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https://www.readbyqxmd.com/read/29763660/docosahexaenoic-acid-derived-oxidized-lipid-metabolites-modulate-the-inflammatory-response-of-lipolysaccharide-stimulated-macrophages
#1
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 12, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29757195/resolvins-in-inflammation-emergence-of-the-pro-resolving-superfamily-of-mediators
#2
Charles N Serhan, Bruce D Levy
Countless times each day, the acute inflammatory response protects us from invading microbes, injuries, and insults from within, as in surgery-induced tissue injury. These challenges go unnoticed because they are self-limited and naturally resolve without progressing to chronic inflammation. Peripheral blood markers of inflammation are present in many common diseases, including inflammatory bowel disease, cardiovascular disease, neurodegenerative disease, and cancer. While acute inflammation is protective, excessive swarming of neutrophils amplifies collateral tissue damage and inflammation...
May 14, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29730187/identification-of-proresolving-and-inflammatory-lipid-mediators-in-human-psoriasis
#3
Alexander V Sorokin, Paul C Norris, Justin T English, Amit K Dey, Abhishek Chaturvedi, Yvonne Baumer, Joanna Silverman, Martin P Playford, Charles N Serhan, Nehal N Mehta
BACKGROUND: Psoriasis (PSO) is an immune-mediated inflammatory disease associated with metabolic and cardiovascular comorbidities. It is now known that resolution of inflammation is an active process locally controlled by specialized proresolving mediators (SPMs), named resolvins (Rvs), protectins, and maresins. OBJECTIVE: It is unknown whether these potent lipid mediators (LMs) are involved in PSO pathophysiology and if the skin and blood have disease-specific SPMs phenotype profiles...
April 6, 2018: Journal of Clinical Lipidology
https://www.readbyqxmd.com/read/29700291/protectin-dx-increases-alveolar-fluid-clearance-in-rats-with-lipopolysaccharide-induced-acute-lung-injury
#4
Xiao-Jun Zhuo, Yu Hao, Fei Cao, Song-Fan Yan, Hui Li, Qian Wang, Bi-Huan Cheng, Bin-Yu Ying, Fang Gao Smith, Sheng-Wei Jin
Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10-3  mg/l) was added to the culture medium with LPS for 6 h...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29679485/identification-and-structure-elucidation-of-the-proresolving-mediators-provides-novel-leads-for-resolution-pharmacology
#5
REVIEW
Jesmond Dalli, Charles N Serhan
Inflammatory diseases are a major socioeconomic burden, with the incidence of such conditions on the rise, especially in western societies. For decades, the primary treatment paradigm for many of these conditions was to develop drugs that inhibit or antagonize the production and biological actions of molecules that were thought to be the culprits in propagating disease, these include cytokines and eicosanoids. This approach is effective in controlling disease propagation; however, long-term exposure to these anti-inflammatories is also associated with many side effects, some of which severe, including immune-suppression...
April 21, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29674943/maresins-specialized-proresolving-lipid-mediators-and-their-potential-role-in-inflammatory-related-diseases
#6
REVIEW
Shi Tang, Ming Wan, Wei Huang, R C Stanton, Yong Xu
Acute inflammatory responses are host-protective and normally self-limited; these responses can maintain cell homeostasis and promote defense against various infections and damage factors. However, when improperly managed or inappropriately activated, acute inflammation can lead to persistent and uncontrolled chronic inflammation, which is associated with many other chronic diseases including cardiovascular disease and metabolic disease. Recently, studies have shown that resolution of acute inflammation is a biosynthetically active process...
2018: Mediators of Inflammation
https://www.readbyqxmd.com/read/29664060/specialized-pro-resolving-mediators-regulate-alveolar-fluid-clearance-during-acute-respiratory-distress-syndrome
#7
REVIEW
Qian Wang, Song-Fan Yan, Yu Hao, Sheng-Wei Jin
Objective: Acute respiratory distress syndrome (ARDS) is an acute and lethal clinical syndrome that is characterized by the injury of alveolar epithelium, which impairs active fluid transport in the lung, and impedes the reabsorption of edema fluid from the alveolar space. This review aimed to discuss the role of pro-resolving mediators on the regulation of alveolar fluid clearance (AFC) in ARDS. Data Sources: Articles published up to September 2017 were selected from the PubMed, with the keywords of "alveolar fluid clearance" or "lung edema" or "acute lung injury" or "acute respiratory distress syndrome", and "specialized pro-resolving mediators" or "lipoxin" or "resolvin" or "protectin" or "maresin" or "alveolar epithelial cells" or "aspirin-triggered lipid mediators" or "carbon monoxide and heme oxygenase" or "annexin A1"...
