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https://www.readbyqxmd.com/read/28641140/effect-of-c1-inh-on-ischemia-reperfusion-injury-in-a-porcine-limb-ex-vivo-perfusion-model
#1
Mai M Abdelhafez, Jane Shaw, Damian Sutter, Jonas Schnider, Yara Banz, Hansjörg Jenni, Esther Voegelin, Mihai A Constantinescu, Robert Rieben
Revascularization of an amputated limb within 4-6h is essential to avoid extensive ischemia/reperfusion (I/R) injury leading to vascular leakage, edema and tissue necrosis. I/R injury is a pathological inflammatory condition that occurs during reperfusion of an organ or tissue after prolonged ischemia. It is characterized by a complex crosstalk between endothelial cell activation and the activation of plasma cascades. Vasculoprotective pharmacological intervention to prevent I/R injury might be an option to prolong the time window between limb amputation and successful replantation...
June 19, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28632184/crude-fucoidan-extracts-impair-angiogenesis-in-models-relevant-for-bone-regeneration-and-osteosarcoma-via-reduction-of-vegf-and-sdf-1
#2
Fanlu Wang, Harald Schmidt, Dijana Pavleska, Thees Wermann, Andreas Seekamp, Sabine Fuchs
The marine origin polysaccharide fucoidan combines multiple biological activities. As demonstrated by various studies in vitro and in vivo, fucoidans show anti-viral, anti-tumor, anti-oxidant, anti-inflammatory and anti-coagulant properties, although the detailed molecular action remains to be elucidated. The aim of the present study is to assess the impact of crude fucoidan extracts, on the formation of vascular structures in co-culture models relevant for bone vascularization during bone repair and for vascularization processes in osteosarcoma...
June 20, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28601681/mutation-of-angiopoietin-1-gene-associates-with-a-new-type-of-hereditary-angioedema
#3
Valeria Bafunno, Davide Firinu, Maria D'Apolito, Giorgia Cordisco, Stefania Loffredo, Angelica Leccese, Maria Bova, Maria Pina Barca, Rosa Santacroce, Marco Cicardi, Stefano Del Giacco, Maurizio Margaglione
BACKGROUND: Hereditary angioedema (HAE) is a rare genetic disease usually due to mutation within the C1 inhibitor or the coagulation Factor XII gene. However, in a series of patients with HAE no causative variants have been described and the pathophysiology of the disease remains unknown (U-HAE). Identification of causative genes in U-HAE is valuable for understanding the cause of the disease. OBJECTIVE: We conducted genetic studies in Italian patients with U-HAE to identify novel causative genes...
June 7, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28595568/differences-in-responses-of-grass-carp-to-different-types-of-grass-carp-reovirus-gcrv-and-the-mechanism-of-hemorrhage-revealed-by-transcriptome-sequencing
#4
Libo He, Aidi Zhang, Yongyan Pei, Pengfei Chu, Yongming Li, Rong Huang, Lanjie Liao, Zuoyan Zhu, Yaping Wang
BACKGROUND: Grass carp is an important farmed fish in China that is affected by serious disease, especially hemorrhagic disease caused by grass carp reovirus (GCRV). The mechanism underlying the hemorrhagic symptoms in infected fish remains to be elucidated. Although GCRV can be divided into three distinct subtypes, differences in the pathogenesis and host immune responses to the different subtypes are still unclear. The aim of this study was to provide a comprehensive insight into the grass carp response to different GCRV subtypes and to elucidate the mechanism underlying the hemorrhagic symptoms...
June 8, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28589128/low-density-lipoprotein-receptor-related-protein-1-signaling-in-angiogenesis
#5
REVIEW
Hua Mao, Liang Xie, Xinchun Pi
Low-density lipoprotein receptor-related protein-1 (LRP1) plays multifunctional roles in lipid homeostasis, signaling transduction, and endocytosis. It has been recognized as an endocytic receptor for many ligands and is involved in the signaling pathways of many growth factors or cytokines. Dysregulation of LRP1-dependent signaling events contributes to the development of pathophysiologic processes such as Alzheimer's disease, atherosclerosis, inflammation, and coagulation. Interestingly, recent studies have linked LRP1 with endothelial function and angiogenesis, which has been underappreciated for a long time...
