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Weifeng Yuan, Shaohua Hou, Hong Jia, Zhizhao Qiu, Tao Liu, Xinsheng Chen, Hongjun Li, Yanchen Sun, Lin Liang, Xiukun Sui, Xinghui Zhao, Zhanzhong Zhao
Gingivitis is evidenced by inflammation of the free gingiva, and still reversible. If left untreated, it may then progress to periodontitis. In the present study, the therapeutical effect of ketotifen fumarate on gingivitis was explored. Domestic cats with varying degrees of gingivitis naturally were enrolled in this study. Subgroups of animals were treated twice daily for one week with or without ketotifen fumarate (5 mg/kg). Effects of ketotifen fumarate were measured on gingival index, cells accumulation, mediators release, receptor-ligand interaction, oxidative stress, MAPK and NF-κB pathways, epithelial barrier and apoptosis...
October 10, 2018: International Immunopharmacology
Mariyana Hristova, Spaska Stanilova, Lyuba Miteva
BACKGROUND: Renin-angiotensin system (RAS) is a complex network of enzymes and peptides with the essential role in blood pressure control. The relationships between RAS components, RAS-related genetic polymorphisms and therapy response in essential hypertension (EH) were widely explored but the results were inconclusive. AIM: The aim of this study was to explore the functional role of ACE insertion/deletion (I/D) polymorphism on the systemic quantity of angiotensin-converting enzyme (ACE), its homolog - ACE2, chymase and angiotensin II in EH patients with respect to achieved therapeutic blood pressure control...
October 11, 2018: Clinical and Experimental Hypertension: CHE
Nicholas G Kounis, Gianfranco Cervellin, Ioanna Koniari, Laura Bonfanti, Periklis Dousdampanis, Nikolaos Charokopos, Stelios F Assimakopoulos, Stavros K Kakkos, Ioannis G Ntouvas, George D Soufras, Ioannis Tsolakis
The first reported human anaphylactic death is considered to be the Pharaoh Menes death, caused by a wasp sting. Currently, anaphylactic cardiovascular events represent one of most frequent medical emergencies. Rapid diagnosis, prompt and appropriate treatment can be life saving. The main concept beyond anaphylaxis lies to myocardial damage and ventricular dysfunction, thus resulting in cardiovascular collapse. Cardiac output depression due to coronary hypoperfusion from systemic vasodilation, leakage of plasma and volume loss due to increased vascular permeability, as well as reduced venous return, are regarded as the main causes of cardiovascular collapse...
September 2018: Annals of Translational Medicine
S M Pilkington, M J Barron, R E B Watson, C E M Griffiths, S Bulfone-Paus
BACKGROUND: Skin health declines with age and this is partially attributed to immunosenescence. Mast cells (MCs) are innate immune cells which coordinate tissue immune responses integral to skin homeostasis and disease. OBJECTIVES: To understand how MCs contribute to human skin ageing, we investigated how intrinsic ageing impacts MC phenotype and MC relationships with other immune cells and skin structures. METHODS: In photoprotected skin biopsies from young (≤30yrs) and aged (≥75yrs) individuals immunostaining and spatial morphometry were performed to identify changes in MC phenotype, number, distribution and interaction with the vasculature and nerve fibres...
October 6, 2018: British Journal of Dermatology
Sarfaraz Ahmad, Carlos M Ferrario
Chymase is primarily found in mast cells (MCs), fibroblasts, and vascular endothelial cells. MC chymase is released into the extracellular interstitium in response to inflammatory signals, tissue injury, and cellular stress. Among many functions, chymase is a major extravascular source for angiotensin II (Ang II) generation. Several recent pre-clinical and a few clinical studies point to the relatively unrecognized fact that chymase inhibition may have significant therapeutic advantages over other treatments in halting progression of cardiac and vascular disease...
