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  1. Article ; Online: Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease.

    Fredman, Gabrielle / Serhan, Charles N

    Nature reviews. Cardiology

    2024  

    Abstract: Timely resolution of the acute inflammatory response (or inflammation resolution) is an active, highly coordinated process that is essential to optimal health. Inflammation resolution is regulated by specific endogenous signalling molecules that function ...

    Abstract Timely resolution of the acute inflammatory response (or inflammation resolution) is an active, highly coordinated process that is essential to optimal health. Inflammation resolution is regulated by specific endogenous signalling molecules that function as 'stop signals' to terminate the inflammatory response when it is no longer needed; to actively promote healing, regeneration and tissue repair; and to limit pain. Specialized pro-resolving mediators are a superfamily of signalling molecules that initiate anti-inflammatory and pro-resolving actions. Without an effective and timely resolution response, inflammation can become chronic, a pathological state that is associated with many widely occurring human diseases, including atherosclerotic cardiovascular disease. Uncovering the mechanisms of inflammation resolution failure in cardiovascular diseases and identifying useful biomarkers for non-resolving inflammation are unmet needs. In this Review, we discuss the accumulating evidence that supports the role of non-resolving inflammation in atherosclerosis and the use of specialized pro-resolving mediators as therapeutic tools for the treatment of atherosclerotic cardiovascular disease. We highlight open questions about therapeutic strategies and mechanisms of disease to provide a framework for future studies on the prevention and treatment of atherosclerosis.
    Language English
    Publishing date 2024-01-12
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2490375-9
    ISSN 1759-5010 ; 1759-5002
    ISSN (online) 1759-5010
    ISSN 1759-5002
    DOI 10.1038/s41569-023-00984-x
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  2. Article: Resolvins and cysteinyl-containing pro-resolving mediators activate resolution of infectious inflammation and tissue regeneration.

    Serhan, Charles N / Chiang, Nan

    Prostaglandins & other lipid mediators

    2023  Volume 166, Page(s) 106718

    Abstract: This review is a synopsis of the main points from the opening presentation by the authors in the Resolution of Inflammation session at the 8th European Workshop on Lipid Mediators held at the Karolinska Institute, Stockholm, Sweden, June 29th, 2022. ... ...

    Abstract This review is a synopsis of the main points from the opening presentation by the authors in the Resolution of Inflammation session at the 8th European Workshop on Lipid Mediators held at the Karolinska Institute, Stockholm, Sweden, June 29th, 2022. Specialized pro-resolving mediators (SPM) promote tissue regeneration, control infections and resolution of inflammation. These include resolvins, protectins, maresins and the newly identified conjugates in tissue regeneration (CTRs). We reported mechanisms of CTRs in activating primordial regeneration pathways in planaria using RNA-sequencing. Also, the 4S,5S-epoxy-resolvin intermediate in the biosynthesis of resolvin D3 and resolvin D4 was prepared by total organic synthesis. Human neutrophils convert this to resolvin D3 and resolvin D4, while human M2 macrophages transformed this labile epoxide intermediate to resolvin D4 and a novel cysteinyl-resolvin that is a potent isomer of RCTR1. The novel cysteinyl-resolvin significantly accelerates tissue regeneration with planaria and inhibits human granuloma formation.
    MeSH term(s) Humans ; Inflammation/drug therapy ; Inflammation/metabolism ; Macrophages/metabolism ; Docosahexaenoic Acids/pharmacology ; Docosahexaenoic Acids/metabolism ; Neutrophils/metabolism ; Inflammation Mediators/metabolism
    Chemical Substances Docosahexaenoic Acids (25167-62-8) ; Inflammation Mediators
    Language English
    Publishing date 2023-02-21
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 1426962-4
    ISSN 2212-196X ; 1098-8823 ; 0090-6980
    ISSN (online) 2212-196X
    ISSN 1098-8823 ; 0090-6980
    DOI 10.1016/j.prostaglandins.2023.106718
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  3. Article ; Online: Resolution medicine in cancer, infection, pain and inflammation: are we on track to address the next Pandemic?

