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https://www.readbyqxmd.com/read/28223242/fviia-prevents-the-progressive-hemorrhaging-of-a-brain-contusion-by-protecting-microvessels-via-formation-of-the-tf-fviia-fxa-complex
#1
Qiang Yuan, Dalong Zhang, Sirong Wu, Jian Yu, Lei Yu, Yirui Sun, Zhuoying Du, Zhiqi Li, Liangfu Zhou, Xing Wu, Jin Hu
Factor VII (FVII) plays a key role in the initiation of the coagulation cascade and, in clinical situations, recombinant activated FVII (rFVIIa) effectively prevents progressive hemorrhaging after a brain contusion. However, it remains unclear whether decreases in FVII activity directly lead to progressive hemorrhaging and, moreover, the precise mechanisms underlying this process are not yet known. The present study demonstrated that decreased FVII activity directly led to progressive hemorrhaging of the cerebral contusions...
February 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28191683/immediate-type-allergic-and-protease-mediated-reactions-are-involved-in-scratching-behavior-induced-by-topical-application-of-dermatophagoides-farinae-extract-in-nc-nga-mice
#2
Yoshihito Yamada, Yuhki Ueda, Aki Nakamura, Shoji Kanayama, Rie Tamura, Kei Hashimoto, Tatsumi Matsumoto, Ritsuko Ishii
Atopic dermatitis (AD)-like dermatitis can be induced by repeated topical application of an ointment containing Dermatophagoides farinae body (Dfb) extract in NC/Nga mice. This AD-like murine model also exhibits a biphasic increase in the number of scratching behavior after topical application of Dfb ointment. In this study, we investigated the possible mechanisms underlying the scratching behavior in each phase. An increase in the content of mast cell derived mediators such as histamine and 5-hydroxytryptamine in the lesional skin and increased vascular permeability were observed in the early phase after the Dfb ointment application...
February 13, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28184250/meiotic-outcome-in-two-carriers-of-y-autosome-reciprocal-translocations-selective-elimination-of-certain-segregants
#3
Harita Ghevaria, Roy Naja, Sioban SenGupta, Paul Serhal, Joy Delhanty
BACKGROUND: Reciprocal Y autosome translocations are rare but frequently associated with male infertility. We report on the meiotic outcome in embryos fathered by two males with the karyotypes 46,X,t(Y;4)(q12;p15.32) and 46,X,t(Y;16)(q12;q13). The two couples underwent preimplantation genetic diagnosis (PGD) enabling determination of the segregation types that were compatible with fertilization and preimplantation embryo development. Both PGD and follow up analysis were carried out via fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (aCGH) allowing the meiotic segregation types to be determined in a total of 27 embryos...
2017: Molecular Cytogenetics
https://www.readbyqxmd.com/read/28169521/biased-signaling-by-peptide-agonists-of-protease-activated-receptor-2
#4
Yuhong Jiang, Mei-Kwan Yau, W Mei Kok, Junxian Lim, Kai-Chen Wu, Ligong Liu, Timothy A Hill, Jacky Y Suen, David P Fairlie
Protease activated receptor 2 (PAR2) is associated with metabolism, obesity, inflammatory, respiratory and gastrointestinal disorders, pain, cancer and other diseases. The extracellular N-terminus of PAR2 is a common target for multiple proteases, which cleave it at different sites to generate different N-termini that activate different PAR2-mediated intracellular signaling pathways. There are no synthetic PAR2 ligands that reproduce the same signaling profiles and potencies as proteases. Structure-activity relationships here for 26 compounds spanned a signaling bias over 3 log units, culminating in three small ligands as biased agonist tools for interrogating PAR2 functions...