April 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29584445/protectin-dx-attenuates-lps-induced-inflammation-and-insulin-resistance-in-adipocytes-via-ampk-mediated-suppression-of-the-nf%C3%AE%C2%BAb-pathway
#8
Tae Woo Jung, Yoon Hee Chung, Hyoung-Chun Kim, A M Abd El-Aty, Ji Hoon Jeong
Several studies have demonstrated that protectins, which are ω-3 fatty acid-derived proresolution mediators, may ameliorate inflammation. Recently, protectin DX (PDX) was also reported to attenuate inflammation and insulin resistance in several cell types. However, the effects of PDX on inflammation in adipocytes remain unclear. In this study, we found that PDX treatment suppressed adipogenesis as well as lipid accumulation during 3T3-L1 differentiation. Treatment of differentiated 3T3-L1 cells with PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation in a dose-dependent manner...
March 27, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29572342/protectin-dx-ameliorates-hepatic-steatosis-by-suppression-of-endoplasmic-reticulum-stress-via-ampk-induced-orp150-expression
#9
Tae Woo Jung, Eun Jung Kyung, Hyoung-Chun Kim, Yong Kyu Shin, Sung Hoon Lee, Eon Sub Park, Ahmet Hacimuftuoglu, A M Abd El-Aty, Ji Hoon Jeong
Docosahexaenoic acid (DHA) and its bioactive compounds may have suppressive effects on inflammation, endoplasmic reticulum (ER) stress, and insulin resistance. Protectin DX (PDX), a double lipoxygenase product from docosahexaenoic acid (DHA) has shown a suppressive effect on inflammation and insulin resistance. However, the effects of PDX on ER stress and hepatic steatosis have not been elucidated yet. Herein we have found that PDX could stimulate the AMP-activated protein kinase (AMPK) phosphorylation, thereby upregulating oxygen-regulated protein 150 (ORP150) expression in a dose-dependent manner...
March 23, 2018: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29571326/identification-and-complete-stereochemical-assignments-of-the-new-resolvin-conjugates-in-tissue-regeneration-in-human-tissues-that-stimulate-proresolving-phagocyte-functions-and-tissue-regeneration
#10
Xavier de la Rosa, Paul C Norris, Nan Chiang, Ana R Rodriguez, Bernd W Spur, Charles N Serhan
Resolvin conjugates in tissue regeneration (RCTRs) are new chemical signals that accelerate resolution of inflammation, infection, and tissue regeneration. Herein, using liquid chromatography-tandem mass spectrometry-based metabololipidomics, we identified RCTRs in human spleen, lymph node, bone marrow, and brain. In human spleen incubated with Staphylococcus aureus, endogenous RCTRs were increased along with conversion of deuterium-labeled docosahexaenoic acid, conferring pathway activation. Physical and biological properties of endogenous RCTRs were matched with those prepared by total organic synthesis...
April 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29563331/pro-resolving-mediators-promote-resolution-in-a-human-skin-model-of-uv-killed-escherichia-coli-driven-acute-inflammation
#11
Madhur P Motwani, Romain A Colas, Marc J George, Julia D Flint, Jesmond Dalli, Angela Richard-Loendt, Roel Ph De Maeyer, Charles N Serhan, Derek W Gilroy
While the treatment of inflammatory disorders is generally based on inhibiting factors that drive onset of inflammation, these therapies can compromise healing (NSAIDs) or dampen immunity against infections (biologics). In search of new antiinflammatories, efforts have focused on harnessing endogenous pathways that drive resolution of inflammation for therapeutic gain. Identification of specialized pro-resolving mediators (SPMs) (lipoxins, resolvins, protectins, maresins) as effector molecules of resolution has shown promise in this regard...
