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Coagulation cascade

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https://www.readbyqxmd.com/read/28937618/novel-fxa-inhibitor-identification-through-integration-of-ligand-and-structure-based-approaches
#1
Carlos F Lagos, Gerardine F Segovia, Nicolás Nuñez-Navarro, Mario A Faúndez, Flavia C Zacconi
Factor Xa (FXa), a vitamin K-dependent serine protease plays a pivotal role in the coagulation cascade, one of the most interesting targets for the development of new anticoagulants. In the present work, we performed a virtual screening campaign based on ligand-based shape and electrostatic similarity search and protein-ligand docking to discover novel FXa-targeted scaffolds for further development of inhibitors. From an initial set of 260,000 compounds from the NCI Open database, 30 potential FXa inhibitors were identified and selected for in vitro biological evaluation...
September 22, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28927687/transcriptome-analysis-of-the-spleen-of-the-darkbarbel-catfish-pelteobagrus-vachellii-in-response-to-aeromonas-hydrophila-infection
#2
Chuanjie Qin, Quan Gong, Zhengyong Wen, Dengyue Yuan, Ting Shao, Jun Wang, Huatao Li
Intensive aquaculture has increased the susceptibility of fish to Aeromonas hydrophila, and this has led to severe economic damage. There has been little study of the host defense mechanism against A. hydrophila infection in scaleless fish. Therefore, in the present study, the transcriptome profiles of the spleen of Pelteobagrus vachellii were examined after infection with A. hydrophila. In total, 37,730 unigenes from 322 KEGG pathways were identified. Following A. hydrophila infection, 27,803 differentially expressed genes were identified, including 13,934 upregulated and 13,869 downregulated genes...
September 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28921918/proteomic-response-of-human-umbilical-vein-endothelial-cells-to-histamine-stimulation
#3
Pelin Esma Emirbayer, Ankit Sinha, Vladimir Ignatchenko, Stefanie Hoyer, Jan Dörrie, Niels Schaft, Monika Pischetsrieder, Thomas Kislinger
The histamine receptors (HRs) represent a subclass of G protein-coupled receptors (GPCRs) and comprise four subtypes. Due to their numerous physiological and pathological effects, HRs are popular drug targets for the treatment of allergic reactions or the regulation of gastric acid secretion. Hence, an understanding of the functional selectivity of HR ligands has gained importance. These ligands can bind to specific GPCRs and selectively activate defined pathways. Supporting the activation of a therapeutically necessary pathway without the activation of other signaling cascades can result in drugs with more specific activity and fewer side effects...
September 18, 2017: Proteomics
https://www.readbyqxmd.com/read/28921445/quantification-of-coagulation-factor-viii-by-selective-reaction-monitoring
#4
Edson Galdino do Nascimento Filho, Guilherme Pauperio Lanfredi, Mário Soares Abreu-Neto, Dimas Tadeu Covas, Vitor Marcel Faça
Coagulation factor VIII (FVIII) is an important glycoprotein involved in the extrinsic coagulation cascade. Mutations in FVIII gene results in hemophilia A, a recessive coagulation disorder that is clinically managed by administration of purified FVIII from blood donors or recombinant FVIII. Because of its fundamental therapeutic application, biotechnological production of FVIII requires rigid quality control and monitoring in patients and clinical trials. Here, we describe a protocol for a mass spectrometry based approach termed selective reaction monitoring (SRM) as an important alternative tool for accurate and sensitive quantitation of purified or recombinant FVIII...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28916360/trancriptome-profiles-of-amur-sturgeon-spleen-in-response-to-yersinia-ruckeri-infection
#5
Shaowu Li, Ying Zhang, Yongsheng Cao, Di Wang, Hongbai Liu, Tongyan Lu
Yersinia ruckeri (YR) is the causative agent of yersiniosis which has caused significant economic losses in fish culture worldwide, including in Amur sturgeon (Acipenser schrenckii) culture. To better understand the mechanism of the immune responses to YR in Amur sturgeon, the transcriptomic profiles of the spleens from YR-infected and non-infected groups were obtained using RNA-seq techniques. The de novo assemblies yielded totally 145 670 unigenes from the two libraries. The total numbers of transcripts in YR-infected and non-infected groups were from 110 893 to 147 336, with the mean length varying from 560 to 631 (N50: from 882 to 1083)...