2017: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/28587383/mechanism-of-the-protective-effects-of-the-combined-treatment-with-rhynchophylla-total-alkaloids-and-sinapine-thiocyanate-against-a-prothrombotic-state-caused-by-vascular-endothelial-cell-inflammatory-damage
#6
Yunlun Li, Xinya Zhang, Wenqing Yang, Chao Li, Yanjun Chu, Haiqiang Jiang, Zhenzhen Shen
The aim of the present study was to investigate the effect and the underlying mechanism of the combined treatment of rhynchophylla total alkaloids (RTA) and sinapine thiocyanate for protection against a prothrombotic state (PTS) associated with the tumor necrosis factor-alpha (TNF-α)-induced inflammatory injury of vascular endothelial cells (VECs). A TNF-α-induced VEC inflammatory injury model was established, and cell morphology of VECs was evaluated using scanning electron microscopy. In addition, reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to examine the mRNA and protein expression of coagulation-related factors, including nuclear factor-κB (NF-κB), transforming growth factor-β1 (TGF-β1), tissue factor (TF), plasminogen activator inhibitor (PAI-1), protease-activation receptors (PAR-1) and protein kinase C (PKC-α) in VECs...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28576878/the-disulfide-isomerase-erp72-supports-arterial-thrombosis-in-mice
#7
Junsong Zhou, Yi Wu, Fengwu Chen, Lu Wang, Lubica Rauova, Vincent M Hayes, Mortimer Poncz, Hong Li, Tong Liu, Junling Liu, David W Essex
Several CGHC motif-containing disulfide isomerases support thrombosis. We here report that ERp72, with three CGHC redox-active sites (a(o), a, and a'), supports thrombosis. We generated a new conditional knockout mouse model, and found that Tie2-Cre/ERp72(fl/fl) mice with blood and endothelial cells lacking ERp72 had prolonged tail bleeding times, and decreased platelet accumulation in laser-induced cremaster arteriole injury and FeCl3-induced mesenteric arterial injury. Fibrin deposition was decreased in the laser injury model...
June 2, 2017: Blood
https://www.readbyqxmd.com/read/28570958/interplay-between-alternatively-spliced-tissue-factor-and-full-length-tissue-factor-in-modulating-coagulant-activity-of-endothelial-cells
#8
B Ünlü, V Y Bogdanov, H H Versteeg
BACKGROUND: Full length Tissue factor (flTF) is a key player in hemostasis and also likely contributes to venous thromboembolism (VTE), the third most common cardiovascular disease. flTF and its minimally coagulant isoform, alternatively spliced TF (asTF), have been detected in thrombi, suggesting participation of both isoforms in thrombogenesis, but data on participation of asTF in hemostasis is lacking. Therefore, we assessed the role of asTF in flTF cofactor activity modulation, using a co-expression system...
May 25, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28570146/recombinant-c1-esterase-inhibitor-reduces-cytokine-storm-in-an-ex-vivo-whole-blood-model
#9
Vladimir A Bobkov, Roman V Tikhonov, Alexander M Shuster, Dmitry A Poteryaev, Veronika N Bade
C1 esterase inhibitor (C1INH) is an abundant component of blood plasma (the average concentration is 250 mg/L); it is known to be involved in several biological processes, for instance, in the regulation of the coagulation system, adhesion of leukocytes on endothelial cells, and in the regulation of complement and kallikrein cascades. Lately, the role of C1INH in immunomodulation has gained considerable attention. We used an ex vivo whole blood model to examine the influence of C1INH and its mutated variants on the inflammatory cytokines interleukin (IL)-6, tumor necrosis factor-α (TNFα), and IL-1β...
