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Wang H, Li Y, Zhang L, Lu M, Li C, Li Y. Anti-Inflammatory Lipid Mediators from Polyunsaturated Fatty Acids: Insights into their Role in Atherosclerosis Microenvironments. Curr Atheroscler Rep 2025; 27:48. [PMID: 40198469 DOI: 10.1007/s11883-025-01285-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/05/2025] [Indexed: 04/10/2025]
Abstract
PURPOSE OF REVIEW Inflammation has become a major residual risk factor for atherosclerotic cardiovascular disease (ASCVD). Certain lipid mediators, known as specialized proresolving mediators (SPMs), are mainly derived from polyunsaturated fatty acids (PUFAs) and can promote inflammation resolution while maintaining host autoimmunity. This review investigates the synthesis and ligand action pathways of these lipid mediators, as well as their regulatory mechanisms in the microenvironment of atherosclerotic plaques. Furthermore, it explores their clinical therapeutic potential, aiming to offer new insights into novel anti-inflammatory drug targets for the treatment of ASCVD. RECENT FINDINGS Reduced levels of SPMs are associated with the progression of atherosclerosis. SPMs inhibit inflammatory responses in the plaque microenvironment by limiting immune cell infiltration, reducing oxidative stress, and promoting the clearance of apoptotic cells, all of which contribute to plaque stabilization. Tyrosine-protein kinase Mer (MerTK), TRIF-related adaptor molecule (TRAM), and high mobility group box 1 (HMGB1) play crucial roles in the modulation of SPM production. Clinical use of ω-3 PUFAs has been shown to reduce the incidence of fatal cardiovascular events. Furthermore, aspirin not only initiates the synthesis of specific SPMs but also extends their activity within the body. The enhanced production of SPMs promotes inflammation resolution in the plaque microenvironment without inducing immunosuppression. This characteristic highlights MerTK, TRAM, and HMGB1 as potential targets for the development of anti-inflammatory drugs. Investigating targets and compounds that enhance the production of SPMs presents a promising strategy for developing future anti-inflammatory agents.
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Affiliation(s)
- Hongqin Wang
- Post-doctoral Mobile Station of Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- , Daxue Road No. 4655, Changqing District, Jinan, Shandong Province, People's Republic of China
| | - Yuan Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- , Daxue Road No. 4655, Changqing District, Jinan, Shandong Province, People's Republic of China
| | - Lei Zhang
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Mengkai Lu
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- , Daxue Road No. 4655, Changqing District, Jinan, Shandong Province, People's Republic of China
| | - Chao Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- , Daxue Road No. 4655, Changqing District, Jinan, Shandong Province, People's Republic of China.
| | - Yunlun Li
- Innovation Research Institute of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
- Department of Cardiovascular, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
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Chambers JP, Daum LT, Arulanandam BP, Valdes JJ. Polyunsaturated Fatty Acid Imbalance-A Contributor to SARS CoV-2 Disease Severity. J Nutr Metab 2025; 2025:7075883. [PMID: 40166706 PMCID: PMC11957867 DOI: 10.1155/jnme/7075883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Accepted: 01/18/2025] [Indexed: 04/02/2025] Open
Abstract
Overview: SARS CoV-2 infection is accompanied by the development of acute inflammation, resolution of which determines the course of infection and its outcome. If not resolved (brought back to preinjury status), the inflamed state progresses to a severe clinical presentation characterized by uncontrolled cytokine release, systemic inflammation, and in some death. In severe CoV-2 disease, the required balance between protective inflammation and its resolution appears missing, suggesting that the ω-3-derived specialized proresolving mediators (SPMs) needed for resolution are either not present or present at ineffective levels compared to competing ω-6 polyunsaturated fatty acid (PUFA) metabolic derivatives. Aim: To determine whether ω-6 PUFA linoleic acid (LA) metabolites increased in those infected with severe disease compared to uninfected controls. Findings: Increased levels of ω-6 LA metabolites, e.g., arachidonic acid (AA), epoxyeicosatrienoic (EET) acid derivatives of AA (8,9-, 11,12-, and 14,15-EETs), AA-derived hydroxyeicosatetraenoic (HETE) acid, dihydroxylated diols (leukotoxin and isoleukotoxin), and prostaglandin E2 with decreased levels of ω-3-derived inflammation resolving SPMs. Therapeutic treatment of SARS CoV-2 patients with ω-3 PUFA significantly increased 18-HEPE (SPM precursor) and EPA-derived diols (11,12- and 14,15-diHETE), while toxic 9,10- and 12,13-diHOMEs (leukotoxin and iosleukotoxin, respectively) decreased. Conclusion: Unbalanced dietary intake of ω-6/ω-3 PUFAs contributed to SARS CoV-2 disease severity by decreasing ω-3-dependent SPM resolution of inflammation and increasing membrane-associated ferroptotic AA peroxidation.
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Affiliation(s)
- James P. Chambers
- Department of Molecular Microbiology and Immunology, The University of Texas at San Antonio, San Antonio, Texas 78249, USA
| | - Luke T. Daum
- Lujo BioScience Laboratory, San Antonio, Texas 78209, USA
| | - Bernard P. Arulanandam
- Department of Immunology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
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Finney LJ, Mah J, Duvall M, Wiseman D, Kamal F, Fenwick P, Ritchie AI, Kebadze T, Orton C, Bhavsar P, Allinson JP, Macleod M, Mackay AJ, Baraldi F, Kemp S, Singanayagam A, Johnston SL, Byrne A, Levy BD, Wedzicha JA. Select Airway Specialized Pro-Resolving Mediators Are Associated with Recovery from Non-Viral COPD Exacerbations. Am J Respir Crit Care Med 2025; 211:803-813. [PMID: 40043205 DOI: 10.1164/rccm.202407-1325oc] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2024] [Accepted: 03/05/2025] [Indexed: 05/22/2025] Open
Abstract
RATIONALE Recovery from chronic obstructive pulmonary disease (COPD) exacerbations is heterogeneous and has a profound impact on disease trajectories. Resolution of airway inflammation is an active process which may be driven by Specialized Pro-resolving Mediators (SPMs). OBJECTIVES To characterize the temporal change in SPMs in the sputum of COPD patients during COPD exacerbations, their association with exacerbation triggers and exacerbation recovery. METHODS Participants were recruited from the London COPD Exacerbation Cohort between 01/11/2016 and 01/04/2018. Participants were reviewed at baseline, exacerbation onset, 1 week, 2 weeks and 6 weeks during their exacerbation recovery. Sputum, nasopharyngeal swabs, phlebotomy, quality of life questionnaires and spirometry were performed at each visit. SPMs were measured in sputum by liquid chromatography tandem mass spectrometry. Respiratory viruses were measured by quantitative PCR and bacteria by microbiological culture. MEASUREMENTS AND MAIN RESULTS There were 68 exacerbations during the study period. Median time to symptomatic recovery was 21 days for viral exacerbations compared to 13 days in non-viral exacerbations (P<0.001). There was a significant increase in Resolvin D1 (RvD1) at exacerbation onset in bacterial exacerbations but not viral exacerbations. Lower levels of RvD1 were associated with prolonged respiratory symptoms during the 1-week and 2-week recovery time points. Exogenous RvD1 significantly reduced IL-6 and CXCL8 response to rhinovirus infection in COPD bronchial epithelial cells. CONCLUSIONS There is a dynamic temporal change in airway SPMs during COPD exacerbations. Reduced levels of RvD1 were associated with prolonged respiratory symptoms. SPMs may be a potential therapeutic approach to promote exacerbation recovery.
