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

Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response.

Fri, 13/04/2018 - 14:05
Peptide Vaccine Formulation Controls the Duration of Antigen Presentation and Magnitude of Tumor-Specific CD8+ T Cell Response. J Immunol. 2018 Apr 11;: Authors: Khong H, Volmari A, Sharma M, Dai Z, Imo CS, Hailemichael Y, Singh M, Moore DT, Xiao Z, Huang XF, Horvath TD, Hawke DH, Overwijk WW Abstract Despite remarkable progresses in vaccinology, therapeutic cancer vaccines have not achieved their full potential. We previously showed that an excessively long duration of Ag presentation critically reduced the quantity and quality of vaccination-induced T cell responses and subsequent antitumor efficacy. In this study, using a murine model and tumor cell lines, we studied l-tyrosine amino acid-based microparticles as a peptide vaccine adjuvant with a short-term Ag depot function for the induction of tumor-specific T cells. l-Tyrosine microparticles did not induce dendritic cell maturation, and their adjuvant activity was not mediated by inflammasome activation. Instead, prolonged Ag presentation in vivo translated into increased numbers and antitumor activity of vaccination-induced CD8+ T cells. Indeed, prolonging Ag presentation by repeated injection of peptide in saline resulted in an increase in T cell numbers similar to that observed after vaccination with peptide/l-tyrosine microparticles. Our results show that the duration of Ag presentation is critical for optimal induction of antitumor T cells, and can be manipulated through vaccine formulation. PMID: 29643190 [PubMed - as supplied by publisher]

Robust volcano plot: identification of differential metabolites in the presence of outliers.

Fri, 13/04/2018 - 14:05
Robust volcano plot: identification of differential metabolites in the presence of outliers. BMC Bioinformatics. 2018 Apr 11;19(1):128 Authors: Kumar N, Hoque MA, Sugimoto M Abstract BACKGROUND: The identification of differential metabolites in metabolomics is still a big challenge and plays a prominent role in metabolomics data analyses. Metabolomics datasets often contain outliers because of analytical, experimental, and biological ambiguity, but the currently available differential metabolite identification techniques are sensitive to outliers. RESULTS: We propose a kernel weight based outlier-robust volcano plot for identifying differential metabolites from noisy metabolomics datasets. Two numerical experiments are used to evaluate the performance of the proposed technique against nine existing techniques, including the t-test and the Kruskal-Wallis test. Artificially generated data with outliers reveal that the proposed method results in a lower misclassification error rate and a greater area under the receiver operating characteristic curve compared with existing methods. An experimentally measured breast cancer dataset to which outliers were artificially added reveals that our proposed method produces only two non-overlapping differential metabolites whereas the other nine methods produced between seven and 57 non-overlapping differential metabolites. CONCLUSION: Our data analyses show that the performance of the proposed differential metabolite identification technique is better than that of existing methods. Thus, the proposed method can contribute to analysis of metabolomics data with outliers. The R package and user manual of the proposed method are available at https://github.com/nishithkumarpaul/Rvolcano . PMID: 29642836 [PubMed - in process]

Pasture Feeding Changes the Bovine Rumen and Milk Metabolome.