September 13, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28912679/proteomic-differences-in-blood-plasma-associated-with-antidepressant-treatment-response
#6
Christoph W Turck, Paul C Guest, Giuseppina Maccarrone, Marcus Ising, Stefan Kloiber, Susanne Lucae, Florian Holsboer, Daniel Martins-de-Souza
The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28906455/deep-circular-rna-sequencing-provides-insights-into-the-mechanism-underlying-grass-carp-reovirus-infection
#7
Libo He, Aidi Zhang, Lv Xiong, Yongming Li, Rong Huang, Lanjie Liao, Zuoyan Zhu, And Yaping Wang
Grass carp hemorrhagic disease, caused by the grass carp reovirus (GCRV), is a major disease that hampers the development of grass carp aquaculture in China. The mechanism underlying GCRV infection is still largely unknown. Circular RNAs (circRNAs) are important regulators involved in various biological processes. In the present study, grass carp were infected with GCRV, and spleen samples were collected at 0 (control), 1, 3, 5, and 7 days post-infection (dpi). Samples were used to construct and sequence circRNA libraries, and a total of 5052 circRNAs were identified before and after GCRV infection, of which 41 exhibited differential expression compared with controls...
September 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28904799/clinical-significance-of-measuring-plasminogen-activator-inhibitor-1-in-sepsis
#8
Toshiaki Iba, Jecko Thachil
BACKGROUND: Disseminated thrombotic process in the microcirculation is considered to be an important cause of multiple organ dysfunction in sepsis. The fundamental purpose of this prothrombotic change was believed to be in the host defense against microbial dissemination. In that process, antifibrinolytic property plays an important role. MAIN BODY: For the understanding of pathophysiology of sepsis, it is quite useful to grasp the alterations in coagulation/fibrinolytic parameters, i...
2017: Journal of Intensive Care
https://www.readbyqxmd.com/read/28903486/nonalcoholic-fatty-liver-disease-is-a-susceptibility-factor-for-perchloroethylene-induced-liver-effects-in-mice
#9
Joseph A Cichocki, Shinji Furuya, Yu-Syuan Luo, Yasuhiro Iwata, Kranti Konganti, Weihsueh A Chiu, David W Threadgill, Igor P Pogribny, Ivan Rusyn
Nonalcoholic fatty liver disease (NAFLD) is the most prevalent pathological liver condition in developed countries. NAFLD results in severe alterations in liver function, including xenobiotic metabolism. Perchloroethylene (PERC) is a ubiquitous environmental pollutant, a known hepatotoxicant in rodents, and a probable human carcinogen. It is known that PERC disposition and metabolism are affected by NAFLD in mice; here, we examined how NAFLD changes PERC-associated liver effects. Male C57Bl6/J mice were fed a low-fat diet (LFD), high-fat diet (HFD), or methionine/folate/choline-deficient diet (MCD) to model a healthy liver, or mild and severe forms of NAFLD, respectively...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28901457/screening-and-identification-of-key-biomarkers-in-hepatocellular-carcinoma-evidence-from-bioinformatic-analysis
#10
Lin Li, Qingsong Lei, Shujun Zhang, Lingna Kong, Bo Qin
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Intense efforts have been made to elucidate the pathogeny, but the molecular mechanisms of HCC are still not well understood. To identify the candidate genes in the carcinogenesis and progression of HCC, microarray datasets GSE19665, GSE33006 and GSE41804 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified, and function enrichment analyses were performed. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape...
