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Chuangjia Hu, Bin Liu, Hui Li, Xiangzhong Wu, Tingting Guo, Wenhong Luo, Yingbi Zhou
Prostaglandin (PG) D2 , a prostanoid known to have hypotensive effect, can evoke increased in vitro prepartum myometrial contraction resulting from up-regulation of the F prostanoid (FP) receptor. The present study further determined postpartum rat uterine responses to PGD2 to evaluate the possibility of the prostanoid becoming a therapeutic for postpartum uterine atony, a major cause of postpartum hemorrhage that can lead to maternal morbidity. In vitro and in vivo postpartum uterine responses to PGD2 were determined and compared to those of prepartum rats...
August 11, 2018: European Journal of Pharmacology
Sachin Kumar, Akanksha Sharma, Rinkesh Kumar Gupta, Ajay Kumar Verma, Premendra D Dwivedi
Tree nuts are among "Big Eight" and have been reported globally for causing allergy. Buchanania lanzan (Bl) is one of the major tree nuts consumed by Indian population. However, very little is known about B. lanzan's induced allergic manifestation. Therefore, evaluation of it's allergenic potential was undertaken. Bl-crude protein extract sensitized BALB/c mice sera were used to identify the allergic proteins by it's IgE binding capability. The major IgE binding proteins found with molecular weight of 11, 20, 23, 25, 48, 54, and 65 kDa...
August 7, 2018: International Immunopharmacology
Juan A Giménez-Bastida, William E Boeglin, Olivier Boutaud, Michael G Malkowski, Claus Schneider
Aspirin (acetylsalicylic acid) inhibits prostaglandin (PG) synthesis by transfer of its acetyl group to a serine residue in the cyclooxygenase (COX) active site. Acetylation of Ser530 inhibits catalysis by preventing access of arachidonic acid substrate in the COX-1 isoenzyme. Acetylated COX-2, in contrast, gains a new catalytic activity and forms 15 R hydroxy-eicosatetraenoic acid (15 R-HETE) as alternate product. Here we show that acetylated COX-2 also retains COX activity, forming predominantly 15 R-configuration PGs (70 or 62% 15 R, respectively, determined using radiolabeled substrate or LC-MS analysis)...
August 10, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
R Stokes Peebles
Prostaglandins are synthesized through the metabolism of arachidonic acid via the cyclooxygenase pathway. There are five primary prostaglandins, PGD2 , PGE2 , PGF2 , PGI2 , and thromboxane B2 , that all signal through distinct seven transmembrane, G-protein coupled receptors. The receptor through which the prostaglandins signal determines their immunologic or physiologic effects. For instance, the same prostaglandin may have opposing properties, dependent upon the signaling pathways activated. In this article, we will detail how inhibition of cyclooxygenase metabolism and regulation of prostaglandin signaling regulates allergic airway inflammation and asthma physiology...
August 3, 2018: Pharmacology & Therapeutics
Jeevan Kumar Jadapalli, Griffin M Wright, Vasundhara Kain, Mohammad Asif Sherwani, Nabiha Yusuf, Ganesh V Halade
Doxorubicin (DOX) is a widely used drug for cancer treatment as a chemotherapeutic agent. However, the cellular and integrative mechanism of DOX-induced immunometabolism is unclear. Two-months-old male C57BL/6J mice were divided into high and low dose DOX-treated groups maintaining saline control. The first group was injected with high DOX 15mg/kg/week (H-DOX) and the second group was injected with 7.5mg/kg/week as latent low DOX (LL-DOX). Given that H-DOX led to complete mortality in two weeks and 70% survival in LL-DOX were compared with saline controls...