Fri, 13/04/2018 - 14:05
Pasture Feeding Changes the Bovine Rumen and Milk Metabolome. Metabolites. 2018 Apr 06;8(2): Authors: O'Callaghan TF, Vázquez-Fresno R, Serra-Cayuela A, Dong E, Mandal R, Hennessy D, McAuliffe S, Dillon P, Wishart DS, Stanton C, Ross RP Abstract The purpose of this study was to examine the effects of two pasture feeding systems-perennial ryegrass (GRS) and perennial ryegrass and white clover (CLV)-and an indoor total mixed ration (TMR) system on the (a) rumen microbiome; (b) rumen fluid and milk metabolome; and (c) to assess the potential to distinguish milk from different feeding systems by their respective metabolomes. Rumen fluid was collected from nine rumen cannulated cows under the different feeding systems in early, mid and late lactation, and raw milk samples were collected from ten non-cannulated cows in mid-lactation from each of the feeding systems. The microbiota present in rumen liquid and solid portions were analysed using 16S rRNA gene sequencing, while ¹H-NMR untargeted metabolomic analysis was performed on rumen fluid and raw milk samples. The rumen microbiota composition was not found to be significantly altered by any feeding system in this study, likely as a result of a shortened adaptation period (two weeks' exposure time). In contrast, feeding system had a significant effect on both the rumen and milk metabolome. Increased concentrations of volatile fatty acids including acetic acid, an important source of energy for the cow, were detected in the rumen of TMR and CLV-fed cows. Pasture feeding resulted in significantly higher concentrations of isoacids in the rumen. The ruminal fluids of both CLV and GRS-fed cows were found to have increased concentrations of p-cresol, a product of microbiome metabolism. CLV feeding resulted in increased rumen concentrations of formate, a substrate compound for methanogenesis. The TMR feeding resulted in significantly higher rumen choline content, which contributes to animal health and milk production, and succinate, a product of carbohydrate metabolism. Milk and rumen-fluids were shown to have varying levels of dimethyl sulfone in each feeding system, which was found to be an important compound for distinguishing between the diets. CLV feeding resulted in increased concentrations of milk urea. Milk from pasture-based feeding systems was shown to have significantly higher concentrations of hippuric acid, a potential biomarker of pasture-derived milk. This study has demonstrated that ¹H-NMR metabolomics coupled with multivariate analysis is capable of distinguishing both rumen-fluid and milk derived from cows on different feeding systems, specifically between indoor TMR and pasture-based diets used in this study. PMID: 29642378 [PubMed]

Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB.

Fri, 13/04/2018 - 14:05
Related Articles Regulation of Burkholderia cenocepacia biofilm formation by RpoN and the c-di-GMP effector BerB. Microbiologyopen. 2017 Aug;6(4): Authors: Fazli M, Rybtke M, Steiner E, Weidel E, Berthelsen J, Groizeleau J, Bin W, Zhi BZ, Yaming Z, Kaever V, Givskov M, Hartmann RW, Eberl L, Tolker-Nielsen T Abstract Knowledge about the molecular mechanisms that are involved in the regulation of biofilm formation is essential for the development of biofilm-control measures. It is well established that the nucleotide second messenger cyclic diguanosine monophosphate (c-di-GMP) is a positive regulator of biofilm formation in many bacteria, but more knowledge about c-di-GMP effectors is needed. We provide evidence that c-di-GMP, the alternative sigma factor RpoN (σ54), and the enhancer-binding protein BerB play a role in biofilm formation of Burkholderia cenocepacia by regulating the production of a biofilm-stabilizing exopolysaccharide. Our findings suggest that BerB binds c-di-GMP, and activates RpoN-dependent transcription of the berA gene coding for a c-di-GMP-responsive transcriptional regulator. An increased level of the BerA protein in turn induces the production of biofilm-stabilizing exopolysaccharide in response to high c-di-GMP levels. Our findings imply that the production of biofilm exopolysaccharide in B. cenocepacia is regulated through a cascade involving two consecutive transcription events that are both activated by c-di-GMP. This type of regulation may allow tight control of the expenditure of cellular resources. PMID: 28419759 [PubMed - indexed for MEDLINE]

Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish.

Fri, 13/04/2018 - 14:05
Related Articles Transcriptomic, proteomic, and metabolomic landscape of positional memory in the caudal fin of zebrafish. Proc Natl Acad Sci U S A. 2017 01 31;114(5):E717-E726 Authors: Rabinowitz JS, Robitaille AM, Wang Y, Ray CA, Thummel R, Gu H, Djukovic D, Raftery D, Berndt JD, Moon RT Abstract Regeneration requires cells to regulate proliferation and patterning according to their spatial position. Positional memory is a property that enables regenerating cells to recall spatial information from the uninjured tissue. Positional memory is hypothesized to rely on gradients of molecules, few of which have been identified. Here, we quantified the global abundance of transcripts, proteins, and metabolites along the proximodistal axis of caudal fins of uninjured and regenerating adult zebrafish. Using this approach, we uncovered complex overlapping expression patterns for hundreds of molecules involved in diverse cellular functions, including development, bioelectric signaling, and amino acid and lipid metabolism. Moreover, 32 genes differentially expressed at the RNA level had concomitant differential expression of the encoded proteins. Thus, the identification of proximodistal differences in levels of RNAs, proteins, and metabolites will facilitate future functional studies of positional memory during appendage regeneration. PMID: 28096348 [PubMed - indexed for MEDLINE]

Identification and characterization of amiodarone metabolites in rats using UPLC-ESI-QTOFMS-based untargeted metabolomics approach.