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Affiliation(s)
- Lydia J Finney
- Imperial College London National Heart and Lung Institute, Respiratory Medicine, London, United Kingdom of Great Britain and Northern Ireland;
| | - Jordina Mah
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Melody Duvall
- Boston Children's Hospital, Divison of Critical Care Medicine, Department of Anesthesia, Boston, Massachusetts, United States
| | - Dexter Wiseman
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Faisal Kamal
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Peter Fenwick
- Imperial College London National Heart and Lung Institute, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Andrew I Ritchie
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Tata Kebadze
- Imperial College London National Heart and Lung Institute, Respiratory Medicine, London, United Kingdom of Great Britain and Northern Ireland
| | - Christopher Orton
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Pankaj Bhavsar
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - James P Allinson
- Imperial College London National Heart and Lung Institute, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
| | - Mairi Macleod
- Imperial College London, London, United Kingdom of Great Britain and Northern Ireland
| | - Alexander J Mackay
- National Heart and Lung Institute, Airways Disease Section, London, United Kingdom of Great Britain and Northern Ireland
| | | | - Samuel Kemp
- Nottingham University Hospitals NHS Trust - City Campus, Department of Respiratory Medicine, Nottingham, United Kingdom of Great Britain and Northern Ireland
| | - Aran Singanayagam
- Imperial College London National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
- Imperial College London Centre for Infection Prevention and Management, London, United Kingdom of Great Britain and Northern Ireland
| | - Sebastian L Johnston
- Imperial College London National Heart and Lung Institute, Respiratory Medicine, London, United Kingdom of Great Britain and Northern Ireland
| | - Adam Byrne
- University College Dublin, Dublin, Ireland
| | - Bruce D Levy
- Brigham and Women's Hospital Biomedical Research Institute, Pulmonary and Critical Care Medicine, Boston, Massachusetts, United States
| | - Jadwiga A Wedzicha
- Imperial College London National Heart and Lung Institute, National Heart and Lung Institute, London, United Kingdom of Great Britain and Northern Ireland
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Fukuishi N, Takahama K, Kurosaki H, Ono S, Asai H. The Role of Endogenous Specialized Proresolving Mediators in Mast Cells and Their Involvement in Inflammation and Resolution. Int J Mol Sci 2025; 26:1491. [PMID: 40003957 PMCID: PMC11855587 DOI: 10.3390/ijms26041491] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2025] [Revised: 02/05/2025] [Accepted: 02/10/2025] [Indexed: 02/27/2025] Open
Abstract
Many polyunsaturated fatty acids within cells exhibit diverse physiological functions. Particularly, arachidonic acid is the precursor of highly bioactive prostaglandins and leukotrienes, which are pro-inflammatory mediators. However, polyunsaturated fatty acids, such as arachidonic, docosahexaenoic, and eicosapentaenoic acids, can be metabolized into specialized proresolving mediators (SPMs), which have anti-inflammatory properties. Given that pro-inflammatory mediators and SPMs are produced via similar enzymatic pathways, SPMs can play a crucial role in mitigating excessive tissue damage induced by inflammation. Mast cells are immune cells that are widely distributed and strategically positioned at interfaces with the external environment, such as the skin and mucosa. As immune system sentinels, they respond to harmful pathogens and foreign substances. Upon activation, mast cells release various pro-inflammatory mediators, initiating an inflammatory response. Furthermore, these cells secrete factors that promote tissue repair and inhibit inflammation. This dual function positions mast cells as central regulators, balancing between the body's defense mechanisms and the need to minimize tissue injury. This review investigates the production of SPMs by mast cells and their subsequent effects on these cells. By elucidating the intricate relationship between mast cells and SPMs, this review aims to provide a comprehensive understanding of the mechanism by which these cells regulate the delicate balance between tissue damage and repair at inflammatory sites, ultimately contributing to the resolution of inflammatory responses.
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Affiliation(s)
- Nobuyuki Fukuishi
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kinjo Gakuin University, Nagoya 463-8521, Japan; (H.K.); (S.O.); (H.A.)
| | - Kentaro Takahama
- Technology Center, Tokai National Higher Education and Research System, Nagoya 464-8601, Japan;
| | - Hiromasa Kurosaki
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kinjo Gakuin University, Nagoya 463-8521, Japan; (H.K.); (S.O.); (H.A.)
| | - Sayaka Ono
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kinjo Gakuin University, Nagoya 463-8521, Japan; (H.K.); (S.O.); (H.A.)
| | - Haruka Asai
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kinjo Gakuin University, Nagoya 463-8521, Japan; (H.K.); (S.O.); (H.A.)
