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Masao Morita, Yuichi Kobayashi
The stereoselective synthesis of resolvin D4 (RvD4) was achieved using the Wittig reaction of the C1-C10 dienal with the known C11-C22 phosphonium salt. The (S,E)-enantiomer (S)-10, corresponding to the C1-C8 part, was synthesized in 95% ee by the asymmetric transfer hydrogenation reaction of the corresponding acetylenic ketone followed by Red-Al reduction. Sharpless epoxidation of this alcohol using Ti(O-i-Pr)4/L-(+)-DIPT as a catalyst produced anti epoxy alcohol with >99% ee as the sole product in 82% yield...
March 16, 2018: Journal of Organic Chemistry
Delphine Lumbroso, Soaad Soboh, Avi Maimon, Sagie Schif-Zuck, Amiram Ariel, Tal Burstyn-Cohen
The complete resolution of inflammation requires the uptake of apoptotic polymorphonuclear cells (PMN) by local macrophages (efferocytosis) and the consequent reprogramming of the engulfing phagocytes to reparative and pro-resolving phenotypes. The tyrosine kinase receptors TYRO3, AXL, and MERTK (collectively named TAM) are fundamental mediators in regulating inflammatory responses and efferocytosis. Protein S (PROS1) is a ligand for all TAM receptors that mediates various aspects of their activity. However, the involvement of PROS1 in the resolution of inflammation is incompletely understood...
2018: Frontiers in Immunology
Paul C Norris, Charles N Serhan
Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels...
March 7, 2018: Biochemical and Biophysical Research Communications
Ho Pan Sham, Katherine H Walker, Raja-Elie E Abdulnour, Nandini Krishnamoorthy, David N Douda, Paul C Norris, Ioanna Barkas, Sarah Benito-Figueroa, Jennifer K Colby, Charles N Serhan, Bruce D Levy
Specialized proresolving mediators (SPMs) decrease NF-κB activity to prevent excessive tissue damage and promote the resolution of acute inflammation. Mechanisms for NF-κB regulation by SPMs remain to be determined. In this study, after LPS challenge, the SPMs 15-epi-lipoxin A4 (15-epi-LXA4 ), resolvin D1, resolvin D2, resolvin D3, and 17-epi-resolvin D1 were produced in vivo in murine lungs. In LPS-activated human bronchial epithelial cells, select SPMs increased expression of the NF-κB regulators A20 and single Ig IL-1R-related molecule (SIGIRR)...
March 9, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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
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)...
February 27, 2018: Trends in Pharmacological Sciences
Ganesh V Halade, Laurence M Black, Mahendra Kumar Verma
Fatty acid drug discovery (FADD) is defined as the identification of novel, specialized bioactive mediators that are derived from fatty acids and have precise pharmacological/therapeutic potential. A number of reports indicate that dietary intake of omega-3 fatty acids and limited intake of omega-6 promotes overall health benefits. In 1929, Burr and Burr indicated the significant role of essential fatty acids for survival and functional health of many organs. In reference to specific dietary benefits of differential omega-3 fatty acids, docosahexaenoic and eicosapentaenoic acids (DHA and EPA) are transformed to monohydroxy, dihydroxy, trihydroxy, and other complex mediators during infection, injury, and exercise to resolve inflammation...
February 27, 2018: Biotechnology Advances
Florence Riché, Benjamin G Chousterman, Patrice Valleur, Alexandre Mebazaa, Jean-Marie Launay, Etienne Gayat
BACKGROUND: Sepsis is a leading cause of mortality and critical illness worldwide and is associated with an increased mortality rate in the months following hospital discharge. The occurrence of persistent or new organ dysfunction(s) after septic shock raises questions about the mechanisms involved in the post-sepsis status. The present study aimed to explore the immune profiles of patients one year after being discharged from the intensive care unit (ICU) following treatment for abdominal septic shock...
February 21, 2018: Critical Care: the Official Journal of the Critical Care Forum
Ganesh V Halade, Vasundhara Kain, Charles N Serhan
Resolvins are innate, immune responsive, bioactive mediators generated after myocardial infarction (MI) to resolve inflammation. The MI-induced bidirectional interaction between progressive left ventricle (LV) remodeling and kidney dysfunction is known to advance cardiorenal syndrome (CRS). Whether resolvins limit MI-induced cardiorenal inflammation is unclear. Thus, to define the role of exogenous resolvin D (RvD)-1 in post-MI CRS, we subjected 8-12-wk-old male C57BL/6 mice to coronary artery ligation. RvD1 was injected 3 h after MI...