March 22, 2018: JCI Insight
https://www.readbyqxmd.com/read/29553051/protectin-dx-exhibits-protective-effects-in-mouse-model-of-lipopolysaccharide-induced-acute-lung-injury
#12
Wen Tan, Lin Chen, Ya-Xin Wang, Li-Sha Hu, Wei Xiong, You Shang, Shang-Long Yao
Background: Acute lung injury (ALI) is a severe disease with high mortality and poor prognosis. Protectin DX (PDX), a pro-resolving lipid mediator, exhibits protective effects in ALI. Our experiment aimed to explore the effects and related mechanisms of PDX in mice with ALI induced by lipopolysaccharide (LPS). Methods: BALB/c mice were randomly divided into five groups: sham, LPS, LPS plus 1 ng of PDX (LPS + PDX-1 ng), LPS plus 10 ng of PDX (LPS + PDX-10 ng), and LPS plus 100 ng of PDX (LPS + PDX-100 ng)...
May 20, 2018: Chinese Medical Journal
https://www.readbyqxmd.com/read/29511119/splenic-leukocytes-define-the-resolution-of-inflammation-in-heart-failure
#13
Ganesh V Halade, Paul C Norris, Vasundhara Kain, Charles N Serhan, Kevin A Ingle
Inflammation promotes healing in myocardial infarction but, if unresolved, leads to heart failure. To define the inflammatory and resolving responses, we quantified leukocyte trafficking and specialized proresolving mediators (SPMs) in the infarcted left ventricle and spleen after myocardial infarction, with the goal of distinguishing inflammation from its resolution. Our data suggest that the spleen not only served as a leukocyte reservoir but also was the site where SPMs were actively generated after coronary ligation in mice...
March 6, 2018: Science Signaling
https://www.readbyqxmd.com/read/29499974/specialized-proresolving-mediators-enhancing-nonalcoholic-steatohepatitis-and-fibrosis-resolution
#14
REVIEW
Giovanni Musso, Roberto Gambino, Maurizio Cassader, Elena Paschetta, Antonio Sircana
The resolution of necroinflammation and fibrosis remains a primary clinical target in nonalcoholic steatohepatitis (NASH), the most common chronic liver disease and a major cause of end-stage liver disease. Our understanding of the basic molecular mechanisms driving inflammation and fibrosis and their resolution in obesity-related conditions, including NASH, have led to the proposal of a novel, tractable therapeutic paradigm involving specialized proresolving mediators (SPMs), namely lipoxins (LXs), resolvins (Rvs), protectins (PDs), and maresins (MaRs)...
April 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29482717/a-randomised-double-blind-placebo-controlled-phase-2-trial-of-adjunctive-aspirin-for-tuberculous-meningitis-in-hiv-uninfected-adults
#15
Nguyen Th Mai, Nicholas Dobbs, Nguyen Hoan Phu, Romain A Colas, Le Tp Thao, Nguyen Tt Thuong, Ho Dt Nghia, Nguyen Hh Hanh, Nguyen T Hang, A Dorothee Heemskerk, Jeremy N Day, Lucy Ly, Do DA Thu, Laura Merson, Evelyne Kestelyn, Marcel Wolbers, Ronald Geskus, David Summers, Nguyen Vv Chau, Jesmond Dalli, Guy E Thwaites
Adjunctive dexamethasone reduces mortality from tuberculous meningitis (TBM) but not disability, which is associated with brain infarction. We hypothesised that aspirin prevents TBM-related brain infarction through its anti-thrombotic, anti-inflammatory, and pro-resolution properties. We conducted a randomised controlled trial in HIV-uninfected adults with TBM of daily aspirin 81 mg or 1000 mg, or placebo, added to the first 60 days of anti-tuberculosis drugs and dexamethasone (NCT02237365). The primary safety endpoint was gastro-intestinal or cerebral bleeding by 60 days; the primary efficacy endpoint was new brain infarction confirmed by magnetic resonance imaging or death by 60 days...