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Lovins HB, Mehta A, Leuenberger LA, Yaeger MJ, Schott E, Hutton G, Manke J, Armstrong M, Reisdorph N, Tighe RM, Cochran SJ, Shaikh SR, Gowdy KM. Dietary Eicosapentaenoic Acid Improves Ozone-Induced Pulmonary Inflammation in C57BL/6 Mice. J Nutr 2025; 155:465-475. [PMID: 39536972 PMCID: PMC11867137 DOI: 10.1016/j.tjnut.2024.11.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 11/04/2024] [Accepted: 11/06/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Ambient concentrations of the air pollutant, ozone, are rising with increasing global temperatures. Ozone is known to increase incidence and exacerbation of chronic lung diseases, which will increase as ambient ozone levels rise. Studies have identified diet as a variable that is able to modulate the pulmonary health effects associated with ozone exposure. Eicosapentaenoic acid (EPA) is an n-3 (ω-3) PUFA consumed through diet, which lowers inflammation through conversion to oxylipins including hydroxy-eicosapentaenoic acids (HEPEs). However, the role of dietary EPA in ozone-induced pulmonary inflammation is unknown. OBJECTIVE Therefore, we hypothesized increasing dietary EPA will decrease ozone-induced pulmonary inflammation and injury through the production of HEPEs. METHODS To test this, male C57BL/6J mice were fed a purified control diet or EPA-supplemented diet for 4 wk and then exposed to filtered air or 1 part per million ozone for 3 h. 24 or 48 h after exposure, bronchoalveolar lavage fluid was collected to assess airspace inflammation/injury and lung tissue was collected for targeted liquid chromatography-mass spectrometry lipidomics. RESULTS Following ozone exposure, EPA supplementation did not alter markers of lung injury but decreased ozone-induced airspace neutrophilia. Targeted liquid chromatography-mass spectrometry lipidomics revealed dietary EPA supplementation increased pulmonary EPA-derived metabolites including 5-HEPE and 12-HEPE. Additionally, EPA supplementation decreased pulmonary amounts of proinflammatory arachidonic acid-derived metabolites. To evaluate whether dietary EPA reduces ozone-induced pulmonary inflammation through increased pulmonary HEPEs, C57BL/6J mice were administered 5-HEPEs and 12-HEPEs systemically before filtered air or ozone exposure. Pretreatment with 5-HEPEs and 12-HEPEs reduced ozone-driven increases in airspace macrophages. CONCLUSIONS Together, these data indicate that an EPA-supplemented diet protects against ozone-induced airspace inflammation which is, in part, due to increasing pulmonary amounts of 5-HEPEs and 12-HEPEs. These findings suggest that dietary EPA and/or increasing EPA-derived metabolites in the lung can reduce ozone-driven incidences and exacerbations of chronic pulmonary diseases.
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Affiliation(s)
- Hannah B Lovins
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Anushka Mehta
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Laura A Leuenberger
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Michael J Yaeger
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Evangeline Schott
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Grace Hutton
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Jonathan Manke
- Department of Pharmaceutical Sciences, University of Colorado-AMC, Aurora, CO, United States
| | - Michael Armstrong
- Department of Pharmaceutical Sciences, University of Colorado-AMC, Aurora, CO, United States
| | - Nichole Reisdorph
- Department of Pharmaceutical Sciences, University of Colorado-AMC, Aurora, CO, United States
| | - Robert M Tighe
- Department of Medicine, Duke University Medical Center, Durham, NC, United States
| | - Samuel J Cochran
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States
| | - Saame Raza Shaikh
- Department of Nutrition, Gillings School of Global Public health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
| | - Kymberly M Gowdy
- Division of Pulmonary, Critical Care and Sleep Medicine, The Ohio State University, Columbus, OH, United States.
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Serhan CN, Levy BD. Proresolving Lipid Mediators in the Respiratory System. Annu Rev Physiol 2025; 87:491-512. [PMID: 39303274 PMCID: PMC11810588 DOI: 10.1146/annurev-physiol-020924-033209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2024]
Abstract
Lung inflammation, infection, and injury can lead to critical illness and death. The current means to pharmacologically treat excessive uncontrolled lung inflammation needs improvement because many treatments are or will become immunosuppressive. The inflammatory response evolved to protect the host from microbes, injury, and environmental insults. This response brings phagocytes from the bloodstream to the tissue site to phagocytize and neutralize bacterial invaders and enables airway antimicrobial functions. This physiologic response is ideally self-limited with initiation and resolution phases. Polyunsaturated essential fatty acids are precursors to potent molecules that govern both phases. In the initiation phase, arachidonic acid is converted to prostaglandins and leukotrienes that activate leukocytes to transmigrate from postcapillary venules. The omega-3 fatty acids (e.g., DHA and EPA) are precursors to resolvins, protectins, and maresins, which are families of chemically distinct mediators with potent functions in resolution of acute and chronic inflammation in the respiratory system.
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Affiliation(s)
- Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA;
| | - Bruce D Levy
- Pulmonary and Critical Care Medicine, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA;
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Mısırlıoglu NF, Ergun S, Kucuk SH, Himmetoglu S, Ozen GD, Sayili U, Uzun N, Uzun H. The Importance of Resolvin D1, LXA4, and LTB4 in Patients with Acute Pancreatitis Due to Gallstones. MEDICINA (KAUNAS, LITHUANIA) 2025; 61:239. [PMID: 40005356 PMCID: PMC11857126 DOI: 10.3390/medicina61020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Revised: 12/17/2024] [Accepted: 01/27/2025] [Indexed: 02/27/2025]
Abstract
Background and Objectives: Acute pancreatitis (AP) is an inflammatory disease where there is autodigestion of the pancreas by prematurely activated enzymes which may lead to a systemic inflammatory response. The aim of our study was to investigate the levels of circulating serum leukotriene B4 (LTB4), lipoxin A4 (LXA4), and resolvin D1 (RvD1) in pancreatitis due to gallstones in the etiologic investigation of AP. Materials and Methods: A total of 147 patients with AP (n: 49), AC (n: 49), and combined AP + AC (n: 49) will be included in the study. Healthy volunteers (n: 49) will be included as the control group. Results: RvD1 levels were significantly lower in patient groups compared to controls, while LXA4 levels were lower in patients with combined AP + AC (145.24 ng/L) compared to both controls (312.36 ng/L) and other patient groups. LTB4 levels were elevated in all patient groups compared to controls (335.56 ng/L vs. 65.56 ng/L) and were highest in combined AP + AC. Significant correlations were identified: RvD1 showed a negative correlation with LTB4 (r =-0.676; p < 0.001) and a positive correlation with LXA4 (r = 0.563, p < 0.001). ROC analysis demonstrated high diagnostic accuracy, with LXA4 and LTB4 achieving perfect differentiation (AUC: 1.0) between control and combined AP + AC cases. Conclusions: Our study showed that serum RvD1 and LXA4 levels have powerful anti-inflammatory properties in accordance with the literature. LTB4 may represent new, effective indicators to predict the severity of AP and the presence of necrosis in patients with AP. Despite its low sensitivity and specificity, RvD1 could be used as a complementary marker to the current scoring systems for the initial assessment of AP prognosis. These findings provide a new mechanistic understanding of how RvD1 attenuates inflammation to facilitate resolution, which could help develop novel therapeutic strategies for diseases caused by unresolved inflammation. It is easily obtainable and can provide additional prognostic information to clinicians.