February 13, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Daniela P Vasconcelos, Madalena Costa, Nuno Neves, José H Teixeira, Daniel M Vasconcelos, Susana G Santos, Artur P Águas, Mário A Barbosa, Judite N Barbosa
The aim of this study was to investigate the effect chitosan (Ch) porous 3D scaffolds embedded with resolvin D1 (RvD1), an endogenous pro-resolving lipid mediator, on bone tissue healing. These scaffolds previous developed by us have demonstrated to have immunomodulatory properties namely in the modulation of the macrophage inflammatory phenotypic profile in an in vivo model of inflammation. Herein, results obtained in an in vivo rat femoral defect model demonstrated that two months after Ch+RvD1 scaffolds implantation, an increase in new bone formation, in bone trabecular thickness, and in collagen type I and Coll I/Coll III ratio were observed...
February 17, 2018: Journal of Biomedical Materials Research. Part A
Gang Zuo, Dongping Zhang, Rutao Mu, Haitao Shen, Xiang Li, Zhong Wang, Haiying Li, Gang Chen
Cerebral ischemia/reperfusion (I/R) injury is a critical factor leading to a poor prognosis for ischemic stroke patients. ω-3 fatty acid supplements taken as part of a daily diet have been shown to improve the prognosis of patients with ischemic stroke. In this study, we aimed to investigate the potential effects of resolvin D2 (RvD2), a derivative of ω-3 fatty acids, and its possible advantage on cerebral I/R injury in rats. Cerebral I/R caused by middle cerebral artery occlusion and reperfusion (MCAO/R) was established in Sprague-Dawley rats...
February 13, 2018: Molecular Brain
Mathew Suji Eapen, Sukhwinder Singh Sohal
Airway infections are considered as one of the vital factors driving the pathophysiology of chronic lung disease with significant influences on disease trajectory. Opportunistic lung microbes in diseased conditions induce excessive exacerbations and contribute to airflow limitation. Though there has been considerable amount of information that ascertains their links with airway inflammation, the intricate interaction in clinical conditions are poorly understood and requires further deciphering. Current therapeutic interventions for such pathologies are few and lack the ability to modulate underlying dysfunctional immunity as well as suppress the excessive infectious conditions...
February 14, 2018: Clinical Science (1979-)
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
Ganesh V Halade, Anela Dorbane, Kevin A Ingle, Vasundhara Kain, Jean-Marie Schmitter, Boutayna Rhourri-Frih
Myocardial infarction (MI) and subsequent progressive heart failure pathology is the major cause of death worldwide; however, the mechanism of this pathology remains unclear. The present work aimed at testing the hypothesis whether the inflammatory response is superimposed with the formation of bioactive lipid resolving molecules at the site of the injured myocardium in acute heart failure pathology post-MI. In this view, we used a robust permanent coronary ligation model to induce MI, leading to decreased contractility index with marked wall thinning and necrosis of the infarcted left ventricle...
February 6, 2018: Analytical and Bioanalytical Chemistry
Rima Chattopadhyay, Arul M Mani, Nikhlesh K Singh, Gadiparthi N Rao
In recent years, various studies have demonstrated a role for endogenously derived specialized proresolving mediators such as resolvins in the resolution of inflammation. In exploring the signaling mechanisms, in the present study we show that Resolvin D1 (RvD1) reduces LPS-induced endothelial cell (EC)-monocyte interactions via blocking H2O2-mediated PP2A inactivation, NFκB activation and ICAM1 and VCAM1 expression. In addition, we found that H2O2-mediated SHP2 inhibition leads to tyrosine phosphorylation and inactivation of PP2A by LPS, which in turn, accounts for increased NFκB activation and ICAM1 and VCAM1 expression facilitating EC-monocyte interactions and all these LPS-mediated responses were reduced by RvD1...
February 2, 2018: Free Radical Biology & Medicine
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
Jeremy W Winkler, Stephania Libreros, Xavier De La Rosa, Brian E Sansbury, Paul C Norris, Nan Chiang, David Fichtner, Gregory S Keyes, Nicholas Wourms, Matthew Spite, Charles N Serhan
Local production and downstream metabolism of specialized proresolving lipid mediators (SPMs) are pivotal in regulating their biological actions during resolution of inflammation. Resolvin D4 (RvD4: 4S,5R,17S-trihydroxydocosa-6E,8E,10Z,13Z,15E,19Z hexaenoic acid) is one of the more recently elucidated SPMs with complete stereochemistry biosynthesized from docosahexaenoic acid . Here, we report a new multimilligram commercial synthesis that afforded enough material for matching, validation, and further evaluation of RvD4 functions...
January 29, 2018: Journal of Leukocyte Biology
James Hamilton, Hatice Hasturk, Alpdogan Kantarci, Thomas Van Dyke, Alkystis Phinikaridou
No abstract text is available yet for this article.
August 2017: Atherosclerosis
Damien Dufour, Alia Khalil, Alexandre Rousseau, Caroline Noyon, Melissa Cortese, Cédric Delporte, Jean Nève, Luc Vanhamme, Karim Zouaoui Boudjeltia, Pierre Van Antwerpen
No abstract text is available yet for this article.
August 2017: Atherosclerosis
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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