February 27, 2018: ELife
https://www.readbyqxmd.com/read/29469960/ultra-performance-liquid-chromatography-mass-spectrometry-analysis-of-free-and-esterified-oxygenated-derivatives-from-docosahexaenoic-acid-in-rat-brain
#16
Charlotte Jouvène, Baptiste Fourmaux, Alain Géloën, Laurence Balas, Thierry Durand, Michel Lagarde, Marion Létisse, Michel Guichardant
Docosahexaenoic acid (DHA), a prominent long-chain fatty acid of the omega-3 family, is present at high amount in brain tissues, especially in membrane phospholipids. This polyunsaturated fatty acid is the precursor of various oxygenated lipid mediators involved in diverse physiological and pathophysiological processes. Characterization of DHA-oxygenated metabolites is therefore crucial for better understanding the biological roles of DHA. In this study, we identified and measured, by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry, a number of oxygenated products derived from DHA in exsanguinated and nonexsanguinated brains...
January 2018: Lipids
https://www.readbyqxmd.com/read/29420307/the-roles-of-special-proresolving-mediators-in-pain-relief
#17
Lan-Yu Zhang, Ming-Rui Jia, Tao Sun
The resolution of acute inflammation, once thought to be a passive process, is now recognized as an active one. The productions of endogenous special proresolving mediators (SPMs) are involved in this process. SPMs, including lipoxins, resolvins, protectins, and maresins, are endogenous lipid mediators generated from ω-6 arachidonic acid or ω-3 poly-unsaturated fatty acids during the resolution phase of acute inflammation. They have potent anti-inflammatory and proresolving actions in various inflammatory disorders...
February 8, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29414763/production-of-lipid-mediators-across-different-disease-stages-of-dextran-sodium-sulfate-induced-colitis-in-mice
#18
Taiki Hamabata, Tatsuro Nakamura, Sakura Masuko, Shingo Maeda, Takahisa Murata
Although several studies have revealed the role of different lipid mediators in colitis, the comprehensive analysis of their production across different phases of colitis remained unclear. Here, we performed the following analysis in the dextran sodium sulfate (DSS)-induced colitis model using LC-MS/MS. Oral administration of 2% DSS in mice for 4 days resulted in severe intestinal inflammation by day 7, which gradually subsided by day 18. Based on the disease scoring index (assigned on the basis of fecal condition and weight loss), we defined the phases of colitis as induction (days 0-4), acute inflammation (days 4-7), recovery (days 7-9), and late recovery (days 9-18)...
April 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29379552/differential-action-of-polyunsaturated-fatty-acids-and-eicosanoids-on-bleomycin-induced-cytotoxicity-to-neuroblastoma-cells-and-lymphocytes
#19
Sailaja Polavarapu, Bilikere S Dwarakanath, Undurti N Das
Introduction: This study was conducted to examine whether bleomycin-induced growth inhibitory action on human neuroblastoma cells (IMR-32) is influenced by anti-inflammatory metabolites of polyunsaturated fatty acids (PUFAs): lipoxin A4 (LXA4), resolvin D1 and protectin D1 in vitro . Material and methods: The in vitro study was conducted using monolayer cultures of exponentially growing IMR-32 cells. The effects of various PUFAs and eicosanoids and anti-inflammatory metabolites of PUFAs such as lipoxin A4 (LXA4), resolvin D1 and protectin D1 on the growth of IMR-32 cells and human lymphocytes in vitro were investigated...
January 2018: Archives of Medical Science: AMS
https://www.readbyqxmd.com/read/29363065/lipid-mediator-metabolomics-via-lc-ms-ms-profiling-and-analysis
#20
Jesmond Dalli, Romain A Colas, Mary E Walker, Charles N Serhan
Solid-phase extraction coupled with liquid chromatography tandem mass spectrometry provides a robust and sensitive approach for the identification and quantitation of specialized pro-resolving mediators (lipoxins, resolvins, protectins, and maresins), their pathway markers and the classic eicosanoids. Here, we provide a detailed description of the methodologies employed for the extraction of these mediators from biological systems, setup of the instrumentation, sample processing, and then the procedures followed for their identification and quantitation...
2018: Methods in Molecular Biology
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