October 2, 2018: Expert Opinion on Therapeutic Patents
Martin Houde, Adel Schwertani, Hanène Touil, Louisane Desbiens, Otman Sarrhini, Roger Lecomte, Martin Lepage, Hugo Gagnon, Shinji Takai, Gunnar Pejler, Danielle Jacques, Fernand Gobeil, Robert Day, Pedro D'Orléans-Juste
Chymase, a mast cell serine protease involved in the generation of multiple cardiovascular factors, such as angiotensin II and endothelin-1 (ET-1), is elevated and participates in tissue degeneration after permanent myocardial infarction (PMI). Anesthetized 4-month old male wild-type (WT) C57BL/6J mice and mouse mast cell protease-4 knockout (mMCP-4 KO) congeners were subjected to ligation of the left anterior descending (LAD) coronary artery. A group of mice was then subjected to Kaplan-Meier 28-day survival analysis...
2018: Frontiers in Pharmacology
Guozhu Xie, Tan Cheng, Jie Lin, Lanfang Zhang, Jieling Zheng, Ying Liu, Guobo Xie, Baiyao Wang, Yawei Yuan
BACKGROUND: Current checkpoint immunotherapy has shown potential to control cancer by restoring or activating the immune system. Nevertheless, multiple mechanisms are involved in immunotherapy resistance which limits the clinical benefit of checkpoint inhibitors. An immunosuppressive microenvironment is an important factor mediating the original resistance of tumors to immunotherapy. A previous report by our group has demonstrated that local angiotensin II (AngII) predominantly exists in a tumor hypoxic microenvironment where hypoxic tumour cells produced AngII by a hypoxia-lactate-chymase-dependent mechanism...
September 12, 2018: Journal for Immunotherapy of Cancer
Fanyin Meng, Lindsey Kennedy, Laura Hargrove, Jennifer Demieville, Hannah Jones, Taronish Madeka, Allen Karstens, Kevin Chappell, Gianfranco Alpini, Amelia Sybenga, Pietro Invernizzi, Francesca Bernuzzi, Sharon DeMorrow, Heather Francis
Ursodeoxycholic acid (UDCA) is used to treat biliary disorders; and, bile acids alter mast cell (MC) histamine release. MCs infiltrate Mdr2-/- mice liver (model of primary sclerosing cholangitis (PSC)). MC-derived histamine increases inflammation, hepatic stellate cell (HSC) activation and fibrosis. The objective was to determine the effects of UDCA treatment on MC infiltration, biliary damage, inflammation and fibrosis in Mdr2-/- mice and human PSC. Wild-type and Mdr2-/- mice were fed bile acid control diet or UDCA (0...
August 24, 2018: Laboratory Investigation; a Journal of Technical Methods and Pathology
Tuba M Ansary, Maki Urushihara, Yoshihide Fujisawa, Sayaka Nagata, Hidenori Urata, Daisuke Nakano, Hitomi Hirofumi, Kazuo Kitamura, Shoji Kagami, Akira Nishiyama
NEW FINDINGS: What is the central question of this study? Can chymase inhibition prevent angiotensin I-induced hypertension through inhibiting the conversion of angiotensin I to angiotensin II in the kidney? What is the main finding and its importance? Treatment with TEI-F00806 decreased angiotensin II content of the kidney, renal cortical angiotensinogen protein levels and chymase mRNA expression, and attenuated the development of hypertension. ABSTRACT: The effects of the selective chymase inhibitor TEI-F00806 were examined on angiotensin I (Ang I)-induced hypertension and intrarenal angiotensin II (Ang II) production in salt-treated mice...
August 23, 2018: Experimental Physiology
Miaojuan Qiu, Suchun Li, Lizi Jin, Pinning Feng, Yonglun Kong, Xiaoduo Zhao, Yu Lin, Yunyun Xu, Chunling Li, Weidong Wang
BACKGROUND: Lipotoxicity plays an important role in the pathogenesis of kidney injury. Our previous study demonstrated that activation of local renin-angiotensin system (RAS) was involved in saturated free fatty acids palmitic acid (PA)-induced tubular cell injuries. The current study aims to investigate whether suppression of RAS by combination of direct renin inhibitor aliskiren and noncanonical RAS pathway chymase inhibitor chymostatin attenuates PA or cholesterol induced-endoplasmic reticulum stress (ER stress) and apopotosis in cultured human proximal tubular HK2 cells...