June 1, 2017: Journal of Interferon & Cytokine Research
https://www.readbyqxmd.com/read/28561744/synthesis-and-thrombin-factor-xa-and-u46619-inhibitory-effects-of-non-amidino-and-amidino-n%C3%A2-thiophenecarbonyl-and-n%C3%A2-tosylanthranilamides
#10
Soo Hyun Lee, Wonhwa Lee, ThiHa Nguyen, Il Soo Um, Jong-Sup Bae, Eunsook Ma
Thrombin (factor IIa) and factor Xa (FXa) are key enzymes at the junction of the intrinsic and extrinsic coagulation pathways and are the most attractive pharmacological targets for the development of novel anticoagulants. Twenty non-amidino N²-thiophencarbonyl- and N²-tosyl anthranilamides 1-20 and six amidino N²-thiophencarbonyl- and N²-tosylanthranilamides 21-26 were synthesized to evaluate their activated partial thromboplastin time (aPTT) and prothrombin time (PT) using human plasma at a concentration of 30 µg/mL in vitro...
May 31, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28550640/endogenous-tissue-factor-pathway-inhibitor-in-vascular-smooth-muscle-cells-inhibits-arterial-thrombosis
#11
Jichun Yang, Kaiyue Jin, Jiajun Xiao, Jing Ma, Duan Ma
Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPI(Flox) mice crossbred with Sma-Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis...
May 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28526762/exacerbation-of-thromboinflammation-by-hyperglycemia-precipitates-cerebral-infarct-growth-and-hemorrhagic-transformation
#12
Jean-Philippe Desilles, Varouna Syvannarath, Véronique Ollivier, Clément Journé, Sandrine Delbosc, Célina Ducroux, William Boisseau, Liliane Louedec, Lucas Di Meglio, Stéphane Loyau, Martine Jandrot-Perrus, Louis Potier, Jean-Baptiste Michel, Mikael Mazighi, Benoit Ho-Tin-Noé
BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. METHODS: Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging...
May 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28515093/circulating-soluble-p-selectin-must-dimerize-to-promote-inflammation-and-coagulation-in-mice
#13
Sumith R Panicker, Padmaja Mehta-D'souza, Nan Zhang, Arkadiusz G Klopocki, Bojing Shao, Rodger P McEver
Leukocyte adhesion to P-selectin on activated platelets and endothelial cells induces shedding of the P-selectin ectodomain into the circulation. Plasma soluble P-selectin (sP-selectin) is elevated 3-4-fold in patients with cardiovascular disease. Circulating sP-selectin is thought to trigger signaling in leukocytes that directly contributes to inflammation and thrombosis. However, sP-selectin likely circulates as a monomer, and in vitro studies suggest that sP-selectin must dimerize to induce signaling in leukocytes...
May 17, 2017: Blood
https://www.readbyqxmd.com/read/28509684/histone-complexed-dna-fragments-levels-are-associated-with-coagulopathy-endothelial-cell-damage-and-increased-mortality-after-severe-pediatric-trauma
#14
Robert T Russell, Sarah C Christiaans, Tate Nice, Morgan Banks, Vincent Mortellaro, Charity Morgan, Amy Duhachek-Stapelman, Steven J Lisco, Jeffrey D Kerby, Brant M Wagener, Mike K Chen, Jean-François Pittet
BACKGROUND: The release of damage-associated molecular pattern molecules (DAMPs) in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. METHODS: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013-2016...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28498471/sodium-tanshinone-iia-sulfonate-improves-inflammation-aortic-endothelial-cell-apoptosis-disseminated-intravascular-coagulation-and-multiple-organ-damage-in-a-rat-heat-stroke-model
#15
Fang Chen, Huimin Li, Guoguo Zhu, Xiaojuan Chen, Zhongzhi Tang
The aim of the present study was to investigate the effects of sodium tanshinone IIA sulfonate (STS) on inflammatory responses, aortic endothelial cell apoptosis, disseminated intravascular coagulation (DIC) and multiple organ damage in an animal model of classic heat stroke (CHS). The rats in the heat stroke (HS) and STS‑treated heat stroke (STS‑HS) groups were placed into a pre‑warmed animal temperature controller (ATC) at 35˚C. The moment at which the rectal temperature reached 43.5˚C was considered as the time of onset of HS...