February 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28162529/-292-protease-activated-receptor-2-par2-is-a-mediator-of-nociception-in-a-mouse-model-of-migraine
#5
S Hassler, T Price, G Dussor, S Boitano, J Vagner
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28120492/the-role-of-toll-like-and-protease-activated-receptors-and-associated-intracellular-signaling-in-porphyromonas-gingivalis-infected-gingival-fibroblasts
#6
Eleonor Palm, Isak Demirel, Torbjörn Bengtsson, Hazem Khalaf
Porphyromonas gingivalis, which is considered a keystone agent in periodontitis, has evolved elaborate mechanisms to grow and survive in a hostile milieu. The gingival fibroblast is the major cell type in the gingiva and is considered to be important in the periodontitis-associated inflammation. As a part of the innate immune response, they produce cytokines such as CXCL8 and interleukin (IL)-6 which are believed to contribute to the destruction of the tooth-supporting tissues. This study investigates how the expression of protease-activated receptors (PAR1, PAR2) and toll-like receptors (TLR2, TLR4) changes with P...
February 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28116092/teleocidin-a2-inhibits-human-proteinase-activated-receptor-2-signaling-in-tumor-cells
#7
Sonja Stahn, Lisa Thelen, Ina-Maria Albrecht, Jens Bitzer, Thomas Henkel, Nicole Elisabeth Teusch
Enhanced expression of the proteinase-activated receptor 2 (PAR2) is linked to cell proliferation and migration in many cancer cell types. The role of PAR2 in cancer progression strongly illustrates the need for PAR2-inhibiting compounds. However, to date, potent and selective PAR2 antagonists have not been reported. The natural product teleocidin A2 was characterized against PAR2-activating peptide SLIGKV-NH 2, and trypsin-induced PAR2-dependent intracellular Ca(2+) mobilization in tumor and in primary endothelial or epithelial cells...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28109095/-establishment-of-a-sd-rat-model-of-vulvar-lichen-simplex-chronicus-and-detection-of-the-expression-of-protease-activated-receptor-2
#8
Huan Yang, Zhen-Hua Fu, Hua-Jun Tang, Cheng-Zhi Li
OBJECTIVE: To establish a SD rat model of vulvar lichen simplex chronicus (LSC) and investigate the expression of protease activated receptor 2 (PAR2) in the genital skin. METHODS: Seventy female SD rats were randomly divided into group A (blank control group, n=10), group B (with application of acetone solution 3 times per week for 10 weeks, n=10), group C (with chronic mechanical irritation 3 times per week for 10 weeks, n=10), and group D (with topical treatment with 0...
January 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28104984/role-of-mast-cell-mir-490-5p-in-irritable-bowel-syndrome
#9
Hai-Xia Ren, Fa-Can Zhang, He-Sheng Luo, Guo Zhang, Lie-Xin Liang
AIM: To determine the functional role of miR-490-5p in mast cell proliferation and apoptosis, and in the mast cell tryptase/PAR-2 signal pathway. METHODS: The 3(rd) generation of lentivirus vector systems containing enhanced green fluorescent protein (EGFP) (Ruisai Inc., Shanghai, China), which acts as a reporter gene was used to construct the mmu-miR-490-5p lentivirus expression vector pEGFP-antagomiR-490-5p, and the lentivirus vector pEGFP-negative was used as a negative control...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28103056/age-related-changes-to-vascular-protease-activated-receptor-2-in-metabolic-syndrome-a-relationship-between-oxidative-stress-receptor-expression-and-endothelium-dependent-vasodilation
#10
Kana Maruyama, Satomi Kagota, John J McGuire, Hirokazu Wakuda, Noriko Yoshikawa, Kazuki Nakamura, Kazumasa Shinozuka
Protease-activated receptor 2 (PAR2) is expressed in vascular endothelium. Nitric oxide (NO) - cyclic GMP-mediated vasodilation in response to 2-furoyl-LIGRLO-amide (2fLIGRLO), a PAR2-activating peptide, is impaired in aortas from aged SHRSP.Z-Lepr(fa)/IzmDmcr (SHRSP.ZF) rats with metabolic syndrome. Here we investigated mechanisms linking PAR2's vascular effects to phenotypic characteristics of male SHRSP.ZF rats at 10, 20, and 30 weeks of age. We found vasodilation responses to either 2fLIGRLO or enzyme-mediated PAR2 activation by trypsin were sustained until 20 weeks and lessened at 30 weeks...