August 3, 2018: American Journal of Physiology. Heart and Circulatory Physiology
S K Kritas, C E Gallenga, C D Ovidio, G Ronconi, Al Caraffa, E Toniato, D Lauritano, P Conti
Molds include all species of microscopic fungi, the spores of which are small molecules, ubiquitous, mostly found in soil with higher rainfall and high humidity, in the atmosphere of urban and rural settings and in decaying vegetation. They originate from pathogenic fungi and have a crucial role in inflammatory response, causing a broad range of diseases. Immune suppressed subjects may develop mycoses caused by opportunistic common pathogenic fungi. Mast cells (MCs) are immune cells involved in the pathophysiology of infected skin, lung, and organs, where there is an increase of angiogenesis...
July 2018: Journal of Biological Regulators and Homeostatic Agents
Dingxin Pan, Kathleen M Buchheit, Sachin K Samuchiwal, Tao Liu, Haley Cirka, Hannah Raff, Joshua A Boyce
BACKGROUND: Classical FcεRI-induced mast cell (MC) activation causes synthesis of arachidonic acid (AA)-derived eicosanoids (leukotriene [LT] C4 , prostaglandin [PG] D2 , and thromboxane A2 ), which mediate vascular leak, bronchoconstriction, and effector cell chemotaxis. Little is known about the significance and regulation of eicosanoid generation in response to nonclassical MC activation mechanisms. OBJECTIVES: We sought to determine the regulation and significance of MC-derived eicosanoids synthesized in response to IL-33, a cytokine critical to innate type 2 immunity...
July 12, 2018: Journal of Allergy and Clinical Immunology
Eri Takeshita, Hirofumi Komaki, Hisateru Tachimori, Kazuhisa Miyoshi, Ikuo Yamamiya, Yuko Shimizu-Motohashi, Akihiko Ishiyama, Takashi Saito, Eiji Nakagawa, Kenji Sugai, Masayuki Sasaki
BACKGROUND: Patients with Duchenne muscular dystrophy (DMD) exhibit increased prostaglandin D2 (PGD2 ) expression in necrotic muscle and increased PGD2 metabolites in their urine. In mouse models, inhibiting PGD2 production suppresses muscle necrosis, suggesting a possible intervention through PGD2 -mediated activities. OBJECTIVE: We investigated the involvement of PGD2 and its potential use as a marker of pathological progression in DMD. METHODS: Sixty-one male children with DMD and thirty-five age-matched controls were enrolled in the study...
July 10, 2018: Brain & Development
Ana M Valdes, Srinivasarao Ravipati, Petros Pousinis, Cristina Menni, Massimo Mangino, Abhishek Abhishek, Victoria Chapman, David A Barrett, Michael Doherty
Omega-6 fatty acids are important inflammatory mediators increased in joints with osteoarthritis (OA) joints. To investigate the relationship between omega-6 fatty acids and knee OA 22 omega-6 lipids (arachidonic acid, linoleic acid and 20 oxylipins) were measured using liquid chromatography-mass-spectrometry in synovial fluid from 112 knees of 102 individuals (knee OA n=58; controls n=44). Thsese were tested for association with presence of knee OA adjusting for covariates and NSAID use. Validation was performed in samples from 10 individuals with unilateral knee OA comparing affected to unaffected knees...
July 9, 2018: Journal of Lipid Research
S J Kumari A Ubhayasekera, Santosh R Acharya, Jonas Bergquist
The development of a rapid, sensitive and reliable method for the quantification of bioactive arachidonic acid metabolites (AA-metabolites) in biological samples is quite challenging due to the minute concentration, short half-life and their structural complexity arising from different isomers. In this study, a simple, fast and environmentally friendly supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was developed and validated for simultaneous measurement of five (PGD2, PGE2, PGF2α, 6KetoPGF1α and LTB4) AA-metabolites in biological samples...
