PubMed

Isolation, purification and characterization of proteinaceous fungal α-amylase inhibitor from rhizome of Cheilocostus speciosus (J.Koenig) C.D.Specht. Int J Biol Macromol. 2018 Jan 02;: Authors: Balasubramanian A, Bhattacharjee M, Sakthivel M, Thirumavalavan M, Madhavan T, Nagarajan SK, Palaniyandi V, Raman P Abstract As the aim of this present study, a proteinaceous α-amylase inhibitor has been isolated from the rhizome of Cheilocostus specious (C. speciosus) and was purified using DEAE cellulose anion exchange chromatography followed by gel filtration using Sephacryl-S-200 column. The purity and molecular mass of the purified inhibitor was determined by SDS-PAGE and LC-MS respectively. The molecular mass of the purified inhibitor was determined to be 31.18kDa. Protein-protein docking was also carried out as molecular model. Model validation methods such as Ramachandran plot and Z-score plot were adopted to validate the structural description (sequence analysis) of proteins. The inhibitory activity was confirmed using spectrophotometric and reverse zymogram analyses. This 31.18kDa protein from C. speciosus inhibited the activity of fungal α-amylase by 71% at the level of ion exchange chromatography and 96% after gel filtration. The inhibition activity of the α-amylase inhibitor was stable and high at optimum pH6 (52.2%) and temperatures of 30-40°C (72.2%). Thus it was suggested that the main responsible for the versatile biological and pharmacological activities of C. speciosus is due to its primary metabolites (proteins) only. PMID: 29305211 [PubMed - as supplied by publisher]

Related Articles Metabolomics technology and bioinformatics for precision medicine. Brief Bioinform. 2018 Jan 03;: Authors: Azad RK, Shulaev V Abstract Precision medicine is rapidly emerging as a strategy to tailor medical treatment to a small group or even individual patients based on their genetics, environment and lifestyle. Precision medicine relies heavily on developments in systems biology and omics disciplines, including metabolomics. Combination of metabolomics with sophisticated bioinformatics analysis and mathematical modeling has an extreme power to provide a metabolic snapshot of the patient over the course of disease and treatment or classifying patients into subpopulations and subgroups requiring individual medical treatment. Although a powerful approach, metabolomics have certain limitations in technology and bioinformatics. We will review various aspects of metabolomics technology and bioinformatics, from data generation, bioinformatics analysis, data fusion and mathematical modeling to data management, in the context of precision medicine. PMID: 29304189 [PubMed - as supplied by publisher]

Related Articles Integration of metabolomics and transcriptomics in nanotoxicity studies. BMB Rep. 2018 Jan 05;: Authors: Shin TH, Lee DY, Lee HS, Park HJ, Jin MS, Paik MJ, Manavalan B, Mo JS, Lee G Abstract Biomedical research involving nanoparticles has produced useful products with medical applications. However, the potential toxicity of nanoparticles in biofluids, cells, tissues, and organisms is a major challenge. The '-omics' analyses provide molecular profiles of multifactorial biological systems instead of focusing on a single molecule. The 'omics' approaches are necessary to evaluate nanotoxicity because classical methods for the detection of nanotoxicity have limited ability in detecting miniscule variations within a cell and do not accurately reflect the actual levels of nanotoxicity. In addition, the 'omics' approaches allow analyses of in-depth changes and compensate for the differences associated with high-throughput technologies between actual nanotoxicity and results from traditional cytotoxic evaluations. However, compared with a single omics approach, integrated omics provides precise and sensitive information by integrating complex biological conditions. Thus, these technologies contribute to extended safety evaluations of nanotoxicity and allow the accurate diagnoses of diseases far earlier than was once possible in the nanotechnology era. Here, we review a novel approach for evaluating nanotoxicity by integrating metabolomics with metabolomic profiling and transcriptomics, which is termed "metabotranscriptomics." PMID: 29301609 [PubMed - as supplied by publisher]

Related Articles A quantitative multimodal metabolomic assay for colorectal cancer. BMC Cancer. 2018 Jan 04;18(1):26 Authors: Farshidfar F, Kopciuk KA, Hilsden R, McGregor SE, Mazurak VC, Buie WD, MacLean A, Vogel HJ, Bathe OF Abstract BACKGROUND: Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. METHODS: The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. RESULTS: The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93-1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72-0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. CONCLUSION: The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker. PMID: 29301511 [PubMed - in process]