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Affiliation(s)
- Naile Fevziye Mısırlıoglu
- Department of Biochemistry, Gaziosmanpaşa Training and Research Hospital, University of Health Sciences, 34255 Istanbul, Turkey
| | - Sefa Ergun
- Department of General Surgery, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey;
| | - Suat Hayri Kucuk
- Department of Biochemistry, Istanbul Physical Medicine and Rehabilitation Training and Research Hospital, University of Health Sciences, 34186 Istanbul, Turkey;
| | - Solen Himmetoglu
- Department of Medical Biochemistry, Faculty of Medicine, Biruni University, 34015 Istanbul, Turkey;
- Biruni University Research Center (B@MER), Biruni University, 34015 Istanbul, Turkey
| | | | - Ugurcan Sayili
- Department of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey;
| | - Nedim Uzun
- Department of Emergency, Gaziosmanpaşa Training and Research Hospital, University of Health Sciences, 34255 Istanbul, Turkey;
| | - Hafize Uzun
- Department of Medical Biochemistry, Faculty of Medicine, Istanbul Atlas University, 34403 Istanbul, Turkey;
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Torres-Vanegas J, Rodríguez-Echevarría R, Campos-Pérez W, Rodríguez-Reyes SC, Reyes-Pérez SD, Pérez-Robles M, Martínez-López E. Effect of a Diet Supplemented with Marine Omega-3 Fatty Acids on Inflammatory Markers in Subjects with Obesity: A Randomized Active Placebo-Controlled Trial. Healthcare (Basel) 2025; 13:103. [PMID: 39857130 PMCID: PMC11764561 DOI: 10.3390/healthcare13020103] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 12/04/2024] [Accepted: 12/10/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Obesity is associated with chronic low-grade inflammation. Polyunsaturated fatty acids (PUFAs) such as omega-3 (n-3), are essential in anti-inflammatory processes. Therefore, the aim of this study was to evaluate the effect of a dietary intervention along with supplementation of 1.8 g of marine n-3 PUFAs on anthropometric, biochemical, and inflammatory markers in adults. METHODS An 8-week double-blind randomized clinical trial was conducted with a diet (200 kcal/day reduction each 4 weeks based on the estimated basal caloric expenditure) containing a n-6/n-3 PUFA ratio ≤ 5:1, along with daily 1.8 g of marine n-3 supplementation (EPA and DHA) vs. active placebo 1.6 g (ALA). A total of 40 subjects were included in the study, 21 in the marine omega-3 group and 19 in the active placebo group. Inclusion criteria included subjects aged 25 to 50 years with obesity as determined by body mass index (BMI) and/or abdominal obesity according to ATP III criteria. RESULTS The marine omega-3 supplemented group had a better effect compared to the active placebo group, increasing Resolvin D1 [129.3 (-90.1-193.5) vs. -16.8 (-237.8-92.5) pg/mL, p = 0.041], IL-10 [1.4 (-0.7-4.6) vs. -2.0 (-5-0.05) pg/mL, p = 0.001], and decreasing IL-6 [-0.67 (2.72--0.59) vs. 0.03 (-0.59-1.84) pg/mL, p = 0.015], and MCP-1 [-29.6 (-94.9-5.50) vs. 18.3 (-97.3-66.35) pg/mL, p = 0.040]. CONCLUSIONS A diet supplemented with marine n-3 improves inflammatory markers by increasing systemic levels of Resolvin D1 and IL-10 and decreasing IL-6 and MCP-1.
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Affiliation(s)
- Joel Torres-Vanegas
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Roberto Rodríguez-Echevarría
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Wendy Campos-Pérez
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Sarai Citlalic Rodríguez-Reyes
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Samantha Desireé Reyes-Pérez
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Doctorado en Ciencias en Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Mariana Pérez-Robles
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
| | - Erika Martínez-López
- Doctorado en Ciencias de la Nutrición Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Instituto de Nutrigenética y Nutrigenómica Traslacional, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Departamento de Biología Molecular y Genómica, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
- Doctorado en Ciencias en Biología Molecular en Medicina, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44100, JA, Mexico
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9
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Peh HY, Chen J. Pro-resolving lipid mediators and therapeutic innovations in resolution of inflammation. Pharmacol Ther 2025; 265:108753. [PMID: 39566561 DOI: 10.1016/j.pharmthera.2024.108753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 11/07/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024]
Abstract
This review summarizes findings presented at the 19th World Congress of Basic & Clinical Pharmacology 2023 (Glasgow, Scotland, July 3rd to 7th, 2023) from 8 speakers in the field of resolution of inflammation, resolution pharmacology and resolution biology. It is now accepted that the acute inflammatory response is protective to defend the host against infection or tissue injury. Acute inflammation is self-limited and programmed to be limited in space and time: this is achieved through endogenous resolution processes that ensure return to homeostasis. Resolution is brought about by agonist mediators that include specialized pro-resolving lipid mediators (SPMs) and pro-resolving proteins and peptides such as annexin A1 and angiotensin-(1-7), all acting to initiate anti-inflammatory and pro-resolving processes. If the inflammatory reaction remains unchecked through dysfunctional resolution mechanism, it can become chronic and contribute to a plethora of human diseases, including respiratory, cardiovascular, metabolic, allergic diseases, and arthritis. Herein, we discuss how non-resolving inflammation plays a role in the pathogenesis of these diseases. In addition to SPMs, we highlight the discovery, biosynthesis, biofunctions, and latest research updates on innovative therapeutics (including annexin-A1 peptide-mimetic RTP-026, small molecule FPR2 agonist BM-986235/LAR-1219, biased agonist for FPR1/FPR2 Cmpd17b, lipoxin mimetics AT-01-KG and AT-02-CT, melanocortin receptor agonist AP1189, gold nanoparticles, angiotensin-(1-7), and CD300a) that can promote resolution of inflammation directly or through modulation of SPMs production. Drug development strategies based on the biology of the resolution of inflammation can offer novel therapeutic means and/or add-on therapies for the treatment of chronic diseases.
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Affiliation(s)
- Hong Yong Peh
- Immunology Translational Research Programme, Yong Loo Lin School of Medicine, Department of Pharmacology, Singapore; Immunology Programme and Singapore Lipidomics Incubator (SLING), Life Sciences Institute, National University of Singapore, Singapore; Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
| | - Jianmin Chen
- William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; Centre for inflammation and Therapeutic Innovation, Queen Mary University of London, London, United Kingdom
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10
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Lamon-Fava S. Associations between omega-3 fatty acid-derived lipid mediators and markers of inflammation in older subjects with low-grade chronic inflammation. Prostaglandins Other Lipid Mediat 2025; 176:106948. [PMID: 39756792 PMCID: PMC11835203 DOI: 10.1016/j.prostaglandins.2025.106948] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2024] [Revised: 01/02/2025] [Accepted: 01/02/2025] [Indexed: 01/07/2025]
Abstract
Cardiovascular disease (CVD), the leading cause of death in the United States and globally, is a chronic inflammatory disease likely caused by an impaired ability to resolve inflammation. Pre-clinical studies have provided strong evidence of the activating role of specialized pro-resolving lipid mediators (SPMs) derived from the omega-3 fatty acids eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) on the resolution of inflammation. However, there is a dearth of information on the role of SPMs on inflammation in humans. Therefore, the aim of this study was to assess whether plasma concentrations of omega-3 fatty acids and their derived SPMs are associated with inflammatory markers in subjects with low-grade chronic inflammation (C-reactive protein >2 µg/mL). The plasma phospholipid content of omega-3 fatty acids, a marker of dietary intake, plasma concentrations of SPMs, and serum concentrations of inflammatory markers were measured in 21 older men and postmenopausal women (age 53-73 y) at the end of a four-week placebo phase (3 g/day high oleic acid sunflower oil). The phospholipid DHA content was inversely related to interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and IL-10 concentrations. Moreover, MCP-1 was inversely associated with the DHA-derived 14-HDHA and 4-HDHA, and IL-10 was inversely associated with EPA-derived 18-HEPE, 12-HEPE and 5-HEPE, DPA-derived Rv5DPA, and DHA-derived 4-HDHA. These findings support the anti-inflammatory effect of dietary omega-3 fatty and suggest that lipid mediators derived from EPA, DPA, and DHA participate in the regulation of inflammation in subjects with chronic inflammation.
