Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.5 (thrombin)
33,306 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Analysis of oxylipins by liquid chromatography mass spectrometry (LC/MS) is challenging because of the small mass range occupied by this diverse lipid class, the presence of numerous structural isomers, and their low abundance in biological samples. Although highly sensitive LC/MS/MS methods are commonly used, further separation is achievable by using drift tube ion mobility coupled with high-resolution mass spectrometry (DTIM-MS). Herein, we present a combined analytical and computational method for the identification of oxylipins and fatty acids. We use a reversed-phase LC/DTIM-MS workflow able to profile and quantify (based on chromatographic peak area) the oxylipin and fatty acid content of biological samples while simultaneously acquiring full scan and product ion spectra. The information regarding accurate mass, collision-cross-section values in nitrogen (^DTCCS_N2), and retention times of the species found are compared to an internal library of lipid standards as well as the LIPID MAPS Structure Database by using specifically developed processing tools. Features detected within the ^DTCCS_N2 and m/ z ranges of the analyzed standards are flagged as oxylipin-like species, which can be further characterized using drift-time alignment of product and precursor ions distinctive of DTIM-MS. This not only helps identification by reducing the number of annotations from LIPID MAPS but also guides discovery studies of potentially novel species. Testing the methodology on Salmonella enterica serovar Typhimurium-infected murine bone-marrow-derived macrophages and thrombin activated human platelets yields results in agreement with literature. This workflow has also annotated features as potentially novel oxylipins, confirming its ability in providing further insights into lipid analysis of biological samples.
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PMID:A Comprehensive UHPLC Ion Mobility Quadrupole Time-of-Flight Method for Profiling and Quantification of Eicosanoids, Other Oxylipins, and Fatty Acids. 3107 60

Gastric cancer (GC) is a malignant tumor that affects individuals worldwide, and miRNA and mRNA are closely connected to this disease. However, it is still unclear how these molecules affect GC and whether their effects are associated with circRNA in GC patients. Therefore, we obtained the miRNA, mRNA and circRNA expression profiles of GC patients from the GEO database. For comparison, shared miRNAs and mRNAs from the results of microarrays were annotated by gene ontology (GO) and pathway analysis. We also identified mRNAs that were targeted by miRNA through TargetScan 7.2 and circRNAs that were targeted by miRNA through CircInteractome. A comprehensive analysis of the microarray results revealed 72 shared miRNAs, and the expression profiles of 6 miRNAs were significantly different between the tumor and control groups (the absolute value of fold change>2, P<0.05). Hsa-miR-1, hsa-miR-142-3p, hsa-miR-95, hsa-miR-133a and hsa-miR-181d were upregulated in GC, whereas hsa-miR-375 was downregulated. The analysis results also revealed 1201 shared mRNAs and 27 mRNAs, respectively, by microarray and TargetScan. Pathway analysis demonstrated that the Glypican pathway, Proteoglycan syndecan-mediated signalling events, Glypican 1 network and PAR1-mediated thrombin signalling events play important roles. GO analysis revealed significant enrichment in the three terms cellular component, molecular function and biological process, suggesting that organelles, enzyme binding, RNA-binding and nitrogen metabolism may have a strong relationship in GC. The increase in PAX6 in GC may be related to hsa-miR-375. Three circRNAs, hsa_circ_0001658, hsa_circ_0004928 and hsa_circ_0000376, were then found to be significantly differentially expressed between GC and normal tissues (the absolute value of fold change>2, P<0.05). In conclusion, the circ0001658/circ0004928/circ0000376-miR-375-PAX6 axis may represent a new regulatory network that should be further investigated, and the results of this study provide a better understanding of GC.
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PMID:miRNA and mRNA expression profiles in gastric cancer patients and the relationship with circRNA. 3130 99

