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https://www.readbyqxmd.com/read/29619369/cell-receptor-and-cofactor-interactions-of-the-contact-activation-system-and-factor-xi
#1
REVIEW
Monika Pathak, Bubacarr Gibril Kaira, Alexandre Slater, Jonas Emsley
The contact activation system (CAS) or contact pathway is central to the crosstalk between coagulation and inflammation and contributes to diverse disorders affecting the cardiovascular system. CAS initiation contributes to thrombosis but is not required for hemostasis and can trigger plasma coagulation via the intrinsic pathway [through factor XI (FXI)] and inflammation via bradykinin release. Activation of factor XII (FXII) is the principal starting point for the cascade of proteolytic cleavages involving FXI, prekallikrein (PK), and cofactor high molecular weight kininogen (HK) but the precise location and cell receptor interactions controlling these reactions remains unclear...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29587641/the-prevalence-of-heterozygous-f12-mutations-in-chinese-population-and-its-relevance-to-incidents-of-thrombosis
#2
Xi Wu, Qiulan Ding, Xuefeng Wang, Jing Dai, Wenman Wu
BACKGROUND: The contribution of moderate coagulation factor XII (FXII) deficiency to development of thromboembolism is still undetermined. We have tried to show the relevance of FXII deficiency to incidences of venous thrombosis by exploring the prevalence of F12 gene mutations in Chinese patients with thrombotic disorders. METHODS: One hundred and six patients with venous thromboembolism (VTE) and 220 healthy controls were enrolled in study. The coding region and flanking sequences of F12 gene were amplified and sequenced to identify genetic variances...
March 27, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29548426/a-missense-mutation-in-the-plasminogen-gene-within-the-plasminogen-kringle-3-domain-in-hereditary-angioedema-with-normal-c1-inhibitor
#3
Georg Dewald
Hereditary angioedema (HAE) is a genetically heterogeneous disease that is characterized by recurrent skin swelling, abdominal pain attacks, and potentially life-threatening upper airway obstruction. The two classic types, HAE types I and II, are both caused by mutations in the complement C1 inhibitor (SERPING1) gene resulting either in a quantitative or a qualitative deficiency of C1 inhibitor. In so-called HAE type III, in contrast, patients show normal C1 inhibitor measurements in plasma ('HAE with normal C1 inhibitor')...
March 25, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29541637/establishment-of-the-world-health-organization-first-international-standard-for-factor-xii-plasma-human
#4
Helen V Wilmot, Jason Hockley, Peter Rigsby, Elaine Gray
Until recently, the role of factor XII (FXII) in hemostasis was not considered to be important since patients with FXII deficiency do not present with bleeding. The activation of FXII by agents including mast cells and platelet polyphosphates suggests that it may have a role in thrombogenesis. The inhibition of FXII therefore presents an option for antithrombotic therapy, and antibodies and inhibitors are already in development. Assays for FXII will be required to support these technologies, and an international standard (IS) for FXII would be useful for the development of these methods and for the clinical monitoring of patients...
2018: Frontiers in Medicine
https://www.readbyqxmd.com/read/29507382/neutrophil-extracellular-trap-microparticle-complexes-enhance-thrombin-generation-via-the-intrinsic-pathway-of-coagulation-in-mice
#5
Yongzhi Wang, Lingtao Luo, Oscar Ö Braun, Johannes Westman, Raed Madhi, Heiko Herwald, Matthias Mörgelin, Henrik Thorlacius
Abdominal sepsis is associated with dysfunctional hemostasis. Thrombin generation (TG) is a rate-limiting step in systemic coagulation. Neutrophils can expell neutrophil extracellular traps (NETs) and/or microparticles (MPs) although their role in pathological coagulation remains elusive. Cecal ligation and puncture (CLP)-induced TG in vivo was reflected by a reduced capacity of plasma from septic animals to generate thrombin. Depletion of neutrophils increased TG in plasma from CLP mice. Sepsis was associated with increased histone 3 citrullination in neutrophils and plasma levels of cell-free DNA and DNA-histone complexes and administration of DNAse not only eliminated NET formation but also elevated TG in sepsis...