October 19, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28088386/trypsin-induces-biphasic-muscle-contraction-and-relaxation-via-transient-receptor-potential-vanilloid-1-and-neurokinin-receptors-1-2-in-porcine-esophageal-body
#11
Bai Xiaopeng, Yoshimasa Tanaka, Eikichi Ihara, Katsuya Hirano, Kayoko Nakano, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura
Duodenal reflux of fluids containing trypsin relates to refractory gastroesophageal reflux disease (GERD). Esophageal peristalsis and clearance are important factors in GERD pathogenesis. However, the function of trypsin in esophageal body contractility is not fully understood. In this study, effects of trypsin on circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) of the porcine esophageal body were examined. Trypsin elicited a concentration dependent biphasic response, a major contraction and a subsequent relaxation only in CSM...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28057878/pseudoautosomal-abnormalities-in-terminal-azfb-c-deletions-are-associated-with-isochromosomes-yp-and-may-lead-to-abnormal-growth-and-neuropsychiatric-function
#12
A Castro, F Rodríguez, M Flórez, P López, B Curotto, D Martínez, A Maturana, M C Lardone, C Palma, V Mericq, M Ebensperger, F Cassorla
STUDY QUESTION: Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? SUMMARY ANSWER: Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders...
January 5, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28030866/increase-of-mast-cell-nerve-association-and-neuropeptide-receptor-expression-on-mast-cells-in-perennial-allergic-rhinitis
#13
Duc Dung Le, David Schmit, Sebastian Heck, Albert Joachim Omlor, Martina Sester, Christian Herr, Bernhard Schick, François Daubeuf, Sebastian Fähndrich, Robert Bals, Nelly Frossard, Basel Al Kadah, Quoc Thai Dinh
OBJECTIVES: Mast cells (MCs) and nerves play an important role in allergic rhinitis (AR), but little is known about their crosstalk in AR. The aim of this study was to investigate MC-nerve interaction in the human nasal mucosa during AR. METHODS: The association between MCs and nerves, the expression of neuropeptide receptors (neurokinin 1 receptor [NK1R], neurokinin 2 receptor [NK2R], calcitonin gene-related peptide receptor [CGRPR], and MrgX2) on MCs, and protease-activated receptor 2 (PAR2) and tyrosine receptor kinase A (TrkA) on nerve fibres in the human nasal mucosa were investigated with immunofluorescence and real-time PCR...
December 29, 2016: Neuroimmunomodulation
https://www.readbyqxmd.com/read/28025140/protease-activated-receptor-2-exacerbates-adenine-induced-renal-tubulointerstitial-injury-in-mice
#14
Sakiko Hayashi, Yuji Oe, Tomofumi Fushima, Emiko Sato, Hiroshi Sato, Sadayoshi Ito, Nobuyuki Takahashi
Hypercoagulability is associated with chronic kidney disease (CKD). Tissue factor/factor VIIa complex and factor Xa in the coagulation cascade are known to activate protease-activated receptor 2 (PAR2), and to cause inflammation and tissue injury. Although PAR2 is highly expressed in the kidney, it is unclear whether PAR2 plays a pathogenic role in CKD. To test this, we fed the mice lacking Par2 (F2rl1(-/-)) and wild type (F2rl1(+/+)) mice with adenine diet to induce tubulointerstitial injury, a hallmark of CKD...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27994760/par2-modulators-derived-from-gb88
#15
Mei-Kwan Yau, Ligong Liu, Jacky Y Suen, Junxian Lim, Rink-Jan Lohman, Yuhong Jiang, Adam J Cotterell, Grant D Barry, Jeffrey Y W Mak, David A Vesey, Robert C Reid, David P Fairlie
PAR2 antagonists have potential for treating inflammatory, respiratory, gastrointestinal, neurological, and metabolic disorders, but few antagonists are known. Derivatives of GB88 (3) suggest that all four of its components bind at distinct PAR2 sites with the isoxazole, cyclohexylalanine, and isoleucine determining affinity and selectivity, while the C-terminal substituent determines agonist/antagonist function. Here we report structurally similar PAR2 ligands with opposing functions (agonist vs antagonist) upon binding to PAR2...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27993717/mapping-transmembrane-residues-of-proteinase-activated-receptor-2-par2-that-influence-ligand-modulated-calcium-signaling
#16
J Y Suen, M N Adams, J Lim, P K Madala, W Xu, A J Cotterell, Y He, M K Yau, J D Hooper, D P Fairlie
Proteinase-activated receptor 2 (PAR2) is a G protein-coupled receptor involved in metabolism, inflammation, and cancers. It is activated by proteolysis, which exposes a nascent N-terminal sequence that becomes a tethered agonist. Short synthetic peptides corresponding to this sequence also activate PAR2, while small organic molecules show promising PAR2 antagonism. Developing PAR2 ligands into pharmaceuticals is hindered by a lack of knowledge of how synthetic ligands interact with and differentially modulate PAR2...
