sensitivity to oxygen.Objective
To develop a simple anaerobic protocol to enable reliable THFs quantification from bioreactors.Methods
Anaerobic cultures were mixed with anaerobic acetonitrile for extraction. Targeted LC–MS/MS was used for quantification.Results
Tetrahydrofolates can only be quantified if sampled anaerobically. THF levels showed a strong correlation to acetyl-CoA, the end product of the WLP.Conclusion
Our method is useful for relative quantification of THFs across different growth conditions. Absolute quantification of THFs requires the use of labelled standards.12.
Xiaofeng Yang Zhengxiang Lv Guohua Xie Feng Xue Chao Chen Jianwei Wang 《Biotechnology letters》2018,40(3):521-526
Objective
To determine the efficacy of Helicobacter pylori γ-glutamyl-transpeptidase (GGT) in osteoarthritis (OA) therapy.Results
Oral administration of rats with rGGT alleviated joint pain in the acute phase of iodoacetate (IA)-induced OA. The CXCL1/IL-6 in blood and in articular tissue as well as circulating granulocytes in the recipients of GGT, were reduced. This might be associated with the expansion of regulatory T cells in the inguinal lymph nodes and increased articular IL-10.Conclusion
We provide preclinical evidence that H. pylori GGT may represent a promising candidate for OA therapy.13.
Andrew Brandmaier Sheng-Qi Hou Sandra Demaria Silvia C. Formenti Wen H. Shen 《生物学前沿》2017,12(3):163-174
Background
PTEN is well known to function as a tumor suppressor that antagonizes oncogenic signaling and maintains genomic stability. The PTEN gene is frequently deleted or mutated in human cancers and the wide cancer spectrum associated with PTEN deficiency has been recapitulated in a variety of mouse models of Pten deletion or mutation. Pten mutations are highly penetrant in causing various types of spontaneous tumors that often exhibit resistance to anticancer therapies including immunotherapy. Recent studies demonstrate that PTEN also regulates immune functionality.Objective
To understand the multifaceted functions of PTEN as both a tumor suppressor and an immune regulator.Methods
This review will summarize the emerging knowledge of PTEN function in cancer immunoediting. In addition, the mechanisms underlying functional integration of various PTEN pathways in regulating cancer evolution and tumor immunity will be highlighted.Results
Recent preclinical and clinical studies revealed the essential role of PTEN in maintaining immune homeostasis, which significantly expands the repertoire of PTEN functions. Mechanistically, aberrant PTEN signaling alters the interplay between the immune system and tumors, leading to immunosuppression and tumor escape.Conclusion
Rational design of personalized anti-cancer treatment requires mechanistic understanding of diverse PTEN signaling pathways in modulation of the crosstalk between tumor and immune cells.14.
Nadine Strehmel David Strunk Veronika Strehmel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):135
Introduction
Aqueous–methanol mixtures have successfully been applied to extract a broad range of metabolites from plant tissue. However, a certain amount of material remains insoluble.Objectives
To enlarge the metabolic compendium, two ionic liquids were selected to extract the methanol insoluble part of trunk from Betula pendula.Methods
The extracted compounds were analyzed by LC/MS and GC/MS.Results
The results show that 1-butyl-3-methylimidazolium acetate (IL-Ac) predominantly resulted in fatty acids, whereas 1-ethyl-3-methylimidazolium tosylate (IL-Tos) mostly yielded phenolic structures. Interestingly, bark yielded more ionic liquid soluble metabolites compared to interior wood.Conclusion
From this one can conclude that the application of ionic liquids may expand the metabolic snapshot.15.
Zhongwei Xu Kaimin Xu Shijia Ding Jiao Luo Tingmei Chen Aiguo Zhou Zhenxing Wen Jian Zhang 《Metabolomics : Official journal of the Metabolomic Society》2017,13(6):73
Introduction
Non-traumatic osteonecrosis of the femoral head (NTONFH) is a progressive disease, always leading to hip dysfunction if no early intervention was applied. The difficulty for early diagnosis of NTONFH is due to the slight symptoms at early stages as well as the high cost for screening patients by using magnetic resonance imaging.Objective
The aim was to detect biomarkers of early-stage NTONFH, which was beneficial to the exploration of a cost-effective approach for the early diagnose of the disease.Methods
Metabolomic approaches were employed in this study to detect biomarkers of early-stage NTONFH (22 patients, 23 controls), based on the platform of ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) and the uses of multivariate statistic analysis, putative metabolite identification, metabolic pathway analysis and biomarker analysis.Results
In total, 33 serum metabolites were found altered between NTONFH group and control group. In addition, glycerophospholipid metabolism and pyruvate metabolism were highly associated with the disease.Conclusion
The combination of LysoPC (18:3), l-tyrosine and l-leucine proved to have a high diagnostic value for early-stage NTONFH. Our findings may contribute to the protocol for early diagnosis of NTONFH and further elucidate the underlying mechanisms of the disease.16.