March 5, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29495652/carbonic-anhydrases-role-in-ph-control-and-cancer
#6
REVIEW
Mam Y Mboge, Brian P Mahon, Robert McKenna, Susan C Frost
The pH of the tumor microenvironment drives the metastatic phenotype and chemotherapeutic resistance of tumors. Understanding the mechanisms underlying this pH-dependent phenomenon will lead to improved drug delivery and allow the identification of new therapeutic targets. This includes an understanding of the role pH plays in primary tumor cells, and the regulatory factors that permit cancer cells to thrive. Over the last decade, carbonic anhydrases (CAs) have been shown to be important mediators of tumor cell pH by modulating the bicarbonate and proton concentrations for cell survival and proliferation...
February 28, 2018: Metabolites
https://www.readbyqxmd.com/read/29483100/coagulation-factor-xii-in-thrombosis-and-inflammation
#7
Coen Maas, Thomas Renné
Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. The factor XII-driven-contact system starts coagulation and inflammatory mechanisms via the intrinsic pathway of coagulation and the bradykinin-producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. Challenging the concept of the coagulation balance, targeting factor XII or its activator polyphosphate provides protection from thromboembolic diseases without interfering with hemostasis...
February 26, 2018: Blood
https://www.readbyqxmd.com/read/29474926/the-fibrogenic-actions-of-the-coagulant-and-plasminogen-activation-systems-in-pulmonary-fibrosis
#8
REVIEW
Michael Schuliga, Christopher Grainge, Glen Westall, Darryl Knight
Fibrosis causes irreversible damage to lung structure and function in restrictive lung diseases such as idiopathic pulmonary fibrosis (IPF). Extravascular coagulation involving fibrin formation in the intra-alveolar compartment is postulated to have a pivotal role in the development of pulmonary fibrosis, serving as a provisional matrix for migrating fibroblasts. Furthermore, proteases of the coagulation and plasminogen activation (plasminergic) systems that form and breakdown fibrin respectively directly contribute to pulmonary fibrosis...
February 20, 2018: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29467753/the-plasma-kallikrein-kininogen-pathway-is-critical-in-the-pathogenesis-of-colitis-in-mice
#9
Bo Wang, Aizhen Yang, Zhenzhen Zhao, Chao He, Yuanyuan Liu, Robert W Colman, Jihong Dai, Yi Wu
The kallikrein-kinin system (KKS) consists of two serine proteases, prekallikrein (pKal) and factor XII (FXII), and a cofactor, high-molecular-weight kininogen (HK). Upon activation of the KKS, HK is cleaved to release bradykinin. Although the KKS is activated in humans and animals with inflammatory bowel disease (IBD), its role in the pathogenesis of IBD has not been characterized. In the present study, we determined the role of the KKS in the pathogenesis of IBD using mice that lack proteins involved in the KKS...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29419864/-analysis-of-a-consanguineous-pedigree-affected-with-hereditary-coagulation-factor-xii-deficiency-caused-by-homozygous-gly341arg-mutation
#10
Lihong Yang, Saiyan Jin, Weidan Ji, Xiaoli Cheng, Xiaolong Li, Yanhui Jin, Mingshan Wang
OBJECTIVE To analyze the laboratory phenotype and FXII gene mutation in a consanguineous Chinese pedigree affected with factor XII (FXII) deficiency. METHODS Activated partial thromboplastin time (APTT), FXII activity (FXII:C) and FXII antigen (FXII:Ag) of the proband and her family members (10 individuals from 3 generations) were determined. Sanger sequencing was used to detect potential mutation within the 14 exons, their flanking regions and 5',3'-untranslated regions of the FXII gene. Suspected mutations were verified by backward sequencing...
February 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29407154/porous-chitosan-microspheres-containing-zinc-ion-for-enhanced-thrombosis-and-hemostasis
#11
Meng Pan, Zonghao Tang, Jianbing Tu, Zhengchao Wang, Qinhui Chen, Rongdong Xiao, Haiqing Liu
Quick hemostats for non-lethal massive traumatic bleeding in battlefield and civilian accidents are important for reducing mortality and medical costs. Chitosan (CS) has been widely used as a clinic hemostat. To enhance its hemostatic efficiency, Zn2+ in the form of zinc alginate (ZnAlg) was introduced to CS to make porous CS@ZnAlg microspheres with ZnAlg component on the surface. Such microspheres were prepared by successive steps of micro-emulsion, polyelectrolyte adhesion, and thermally induced phase separation...