Related Articles SistematX, an Online Web-Based Cheminformatics Tool for Data Management of Secondary Metabolites. Molecules. 2018 Jan 03;23(1): Authors: Scotti MT, Herrera-Acevedo C, Oliveira TB, Costa RPO, Santos SYKO, Rodrigues RP, Scotti L, Da-Costa FB Abstract The traditional work of a natural products researcher consists in large part of time-consuming experimental work, collecting biota to prepare and analyze extracts and to identify innovative metabolites. However, along this long scientific path, much information is lost or restricted to a specific niche. The large amounts of data already produced and the science of metabolomics reveal new questions: Are these compounds known or new? How fast can this information be obtained? To answer these and other relevant questions, an appropriate procedure to correctly store information on the data retrieved from the discovered metabolites is necessary. The SistematX (http://sistematx.ufpb.br) interface is implemented considering the following aspects: (a) the ability to search by structure, SMILES (Simplified Molecular-Input Line-Entry System) code, compound name and species; (b) the ability to save chemical structures found by searching; (c) compound data results include important characteristics for natural products chemistry; and (d) the user can find specific information for taxonomic rank (from family to species) of the plant from which the compound was isolated, the searched-for molecule, and the bibliographic reference and Global Positioning System (GPS) coordinates. The SistematX homepage allows the user to log into the data management area using a login name and password and gain access to administration pages. In this article, we introduced a modern and innovative web interface for the management of a secondary metabolite database. With its multiplatform design, it is able to be properly consulted via the internet and managed from any accredited computer. The interface provided by SistematX contains a wealth of useful information for the scientific community about natural products, highlighting the locations of species from which compounds are isolated. PMID: 29301376 [PubMed - in process]

Related Articles Identification of Conserved and Diverse Metabolic Shift of the Stylar, Intermediate and Peduncular Segments of Cucumber Fruit during Development. Int J Mol Sci. 2018 Jan 03;19(1): Authors: Hu C, Zhao H, Wang W, Xu M, Shi J, Nie X, Yang G Abstract Cucumber (Cucumis sativus L.) is one of the most important vegetables and contains a high content of nutritionally beneficial metabolites. However, little is known about the metabolic variations among different parts of cucumber fruit and their kinetics during growth. In this study, the dynamic metabolic profiles in the stylar end, the intermediate segment and the peduncular end of cucumber fruit during the development were investigated by employing a non-targeted metabolomics approach, where 238 metabolites were identified. Statistical analyses revealed that both development time and tissue type influenced metabolic changes, while development time seemed to exert more effects than tissue type on the cucumber fruit metabolome. The levels of the most of the detected metabolites decreased gradually, while those of some amino acids, carbohydrates and flavonoids increased across development. The metabolomes of the stylar end and the intermediate segment were similar, although all three parts of the cucumber fruit were separated from each other in orthogonal partial least squares projection to latent structures-discriminant analysis (OPLS-DA) plots. Metabolites association analysis revealed that sn-1 and sn-2 lysophospholipids are synthesized via independent pathways in cucumber fruit. In sum, this study demonstrated both conserved and diverse metabolic kinetics of three parts of cucumber fruit, which will facilitate further study of the regulation of cucumber fruit development as well as their potential applications in nutritious quality improvement of cucumber fruit. PMID: 29301359 [PubMed - in process]

Related Articles Guaianolide sesquiterpene lactones and aporphine alkaloids from the stem bark of Guatteria friesiana. Phytochemistry. 2018 Jan;145:18-25 Authors: Costa EV, Soares LN, Pinheiro MLB, Maia BHLNS, Marques FA, Barison A, Almeida JRGS, Sousa IL, Galaverna RS, Heerdt G, Morgon NH, Acho LDR, Lima ES, da Silva FMA, Koolen HHF Abstract Three guaianolide sesquiterpenes, denoted guatterfriesols A-C, and four aporphine alkaloid derivatives were isolated from the stem bark of the Amazonian plant Guatteria friesiana. Thus far, sesquiterpene lactones have not been described in Annonaceae. Structures of the previously undescribed compounds were established by using 1D and 2D NMR spectroscopy in combination with MS. The absolute stereochemistry was assigned via NOE NMR experiments, ECD spectroscopy, and theoretical calculations using the TDDFT approach. Among the isolated compounds, the alkaloid guatterfriesidine showed anti-glycation activity by inhibiting the formation of advanced glycation end-products (AGEs) through the prevention of oxidation in both BSA/methylglyoxal and BSA/fructose systems. PMID: 29059536 [PubMed - indexed for MEDLINE]