Thijs Welle Anna T. Hoekstra Ineke A. J. J. M. Daemen Celia R. Berkers Matheus O. Costa 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):83
Introduction
Swine dysentery caused by Brachyspira hyodysenteriae is a production limiting disease in pig farming. Currently antimicrobial therapy is the only treatment and control method available.Objective
The aim of this study was to characterize the metabolic response of porcine colon explants to infection by B. hyodysenteriae.Methods
Porcine colon explants exposed to B. hyodysenteriae were analyzed for histopathological, metabolic and pro-inflammatory gene expression changes.Results
Significant epithelial necrosis, increased levels of l-citrulline and IL-1α were observed on explants infected with B. hyodysenteriae.Conclusions
The spirochete induces necrosis in vitro likely through an inflammatory process mediated by IL-1α and NO.17.
Ferran Casbas Pinto Srinivarao Ravipati David A. Barrett T. Charles Hodgman 《Metabolomics : Official journal of the Metabolomic Society》2017,13(7):81
Introduction
It is difficult to elucidate the metabolic and regulatory factors causing lipidome perturbations.Objectives
This work simplifies this process.Methods
A method has been developed to query an online holistic lipid metabolic network (of 7923 metabolites) to extract the pathways that connect the input list of lipids.Results
The output enables pathway visualisation and the querying of other databases to identify potential regulators. When used to a study a plasma lipidome dataset of polycystic ovary syndrome, 14 enzymes were identified, of which 3 are linked to ELAVL1—an mRNA stabiliser.Conclusion
This method provides a simplified approach to identifying potential regulators causing lipid-profile perturbations.18.
Sonia Liggi Christine Hinz Zoe Hall Maria Laura Santoru Simone Poddighe John Fjeldsted Luigi Atzori Julian L. Griffin 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):52
Introduction
Data processing is one of the biggest problems in metabolomics, given the high number of samples analyzed and the need of multiple software packages for each step of the processing workflow.Objectives
Merge in the same platform the steps required for metabolomics data processing.Methods
KniMet is a workflow for the processing of mass spectrometry-metabolomics data based on the KNIME Analytics platform.Results
The approach includes key steps to follow in metabolomics data processing: feature filtering, missing value imputation, normalization, batch correction and annotation.Conclusion
KniMet provides the user with a local, modular and customizable workflow for the processing of both GC–MS and LC–MS open profiling data.19.
Miguel A. Velasco Rafael Raya Luca Muzzioli Daniela Morelli Abraham Otero Marco Iosa Febo Cincotti Eduardo Rocon 《Biomedical engineering online》2017,16(1):74
Background
This paper presents the preliminary results of a novel rehabilitation therapy for cervical and trunk control of children with cerebral palsy (CP) based on serious videogames and physical exercise.Materials
The therapy is based on the use of the ENLAZA Interface, a head mouse based on inertial technology that will be used to control a set of serious videogames with movements of the head.Methods
Ten users with CP participated in the study. Whereas the control group (n = 5) followed traditional therapies, the experimental group (n = 5) complemented these therapies with a series of ten sessions of gaming with ENLAZA to exercise cervical flexion–extensions, rotations and inclinations in a controlled, engaging environment.Results
The ten work sessions yielded improvements in head and trunk control that were higher in the experimental group for Visual Analogue Scale, Goal Attainment Scaling and Trunk Control Measurement Scale (TCMS). Significant differences (27% vs. 2% of percentage improvement) were found between the experimental and control groups for TCMS (p < 0.05). The kinematic assessment shows that there were some improvements in the active and the passive range of motion. However, no significant differences were found pre- and post-intervention.Conclusions
Physical therapy that combines serious games with traditional rehabilitation could allow children with CP to achieve larger function improvements in the trunk and cervical regions. However, given the limited scope of this trial (n = 10) additional studies are needed to corroborate this hypothesis.20.
Nicholas J. Bond Albert Koulman Julian L. Griffin Zoe Hall 《Metabolomics : Official journal of the Metabolomic Society》2017,13(11):128