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Affiliation(s)
- Stefania Lamon-Fava
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging and Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, United States.
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11
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Quinlivan KM, Howard IV, Southan F, Bayer RL, Torres KL, Serhan CN, Panigrahy D. Exploring the unique role of specialized pro-resolving mediators in cancer therapeutics. Prostaglandins Other Lipid Mediat 2024; 178:106944. [PMID: 39722403 DOI: 10.1016/j.prostaglandins.2024.106944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 11/26/2024] [Accepted: 12/16/2024] [Indexed: 12/28/2024]
Abstract
Unresolved chronic inflammation, a hallmark of cancer, promotes tumor growth and metastasis in various cancer types. In contrast to blocking inflammation, stimulation of resolution of inflammation is an entirely novel approach to "resolve" inflammation. Resolution of inflammation mechanisms in cancer includes clearance of tumor debris, counter-regulation of pro-inflammatory eicosanoids and cytokines, and suppression of leukocyte infiltration. Conventional cytotoxic chemotherapy, radiation, anti-angiogenic therapy, and immune checkpoint inhibitors directly or indirectly can lead to the generation of pro-tumorigenic cellular debris. Over the past two decades, a potential paradigm shift has emerged in the inflammation field with the discovery of specialized pro-resolving mediators (SPMs), including resolvins, lipoxins, maresins, and protectins. SPMs are structurally distinct families of mediators grouped together by their pro-resolving "debris-clearing" functions. "Pro-resolving" therapies are in clinical development for various inflammation-driven diseases, including cancer. SPMs, as novel cancer therapeutics, have tremendous potential to enhance current cancer therapy. The mechanisms of SPMs as anti-cancer therapeutics are under active investigation by various laboratories worldwide. Here, we explore the current appreciation of the SPMs as innovative potential treatments designed to harness the unique anti-cancer activity of SPMs.
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Affiliation(s)
- Katherine M Quinlivan
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States.
| | - Isabella V Howard
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Franciska Southan
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Rachel L Bayer
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Kimberly L Torres
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
| | - Dipak Panigrahy
- Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, United States
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12
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Regidor PA, Eiblwieser J, Steeb T, Rizo JM. Omega-3 long chain fatty acids and their metabolites in pregnancy outcomes for the modulation of maternal inflammatory- associated causes of preterm delivery, chorioamnionitis and preeclampsia. F1000Res 2024; 13:882. [PMID: 39931317 PMCID: PMC11809487 DOI: 10.12688/f1000research.153569.2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/18/2024] [Indexed: 02/13/2025] Open
Abstract
Preterm birth is a major cause of perinatal complications and neonatal deaths. Furthermore, in the field of obstetrics many clinical entities like uterine contractions or the occurrence of pre- eclampsia remain to be serious complications during pregnancy and represent a major psychological, financial, and economic burden for society. Several published guidelines, studies and recommendations have highlighted the importance of supplementation of omega-3 long chain polyunsaturated fatty acids (PUFAs) during pregnancy. This narrative review aims at giving an overview on the modern perception of inflammatory processes and the role of specialized pro-resolving mediators (SPMs) in their resolution, especially in obstetrics. Additionally, we highlight the possible role of SPMs in the prevention of obstetric complications through oral supplementation using enriched marine oil nutritional's. The intake of PUFAs may result in an overall improvement of pregnancy outcomes by contributing to fetal brain growth and neurological development but more importantly though modulation of inflammation-associated pathologies. Especially the use of SPMs represents a promising approach for the management of obstetric and perinatal complications. SPMs are monohydroxylates derived from enriched marine oil nutritional's that involve certain pro-resolutive metabolites of omega-3 long chains PUFAs and may contribute to an attenuation of inflammatory diseases. This may be obtained through various mechanisms necessary for a proper resolution of inflammation such as the termination of neutrophil tissue infiltration, initiation of phagocytosis, downregulation of pro-inflammatory cytokines or tissue regeneration. In this way, acute and chronic inflammatory diseases associated with serious obstetrical complications can be modulated, which might contribute to an improved pregnancy outcome.
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Affiliation(s)
| | - Johanna Eiblwieser
- Medical Department, Exeltis Germany, Ismaning, Adalperostr. 84, 85737, Germany
| | - Theresa Steeb
- Medical Department, Exeltis Germany, Ismaning, Adalperostr. 84, 85737, Germany
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13
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Tian Y, Sun J, Jiao D, Zhang W. The potential role of n-3 fatty acids and their lipid mediators on asthmatic airway inflammation. Front Immunol 2024; 15:1488570. [PMID: 39720728 PMCID: PMC11666451 DOI: 10.3389/fimmu.2024.1488570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2024] [Accepted: 11/21/2024] [Indexed: 12/26/2024] Open
Abstract
Asthma, is a common, significant and diverse condition marked by persistent airway inflammation, with a major impact on human health worldwide. The predisposing factors for asthma are complex and widespread. The beneficial effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) in asthma have increasingly attracted attention recently. In asthma therapy, n-3 PUFAs may reduce asthma risk by controlling on levels of inflammatory cytokines and regulating recruitment of inflammatory cells in asthma. The specialized pro-resolving mediators (SPMs) derived from n-3 PUFAs, including the E- and D-series resolvins, protectins, and maresins, were discovered in inflammatory exudates and their biosynthesis by lipoxygenase mediated pathways elucidated., SPMs alleviated T-helper (Th)1/Th17 and type 2 cytokine immune imbalance, and regulated macrophage polarization and recruitment of inflammatory cells in asthma via specific receptors such as formyl peptide receptor 2 (ALX/FPR2) and G protein-coupled receptor 32. In conclusion, the further study of n-3 PUFAs and their derived SPMs may lead to novel anti-inflammatory asthma treatments.