Related Articles Characterization of a protein-bound polysaccharide from Herba Epimedii and its metabolic mechanism in chronic fatigue syndrome. J Ethnopharmacol. 2017 May 05;203:241-251 Authors: Chi A, Shen Z, Zhu W, Sun Y, Kang Y, Guo F Abstract OBJECTIVES: Herba Epimedii is one of the famous Traditional Chinese Medicines used to treat the chronic fatigue syndrome (CFS). The polysaccharides are the main active components in H. epimedii. The aim of this study is to discover the therapeutic effect and metabolic mechanism of H. epimedii polysaccharides against CFS. METHODS: The polysaccharide conjugates named HEP2-a were isolated from the leaves of H. epimedii using a water extraction method, and the general physicochemical properties of HEP2-a were analysed. In addition, a CFS rat model was established, and then, urinary metabonomic studies were performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) in combination with multivariate statistical analysis. RESULTS: The physicochemical properties revealed that HEP2-a had an average molecular weight of 13.6×104Da and consisted of mannose (4.41%), rhamnose (5.43%), glucose (31.26%), galactose (27.07%), arabinose (23.43%), and galacturonic acid (8.40%). The amino acids in HEP2-a include glutamate, cysteine, leucine, tyrosine, lysine, and histidine. Molecular morphology studies revealed many highly curled spherical particles with diameters of 5-10µm in solids and 100-200nm for particles in water. Five metabolites in the HEP2-a group were oppositely and significantly changed compared to the CFS model group. CONCLUSION: Two metabolic pathways were identified as significant metabolic pathways involved with HEP2-a. The therapeutic effects of HEP2-a on CFS were partially due to the restoration of these disturbed pathways. PMID: 28359851 [PubMed - indexed for MEDLINE]

Related Articles Adulteration of herbal sexual enhancers and slimmers: The wish for better sexual well-being and perfect body can be risky. Food Chem Toxicol. 2017 Oct;108(Pt B):355-364 Authors: Skalicka-Woźniak K, Georgiev MI, Orhan IE Abstract The popularity of herbal medicines and dietary supplements is increasing all over the world due to the many side-effects assigned to synthetic drugs. Herbal remedies should be considered as safe, with no side-effects, but unfortunately, even if they are labelled as natural, large numbers of adulterants, not only with toxic heavy metals but also with undeclared synthetic substances, have been detected up to date. In this review, the most frequent instances of adulteration of herbal medicines and dietary supplements acting as sexual enhancers and slimming products are thoroughly discussed. The great success of synthetic phosphodiesterase type-5 (PDE-5) inhibitory drugs like sildenafil, vardenafil and tadalafil, used for the treatment of erectile dysfunction has made them, as well as their unapproved analogues, popular as adulterants in herbal dietary supplements. The second group among blockbuster products are herbal preparations for slimming purpose, as obesity and gaining weight are major problems worldwide. Here, sibutramine hydrochloride monohydrate, an anti-obesity drug which inhibits serotonergic and noradrenergic reuptake, seems to be the most common adulterant. Together with large numbers of its analogues, thyroid hormones, anorexigens, diuretics, stimulants, and laxative agents are also detected in most of tested diet supplements. PMID: 27338710 [PubMed - indexed for MEDLINE]