December 16, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27981668/activation-of-protease-activated-receptor-2-mediates-cutaneous-vasodilatation-but-not-sweating-roles-of-nitric-oxide-synthase-and-cyclo-oxygenase
#17
Naoto Fujii, Brendan D McNeely, Sarah Y Zhang, Yasmine C Abdellaoui, Mercy O Danquah, Glen P Kenny
What is the central question of this study? Protease-activated receptor 2 (PAR2) is located in the endothelial cells of skin vessels and eccrine sweat glands. However, a functional role of PAR2 in the control of cutaneous blood flow and sweating remains to be assessed in humans in vivo. What is the main finding and its importance? Our results demonstrate that in normothermic resting humans in vivo, activation of PAR2 elicits cutaneous vasodilatation partly through nitric oxide synthase-dependent mechanisms, but does not mediate sweating...
February 1, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/27979585/the-differential-expression-of-protease-activated-receptors-contributes-to-functional-differences-between-dark-and-fair-keratinocytes
#18
Meilang Xue, Haiyan Lin, Ruilong Zhao, Hai Po Helena Liang, Christopher Jackson
BACKGROUND: Dark skin has different properties in comparison to fair skin. Melanocytes have been shown to partly contribute to these differences, however, the involvement of keratinocytes from dark or fair skin is not well demonstrated. OBJECTIVES: This study investigated the proliferation and barrier function of dark keratinocytes (DK) and fair keratinocytes (FK), and the role of protease activated receptor (PAR)1 and PAR2. METHODS: DK and FK were isolated from human neonatal foreskins...
December 5, 2016: Journal of Dermatological Science
https://www.readbyqxmd.com/read/27925497/anti-inflammatory-and-anticancer-effects-of-flavonol-glycosides-from-diplotaxis-harra-through-gsk3%C3%AE-regulation-in-intestinal-cells
#19
Imen Nasri, Rachid Chawech, Cynthia Girardi, Emmanuel Mas, Audrey Ferrand, Nathalie Vergnolle, Nicolas Fabre, Raoudha Mezghani-Jarraya, Claire Racaud-Sultan
CONTEXT AND OBJECTIVE: Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) is traditionally used as an antidiabetic, anti-inflammatory or anticancer agent. In these pathologies, the glycogen synthase kinase 3 β (GSK3β) is overactivated and represents an interesting therapeutic target. Several flavonoids can inhibit GSK3β and the purpose of this study was to search for the compounds in Diplotaxis harra which are able to modulate GSK3β. MATERIALS AND METHODS: Methanol extracts from D...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/27916875/proteinase-activated-receptor-2-is-a-novel-regulator-of-tgf-%C3%AE-signaling-in-pancreatic-cancer
#20
REVIEW
David Witte, Franziska Zeeh, Thomas Gädeken, Frank Gieseler, Bernhard H Rauch, Utz Settmacher, Roland Kaufmann, Hendrik Lehnert, Hendrik Ungefroren
TGF-β has a dual role in tumorigenesis, acting as a tumor suppressor in normal cells and in the early stages of tumor development while promoting carcinogenesis and metastasis in advanced tumor stages. The final outcome of the TGF-β response is determined by cell-autonomous mechanisms and genetic alterations such as genomic instability and somatic mutations, but also by a plethora of external signals derived from the tumor microenvironment, such as cell-to-cell interactions, growth factors and extracellular matrix proteins and proteolytic enzymes...
November 30, 2016: Journal of Clinical Medicine
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