    Serhan, Charles N / Sulciner, Megan L

    Cancer metastasis reviews

    2023  Volume 42, Issue 1, Page(s) 13–17

    Abstract: Uncontrolled inflammation giving rise to excessive tissue inflammation can lead to chronic inflammation that enhances tissue destruction, amplifying many chronic human pathologies. Normally the acute inflammatory response is protective and should be self- ...

    Abstract Uncontrolled inflammation giving rise to excessive tissue inflammation can lead to chronic inflammation that enhances tissue destruction, amplifying many chronic human pathologies. Normally the acute inflammatory response is protective and should be self-limited returning tissues to functional homeostasis with endogenous programmed resolution via leukocyte vasculature cell-cell interactions and crosstalk that biosynthesize pro-resolving mediators. When failed resolution takes place, as with the use of NSAIDs, tissues undergo chronic inflammation and fibrosis. Herein, we discuss these mechanisms and the role of specialized proresolving mediators, the resolvins, protectins and maresins produced from essential omega-3 fatty acids EPA and DHA, and their contributions via their cognate cell surface receptors, to the resolution response. Harnessing these pathways and their cellular mechanisms can help in providing new therapeutic approaches to many human diseases, infections, organ protection and trauma via resolution medicine to enhance the body's own resilience to challenge.
    MeSH term(s) Humans ; Docosahexaenoic Acids/therapeutic use ; Docosahexaenoic Acids/metabolism ; Pandemics ; Inflammation/metabolism ; Pain ; Neoplasms
    Chemical Substances Docosahexaenoic Acids (25167-62-8)
    Language English
    Publishing date 2023-02-13
    Publishing country Netherlands
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 604857-2
    ISSN 1573-7233 ; 0167-7659
    ISSN (online) 1573-7233
    ISSN 0167-7659
    DOI 10.1007/s10555-023-10091-5
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  4. Article ; Online: Stereocontrolled total synthesis of Resolvin D4 and 17(

    Nshimiyimana, Robert / Glynn, Stephen J / Serhan, Charles N / Petasis, Nicos A

    Organic & biomolecular chemistry

    2023  Volume 21, Issue 8, Page(s) 1667–1673

    Abstract: The total synthesis of Resolvin D4 and its 17( ...

    Abstract The total synthesis of Resolvin D4 and its 17(
    MeSH term(s) Humans ; Fatty Acids, Unsaturated/chemistry ; Docosahexaenoic Acids ; Inflammation ; Stereoisomerism
    Chemical Substances resolvin D4 ; Fatty Acids, Unsaturated ; Docosahexaenoic Acids (25167-62-8)
    Language English
    Publishing date 2023-02-22
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2097583-1
    ISSN 1477-0539 ; 1477-0520
    ISSN (online) 1477-0539
    ISSN 1477-0520
    DOI 10.1039/d2ob01697d
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  5. Book: Fundamentals of inflammation

    Serhan, Charles N. / Ward, Peter A. / Gilroy, Derek W.

    2010  

    Author's details ed. by Charles N. Serhan ; Peter A. Ward ; Derek W. Gilroy
    Keywords Inflammation / immunology ; Immunity, Cellular / physiology
    Language English
    Size XIV, 473 S. : Ill., graph. Darst., 28 cm
    Publisher Cambridge Univ. Press
    Publishing place Cambridge
    Publishing country Great Britain
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT016443043
    ISBN 978-0-521-88729-8 ; 0-521-88729-1
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    2010 A 3662 order for loan Magazin

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  6. Article ; Online: Bang and Dyerberg's omega-3 discovery turns fifty.

    Harris, William S / Calder, Philip C / Mozaffarian, Dariush / Serhan, Charles N

    Nature food

    2022  Volume 2, Issue 5, Page(s) 303–305

    Language English
    Publishing date 2022-11-15
    Publishing country England
    Document type Letter
    ISSN 2662-1355
    ISSN (online) 2662-1355
    DOI 10.1038/s43016-021-00289-7
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  7. Article ; Online: ALX/FPR2 Activation by Stereoisomers of D1 Resolvins Elucidating with Molecular Dynamics Simulation.