July 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28459353/role-of-coagulopathy-in-glucocorticoid-induced-osteonecrosis-of-the-femoral-head
#16
Qiankun Zhang, Jin L V, Lie Jin
The two major theories of glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) are apoptosis and ischaemia. The traditional theory implicates ischaemia as the main aetiological factor because the final common pathway of ONFH is interruption of blood supply to the bone. The most common causes of interruption of blood supply include fat embolism and coagulation disorders. GCs can directly or indirectly lead to coagulation disorders, producing a hypercoagulable state, followed by poor blood flow, ischaemia, and eventually ONFH...
January 1, 2017: Journal of International Medical Research
https://www.readbyqxmd.com/read/28458284/cancer-stromal-targeting-therapy
#17
Yasuhiro Matsumura
 Recent advances in antibody-drug conjugate (ADC) technology have shown considerable promise in targeted cancer therapy. The ADC strategy should be confined to highly toxic anticancer agents and not to ordinary anti-cancer agents (ACAs) because the affinity of monoclonal antibodies (mAbs) diminishes if more than three ACA molecules are conjugated. According to this principle, higher amounts of ADC should be administered so that each of the ACAs is conjugated to the mAbs. Therefore for an ordinary ACA, nanoparticles should be the preferred drug delivery system (DDS)...
2017: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
https://www.readbyqxmd.com/read/28450451/a-novel-munc13-4-s100a10-annexin-a2-complex-promotes-weibel-palade-body-exocytosis-in-endothelial-cells
#18
Tarek Chehab, Nina Criado Santos, Anna Holthenrich, Sophia N Koerdt, Jennifer Disse, Christian Schuberth, Ali Reza Nazmi, Maaike Neeft, Henriette Koch, Kwun Nok M Man, Sonja M Wojcik, Thomas F J Martin, Peter van der Sluijs, Nils Brose, Volker Gerke
Endothelial cells respond to blood vessel injury by the acute release of the procoagulant von Willebrand factor, which is stored in unique secretory granules called Weibel-Palade bodies (WPBs). Stimulated WPB exocytosis critically depends on their proper recruitment to the plasma membrane, but factors involved in WPB-plasma membrane tethering are not known. Here we identify Munc13-4, a protein mutated in familial hemophagocytic lymphohistiocytosis 3, as a WPB-tethering factor. Munc13-4 promotes histamine-evoked WPB exocytosis and is present on WPBs, and secretagogue stimulation triggers an increased recruitment of Munc13-4 to WPBs and a clustering of Munc13-4 at sites of WPB-plasma membrane contact...
June 15, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28450294/gas6-growth-arrest-specific-6-promotes-inflammatory-ccr2-hi-cx3cr1-lo-monocyte-recruitment-in-venous-thrombosis
#19
Sandrine Laurance, François-René Bertin, Talin Ebrahimian, Yusra Kassim, Ryan N Rys, Stéphanie Lehoux, Catherine A Lemarié, Mark D Blostein
OBJECTIVES: Coagulation and inflammation are inter-related. Gas6 (growth arrest-specific 6) promotes venous thrombosis and participates to inflammation through endothelial-innate immune cell interactions. Innate immune cells can provide the initiating stimulus for venous thrombus development. We hypothesize that Gas6 promotes monocyte recruitment during venous thrombosis. APPROACH AND RESULTS: Deep venous thrombosis was induced in wild-type and Gas6-deficient (-/-) mice using 5% FeCl3 and flow reduction in the inferior vena cava...
April 27, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28431948/serum-peptides-as-putative-modulators-of-inflammation-in-psoriasis
#20
Tetsuhiko Matsuura, Masaaki Sato, Kouhei Nagai, Toshiyuki Sato, Mitsumi Arito, Kazuki Omoteyama, Naoya Suematsu, Kazuki Okamoto, Tomohiro Kato, Yoshinao Soma, Manae S Kurokawa
BACKGROUND: Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood. OBJECTIVE: We tried to identify novel serum peptides associated with the pathophysiology of psoriasis. METHODS: Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry...
March 27, 2017: Journal of Dermatological Science
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