Related Articles Serum metabolomic profiling of human gastric cancer and its relationship with the prognosis. Oncotarget. 2017 Dec 15;8(66):110000-110015 Authors: Wang D, Li W, Zou Q, Yin L, Du Y, Gu J, Suo J Abstract Objective: This study was aimed to investigate serum metabolites in gastric cancer (GC) patients and their relationships with the prognosis of GC in order to find potential specific serum biomarkers for GC. Methods: Blood samples of 125 GC patients of unifocal GC at initial stage and 38 healthy people recruited in our hospital from September 2008 to August 2009 were analyzed by using high performance liquid chromatography coupled with electrospray ionization/quadrupole-time-of-flight mass spectrometry (HPLCESI/Q-TOFMS). Multiple statistical methods like principal component analysis (PCA), hierarchical clustering analysis, partial least squares discriminant analysis (PLS-DA), multivariate COX regression analysis, variance analysis and K-M survival curve were applied to analyze the raw obtained mass data in order to analyze the independent prognostic factors of GC. The structures of these metabolites were confirmed by comparing the m/z ratio and ion mode of with the data published from HMDB (www.hmdb.ca) databases. Results: By PLS-DA test, 16 serum metabolites in ESI+ mode of VIP>1 in both test group and validation group could definitely distinguish GC patients from healthy peoples (p<0.05). Multivariate COX regression analysis showed TNM staging, 2,4-hexadienoic acid, 4-methylphenyl dodecanoate and glycerol tributanoate were independent prognostic factors of GC (p<0.05). In the K-M survival analysis, the survival rate in high level group of the 3 selected serum metabolites together or alone was significant lower than in those in low level group (p<0.05). Conclusion: Low serum levels of 2,4-hexadienoic acid, 4-methylphenyl dodecanoate and glycerol tributanoate may be important independent prognostic factors of GC. PMID: 29299125 [PubMed]

Related Articles Potential serum biomarkers and metabonomic profiling of serum in ischemic stroke patients using UPLC/Q-TOF MS/MS. PLoS One. 2017;12(12):e0189009 Authors: Sun H, Zhao J, Zhong D, Li G Abstract BACKGROUND: Stroke still has a high incidence with a tremendous public health burden and it is a leading cause of mortality and disability. However, biomarkers for early diagnosis are absent and the metabolic alterations associated with ischemic stroke are not clearly understood. The objectives of this case-control study are to identify serum biomarkers and explore the metabolic alterations of ischemic stroke. METHODS: Metabonomic analysis was performed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis was employed to study 60 patients with or without ischemic stroke (30 cases and 30 controls). RESULTS: Serum metabolic profiling identified a series of 12 metabolites with significant alterations, and the related metabolic pathways involved glycerophospholipid, sphingolipid, phospholipid, fat acid, acylcarnitine, heme, and purine metabolism. Subsequently, multiple logistic regression analyses of these metabolites showed uric acid, sphinganine and adrenoyl ethanolamide were potential biomarkers of ischemic stroke with an area under the receiver operating characteristic curve of 0.941. CONCLUSIONS: These findings provide insights into the early diagnosis and potential pathophysiology of ischemic stroke. PMID: 29228037 [PubMed - indexed for MEDLINE]

Related Articles The organophosphate malathion disturbs gut microbiome development and the quorum-Sensing system. Toxicol Lett. 2018 Feb;283:52-57 Authors: Gao B, Chi L, Tu P, Bian X, Thomas J, Ru H, Lu K Abstract The gut microbiome has tremendous potential to impact health and disease. Various environmental toxicants, including insecticides, have been shown to alter gut microbiome community structures. However, the mechanism that compositionally and functionally regulates gut microbiota remains unclear. Quorum sensing is known to modulate intra- and interspecies gene expression and coordinate population responses. It is unknown whether quorum sensing is disrupted when environmental toxicants cause perturbations in the gut microbiome community structure. To reveal the response of the quorum-sensing system to environmental exposure, we use a combination of Illumina-based 16S rRNA gene amplicon and shotgun metagenome sequencing to examine the impacts of a widely used organophosphate insecticide, malathion, on the gut microbiome trajectory, quorum sensing system and behaviors related to quorum sensing, such as motility and pathogenicity. Our results demonstrated that malathion perturbed the gut microbiome development, quorum sensing and quorum sensing related behaviors. These findings may provide a novel mechanistic understanding of the role of quorum-sensing in the gut microbiome toxicity of malathion. PMID: 29097220 [PubMed - indexed for MEDLINE]