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Affiliation(s)
- Yuan Tian
- School of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun, China
| | - JingMeng Sun
- Department of Pharmacy, First Hospital of Jilin University, Changchun, China
| | - DongMei Jiao
- Analytical Preparation Process Department, Shouyao Holdings (Beijing) Co., Ltd, Beijing, China
| | - WeiYu Zhang
- School of Pharmacy, Changchun University of Traditional Chinese Medicine, Changchun, China
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14
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Ervik K, Li YZ, Ji RR, Serhan CN, Hansen TV. Synthesis of the methyl ester of 17( R/ S)-Me-RvD5 n-3 DPA and relief of postoperative pain in male mice. Org Biomol Chem 2024; 22:9266-9270. [PMID: 39513388 PMCID: PMC11563200 DOI: 10.1039/d4ob01534g] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2024] [Accepted: 10/30/2024] [Indexed: 11/15/2024]
Abstract
The synthesis and biological evaluation of 17(R/S)-Me-RvD5n-3 DPA, an analog of the specialized pro-resolving mediators RvD5 and RvD5n-3 DPA, are presented. The synthesis was successfully accomplished utilizing Midland Alpine borane reduction, Sonogashira cross-coupling and a one-pot hydrozirconation/iodination protocol. In vivo evaluation of RvD5, RvD5n-3 DPA and 17(R/S)-Me-RvD5n-3 DPA in a mouse model of fracture revealed that all three compounds inhibited postoperative pain in male mice, but not in female mice.
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Affiliation(s)
- Karina Ervik
- Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O Box 1068, 0316 Oslo, Norway.
| | - Yi-Ze Li
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, NC 27710, USA
| | - Ru-Rong Ji
- Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina, NC 27710, USA
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Hale Building for Transformative Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USA
| | - Trond V Hansen
- Department of Pharmacy, Section for Pharmaceutical Chemistry, University of Oslo, P.O Box 1068, 0316 Oslo, Norway.
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15
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Nunes VS, Rogério AP, Abrahão O, Serhan CN. Leukotriene B4 receptor 1 (BLT1) activation by leukotriene B4 (LTB 4) and E resolvins (RvE1 and RvE2). Comput Biol Chem 2024; 113:108236. [PMID: 39395248 PMCID: PMC11645204 DOI: 10.1016/j.compbiolchem.2024.108236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2024] [Revised: 09/16/2024] [Accepted: 09/30/2024] [Indexed: 10/14/2024]
Abstract
Leukotriene B4 (LTB4) is a lipid inflammatory mediator derived from arachidonic acid (AA). Leukotriene B4 receptor 1 (BLT1), a G protein-coupled receptor (GPCR), is a receptor of LTB4. Nonetheless, the resolution of inflammation is driven by specialized pro-resolving lipid mediators (SPMs) such as resolvins E1 (RvE1) and E2 (RvE2). Both resolvins are derived from omega-3 fatty acid eicosapentaenoic acid (EPA). Here, long-term molecular dynamics simulations (MD) were performed to investigate the activation of the BLT1 receptor using two pro-resolution agonists (RvE1 and RvE2) and an inflammatory agonist (LTB4). We have analyzed the receptor's activation state, electrostatic interactions, and the binding affinity the Molecular Mechanics Poisson-Boltzmann Surface Area (MMPBSA) approach. The results showed that LTB4 and RvE1 have kept the receptor in an active state by higher simulation time. MD showed that the ligand-receptor interactions occurred mainly through residues H94, R156, and R267. The MMPBSA calculations showed residues R156 and R267 were the two mainly hotspots. Our MMPBSA results were compatible with experimental results from other studies. Overall, the results from this study provide new insights into the activation mechanisms of the BLT1 receptor, reinforcing the role of critical residues and interactions in the binding of pro-resolution and pro-inflammatory agonists.
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Affiliation(s)
- Vinicius S Nunes
- Programa de Pós-Graduação em Produtos Bioativos e Biociências, Universidade Federal do Rio de Janeiro, Macaé, Rio de Janeiro, Brazil; Laboratório Nacional de Computação Científica, Petrópolis, Rio de Janeiro, Brazil.
| | - Alexandre P Rogério
- Laboratório de Imunofarmacologia Experimental, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Odonírio Abrahão
- Laboratório de Química Computacional Medicinal, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, MassGeneral Brigham (MGB) and Harvard Medical School, Boston, MA, USA
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16
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Neprelyuk OA, Irza OL, Kriventsov MA. Omega-3 fatty acids as a treatment option in periodontitis: Systematic review of preclinical studies. Nutr Health 2024; 30:671-685. [PMID: 39319422 DOI: 10.1177/02601060241284694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/26/2024]
Abstract
Background: Periodontitis presents as a chronic inflammatory disease that affects the gingival tissues and structures surrounding the tooth. However, the existing approaches for periodontitis do not allow complete control of the disease. In this regard, an active search is being carried out both in preclinical and clinical studies for new approaches based, among other things, on nutraceuticals. Aim: This systematic review aimed to summarize and systematize data from preclinical studies on the effects of the use of polyunsaturated omega-3 fatty acids in experimentally induced periodontitis. Methods: A systematic search for research articles was performed using electronic scientific databases. Only original in vivo experimental studies investigating the use of omega-3 polyunsaturated fatty acids in experimentally induced periodontitis were included. Quality and risk of bias assessment (Systematic Review Centre for Laboratory Animal Experimentation) and quality of evidence assessment (using the modified Grading of Recommendations Assessment, Development and Evaluation approach) were performed. Results: Nineteen studies were included in this systematic review. It has been shown that omega-3 polyunsaturated fatty acids may decrease the progression of periodontitis with amelioration of alveolar bone loss along with decreased pro-inflammatory response and inhibition of osteoclasts. Despite the promising results, most of the analyzed studies were characterized by low to moderate quality and a significant risk of bias. Conclusion: Based on the retrieved data, the possibility of extrapolating the obtained results to humans is limited, indicating the need for additional studies to elucidate the key patterns and mechanisms of action of omega-3 polyunsaturated fatty acids and their endogenous metabolites in experimentally induced periodontitis.