July 23, 2018: Analyst
Emily MacLean Scott, Lauren A Solomon, Courtney Davidson, Jessica Storie, Nami Shrestha Palikhe, Lisa Cameron
CRTh2 (encoded by PTGDR2) is a G-protein coupled receptor expressed by Th2 cells as well as eosinophils, basophils and innate lymphoid cells (ILC)2s. Activation of CRTh2, by its ligand prostaglandin (PG)D2, mediates production of type 2 cytokines (IL-4, IL-5 and IL-13), chemotaxis and inhibition of apoptosis. As such, the PGD2-CRTh2 pathway is considered important to the development and maintenance of allergic inflammation. Expression of CRTh2 is mediated by the transcription factor GATA3 during Th2 cell differentiation and within ILC2s...
2018: PloS One
Alexandros Theodoros Panagopoulos, Renata Nascimento Gomes, Fernando Gonçalves Almeida, Felipe da Costa Souza, José Carlos Esteves Veiga, Anna Nicolaou, Alison Colquhoun
Prostanoids derived from the activity of cyclooxygenases and their respective synthases contribute to both active inflammation and immune response in the tumor microenvironment. Their synthesis, deactivation and role in glioma biology have not yet been fully explored and require further study. Using quantitative real time PCR, gas chromatography/ electron impact mass spectrometry and liquid chromatography/ electrospray ionization tandem mass spectrometry, we have further characterized the prostanoid pathway in grade IV glioblastoma (GBM)...
July 2018: Prostaglandins & Other Lipid Mediators
Hong Ping Zhang, Lei Wang, Zhen Wang, Xian Rong Xu, Xian Mei Zhou, Gang Liu, Lv Yuan He, Jun Wang, Alan Hsu, Wei Min Li, Gang Wang
BACKGROUND: Despite advances in asthma management, exacerbations constitute a significant health economic burden. OBJECTIVE: To observe the efficacy and safety of Chinese herbal medicine formula entitled PingchuanYiqi (PCYQ) granule, on acute asthma and to explore its possible mechanism. MATERIALS AND METHODS: This proof-of-concept study consisted of a randomized, double-blind, placebo-controlled trial in patients with acute asthma (n = 300)...
July 2018: Respiratory Medicine
Tetsuya Tachibana, Yasua Nakai, Ryosuke Makino, Md Sakirul Islam Khan, Mark A Cline
Prostaglandin D2 (PGD2) is associated with a diverse array of functions in mammals including regulation of appetite, body temperature, sleep, and immune responses. Although much is known about the effects of PGD2 in mammals, there is a lack of information about its effects in birds. Therefore, the purpose of the present study was to determine if intracerebroventricular (ICV) and intraperitoneal (IP) injections of PGD2 affect feeding, voluntary movement, crop-emptying rate, corticosterone release, and cloacal temperature in chicks (Gallus gallus)...
July 2018: Prostaglandins & Other Lipid Mediators
Bart Hilvering, Timothy S C Hinks, Linda Stöger, Emanuele Marchi, Maryam Salimi, Rahul Shrimanker, Wei Liu, Wentao Chen, Jian Luo, Simei Go, Timothy Powell, Jennifer Cane, Samantha Thulborn, Ayako Kurioka, Tianqi Leng, Jamie Matthews, Clare Connolly, Catherine Borg, Mona Bafadhel, Christian B Willberg, Adaikalavan Ramasamy, Ratko Djukanović, Graham Ogg, Ian D Pavord, Paul Klenerman, Luzheng Xue
Human type-2 CD8+ T cells are a cell population with potentially important roles in allergic disease. We investigated this in the context of severe asthma with persistent airway eosinophilia-a phenotype associated with high exacerbation risk and responsiveness to type-2 cytokine-targeted therapies. In two independent cohorts we show that, in contrast to Th2 cells, type-2 cytokine-secreting CD8+ CRTH2+ (Tc2) cells are enriched in blood and airways in severe eosinophilic asthma. Concentrations of prostaglandin D2 (PGD2 ) and cysteinyl leukotriene E4 (LTE4 ) are also increased in the airways of the same group of patients...
