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Prostaglandins & Other Lipid Mediators

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)...
June 29, 2018: Prostaglandins & Other Lipid Mediators
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)...
June 21, 2018: Prostaglandins & Other Lipid Mediators
Karolina Serhan, Allison Gartung, Dipak Panigrahy
Ovarian cancer is the most lethal gynecologic malignancy among women. Due to the heterogeneity and complexity of the disease, as well as the insidious onset of symptoms, timely diagnosis remains extremely challenging. Despite recent advances in chemotherapy regimens for ovarian cancer patients, many still suffer from recurrence and ultimately succumb to the disease; thus, there is an urgent need for the identification of novel therapeutic targets. Within this rapidly evolving field, the role of platelets in the ovarian cancer tumor microenvironment has garnered increased attention...
June 19, 2018: Prostaglandins & Other Lipid Mediators
Joseph Schragenheim, Lars Bellner, Jian Cao, Shailendra P Singh, David Bamshad, John A McClung, Omri Maayan, Aliza Meissner, Ilana Grant, Charles T Stier, Nader G Abraham
BACKGROUND: We have previously reported that epoxyeicosatrienoic acid (EET) has multiple beneficial effects on renal and adipose tissue function, in addition to its vasodilatory action; it increases insulin sensitivity and inhibits inflammation. In an examination of the signaling mechanisms by which EET reduces renal and peri-renal fat function, we hypothesized that EET ameliorates obesity-induced renal dysfunction by improving sodium excretion, reducing the sodium-chloride cotransporter NCC, lowering blood pressure, and enhancing mitochondrial and thermogenic gene levels in PGC-1α dependent mice...
May 19, 2018: Prostaglandins & Other Lipid Mediators
Fen Xu, Xiaoyan Zhou, Jian Hao, Hua Dai, Jian Zhang, Yuanqiao He, Hua Hao
Epithelial-mesenchymal Transition (EMT) and migration play an important role in tumor progression, and lipoxin (LX), the 'stop signal' for inflammation, has been studied in basic research for its anti-inflammatory or inflammatory pro-resolving properties. Here, in the in vitro experiment, we showed that LXA4 could inhibit the EMT and migration in phorbol myristate acetate (PMA) or activated conditioned medium (ACM)-stimulated Hep3B cells by downregulation of integrin-linked kinase (ILK), a pseudokinase in cytoplasm and these effects were via inhibiting the phosphorylation of Akt and GSK3β...
May 19, 2018: Prostaglandins & Other Lipid Mediators
Karan Agrawal, Rémy Bosviel, Brian D Piccolo, John W Newman
Sweat contains a variety of lipid mediators, but whether they originate from the plasma filtrate or from the cutaneous sweat glandular tissues themselves is unknown. To explore this knowledge gap, we collected plasma and sweat from healthy men (n = 9) immediately before and 0.5, 2 and 4 h after oral administration of 400 mg ibuprofen. Of the over 100 lipid mediators assayed by liquid chromatography-tandem mass spectrometry, ∼45 were detected in both plasma and sweat, and 36 were common to both matrices...
May 17, 2018: Prostaglandins & Other Lipid Mediators
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...
May 12, 2018: Prostaglandins & Other Lipid Mediators
John P Caron, Jeffrey C Gandy, Jennifer L Brown, Lorraine M Sordillo
Docosahexaenoic acid (DHA) supplementation has demonstrated beneficial effects in a number of inflammatory diseases. Increasingly, important contributions to its favorable effects are attributed downstream metabolites called docosanoids. Herein, we investigated the role of DHA-derived oxidized lipid metabolites on inflammatory mediator expression by RAW 264.7 murine macrophages. Specifically, macrophage incorporation of DHA, and the resultant biosynthesis of selected pro-resolving docosanoids was quantified...
May 2018: Prostaglandins & Other Lipid Mediators
S Abhilash, R Siviyasankar, P Binu, P Arathi, R Harikumaran Nair
Docosahexaenoic acid (DHA) obtained from fish and plant sources is an essential dietary fatty acid and an important cell membrane structural component. The acute promyelocytic leukemia (APL) drug arsenic trioxide (As2 O3 ), causes hepatotoxicity. We evaluated the protective potential of DHA as pre/combination/post-administration patterns against As2 O3 induced toxicity. The therapeutic concentration of As2 O3 (10 μM) resulted in cytotoxicity with a significant (p < 0.05) variation from the control group...