    Nunes, Vinicius S / Abrahão, Odonírio / Rogério, Alexandre P / Serhan, Charles N

    The journal of physical chemistry. B

    2023  Volume 127, Issue 29, Page(s) 6479–6486

    Abstract: Chronic inflammation contributes to several diseases, but its resolution is driven by specialized pro-resolving mediators (SPM) such as resolvin D1 (RvD1) and its epimer aspirin-triggered resolvin D1 (AT-RvD1), both biosynthesized from ω-3 fatty ... ...

    Abstract Chronic inflammation contributes to several diseases, but its resolution is driven by specialized pro-resolving mediators (SPM) such as resolvin D1 (RvD1) and its epimer aspirin-triggered resolvin D1 (AT-RvD1), both biosynthesized from ω-3 fatty docosahexaenoic acid (DHA). RvD1 and AT-RvD1 have anti-inflammatory and pro-resolution potentials, and their effects could be mediated by formyl peptide receptor type 2 receptor ALX/FPR2, a G-protein-coupled receptor (GPCR). In this work, we performed 44 μs of molecular dynamics simulations with two complexes: FPR2@AT-RvD1 and FPR2@RvD1. Our results show the following: (i) in the AT-RvD1 simulations, the ALX/FPR2 receptor remained in the active state in 62% of the frames, while in the RVD1 simulations, the receptor remained in the active state in 74% of the frames; (ii) two residues, R201 and R205, of ALX/FPR2 appear, establishing interactions with both resolvins in all simulations (22 in total); (iii) RvD1 hydrogen bonds with R201 and R205 presented higher frequency than AT-RvD1; and (iv) residues R201 and R205 are the two receptor hotspots, demonstrated by the binding free calculations. Such results show that the ALX/FPR2 receptor remained in the active state for longer in the FPR2@RvD1 simulations than in the FPR2@AT-RvD1 simulations.
    MeSH term(s) Humans ; Receptors, Formyl Peptide/metabolism ; Molecular Dynamics Simulation ; Stereoisomerism ; Inflammation/metabolism ; Aspirin ; Receptors, Lipoxin/physiology
    Chemical Substances Receptors, Formyl Peptide ; Aspirin (R16CO5Y76E) ; FPR2 protein, human ; Receptors, Lipoxin
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 1520-5207
    ISSN (online) 1520-5207
    DOI 10.1021/acs.jpcb.3c01787
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  8. Article ; Online: Infectious neutrophil deployment is regulated by resolvin D4.

    Libreros, Stephania / Nshimiyimana, Robert / Lee, Brendon / Serhan, Charles N

    Blood

    2023  Volume 142, Issue 6, Page(s) 589–606

    Abstract: Neutrophils reside in the bone marrow (BM), ready for deployment to sites of injury/infection, initiating inflammation and its resolution. Here, we report that distal infections signal to the BM via resolvins to regulate granulopoiesis and BM neutrophil ... ...