September 7, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900700/auxiliary-activation-of-the-complement-system-and-its-importance-for-the-pathophysiology-of-clinical-conditions
#11
REVIEW
Markus Huber-Lang, Kristina N Ekdahl, Rebecca Wiegner, Karin Fromell, Bo Nilsson
Activation and regulation of the cascade systems of the blood (the complement system, the coagulation/contact activation/kallikrein system, and the fibrinolytic system) occurs via activation of zymogen molecules to specific active proteolytic enzymes. Despite the fact that the generated proteases are all present together in the blood, under physiological conditions, the activity of the generated proteases is controlled by endogenous protease inhibitors. Consequently, there is remarkable little crosstalk between the different systems in the fluid phase...
September 12, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28894971/identification-of-genes-associated-with-primary-open-angle-glaucoma-by-bioinformatics-approach
#12
Haiyan Qiu, Benhu Zhu, Shengrong Ni
PURPOSE: This study aimed to identify associated genes with primary open-angle glaucoma (POAG) and explore the potentially modular mechanism underlying POAG. METHODS: We downloaded gene expression profiles data GSE27276 from gene expression omnibus and identified differentially expressed genes between POAG patients and normal controls. Then, gene ontology analysis and kyoto encyclopedia of genes and genomes pathway enrichment were performed to predict the DEGs functions, followed with the construction, centrality analysis, and module mining of protein-protein interaction network...
September 11, 2017: International Ophthalmology
https://www.readbyqxmd.com/read/28894574/decreased-activity-of-plasma-adamts13-are-related-to-enhanced-cytokinemia-and-endotoxemia-in-patients-with-acute-liver-failure
#13
Hiroaki Takaya, Hitoshi Yoshiji, Hideto Kawaratani, Kazuya Sakai, Masanori Matsumoto, Yoshihiro Fujimura, Hiroshi Fukui
Deficient ADAM metalloproteinase with thrombospondin type-1 motif, member 13 (ADAMTS13) activity (ADAMTS13:AC) results in the accumulation of unusually large von Willebrand factor multimers (UL-VWFM) and causes microcirculatory disturbances and multiple organ failure, while endotoxins trigger the activation of a coagulation cascade. The objective of the present study was to explore the role of ADAMTS13 in endotoxemia in patients with acute liver failure (ALF). Plasma concentrations of endotoxin and cytokines, including interleukin (IL)-6 and IL-8, and activity of the plasma ADAMTS13 inhibitor were determined, along with ADAMTS13:AC, the VWF antigen (VWF:Ag) and UL-VWFM, in 27 patients with acute hepatitis (AH), 11 patients with ALF, and 10 healthy controls...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28886691/impaired-response-of-the-bronchial-epithelium-to-inflammation-characterizes-severe-equine-asthma
#14
Laurence Tessier, Olivier Côté, Mary Ellen Clark, Laurent Viel, Andrés Diaz-Méndez, Simon Anders, Dorothee Bienzle
BACKGROUND: Severe equine asthma is a naturally occurring lung inflammatory disease of mature animals characterized by neutrophilic inflammation, bronchoconstriction, mucus hypersecretion and airway remodeling. Exacerbations are triggered by inhalation of dust and microbial components. Affected animals eventually are unable of aerobic performance. In this study transcriptomic differences between asthmatic and non-asthmatic animals in the response of the bronchial epithelium to an inhaled challenge were determined...
September 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28872471/lung-xenotransplantation
#15
Hisashi Sahara, Hironosuke Watanabe, Thomas Pomposelli, Kazuhiko Yamada
PURPOSE OF REVIEW: This review describes the most recent progress in xeno lung transplantation (XLTx) to date. It describes the potential mechanisms of early xeno lung graft loss, as well as the latest therapeutic strategies to overcome them. RECENT FINDINGS: Using ex-vivo perfusion models of porcine lungs with human blood, the use of genetically modified pig lungs along with novel pharmaceutical approaches has recently been studied. Strategies that have demonstrated improved lung survival include the knockout of known xenoantigens (GalTKO and N-glycolylneuraminic acid-KO), genes that regulate complement activation (hCD46 and hCD55), as well as the inflammation/coagulation cascade (human leukocyte antigen-E, human thrombomodulin, human endothelial protein C receptor, hCD47, hCD39, hCD73 and heme oxygenase-1)...