Thu, 12/04/2018 - 13:37
Identification and characterization of amiodarone metabolites in rats using UPLC-ESI-QTOFMS-based untargeted metabolomics approach. J Toxicol Environ Health A. 2018 Apr 11;:1-12 Authors: Jeong ES, Kim G, Yim D, Moon KS, Lee SJ, Shin JG, Kim DH Abstract Amiodarone is a class III anti-arrhythmic benzofuran derivative extensively utilized in treatment of life-threatening ventricular and supraventricular arrhythmias. However, amiodarone also produces adverse side effects including liver injury due to its metabolites rather than parent drug. The purpose of the present study was to identify metabolites of amiodarone in the plasma and urine of rats administered the drug by using an untargeted metabolomics approach. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS) and results subjected to multivariate data analysis. A total of 49 amiodarone metabolites were identified and their structures were characterized by tandem mass spectrometry. Amiodarone metabolites are presumed to be generated via five major types of metabolic reactions including N-desethylation, hydroxylation, carboxylation (oxo/hydroxylation), de-iodination, and glucuronidation. Data demonstrated that an untargeted metabolomics approach appeared to be a reliable tool for identifying unknown metabolites in a complex biological matrix. PMID: 29641932 [PubMed - as supplied by publisher]

Transformation, Conjugation, and Sequestration Following the Uptake of Triclocarban by Jalapeno Pepper Plants.

Thu, 12/04/2018 - 13:37
Transformation, Conjugation, and Sequestration Following the Uptake of Triclocarban by Jalapeno Pepper Plants. J Agric Food Chem. 2018 Apr 11;: Authors: Huynh K, Banach E, Reinhold D Abstract Plant uptake and metabolism of emerging organic contaminants, such as personal-care products, pose potential risks to human health. In this study, jalapeno pepper ( Capsicum annuum) plants cultured in hydroponic media were exposed to both 14C-labeled and unlabeled triclocarban (TCC) to investigate the accumulation, distribution, and metabolism of TCC following plant uptake. The results revealed that TCC was detected in all plant tissues; after 12 weeks, the TCC concentrations in root, stem, leaf, and fruit tissues were 19.74 ± 2.26, 0.26 ± 0.04, 0.11 ± 0.01, and 0.03 ± 0.01 mg/kg dry weight, respectively. More importantly, a substantial portion of the TCC taken up by plants was metabolized, especially in the stems, leaves, and fruits. Hydroxylated TCC (e.g., 2'-OH TCC and 6-OH TCC) and glycosylated OH-TCC were the main phase I and phase II metabolites in plant tissues, respectively. Bound (or nonextractable) residues of TCC accounted for approximately 44.6, 85.6, 69.0, and 47.5% of all TCC species that accumulated in roots, stems, leaves, and fruits, respectively. The concentrations of TCC metabolites were more than 20 times greater than the concentrations of TCC in the above-ground tissues of the jalapeno pepper plants after 12 weeks; crucially, approximately 95.6% of the TCC was present as metabolites in the fruits. Consequently, human exposure to TCC through the consumption of pepper fruits is expected to be substantially higher when phytometabolism is considered. PMID: 29637774 [PubMed - as supplied by publisher]

Magnetic Resonance Spectroscopy (MRS)-Based Methods for Examining Cancer Metabolism in Response to Oncogenic Kinase Drug Treatment.

Thu, 12/04/2018 - 13:37
Related Articles Magnetic Resonance Spectroscopy (MRS)-Based Methods for Examining Cancer Metabolism in Response to Oncogenic Kinase Drug Treatment. Methods Mol Biol. 2017;1636:393-404 Authors: Chung YL Abstract Magnetic resonance spectroscopy (MRS) is an analytical technique that has been extensively used to examine reprogrammed metabolism and treatment response in cancer cells and solid tumors both in vivo and ex vivo. High-resolution MRS (HR-MRS) is one of the best methods for metabolic profiling, as it is highly quantitative, robust, and reproducible. The protocols for dual-phase extraction of cancer cells and tumors and sample preparations for high-resolution 1H and 31P HR-MRS analysis are described here. Descriptions of spectra acquisition and analysis are also included in this chapter. PMID: 28730493 [PubMed - indexed for MEDLINE]

Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome.