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Affiliation(s)
- Olga A Neprelyuk
- Department of Orthopedic Dentistry, Medical Institute named after SI Georgievsky, VI Vernadsky Crimean Federal University, Simferopol, Russia
| | - Oksana L Irza
- Department of Orthopedic Dentistry, Medical Institute named after SI Georgievsky, VI Vernadsky Crimean Federal University, Simferopol, Russia
| | - Maxim A Kriventsov
- Pathomorphology Department, Medical Institute named after SI Georgievsky, VI Vernadsky Crimean Federal University, Simferopol, Russia
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17
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Deng Y, Wang F, Wang T, Zhang X, Chen D, Wang Y, Chen C, Pan G. Research progress in the mechanisms and functions of specialized pro-resolving mediators in neurological diseases. Prostaglandins Other Lipid Mediat 2024; 175:106905. [PMID: 39265777 DOI: 10.1016/j.prostaglandins.2024.106905] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Revised: 08/30/2024] [Accepted: 09/09/2024] [Indexed: 09/14/2024]
Abstract
The nervous system interacts with the immune system through a variety of cellular regulators, signaling pathways, and molecular mechanisms. Disruptions in these interactions lead to the development of multiple neurological diseases. Recent studies have identified that specialized pro-resolving mediators (SPMs) play a regulatory role in the neuroimmune system. This study reviews recent research on the function of SPMs in the inflammatory process and their association with the nervous system. The review aims to provide new perspectives for studying the pathogenesis of neurological diseases and identify novel targets for clinical therapy.
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Affiliation(s)
- Yu Deng
- Guangzhou Hospital of Integrated Chinese and Western Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510800, China
| | - Fei Wang
- Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224000, China; Yancheng TCM Hospital, Yancheng, Jiangsu 224000, China
| | - Tianle Wang
- Guangzhou Hospital of Integrated Chinese and Western Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510800, China
| | - Xu Zhang
- Guangzhou Hospital of Integrated Chinese and Western Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510800, China
| | - Du Chen
- Guangzhou Hospital of Integrated Chinese and Western Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510800, China
| | - Yuhan Wang
- Hubei University of Chinese Medicine, Wuhan, Hubei 430065, China
| | - Chaojun Chen
- Guangzhou Hospital of Integrated Chinese and Western Medicine Affiliated to Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510800, China.
| | - Guangtao Pan
- Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, Jiangsu 224000, China; Yancheng TCM Hospital, Yancheng, Jiangsu 224000, China.
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18
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Li W, Xia Y, Yang J, Sanyal AJ, Shah VH, Chalasani NP, Yu Q. Disrupted balance between pro-inflammatory lipid mediators and anti-inflammatory specialized pro-resolving mediators is linked to hyperinflammation in patients with alcoholic hepatitis. Front Immunol 2024; 15:1377236. [PMID: 39640267 PMCID: PMC11617321 DOI: 10.3389/fimmu.2024.1377236] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 10/31/2024] [Indexed: 12/07/2024] Open
Abstract
Background Alcoholic hepatitis (AH) is characterized by intense systemic and liver inflammation, posing significant risks of health complications and mortality. While inflammation is a crucial defense mechanism against injury and infection, its timely resolution is essential to prevent tissue damage and restore tissue homeostasis. The resolution of inflammation is primarily governed by specialized pro-resolving mediators (SPMs), lipid metabolites derived from w-6 and w-3 poly-unsaturated fatty acids (PUFAs). Currently, the balance between pro-inflammatory lipid mediators (PLMs) and SPMs in the w-6 and w-3 PUFA metabolic pathways and the impact of alcohol abstinence on profiles of PLMs and SPMs in AH patients are not well studied. Methods In this study, we used LC-MS/MS and ELISA to quantify levels of lipid mediators (LMs) and their precursors in the plasma samples from 58 AH patients, 29 heavy drinkers without overt liver diseases (HDCs), and 35 healthy controls (HCs). Subsequently, we assessed correlations of altered LMs with clinical parameters and inflammatory mediators. Furthermore, we conducted a longitudinal study to analyze the effects of alcohol abstinence on LMs over 6- and 12-month follow-ups. Results AH patients exhibited significantly higher plasma levels of w-6 PLMs (PGD2 and LTB4) and SPM RvE1 compared to HDCs or HCs. Conversely, the SPM LXA4 was significantly downregulated in AH patients. Some of these altered LMs were found to correlate with AH disease severity and various inflammatory cytokines. Particularly, the LTB4/LXA4 ratio was substantially elevated in AH patients relative to HDCs and HCs. This altered ratio displayed a positive correlation with the MELD score. Importantly, the majority of dysregulated LMs, particularly PLMs, were normalized following alcohol abstinence.
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Affiliation(s)
- Wei Li
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Ying Xia
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Jing Yang
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Arun J. Sanyal
- Division of Gastroenterology and Hepatology, Department of Medicine, Virginia Commonwealth University, Richmond, VA, United States
| | - Vijay H. Shah
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, United States
| | - Naga P. Chalasani
- Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, United States
| | - Qigui Yu
- Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States
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19
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Sherratt SC, Mason RP, Libby P, Bhatt DL. "A Time to Tear Down and a Time to Mend": The Role of Eicosanoids in Atherosclerosis. Arterioscler Thromb Vasc Biol 2024; 44:2258-2263. [PMID: 39441911 PMCID: PMC11495529 DOI: 10.1161/atvbaha.124.319570] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 08/13/2024] [Indexed: 10/25/2024]
Affiliation(s)
- Samuel C.R. Sherratt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY (S.C.R.S., D.L.B.)
- Elucida Research, Beverly, MA (S.C.R.S., R.P.M.)
| | - R. Preston Mason
- Elucida Research, Beverly, MA (S.C.R.S., R.P.M.)
- Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (R.P.M., P.L.)
| | - Peter Libby
- Department of Medicine, Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA (R.P.M., P.L.)
| | - Deepak L. Bhatt
- Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, NY (S.C.R.S., D.L.B.)
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20
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Giardini E, Moore D, Sadlier D, Godson C, Brennan E. The dual role of lipids in chronic kidney disease: Pathogenic culprits and therapeutic allies. Atherosclerosis 2024; 398:118615. [PMID: 39370307 DOI: 10.1016/j.atherosclerosis.2024.118615] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2024] [Revised: 08/23/2024] [Accepted: 09/19/2024] [Indexed: 10/08/2024]
Abstract
Chronic kidney disease (CKD) is a significant health burden, with rising incidence and prevalence, attributed in part to increasing obesity and diabetes rates. Lipid accumulation in the kidney parenchyma and chronic, low-grade inflammation are believed to significantly contribute to the development and progression of CKD. The effect of dysregulated kidney lipid metabolism in CKD progression, including altered cholesterol and fatty acid metabolism contribute to glomerular and tubular cell injury through the activation of oxidative stress and inflammatory signalling cascades. In contrast, classes of endogenous specialized pro-resolving lipid mediators (SPMs) have been described that act to limit the inflammatory response and promote the resolution of inflammation. This review highlights our current understanding of how lipids can cause damage within the kidney, and classes of protective lipid metabolites that offer therapeutic benefits.