September 1, 2017: Current Opinion in Organ Transplantation
https://www.readbyqxmd.com/read/28866276/deciphering-transcriptome-profile-of-the-yellow-catfish-pelteobagrus-fulvidraco-in-response-to-edwardsiella-ictaluri
#16
Rong Zhu, Xiao-Xiao Liu, Xue Nv, Shun-Yi Li, Ya-Dong Li, Xue-Jing Yu, Xing-Guo Wang
Edwardsiella ictaluri is one of the most important pathogens posing a serious threat for yellow catfish (Pelteobagrus fulvidraco), a highly valuable fish species of increasing commercial interest in China. Here, a transcriptomic strategy was undertaken to investigate the yellow catfish gene expression profile against infection by the bacterial pathogen E. ictaluri. Comparison of the transcriptome profiles between the infected and uninfected samples showed that a massive gene expression change occurred in yellow catfish following bacterial exposure...
August 30, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28866177/biomimetics-in-thin-film-design-niche-like-wrinkles-designed-for-i-cell-progenitor-cell-differentiation
#17
Roman Major, Juergen M Lackner, Marek Sanak, Boguslaw Major
The future and development of science are in interdisciplinary areas, such as biomedical engineering. Self-assembled structures, similar to stem cell niches, inhibit rapid cellular division processes and enable the capture of stem cells from blood flow. By modifying the surface topography and stiffness properties, progenitor cells were differentiated towards the formation of endothelial cell monolayers to effectively inhibit the coagulation cascade. Wrinkled material layers in the form of thin polymeric coatings were prepared...
November 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28859973/histamine-and-tlr-ligands-synergistically-induce-endothelial-cell-gap-formation-by-the-extrinsic-coagulating-pathway
#18
Yuhki Yanase, Satoshi Morioke, Kazumasa Iwamoto, Shunsuke Takahagi, Kazue Uchida, Tomoko Kawaguchi, Kaori Ishii, Izumi Hide, Michihiro Hide
Histamine and LPS synergistically induce the expression of TF by vascular endothelial cells, activating the extrinsic coagulation cascade followed by an increase of vascular permeability.
August 28, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28855397/inflammatory-monocytes-expressing-tissue-factor-drive-siv-and-hiv-coagulopathy
#19
Melissa E Schechter, Bruno B Andrade, Tianyu He, George Haret Richter, Kevin W Tosh, Benjamin B Policicchio, Amrit Singh, Kevin D Raehtz, Virginia Sheikh, Dongying Ma, Egidio Brocca-Cofano, Cristian Apetrei, Russel Tracy, Ruy M Ribeiro, Alan Sher, Ivo M B Francischetti, Ivona Pandrea, Irini Sereti
In HIV infection, persistent inflammation despite effective antiretroviral therapy is linked to increased risk of noninfectious chronic complications such as cardiovascular and thromboembolic disease. A better understanding of inflammatory and coagulation pathways in HIV infection is needed to optimize clinical care. Markers of monocyte activation and coagulation independently predict morbidity and mortality associated with non-AIDS events. We identified a specific subset of monocytes that express tissue factor (TF), persist after virological suppression, and trigger the coagulation cascade by activating factor X...
August 30, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28845386/innate-immunity-and-mobilization-of-hematopoietic-stem-cells
#20
REVIEW
Mateusz Adamiak, Mariusz Z Ratajczak
PURPOSE OF REVIEW: Several mechanisms have been postulated to orchestrate mobilization of hematopoietic stem/progenitor cells (HSPCs), and still more work is needed to better understand this process and to gain better mechanistic insight. RECENT FINDINGS: Evidence accumulated that mobilization of HSPCs is a part of innate immunity response to tissue organ injury, stress, and infection. This evolutionary ancient process is orchestrated by granulocytes and monocytes that trigger activation of complement cascade and the coagulation cascade...
2017: Current Stem Cell Reports
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