    Abstract Neutrophils reside in the bone marrow (BM), ready for deployment to sites of injury/infection, initiating inflammation and its resolution. Here, we report that distal infections signal to the BM via resolvins to regulate granulopoiesis and BM neutrophil deployment. Emergency granulopoiesis during peritonitis evoked changes in BM resolvin D1 (RvD1) and BM RvD4. We found that leukotriene B4 stimulates neutrophil deployment. RvD1 and RvD4 each limited neutrophilic infiltration to infections, and differently regulated BM myeloid populations: RvD1 increased reparative monocytes, and RvD4 regulated granulocytes. RvD4 disengaged emergency granulopoiesis, prevented excess BM neutrophil deployment, and acted on granulocyte progenitors. RvD4 also stimulated exudate neutrophil, monocyte, and macrophage phagocytosis, and enhanced bacterial clearance. This mediator accelerated both neutrophil apoptosis and clearance by macrophages, thus expediting the resolution phase of inflammation. RvD4 stimulated phosphorylation of ERK1/2 and STAT3 in human BM-aspirate-derived granulocytes. RvD4 in the 1 to 100 nM range stimulated whole-blood neutrophil phagocytosis of Escherichia coli. RvD4 increased BM macrophage efferocytosis of neutrophils. Together, these results demonstrate the novel functions of resolvins in granulopoiesis and neutrophil deployment, contributing to the resolution of infectious inflammation.
    MeSH term(s) Humans ; Neutrophils ; Inflammation ; Phagocytosis ; Fatty Acids, Unsaturated ; Communicable Diseases ; Escherichia coli ; Docosahexaenoic Acids/pharmacology
    Chemical Substances resolvin D4 ; Fatty Acids, Unsaturated ; Docosahexaenoic Acids (25167-62-8)
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood.2022019145
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  9. Article ; Online: Maresin 1 activates LGR6 receptor promoting phagocyte immunoresolvent functions.

    Chiang, Nan / Libreros, Stephania / Norris, Paul C / de la Rosa, Xavier / Serhan, Charles N

    The Journal of clinical investigation

    2023  Volume 133, Issue 2

    MeSH term(s) Phagocytes ; Macrophages ; Docosahexaenoic Acids ; Receptors, G-Protein-Coupled/genetics
    Chemical Substances 7,14-dihydroxydocosa-4,8,10,12,16,19-hexaenoic acid ; Docosahexaenoic Acids (25167-62-8) ; Receptors, G-Protein-Coupled
    Language English
    Publishing date 2023-01-17
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 3067-3
    ISSN 1558-8238 ; 0021-9738
    ISSN (online) 1558-8238
    ISSN 0021-9738
    DOI 10.1172/JCI168084
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  10. Article ; Online: Protectins: Their biosynthesis, metabolism and structure-functions.

    Vidar Hansen, Trond / Serhan, Charles N

    Biochemical pharmacology

    2022  Volume 206, Page(s) 115330

    Abstract: ... the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid ...

    Abstract Several lipoxygenase enzymes and cyclooxygenase-2 stereoselectively convert the polyunsaturated fatty acids arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and n-3 docosapentaenoic acid into numerous oxygenated products. Biosynthetic pathway studies have shown, during the resolution phase of acute inflammation, that distinct families of endogenous products are formed. These products were named specialized pro-resolving mediators, given their specialized functions in the inflammation-resolution circuit, enhancing the return of inflamed and injured tissue to homeostasis. The lipoxins, resolvins, protectins and maresins, together with the sulfido-conjugates of the resolvins, protectins and maresins, constitute the four individual families of these local mediators. When administrated in vivo in a wide range of human disease models, the specialized pro-resolving mediators display potent bioactions. The detailed and individual biosynthetic steps constituting the biochemical pathways, the metabolism, recent reports on structure-function studies and pharmacodynamic data of the protectins, are presented herein. Emphasis is on the structure-function results on the recent members of the sulfido conjugated protectins and further metabolism of protectin D1. Moreover, the members of the individual families of specialized pro-resolving mediators and their biosynthetic precursor are presented. Today 43 specialized pro-resolving mediators possessing pro-resolution and anti-inflammatory bioactions are reported and confirmed, constituting a basis for resolution pharmacology. This emerging biomedical field provides a new approach for drug discovery, that is also discussed.
    MeSH term(s) Humans ; CD59 Antigens ; Docosahexaenoic Acids ; Inflammation/metabolism ; Eicosapentaenoic Acid ; Inflammation Mediators/metabolism ; Anti-Inflammatory Agents/pharmacology
    Chemical Substances CD59 Antigens ; Docosahexaenoic Acids (25167-62-8) ; Eicosapentaenoic Acid (AAN7QOV9EA) ; Inflammation Mediators ; Anti-Inflammatory Agents
    Language English
    Publishing date 2022-10-28
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2022.115330
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