July 31, 2018: Lipids in Health and Disease
Lei Zhao, Yasuto Yamaguchi, Xiaomei Ge, William H Robinson, John Morser, Lawrence L K Leung
BACKGROUND: Chemerin is a chemoattractant involved in immunity that also functions as an adipokine. Chemerin is secreted as an inactive precursor (chem163S), and its activation requires proteolytic cleavages at its C-terminus, involving proteases in coagulation, fibrinolysis, and inflammation. Previously, we found chem158K was the dominant chemerin form in synovial fluids from patients with arthritis. In this study, we aimed to characterize a distinct cleaved chemerin form, chem156F, in osteoarthritis (OA) and rheumatoid arthritis (RA)...
July 4, 2018: Arthritis Research & Therapy
T Z Salem, F Zhang, N Sahly, S Thiem
Integral membrane proteins (IMPs) are popular target for drugs, but their resolved structures have been overlooked when compared with cytosolic proteins. The main reason is that IMPs usually need intensive post-translational modifications and they are bound to membranes, which increase the complexity of purifying or crystalizing them. Although different expression systems are used to express IMPs, baculovirus is considered one of the most successful expression systems for those proteins. Despite that, there are always unknown discrepancies in the level of IMPs expression in the baculovirus expression system...
August 2018: Molecular Biotechnology
Friederike Kanefendt, Uwe Thuß, Michael Becka, Stefanie Boxnick, Matthias Berse, Armin Schultz, Christiane Otto
The orally available chymase inhibitor BAY 1142524 is currently being developed as a first-in-class treatment for left-ventricular dysfunction after myocardial infarction. Results from 3 randomized, single-center, phase 1 studies in healthy male volunteers examining the safety, tolerability, and pharmacokinetics of BAY 1142524 are summarized. In this first-in-human study, single oral doses of 1-200 mg were administered in fasted state as liquid service formulation or immediate release (IR) tablets. The relative bioavailability and the effect of a high-fat/high-calorie meal were investigated at the 5-mg dose...
June 7, 2018: Clinical Pharmacology in Drug Development
Nurul A S Binti Mohd Amir, Amanda E Mackenzie, Laura Jenkins, Karim Boustani, Marston C Hillier, Tomoko Tsuchiya, Graeme Milligan, James E Pease
The chemokine CXCL17 is associated with the innate response in mucosal tissues but is poorly characterized. Similarly, the G protein-coupled receptor GPR35, expressed by monocytes and mast cells, has been implicated in the immune response, although its precise role is ill-defined. A recent manuscript reported that GPR35 was able to signal in response to CXCL17, which we set out to confirm in this study. GPR35 was readily expressed using transfection systems but failed to signal in response to CXCL17 in assays of β-arrestin recruitment, inositol phosphate production, calcium flux, and receptor endocytosis...
July 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Takayuki Matsuno, Shota Toyoshima, Tomomi Sakamoto-Sasaki, Jun-Ichi Kashiwakura, Akira Matsuda, Yasuo Watanabe, Hiromitsu Azuma, Kei Kawana, Tatsuo Yamamoto, Yoshimichi Okayama
BACKGROUND: Although rodent decidual mast cells (MCs) reportedly play an important role in implantation and placenta formation, the characterization of human decidual MCs has been not well clarified. The aims of this study were to investigate the distribution and characteristics of MCs in human decidua and to establish a culture system for decidua-derived MCs. METHODS: Decidual tissues were obtained from patients who underwent a legal elective abortion (6th week to 9th week of pregnancy), and decidual MCs were enzymatically dispersed...