Related Articles The liver-gut microbiota axis modulates hepatotoxicity of tacrine in the rat. Hepatology. 2018 Jan;67(1):282-295 Authors: Yip LY, Aw CC, Lee SH, Hong YS, Ku HC, Xu WH, Chan JMX, Cheong EJY, Chng KR, Ng AHQ, Nagarajan N, Mahendran R, Lee YK, Browne ER, Chan ECY Abstract The gut microbiota possesses diverse metabolic activities, but its contribution toward heterogeneous toxicological responses is poorly understood. In this study, we investigated the role of the liver-gut microbiota axis in underpinning the hepatotoxicity of tacrine. We employed an integrated strategy combining pharmacokinetics, toxicology, metabonomics, genomics, and metagenomics to elucidate and validate the mechanism of tacrine-induced hepatotoxicity in Lister hooded rats. Pharmacokinetic studies in rats demonstrated 3.3-fold higher systemic exposure to tacrine in strong responders that experienced transaminitis, revealing enhanced enterohepatic recycling of deglucuronidated tacrine in this subgroup, not attributable to variation in hepatic disposition gene expression. Metabonomic studies implicated variations in gut microbial activities that mapped onto tacrine-induced transaminitis. Metagenomics delineated greater deglucuronidation capabilities in strong responders, based on differential gut microbial composition (e.g., Lactobacillus, Bacteroides, and Enterobacteriaceae) and approximately 9% higher β-glucuronidase gene abundance compared with nonresponders. In the validation study, coadministration with oral β-glucuronidase derived from Escherichia coli and pretreatment with vancomycin and imipenem significantly modulated the susceptibility to tacrine-induced transaminitis in vivo. CONCLUSION: This study establishes pertinent gut microbial influences in modifying the hepatotoxicity of tacrine, providing insights for personalized medicine initiatives. (Hepatology 2018;67:282-295). PMID: 28646502 [PubMed - indexed for MEDLINE]

Related Articles Patient-derived antibody recognizes a unique CD43 epitope expressed on all AML and has antileukemia activity in mice. Blood Adv. 2017 Aug 22;1(19):1551-1564 Authors: Gillissen MA, de Jong G, Kedde M, Yasuda E, Levie SE, Moiset G, Hensbergen PJ, Bakker AQ, Wagner K, Villaudy J, van Helden PM, Spits H, Hazenberg MD Abstract Immunotherapy has proven beneficial in many hematologic and nonhematologic malignancies, but immunotherapy for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is hampered by the lack of tumor-specific targets. We took advantage of the tumor-immunotherapeutic effect of allogeneic hematopoietic stem cell transplantation and searched the B-cell repertoire of a patient with a lasting and potent graft-versus-AML response for the presence of AML-specific antibodies. We identified an antibody, AT1413, that was of donor origin and that specifically recognizes a novel sialylated epitope on CD43 (CD43s). Strikingly, CD43s is expressed on all World Health Organization 2008 types of AML and MDS. AT1413 induced antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity of AML cells in vitro. Of note, AT1413 was highly efficacious against AML cells in a humanized mouse model without affecting nonmalignant human myeloid cells, suggesting AT1413 has potential as a therapeutic antibody. PMID: 29296797 [PubMed]

Related Articles Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats. Blood Adv. 2017 Jul 25;1(17):1296-1305 Authors: Reisz JA, Slaughter AL, Culp-Hill R, Moore EE, Silliman CC, Fragoso M, Peltz ED, Hansen KC, Banerjee A, D'Alessandro A Abstract Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg). Steady-state measurements were accompanied by metabolic flux analysis upon tracing of in vivo-injected 13C15N-glutamine or inhibition of glutaminolysis using the anticancer drug CB-839. RBC metabolic phenotypes recapitulated the systemic metabolic reprogramming observed in plasma from the same rodent model. Results indicate that shock RBCs rely on glutamine to fuel glutathione (GSH) synthesis and pyruvate transamination, whereas abrogation of glutaminolysis conferred early mortality and exacerbated lactic acidosis and systemic accumulation of succinate, a predictor of mortality in the military and civilian critically ill populations. Glutamine is here identified as an essential amine group donor in HS RBCs, plasma, liver, and lungs, providing additional rationale for the central role glutaminolysis plays in metabolic reprogramming and survival following severe hemorrhage. PMID: 29296771 [PubMed]