Thu, 12/04/2018 - 13:37
Related Articles Novel translational approaches to the search for precision therapies for acute respiratory distress syndrome. Lancet Respir Med. 2017 Jun;5(6):512-523 Authors: Meyer NJ, Calfee CS Abstract In the 50 years since acute respiratory distress syndrome (ARDS) was first described, substantial progress has been made in identifying the risk factors for and the pathogenic contributors to the syndrome and in characterising the protein expression patterns in plasma and bronchoalveolar lavage fluid from patients with ARDS. Despite this effort, however, pharmacological options for ARDS remain scarce. Frequently cited reasons for this absence of specific drug therapies include the heterogeneity of patients with ARDS, the potential for a differential response to drugs, and the possibility that the wrong targets have been studied. Advances in applied biomolecular technology and bioinformatics have enabled breakthroughs for other complex traits, such as cardiovascular disease or asthma, particularly when a precision medicine paradigm, wherein a biomarker or gene expression pattern indicates a patient's likelihood of responding to a treatment, has been pursued. In this Review, we consider the biological and analytical techniques that could facilitate a precision medicine approach for ARDS. PMID: 28664850 [PubMed - indexed for MEDLINE]

Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry.

Thu, 12/04/2018 - 13:37
Related Articles Metabolic Profiling of Hoodia, Chamomile, Terminalia Species and Evaluation of Commercial Preparations Using Ultrahigh-Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry. Planta Med. 2017 Nov;83(16):1297-1308 Authors: Avula B, Wang YH, Isaac G, Yuk J, Wrona M, Yu K, Khan IA Abstract Ultrahigh-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UHPLC-QToF-MS) profiling was used for the identification of marker compounds and generation of metabolic patterns that could be interrogated using chemometric modeling software. UHPLC-QToF-MS was used to generate comprehensive fingerprints of three botanicals (Hoodia, Terminalia, and chamomile), each having different classes of compounds. Detection of a broad range of ions was carried out in full scan mode in both positive and negative modes over the range m/z 100-1700 using high-resolution mass spectrometry. Multivariate statistical analysis was used to extract relevant chemical information from the data to easily differentiate between Terminalia species, chamomile varieties, and quality control of Hoodia products. Using nontargeted analysis, identification of 37 compounds contributed to the differences between Terminalia species, 26 flavonoids were identified to show the differences between German and Roman chamomile, and 43 pregnane glycosides were identified from Hoodia gordonii samples. The UHPLC-QToF-MS-based chemical fingerprinting with principal component analysis was able to correctly distinguish botanicals and their commercial products. This work can be used as a basis to assure the quality of botanicals and commercial products. PMID: 28454188 [PubMed - indexed for MEDLINE]

Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer.

Thu, 12/04/2018 - 13:37
Related Articles Lipidomic Profiling of Lung Pleural Effusion Identifies Unique Metabotype for EGFR Mutants in Non-Small Cell Lung Cancer. Sci Rep. 2016 10 14;6:35110 Authors: Ho YS, Yip LY, Basri N, Chong VS, Teo CC, Tan E, Lim KL, Tan GS, Yang X, Yeo SY, Koh MS, Devanand A, Takano A, Tan EH, Tan DS, Lim TK Abstract Cytology and histology forms the cornerstone for the diagnosis of non-small cell lung cancer (NSCLC) but obtaining sufficient tumour cells or tissue biopsies for these tests remains a challenge. We investigate the lipidome of lung pleural effusion (PE) for unique metabolic signatures to discriminate benign versus malignant PE and EGFR versus non-EGFR malignant subgroups to identify novel diagnostic markers that is independent of tumour cell availability. Using liquid chromatography mass spectrometry, we profiled the lipidomes of the PE of 30 benign and 41 malignant cases with or without EGFR mutation. Unsupervised principal component analysis revealed distinctive differences between the lipidomes of benign and malignant PE as well as between EGFR mutants and non-EGFR mutants. Docosapentaenoic acid and Docosahexaenoic acid gave superior sensitivity and specificity for detecting NSCLC when used singly. Additionally, several 20- and 22- carbon polyunsaturated fatty acids and phospholipid species were significantly elevated in the EGFR mutants compared to non-EGFR mutants. A 7-lipid panel showed great promise in the stratification of EGFR from non-EGFR malignant PE. Our data revealed novel lipid candidate markers in the non-cellular fraction of PE that holds potential to aid the diagnosis of benign, EGFR mutation positive and negative NSCLC. PMID: 27739449 [PubMed - indexed for MEDLINE]

metabolomics; +21 new citations

Wed, 11/04/2018 - 22:30
21 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2018/04/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis.