September 2018: Allergology International: Official Journal of the Japanese Society of Allergology
Shabana T Malik, Brian R Birch, David Voegeli, Mandy Fader, Vipul Foria, Alan J Cooper, Andrew F Walls, Bashir A Lwaleed
AIMS: To identify the presence and geographical distribution of mast cell (MC) subtypes: MCT (tryptase positive-chymase negative) and MCTC (tryptase positive-chymase positive) in bladder tissue. METHODS: Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MCT and MCTC ) and anti-MC chymase (for MCTC )...
September 2018: Journal of Clinical Pathology
Miho Inokuchi, Shyam Prakash Dumre, Shusaku Mizukami, Mya Myat Ngwe Tun, Mohamed Gomaa Kamel, Dao Huy Manh, Le Hong Phuc, Nguyen Van Thuong, Tran Van An, Lan Nguyen Weiss, Tarek Turk, Tran Ngoc Dang, Vu Thi Que Huong, Kouichi Morita, Nguyen Tien Huy, Kenji Hirayama
There is no definitive predictor of dengue severity, and this has led to a very large number of unnecessary hospitalizations worldwide. Although mast cell mediators are believed to a play role in dengue severity, the lack of precise kinetic data demands further research on early predictors. We enrolled 111 patients with confirmed dengue and 85 with "other febrile illness" (OFI) in a hospital-based prospective study in Vietnam. Dengue patients were classified as level 1, 2, or 3 based on the clinical intervention received...
September 2018: Archives of Virology
Sankar Devarajan, Eiji Yahiro, Yoshinari Uehara, Rieko Kuroda, Yoshio Hirano, Kaori Nagata, Shinichiro Miura, Keijiro Saku, Hidenori Urata
A novel chymase inhibitor has been reported to have depressor effect in salt-induced hypertension. Therefore, we examined the hypothesis that chymase inhibitory dried young leaves of Polygonum hydropiper (PPH) or young leaves extract of Polygonum hydropiper (PHE) could reduce salt-induced hypertension. In this study, 8-wk old wild-type mice were allocated into three experiments and experiment I included groups, I- normal water drinking, II- high salt (2% NaCl) water (HSW) drinking, and III- HSW plus PPH (500 mg kg-1 , orally) for 12-wk...
June 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Katariina Maaninka, Su Duy Nguyen, Mikko I Mäyränpää, Riia Plihtari, Kristiina Rajamäki, Perttu J Lindsberg, Petri T Kovanen, Katariina Öörni
BACKGROUND AND AIMS: Subendothelial interaction of LDL with extracellular matrix drives atherogenesis. This interaction can be strengthened by proteolytic modification of LDL. Mast cells (MCs) are present in atherosclerotic lesions, and upon activation, they degranulate and release a variety of neutral proteases. Here we studied the ability of MC proteases to cleave apoB-100 of LDL and affect the binding of LDL to proteoglycans. METHODS: Mature human MCs were differentiated from human peripheral blood-derived CD34+ progenitors in vitro and activated with calcium ionophore to generate MC-conditioned medium...
August 2018: Atherosclerosis
Tiankai Li, Xiaowei Zhang, Heng-Jie Cheng, Zhi Zhang, Sarfaraz Ahmad, Jasmina Varagic, Weimin Li, Che Ping Cheng, Carlos M Ferrario
BACKGROUND: Angiotensin-(1-12) [Ang-(1-12)] is a chymase-dependent source for angiotensin II (Ang II) cardiac activity. The direct contractile effects of Ang-(1-12) in normal and heart failure (HF) remain to be demonstrated. We assessed the hypothesis that Ang-(1-12) may modulate [Ca2+ ]i regulation and alter cardiomyocyte contractility in normal and HF rats. METHODS AND RESULTS: We compared left ventricle (LV) myocyte contractile and calcium transient ([Ca2+ ]iT ) responses to angiotensin peptides in 16 SD rats with isoproterenol-induced HF and 16 age-matched controls...
August 1, 2018: International Journal of Cardiology
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