May 2018: Prostaglandins & Other Lipid Mediators
Neeraj Dholia, Umesh C S Yadav
BACKGROUND: Cysteinyl leukotrienes (CysLTs), the potent lipid inflammatory mediators, are elevated in many pathological conditions and implicated in various inflammatory diseases including asthma, however their role in airway epithelial cells modulation is not clearly understood. We have investigated the effects of a CysLT, Leukotriene D4 (LTD4 ) on human airway epithelial cells, and assessed its role and mode of action in these cells. METHODOLOGY: Human small airway epithelial cells (SAECs) and A549 cells were incubated with different concentrations of LTD4 for different time intervals...
May 2018: Prostaglandins & Other Lipid Mediators
Nathani Minaz, Rema Razdan, Bruce D Hammock, Sumanta Kumar Goswami
BACKGROUND: Pharmacological inhibition of soluble epoxide hydrolase (sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with an alteration in the level of neurotransmitters and oxidative stress. METHODS: Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test...
May 2018: Prostaglandins & Other Lipid Mediators
M G Anupriya, Sneha Singh, Neha Vijay Hulyalkar, Easwaran Sreekumar
Dengue has emerged as a major mosquito-borne disease in the tropics and subtropics. In severe dengue, enhanced microvascular endothelial permeability leads to plasma leakage. Direct dengue virus (DENV) infection in human microvascular endothelial cells (HMEC-1) can enhance trans-endothelial leakage. Using a microarray-based analysis, we identified modulation of key endothelial cell signaling pathways in DENV-infected HMEC-1 cells. One among them was the sphingolipid pathway that regulates vascular barrier function...
May 2018: Prostaglandins & Other Lipid Mediators
Shinji Toki, Weisong Zhou, Kasia Goleniewska, Sara Reiss, Daniel E Dulek, Dawn C Newcomb, William E Lawson, R Stokes Peebles
Endogenous prostaglandin I2 (PGI2 ) has inhibitory effects on immune responses against pathogens or allergens; however, the immunomodulatory activity of endogenous PGI2 signaling in endotoxin-induced inflammation is unknown. To test the hypothesis that endogenous PGI2 down-regulates endotoxin-induced lung inflammation, C57BL/6 wild type (WT) and PGI2 receptor (IP) KO mice were challenged intranasally with LPS. Urine 6-keto-PGF1α , a stable metabolite of PGI2, was significantly increased following the LPS-challenge, suggesting that endogenous PGI2 signaling modulates the host response to LPS-challenge...
May 2018: Prostaglandins & Other Lipid Mediators
Anca D Dobrian, Ryan W Huyck, Lindsey Glenn, Vijay Gottipati, Bronson A Haynes, Göran I Hansson, Anna Marley, William L McPheat, Jerry L Nadler
The 12-lipoxygenase (12LO) pathway is a promising target to reduce islet dysfunction, adipose tissue (AT) inflammation and insulin resistance. Optimal pre-clinical models for the investigation of selective12LO inhibitors in this context have not yet been identified. The objective of this study was to characterize the time course of 12LO isoform expression and metabolite production in pancreatic islets and AT of C57BLKS/J-db/db obese diabetic mouse in a pre-diabetic state in order to establish a suitable therapeutic window for intervention with selective lipoxygenase inhibitors...
May 2018: Prostaglandins & Other Lipid Mediators
Nicole L Plenty, Jessica L Faulkner, Joshua Cotton, Shauna-Kay Spencer, Kedra Wallace, Babbette LaMarca, Sydney R Murphy
Few studies exist on cytochrome P450 (CYP450) metabolites of arachidonic acid (AA) pertaining to the pathophysiological events in pregnancy. We hypothesized that metabolism of AA via the CYP450 pathways is altered within the placenta in women with preeclampsia (PE) and contributes to the pathophysiology of the disease. Thus, placental vascular CYP450 enzyme expression and activity were measured in normal pregnant (NP) and preeclamptic (PE) patients. CYP450 isoform expression (CYP4A11, CYP4A22, CYP4F2, and CYP4F3) was found to be elevated within the placenta of women with PE compared to normal pregnant (NP) women and chronic hypertensive (CHTN) pregnant women...