Tue, 10/04/2018 - 12:36
Perturbations in amino acids and metabolic pathways in osteoarthritis patients determined by targeted metabolomics analysis. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Apr 02;1085:54-62 Authors: Chen R, Han S, Liu X, Wang K, Zhou Y, Yang C, Zhang X Abstract Osteoarthritis (OA) is a degenerative synovial joint disease affecting people worldwide. However, the exact pathogenesis of OA remains unclear. Metabolomics analysis was performed to obtain insight into possible pathogenic mechanisms and diagnostic biomarkers of OA. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-MS), followed by multivariate statistical analysis, was used to determine the serum amino acid profiles of 32 OA patients and 35 healthy controls. Variable importance for project values and Student's t-test were used to determine the metabolic abnormalities in OA. Another 30 OA patients were used as independent samples to validate the alterations in amino acids. MetaboAnalyst was used to identify the key amino acid pathways and construct metabolic networks describing their relationships. A total of 25 amino acids and four biogenic amines were detected by UPLC-TQ-MS. Differences in amino acid profiles were found between the healthy controls and OA patients. Alanine, γ-aminobutyric acid and 4-hydroxy-l-proline were important biomarkers distinguishing OA patients from healthy controls. The metabolic pathways with the most significant effects were involved in metabolism of alanine, aspartate, glutamate, arginine and proline. The results of this study improve understanding of the amino acid metabolic abnormalities and pathogenic mechanisms of OA at the molecular level. The metabolic perturbations may be important for the diagnosis and prevention of OA. PMID: 29631251 [PubMed - as supplied by publisher]

Activation of choline kinase drives aberrant choline metabolism in esophageal squamous cell carcinomas.

Tue, 10/04/2018 - 12:36
Activation of choline kinase drives aberrant choline metabolism in esophageal squamous cell carcinomas. J Pharm Biomed Anal. 2018 Mar 31;155:148-156 Authors: Ma W, Wang S, Zhang T, Zhang EY, Zhou L, Hu C, Yu JJ, Xu G Abstract Esophageal squamous cell carcinoma (ESCC) is a major health threat worldwide. Research focused on molecular events associated with ESCC carcinogenesis for diagnosis, treatment and prevention is needed. Our goal is to discover novel biomarkers and investigate the underlying molecular mechanisms of ESCC progression by employing a global metabolomic approach. Sera from 34 ESCC patients and 32 age and sex matched healthy controls were profiled using two-dimensional liquid chromatography-mass spectrometry (2D LC-MS). We identified 120 differential metabolites in ESCC patient serums compared to healthy controls. Several amino acids, serine, arginine, lysine and histidine were significantly changed in ESCC patients. Most importantly, we found dysregulated lipid metabolism as an important characteristic in ESCC patients. Several free fat acids (FFA) and carnitines were found down-regulated in ESCC patients. Choline was significantly increased and phosphatidylcholines (PC) were significantly decreased in ESCC serum. The high expression of choline and low expression of total PC in patient serum were associated with the high expression of choline kinase (Chok) and activated Kennedy pathway in ESCC cells. Chok expression can serve as a significant biomarker for ESCC prognosis. In conclusion, metabolite profiles in the ESCC patient serum were significantly different from those in the healthy controls. Phosphatidylcholines and Chok, the key enzyme in the PC metabolism pathway, may serve as novel biomarkers for ESCC. PMID: 29631075 [PubMed - as supplied by publisher]

Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis.