Related Articles Multiplexed targeted proteomic assay to assess coagulation factor concentrations and thrombosis-associated cancer. Blood Adv. 2017 Jun 27;1(15):1080-1087 Authors: Mohammed Y, van Vlijmen BJ, Yang J, Percy AJ, Palmblad M, Borchers CH, Rosendaal FR Abstract The plasma levels of pro- and anticoagulant proteins are important markers for venous thrombosis (VT) risk and can be affected by both genetic and acquired factors, including cancer. Generally, these markers are measured using activity- or antibody-based assays. Targeted proteomics with stable-isotope-labeled internal standards has proven adept at the rapid, multiplex, and precise quantification of proteins in complex biological samples such as plasma. We used liquid chromatography coupled to multiple reaction monitoring (MRM) mass spectrometry to evaluate the concentrations of 31 coagulation- and fibrinolysis-related proteins in plasma from 25 healthy controls, 25 patients with VT, and 25 patients with VT who were also diagnosed with cancer. The concentration level of 1 to 3 proteotypic peptides per protein was determined, and all samples were previously characterized using traditional antibody- or activity-based methods. When comparing the conventional and the MRM strategies, the mean Pearson correlation for the 13 proteins (covered by 36 target peptides) shared between the 2 approaches was 0.77, indicating a good correlation. Additionally, MRM offers higher sensitivity (mean regression slope, 0.81), higher multiplicity in a single run, and good ability to leverage all measurements to discriminate groups using unsupervised clustering, which identified vitamin K antagonist users as well as patients with VT and cancer. The data collected using MRM show that the combination of coagulation factor levels yields signature information on VT and cancer, which was not obvious from a single measurement. These results encourage the further validation and investigation of MRM in profiling protein signature of disease. PMID: 29296750 [PubMed]

Related Articles Metabolic regulations of a decoction of Hedyotis diffusa in acute liver injury of mouse models. Chin Med. 2017;12:35 Authors: Dai M, Wang F, Zou Z, Xiao G, Chen H, Yang H Abstract Background: Dysfunctional metabolisms are contributed to LPS/GALN-induced hepatitis. However, whether Hedyotis diffusa (HD) employs metabolic strategies against hepatitis is unknown. Methods: We use the cytokines expression, levels of serum alanine transaminase and aspartate transaminase, survival and histological analysis to measure the effect of decoction of HD on acute severe hepatitis of mouse induced by LPS/GALN. Meanwhile, we utilize GC/MS-based metabolomics to characterize the variation of metabolomes. Results: The present study shows the relieving liver damage in HD decoction-treated mice. Metabolic category using differential metabolites indicates the lower percentage of carbohydrates in LPS/GALN + HD group than LPS/GALN group, revealing the value of carbohydrate metabolism in HD decoction-administrated mouse liver. Further pathway enrichment analysis proposes that citrate cycle, galactose metabolism, and starch and sucrose metabolism are three important carbohydrate metabolisms that involve in the protective effect of decoction of HD during acute hepatitis. Furthermore, other important enrichment pathways are biosynthesis of unsaturated fatty acids, alanine, aspartate and glutamate metabolism, and arginine and proline metabolism. Fatty acids or amino acids involved in above-mentioned pathways are also detected in high loading distribution on IC01 and IC02, thereby manifesting the significance of these metabolites. Other key metabolites detect in ICA analysis were cholesterol, lactic acid and tryptophan. Conclusions: The variation tendency of above-mentioned metabolites is totally consistent with the protective nature of decoction of HD. These findings give a viewpoint that HD decoction-effected metabolic strategies are linked to underlying mechanisms of decoction of HD and highlight the importance of metabolic mechanisms against hepatitis. PMID: 29296119 [PubMed]

Related Articles Discovery of human cell selective effector molecules using single cell multiplexed activity metabolomics. Nat Commun. 2018 Jan 02;9(1):39 Authors: Earl DC, Ferrell PB, Leelatian N, Froese JT, Reisman BJ, Irish JM, Bachmann BO Abstract Discovering bioactive metabolites within a metabolome is challenging because there is generally little foreknowledge of metabolite molecular and cell-targeting activities. Here, single-cell response profiles and primary human tissue comprise a response platform used to discover novel microbial metabolites with cell-type-selective effector properties in untargeted metabolomic inventories. Metabolites display diverse effector mechanisms, including targeting protein synthesis, cell cycle status, DNA damage repair, necrosis, apoptosis, or phosphoprotein signaling. Arrayed metabolites are tested against acute myeloid leukemia patient bone marrow and molecules that specifically targeted blast cells or nonleukemic immune cell subsets within the same tissue biopsy are revealed. Cell-targeting polyketides are identified in extracts from biosynthetically prolific bacteria, including a previously unreported leukemia blast-targeting anthracycline and a polyene macrolactam that alternates between targeting blasts or nonmalignant cells by way of light-triggered photochemical isomerization. High-resolution cell profiling with mass cytometry confirms response mechanisms and is used to validate initial observations. PMID: 29295987 [PubMed - in process]

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 2018/01/03PubMed 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.

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 2018/01/03PubMed 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.