May 2018: Prostaglandins & Other Lipid Mediators
Yi-Er Qiu, Jun Qin, Yang Luo, Shao-Lan Qin, Yi-Fei Mu, Ran Cun, Hou-Li Jiang, Jian-Jun Chen, Min-Hao Yu, Ming Zhong
BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues...
May 2018: Prostaglandins & Other Lipid Mediators
Anne E Barden, Sujata Shinde, Valerie Burke, Ian B Puddey, Lawrence J Beilin, Ashley B Irish, Gerald F Watts, Trevor A Mori
BACKGROUND: Neutrophils release leukotriene (LT)B4 and myeloperoxidase (MPO) that may be important mediators of chronic inflammation in chronic kidney disease (CKD). The n-3 fatty acids (n-3 FA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have the potential to attenuate inflammation through production of LTB5 and the Specialized Proresolving Lipid Mediators (SPM) that promote the resolution of inflammation. In animal models, coenzyme Q10 (CoQ) also attenuates inflammation by reducing MPO and LTB4 ...
May 2018: Prostaglandins & Other Lipid Mediators
Stevan Pecic, Amir A Zeki, Xiaoming Xu, Gina Y Jin, Shuwei Zhang, Sean Kodani, Marlin Halim, Christophe Morisseau, Bruce D Hammock, Shi-Xian Deng
We have previously identified and reported several potent piperidine-derived amide inhibitors of the human soluble epoxide hydrolase (sEH) enzyme. The inhibition of this enzyme leads to elevated levels of epoxyeicosatrienoic acids (EETs), which are known to possess anti-inflammatory, vasodilatory, and anti-fibrotic effects. Herein, we report the synthesis of 9 analogs of the lead sEH inhibitor and the follow-up structure-activity relationship and liver microsome stability studies. Our findings show that isosteric modifications that lead to significant alterations in the steric and electronic properties at a specific position in the molecule can reduce the efficacy by up to 75-fold...
May 2018: Prostaglandins & Other Lipid Mediators
Sheuli Afroz, Ayano Yagi, Kouki Fujikawa, M Motiur Rahman, Katsuya Morito, Tatsuya Fukuta, Shiro Watanabe, Emi Kiyokage, Kazunori Toida, Taro Shimizu, Tatsuhiro Ishida, Kentaro Kogure, Akira Tokumura, Tamotsu Tanaka
Lysophosphatidic acid (LPA) is a bioactive phospholipid that induces diverse biological responses. Recently, we found that LPA ameliorates NSAIDs-induced gastric ulcer in mice. Here, we quantified LPA in 21 medicinal herbs used for treatment of gastrointestinal (GI) disorders. We found that half of them contained LPA at relatively high levels (40-240 μg/g) compared to soybean seed powder (4.6 μg/g), which we previously identified as an LPA-rich food. The LPA in peony (Paeonia lactiflora) root powder is highly concentrated in the lipid fraction that ameliorates indomethacin-induced gastric ulcer in mice...
March 2018: Prostaglandins & Other Lipid Mediators
Rajnish Kumar Yadav, Manjari Singh, Subhadeep Roy, Mohd Nazam Ansari, Abdulaziz S Saeedan, Gaurav Kaithwas
Polyunsaturated fatty acids (PUFA's) are majorly classified as ω-3 and ω-6 fatty acids. The eicosapentaenoic acid (EPA, ω-3:20-5), docosahexaenoic acid (DHA, ω-3:22-6) and alpha-linolenic acid (ALA, ω-3:18-3) are known ω-3 fatty acids, extracted from animal (e.g fish oil) and plant sources (e.g flaxseed oil). Furthermore, linoleic acid (LA, ω-6:18-2) is recognized as ω-6 fatty acid and the most prominent biological fatty acid with a pro-inflammatory response. Flaxseed oil has variety of biological roles, due to the significant amount of ω-3/ω-6 fatty acids...
March 2018: Prostaglandins & Other Lipid Mediators
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