Tue, 10/04/2018 - 12:36
Aldose reductase inhibitor protects mice from alcoholic steatosis by repressing saturated fatty acid biosynthesis. Chem Biol Interact. 2018 Apr 06;: Authors: Guo C, Chen L, Huang J, Wang Y, Shi C, Gao J, Hong Y, Chen T, Qiu L Abstract Alcoholic liver injury results in morbidity and mortality worldwide, but there are currently no effective and safe therapeutics. Previously we demonstrated that aldose reductase (AR) inhibitor ameliorated alcoholic hepatic steatosis. To clarify the mechanism whereby AR inhibitor improves alcoholic hepatic steatosis, herein we investigated the effect of AR inhibitor on hepatic metabolism in mice fed a Lieber-DeCarli liquid diet with 5% ethanol. Nontargeted metabolomics showed carbohydrates and lipids were characteristic categories in ethanol diet-fed mice with or without AR inhibitor treatment, whereas AR inhibitor mainly affected carbohydrates and amino acids. Ethanol-induced galactose metabolism and fatty acid biosynthesis are important for the induction of hepatic steatosis, while AR inhibitor impaired galactose metabolism without perturbing fatty acid biosynthesis. In parallel with successful treatment of steatosis, AR inhibitor suppressed ethanol-activated galactose metabolism and saturated fatty acid biosynthesis. Sorbitol in galactose metabolism and stearic acid in saturated fatty acid biosynthesis were potential biomarkers responsible for ethanol or ethanol plus AR inhibitor treatment. In vitro analysis confirmed that exogenous addition of sorbitol augmented ethanol-induced steatosis and stearic acid. These findings not only reveal metabolic patterns associated with disease and treatment, but also shed light on functional biomarkers contribute to AR inhibition therapy. PMID: 29630881 [PubMed - as supplied by publisher]

Human epididymis protein 4 in endometrial cancer: A meta-analysis.

Tue, 10/04/2018 - 12:36
Human epididymis protein 4 in endometrial cancer: A meta-analysis. Clin Chim Acta. 2018 Apr 06;: Authors: Li LM, Zhu YX, Zhong Y, Su T, Fan XM, Xi Q, Li MY, Fu J, Tan H, Liu S Abstract BACKGROUND: Serum human epididymis protein 4 (HE4) is a potential marker for endometrial cancer (EC), however, the diagnostic value of HE4 for EC remains controversial. In this study, we performed a meta-analysis to estimate the diagnostic accuracy of serum HE4 for EC. METHODS: Literature reports of the diagnostic accuracy of serum HE4 for EC were systematically identified using online data-bases. The meta-analysis was performed using STATA 12.0, Meta-Disc 1.4, and Review Manager 5.2. RESULTS: A total of 4182 participants and 23 studies were included in our meta-analysis. The pooled sensitivity (SEC), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.65 (95% CI: 0.56-0.73), 0.91 (95% CI: 0.84-0.95), (95% CI: 4.38-12.64), 0.38 (95% CI: 0.31-0.47), 19.46 (95% CI: 11.61-32.62) and 0.84 (95% CI: 0.81 to 0.87), respectively. Our overall analysis suggested that HE4 is a useful diagnostic marker for EC. Subgroup analysis indicated that studies with benign disease controls showed higher diagnostic accuracies than those with healthy controls. CONCLUSION: Serum HE4 may serve as a potential biomarker for EC diagnosis. Due to certain limitations, this conclusion should to be cautiously interpreted. PMID: 29630870 [PubMed - as supplied by publisher]

A rapid and concise setup for the fast screening of FRET pairs using bioorthogonalized fluorescent dyes.

Tue, 10/04/2018 - 12:36
A rapid and concise setup for the fast screening of FRET pairs using bioorthogonalized fluorescent dyes. Org Biomol Chem. 2018 Apr 09;: Authors: Petrovics R, Söveges B, Egyed A, Knorr G, Kormos A, Imre T, Török G, Zeke A, Kocsmár É, Lotz G, Kele P, Németh K Abstract One of the most popular means to follow interactions between bio(macro)molecules is Förster resonance energy transfer (FRET). There is large interest in widening the selection of fluorescent FRET pairs especially in the region of the red/far red range, where minimal autofluorescence is encountered. A set of bioorthogonally applicable fluorescent dyes, synthesized recently in our lab, were paired (Cy3T/Cy5T; Cy1A/Cy3T and Cy1A/CBRD1A) based on their spectral characteristics in order to test their potential in FRET applications. For fast elaboration of the selected pairs we have created a bioorthogonalized platform based on complementary 17-mer DNA oligomers. The cyclooctynylated strands were modified nearly quantitatively with the fluorophores via bioorthogonal chemistry steps, using azide- (Cy1; CBRD1) or tetrazine-modified (Cy3; Cy5) dyes. Reactions were followed by capillary electrophoresis using a method specifically developed for this project. FRET efficiencies of the fluorescent dye pairs were compared both in close proximity (5' and 3' matched) and at larger distance (5' and 5' matched). The specificity of FRET signals was further elaborated by denaturation and competition studies. Cy1A/Cy3T and Cy1A/CBRD1A introduced here as novel FRET pairs are highly recommended for FRET applications based on the significant changes in fluorescence intensities of the donor and acceptor peaks. Application of one of the FRET pairs was demonstrated in live cells, transfected with labeled oligos. Furthermore, the concise installation of the dyes allows for efficient fluorescence modification of any selected DNA strands as was demonstrated in the construction of Cy3T labeled oligomers, which were used in the FISH-based detection of Helicobacter pylori. PMID: 29629719 [PubMed - as supplied by publisher]

Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites?

Tue, 10/04/2018 - 12:36
Related Articles Can Diet Influence Our Health by Altering Intestinal Microbiota-Derived Fecal Metabolites? mSystems. 2018 Mar-Apr;3(2): Authors: Lyu Q, Hsu CC Abstract The human gastrointestinal tract harbors a diverse, highly mutualistic microbial flora which could produce a myriad of specialized metabolites. These specialized metabolites are the chemical cellphones that gut microflora use to communicate with their human host and could potentially be used to cure diseases. Chemical compounds in diet also shape the gut flora. In order to understand which and how the gut microbe-derived specialized metabolites affect human health, the "gut microbiome-metabolomic-human health axis" is thus proposed. In our laboratory, a strategy combining genomic, chemical, phenotypical analyses has been implemented to mine the treasures of bioactive molecules found in our gut and stool. We believe that the cutting edge metabolomics will bridge microbiology and human health. PMID: 29629422 [PubMed]

Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses.

Tue, 10/04/2018 - 12:36
Related Articles Metabolic profiling of isolated mitochondria and cytoplasm reveals compartment-specific metabolic responses. Metabolomics. 2018;14(5):59 Authors: Pan D, Lindau C, Lagies S, Wiedemann N, Kammerer B Abstract Introduction: Subcellular compartmentalization enables eukaryotic cells to carry out different reactions at the same time, resulting in different metabolite pools in the subcellular compartments. Thus, mutations affecting the mitochondrial energy metabolism could cause different metabolic alterations in mitochondria compared to the cytoplasm. Given that the metabolite pool in the cytosol is larger than that of other subcellular compartments, metabolic profiling of total cells could miss these compartment-specific metabolic alterations. Objectives: To reveal compartment-specific metabolic differences, mitochondria and the cytoplasmic fraction of baker's yeast Saccharomyces cerevisiae were isolated and subjected to metabolic profiling. Methods: Mitochondria were isolated through differential centrifugation and were analyzed together with the remaining cytoplasm by gas chromatography-mass spectrometry (GC-MS) based metabolic profiling. Results: Seventy-two metabolites were identified, of which eight were found exclusively in mitochondria and sixteen exclusively in the cytoplasm. Based on the metabolic signature of mitochondria and of the cytoplasm, mutants of the succinate dehydrogenase (respiratory chain complex II) and of the FOF1-ATP-synthase (complex V) can be discriminated in both compartments by principal component analysis from wild-type and each other. These mitochondrial oxidative phosphorylation machinery mutants altered not only citric acid cycle related metabolites but also amino acids, fatty acids, purine and pyrimidine intermediates and others. Conclusion: By applying metabolomics to isolated mitochondria and the corresponding cytoplasm, compartment-specific metabolic signatures can be identified. This subcellular metabolomics analysis is a powerful tool to study the molecular mechanism of compartment-specific metabolic homeostasis in response to mutations affecting the mitochondrial metabolism. PMID: 29628813 [PubMed]

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

Tue, 10/04/2018 - 12:36
Related Articles LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study. Int J Cardiol. 2018 Mar 29;: Authors: Pichler G, Amigo N, Tellez-Plaza M, Pardo-Cea MA, Dominguez-Lucas A, Marrachelli VG, Monleon D, Martin-Escudero JC, Ascaso JF, Chaves FJ, Carmena R, Redon J Abstract BACKGROUND: The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. METHODS: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. RESULTS: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ± 3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. CONCLUSIONS: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD. PMID: 29628276 [PubMed - as supplied by publisher]

Pages