Non-covalent electrostatic interaction between amide nitrogen and carbonyl carbon of shorter chain length of polyvinylpyrrolidone (PVP-k25) was developed with in-house carboxylic oxidized multiwall carbon nanotubes (O-MWCNT) and then blended with Polyethersulfone (PES) polymer. FTIR analysis was utilized to confirm bonding nature of nano-composites (NCs) of O-MWCNT/PVP-k25 and casting membranes. Non-solvent induces phase separation process developed regular finger-like channels in composite membranes whereas pristine PES exhibited spongy entities as studied by cross sectional analysis report of FESEM. Further, FESEM instrument was also utilized to observe the dispersion of O-MWCNT/PVP based nanocomposite (NCs) with PES and membranes leaching phenomena analysis. Contact angle experiments described 24% improvement of hydrophilic behaviour, leaching ratio of additives was reduced to 1.89%, whereas water flux enhanced up to 6 times. Bovine serum albumin (BSA) and lysozyme based antifouling analysis shown up to 25% improvement, whereas 84% of water flux was regained after protein fouling than pristine PES. Anticoagulant activity was reported by estimating prothrombin, thrombin, plasma re-calcification times and production of fibrinogen cluster with platelets-adhesions photographs and hemolysis experiments. Composite membranes exhibited 3.4 and 3 times better dialysis clearance ratios of urea and creatinine solutes as compared to the raw PES membrane.
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PMID:Hemodialysis performance and anticoagulant activities of PVP-k25 and carboxylic-multiwall nanotube composite blended Polyethersulfone membrane. 3134 44

Thrombomodulin (TM) is a single transmembrane, multidomain glycoprotein receptor for thrombin, and is best known for its role as a cofactor in a clinically important natural anticoagulant pathway. In addition to its anticoagulant function, TM has well-defined anti-inflammatory properties. Soluble TM levels increase significantly in the plasma of septic patients; however, the possible involvement of recombinant human soluble TM (rTM) transduction in the pathogenesis of lipopolysaccharide (LPS)-induced nephrotoxicity, including acute kidney injury (AKI), has remained unclear. Mice were injected intraperitoneally with 15 mg/kg LPS. rTM (3 mg/kg) or saline was administered to the animals before the 3 and 24 h LPS-injection. At 24 and 48 h, blood urea nitrogen, the inflammatory cytokines in sera and kidney, and histological findings were assessed. Cell activation and apoptosis signal was assessed by Western blot analysis. In this study using a mouse model of LPS-induced AKI, we found that rTM attenuated renal damage by reducing both cytokine and cell activation and apoptosis signals with the accumulation of CD4+ T-cells, CD11c+ cells, and F4/80+ cells via phospho c-Jun activations and Bax expression. These findings suggest that the mechanism underlying these effects of TM may be mediated by a reduction in inflammatory cytokine production in response to LPS. These molecules might thereby provide a new therapeutic strategy in the context of AKI with sepsis.
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PMID:Protective Effects of Recombinant Human Soluble Thrombomodulin on Lipopolysaccharide-Induced Acute Kidney Injury. 3226 Apr 74

In this work, we report the development of an ultrasensitive sandwich-type electrochemical aptasensor for protein detection. The aptasensor is fabricated by using nitrogen-doped graphene oxide (N-GO) and Au nanoparticles (AuNPs) as sensing substrates, molybdenum disulfide (MoS₂) spheres as the hybridization chain reaction (HCR) platform, and thrombin as the model protein. When the hybridization reaction is initiated through two biotinylated hairpin probes, vast horseradish peroxidases are immobilized on the long duplex by the biotin-avidin reaction. An electrochemical-chemical-chemical redox cycling reaction then takes place in the detection system, which contains p-dihydroxybenzene, ferrocene carboxylate and tris(2-carboxyethyl)phosphine. Benefiting from the good conductivity and high specific surface area of N-GO/AuNPs and MoS₂ spheres, signal amplification of the HCR and detection system, and excellent selectivity of the aptamer and sandwich-type strategy, the proposed assay shows a wide linear range of 10 fM-0.1 nM towards thrombin with a detection limit of 27 aM (S/N = 3) along with clear distinction from different proteins. The proposed assay is successfully used to detect thrombin in human serum, which would have promising prospects for disease diagnosis and therapy.
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PMID:Molybdenum disulfide sphere-based electrochemical aptasensors for protein detection. 3226 75


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