April 1, 2018: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/29404650/-coagulation-factors-and-multiple-sclerosis-key-factors-in-the-pathogenesis
#12
REVIEW
K Göbel, C Kleinschnitz, S G Meuth
Environmental factors and genetic predisposition influence the individual risk to develop multiple sclerosis (MS). Preclinical results in animal models of MS, such as experimental autoimmune encephalomyelitis (EAE), prove a significant contribution of the corpuscular and plasmatic coagulation system for the severity of MS. It was recently shown that key molecules of the coagulation cascade, such as fibrinogen, thrombin and factor XII can influence neuroinflammatory disorders such as MS. The inhibition of both fibrinogen and factor XII led to a significantly improved disease course in animal models...
February 5, 2018: Der Nervenarzt
https://www.readbyqxmd.com/read/29393169/hereditary-and-acquired-angioedema-heterogeneity-of-pathogenesis-and-clinical-phenotypes
#13
Maria Bova, Giulia De Feo, Roberta Parente, Tiziana De Pasquale, Carmela Gravante, Stefano Pucci, Eustachio Nettis, Massimo Triggiani
Recurrent angioedema (AE) without wheals is increasingly recognized as a clinical entity and a frequent cause of admission to the emergency room. The Hereditary Angioedema Working Group (HAWK) classification allowed the scientific community to go beyond the semantic confusion that dominated this topic for decades. This classification distinguishes hereditary and acquired forms of AE, either related or unrelated to C1 inhibitor deficiency. Recently, additional mechanisms have been involved in the AE pathogenesis, including the uncontrolled activation of factor XII, generation of vasoactive mediators that induce dysregulation of endothelial functions, and bidirectional interactions between mast cell-derived mediators and the plasma contact system...
2018: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/29383625/genetic-analysis-of-a-novel-missense-mutation-gly542ser-with-factor-xii-deficiency-in-a-chinese-patient-of-consanguineous-marriage
#14
Anqing Zou, Mingshan Wang, Yanhui Jin, Xiaoli Cheng, Kankan Su, Lihong Yang
Coagulation factor XII deficiency is a rare autosomal recessive disorder, which could be found in a consanguineous family. We studied a Chinese family in which the activated partial thromboplastin time (APTT) of the proband had clearly prolonged up to 101.7 s, associated with low FXII activity of 3% and FXII antigen < 1%. To analyze the gene mutation in this FXII-deficient patient, we performed FXII mutation screening, and analyzed the DNA sequence of the F12 gene. A ClustalX-2.1-win and four online bioinformatics software services were used to study the conservatism and effects of the mutation...
April 2018: International Journal of Hematology
https://www.readbyqxmd.com/read/29381885/differential-expression-profiles-of-conserved-snail-transcription-factors-in-the-mouse-testis
#15
D J Micati, G R Hime, E A McLaughlin, H E Abud, K L Loveland
Snail transcription factors are key regulators of cellular transitions during embryonic development and tumorigenesis. The closely related SNAI1 and SNAI2 proteins induce epithelial-mesenchymal transitions (EMTs), acting predominantly as transcriptional repressors, while the functions of SNAI3 are unknown. An initial examination of Snai2-deficient mice provided evidence of deficient spermatogenesis. To address the hypothesis that Snail proteins are important for male fertility, this study provides the first comprehensive cellular expression profiles of all three mammalian Snail genes in the post-natal mouse testis...
March 2018: Andrology
https://www.readbyqxmd.com/read/29376892/factor-xii-and-upar-upregulate-neutrophil-functions-to-influence-wound-healing
#16
Evi X Stavrou, Chao Fang, Kara L Bane, Andy T Long, Clément Naudin, Erdem Kucukal, Agharnan Gandhi, Adina Brett-Morris, Michele M Mumaw, Sudeh Izadmehr, Alona Merkulova, Cindy C Reynolds, Omar Alhalabi, Lalitha Nayak, Wen-Mei Yu, Cheng-Kui Qu, Howard J Meyerson, George R Dubyak, Umut A Gurkan, Marvin T Nieman, Anirban Sen Gupta, Thomas Renné, Alvin H Schmaier
Coagulation factor XII (FXII) deficiency is associated with decreased neutrophil migration, but the mechanisms remain uncharacterized. Here, we examine how FXII contributes to the inflammatory response. In 2 models of sterile inflammation, FXII-deficient mice (F12-/-) had fewer neutrophils recruited than WT mice. We discovered that neutrophils produced a pool of FXII that is functionally distinct from hepatic-derived FXII and contributes to neutrophil trafficking at sites of inflammation. FXII signals in neutrophils through urokinase plasminogen activator receptor-mediated (uPAR-mediated) Akt2 phosphorylation at S474 (pAktS474)...