June 15, 2018: Mucosal Immunology
Yuanyuan Li, Weiwei Xia, Fei Zhao, Zhaoying Wen, Aihua Zhang, Songming Huang, Zhanjun Jia, Yue Zhang
Prostaglandins (PGs) are important lipid mediators produced from arachidonic acid via the sequential catalyzation of cyclooxygenases (COXs) and specific prostaglandin synthases. There are five subtypes of PGs, namely PGE2, PGI2, PGD2, PGF2α, and thromboxane A2 (TXA2). PGs exert distinct roles by combining to a diverse family of membrane-spanning G protein-coupled prostanoid receptors. The distribution of these PGs, their specific synthases and receptors vary a lot in the kidney. This review summarized the recent findings of PGs together with the COXs and their specific synthases and receptors in regulating renal function and highlighted the insights into their roles in the pathogenesis of various kidney diseases...
May 29, 2018: Oncotarget
Takashi Hashimoto, Jordan D Rosen, Kristen M Sanders, Gil Yosipovitch
Basophils are blood granulocytes and normally constitute less than 1% of blood peripheral leukocytes. Basophils share some morphological and functional similarities with mast cells, and basophils were once regarded as redundant and negligible circulating mast cells. However, recent studies reveal the indispensable roles of basophils in various diseases, including allergic and pruritic diseases. Basophils may be involved in itch through the mediation of a Th2 immune response, interaction with other cells in the skin, and secretion of a wide variety of itch-related mediators, e...
June 12, 2018: Experimental Dermatology
Xiaoning Zhao, Yiran Li, Jiaxin Huai, Congcong Cheng, Teng Zhang, Linlin Xie, Siqi Wang, Meng Zhang, Ronghua Dai
Phellodendri chinensis cortex (P. C. cortex) and Anemarrhenae rhizoma (A. rhizoma) herb pair is a core component of traditional Chinese medicines used to treat inflammation and benign prostatic hyperplasia (BPH). The present study was designed to profile the arachidonic acid (AA) metabolomic characteristics in rat plasma and prostate after being treated with P. C. cortex and A. rhizoma as well as their combination. Plasma and prostate samples from sham group, BPH model group, herb pair group and two single herb groups were collected on days 7, 14, 21 and 28...
May 28, 2018: Biomedical Chromatography: BMC
Yong Ma, Yu He, Taijun Yin, Haoqing Chen, Song Gao, Ming Hu
Raw264.7 is a murine macrophage-like cell line commonly used to study the anti-inflammatory efficacy of natural compounds. However, the impacts of long-time incubation on the tested compounds are often inappropriately ignored. Among 77 natural phenolic compounds (mainly flavonoids), only 36 remain more than 70% after a 15-h incubation in cell culture medium at 37 °C. Interestingly, for those compounds with a relatively good chemical stability, the presence of Raw264.7 cells could accelerate their disappearance in the medium, indicating that cellular metabolism occurred...
June 20, 2018: Journal of Agricultural and Food Chemistry
Johan Kolmert, Sergio Piñeiro-Hermida, Mats Hamberg, Joshua A Gregory, Icíar P López, Alexander Fauland, Craig E Wheelock, Sven-Erik Dahlén, José G Pichel, Mikael Adner
The profile of activation of lipid mediator (LM) pathways in asthmatic airway inflammation remains unclear. This experimental study quantified metabolite levels of ω3-, ω6- and ω9-derived polyunsaturated fatty acids in bronchoalveolar lavage fluid (BALF) after 4-weeks of repeated house dust mite (HDM) exposure in a murine (C57BL/6) asthma model. The challenge induced airway hyperresponsiveness, pulmonary eosinophil infiltration, but with low and unchanged mast cell numbers. Of the 112 screened LMs, 26 were increased between 2 to >25-fold in BALF with HDM treatment (p < 0...
July 2018: Prostaglandins & Other Lipid Mediators
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