March 1, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29356700/the-effects-of-transport-temperature-and-time-on-routine-and-specialized-coagulation-assays
#17
Yeowon A Kim, Kent B Lewandrowski, Fils-Amie Lucien, Elizabeth M Van Cott
: Coagulation laboratories have largely stopped transporting whole blood specimens on ice, due to adverse effects on factor VIII, von Willebrand factor, and the prothrombin time. However, it is unknown whether ice should be required or avoided for other coagulation assays. Furthermore, the amount of time that specimens remain stable during transportation at room temperature (RT) is also largely unknown for many coagulation tests. Therefore, this study investigated specimen stability on ice and RT for a comprehensive panel of coagulation tests...
March 2018: Blood Coagulation & Fibrinolysis: An International Journal in Haemostasis and Thrombosis
https://www.readbyqxmd.com/read/29354798/activity-of-factor-xii-locarno
#18
Bassem M Mohammed, Ivan Ivanov, Anton Matafonov, Jonas Emsley, David Gailani
Background: Factor XII (FXII) Locarno is a natural variant with proline replacing Arg353 at the activation cleavage site, preventing conversion to the fully active protease factor XIIa (FXIIa). Recently, we showed that FXII restricted to a single chain form (sc-FXII) by replacing Arg353 with alanine expresses proteolytic activity that is enhanced by cofactors such as polyphosphate. Aim: To determine if the Pro353 substitution affects the activity of sc-FXII. Methods: Wild type FXII (FXII-WT), FXII-R353A, and FXII Locarno (FXII-R353P) were tested for their abilities to activate prekallikrein, and to induce thrombin generation and coagulation in plasma in a factor XI-dependent manner...
January 2018: Research and Practice in Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/29277609/ra-xii-exerts-anti-oxidant-and-anti-inflammatory-activities-on-lipopolysaccharide-induced-acute-renal-injury-by-suppressing-nf-%C3%AE%C2%BAb-and-mapks-regulated-by-ho-1-nrf2-pathway
#19
Xusheng An, Futai Shang
Acute kidney injury (AKI) is an abrupt loss of kidney function and severe AKI needs renal replacement therapeutic strategy and has high mortality. RA-XII is a natural cyclopeptide, isolated from the traditional Chinese medicine Rubia yunnanensis, exerting anti-inflammatory and anti-tumor activities. The present study aimed to explore the effects of RA-XII on LPS-induced ACI and the underlying molecular mechanism in TCMK-1 cells in vitro. The results indicated that RA-XII delayed the animal death caused by LPS in mice...
January 15, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29251173/plasmatic-carbonic-anhydrase-ix-as-a-diagnostic-marker-for-clear-cell-renal-cell-carcinoma
#20
Laura Lucarini, Lucia Magnelli, Nicola Schiavone, Alfonso Crisci, Alessio Innocenti, Luca Puccetti, Fabio Cianchi, Sara Peri, Claudiu T Supuran, Laura Papucci, Emanuela Masini
Carbonic anhydrase (CA, EC 4.2.1.1) IX is regarded as a tumour hypoxia marker and CA inhibitors have been proposed as a new class of antitumor agents, with one such agent in Phase II clinical trials. The expression of some CAs, in particular the isoforms CA IX and CA XII, has been correlated with tumour aggressiveness and progression in several cancers. The aim of this study was to evaluate the possibility that CA IX could represent a marker related to clear cell Renal Cell Carcinoma (ccRCC). Bcl-2 and Bax, and the activity of caspase-3, evaluated in tissue biopsies from patients, were congruent with resistance to apoptosis in ccRCCs with respect to healthy controls, respectively...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
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