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Affiliation(s)
- Elena Giardini
- Diabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland
| | - Dean Moore
- Diabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland
| | - Denise Sadlier
- Mater Misericordiae University Hospital, Eccles Street, Dublin 7, Ireland
| | - Catherine Godson
- Diabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland
| | - Eoin Brennan
- Diabetes Complications Research Centre, Conway Institute and School of Medicine, University College Dublin, Dublin, Ireland.
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21
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Fredman G, Serhan CN. Specialized pro-resolving mediators in vascular inflammation and atherosclerotic cardiovascular disease. Nat Rev Cardiol 2024; 21:808-823. [PMID: 38216693 DOI: 10.1038/s41569-023-00984-x] [Citation(s) in RCA: 38] [Impact Index Per Article: 38.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/07/2023] [Indexed: 01/14/2024]
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 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.
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Affiliation(s)
- Gabrielle Fredman
- Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA.
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anaesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
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22
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Rahman MS, Hossain MS. Eicosanoids Signals in SARS-CoV-2 Infection: A Foe or Friend. Mol Biotechnol 2024; 66:3025-3041. [PMID: 37878227 DOI: 10.1007/s12033-023-00919-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2023] [Accepted: 09/25/2023] [Indexed: 10/26/2023]
Abstract
SARS-CoV-2 mediated infection instigated a scary pandemic state since 2019. They created havoc comprising death, imbalanced social structures, and a wrecked global economy. During infection, the inflammation and associated cytokine storm generate a critical pathological situation in the human body, especially in the lungs. By the passage of time of infection, inflammatory disorders, and multiple organ damage happen which might lead to death, if not treated properly. Until now, many pathological parameters have been used to understand the progress of the severity of COVID-19 but with limited success. Bioactive lipid mediators have the potential of initiating and resolving inflammation in any disease. The connection between lipid storm and inflammatory states of SARS-CoV-2 infection has surfaced and got importance to understand and mitigate the pathological states of COVID-19. As the role of eicosanoids in COVID-19 infection is not well defined, available information regarding this issue has been accumulated to address the possible network of eicosanoids related to the initiation of inflammation, promotion of cytokine storm, and resolution of inflammation, and highlight possible strategies for treatment and drug discovery related to SARS-CoV-2 infection in this study. Understanding the involvement of eicosanoids in exploration of cellular events provoked by SARS-CoV-2 infection has been summarized as an important factor to deescalate any upcoming catastrophe imposed by the lethal variants of this micro-monster. Additionally, this study also recognized the eicosanoid based drug discovery, treatment, and strategies for managing the severity of SARS-COV-2 infection.
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Affiliation(s)
- Mohammad Sharifur Rahman
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, 1000, Bangladesh.
| | - Mohammad Salim Hossain
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali, 3814, Bangladesh.
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23
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Li Q, Xu X, Zhao C, Wang Y, Chen X, Liu M, Yue C. PUFA and intrahepatic cholestasis of pregnancy: a two-sample Mendelian randomisation analysis. Br J Nutr 2024; 132:1022-1029. [PMID: 39440684 DOI: 10.1017/s0007114524002095] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2024]
Abstract
This study aimed to explore the potential causal association between PUFA and the risk of intrahepatic cholestasis of pregnancy (ICP) using Mendelian randomisation (MR) analysis. A two-sample MR analysis was conducted utilising large-scale European-based genome-wide association studies summary databases. The primary MR analysis was carried out using the inverse variance-weighted (IVW) method, complemented by other methods such as MR-egger, weighted-median and weighted mode. Sensitivity analysis was also performed to validate the robustness of the findings. Results indicated a 31 % reduced risk of ICP for every 1 standard deviation (sd) increase in n-3 fatty acids levels (OR = 0·69, 95 % CI: 0·54, 0·89, P = 0·004) and in the ratio of n-3 fatty acids to total fatty acids (OR = 0·69, 95 % CI: 0·53, 0·91, P = 0·008). Conversely, there was a 51 % increased risk of ICP for every 1 sd increase in the ratio of n-6 fatty acids to n-3 fatty acids (OR = 1·51, 95 % CI: 1·20, 1·91, P < 0·001) and a 138 % increased risk for every 1 sd increase in the ratio of linoleic fatty acids to total fatty acids (OR = 2·38, 95 % CI: 1·55, 3·66, P < 0·001). The findings suggest that n-3 fatty acids may have a protective effect against the risk of ICP, while n-6 fatty acids and linoleic fatty acids could be potential risk factors for ICP. The supplementation of n-3 fatty acids, as opposed to n-6 fatty acids, could be a promising strategy for the prevention and management of ICP.
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Affiliation(s)
- Qiong Li
- Department of Obstetrics and Gynecology, The First People's Hospital of Chenzhou, Chenzhou, People's Republic of China
| | - Xinchun Xu
- Department of Ultrasound, Zhangjiagang Hospital Affiliated to Soochow University, Suzhou, People's Republic of China
| | - Chenyang Zhao
- Department of Obstetrics and Gynecology, The First People's Hospital of Chenzhou, Chenzhou, People's Republic of China
| | - Yonghong Wang
- Department of Obstetrics and Gynecology, The First People's Hospital of Chenzhou, Chenzhou, People's Republic of China
| | - Xiaohu Chen
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China
| | - Miao Liu
- Department of Obstetrics and Gynecology, The First People's Hospital of Chenzhou, Chenzhou, People's Republic of China
| | - Chaoyan Yue
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, People's Republic of China
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24
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Pitchai A, Shinde A, Swihart JN, Robison K, Shannahan JH. Specialized Pro-Resolving Lipid Mediators Distinctly Modulate Silver Nanoparticle-Induced Pulmonary Inflammation in Healthy and Metabolic Syndrome Mouse Models. NANOMATERIALS (BASEL, SWITZERLAND) 2024; 14:1642. [PMID: 39452978 PMCID: PMC11510677 DOI: 10.3390/nano14201642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 10/02/2024] [Accepted: 10/11/2024] [Indexed: 10/26/2024]
Abstract
Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared to a healthy mouse model, a mouse model of MetS exhibited increased pulmonary inflammation 24 h after exposure to AgNPs. This exacerbated response was associated with decreases in pulmonary levels of specific specialized pro-resolving mediators (SPMs). Supplementation with specific SPMs that are known to be dysregulated in MetS may alter particulate-induced inflammatory responses and be useful in treatment strategies. Our current study hypothesized that administration of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1) following AgNP exposure will differentially regulate inflammatory responses. To examine this hypothesis, healthy and MetS mouse models were exposed to either a vehicle (control) or 50 μg of 20 nm AgNPs via oropharyngeal aspiration. They were then treated 24 h post-exposure with either a vehicle (control) or 400 ng of RvE1, PD1, or MaR1 via oropharyngeal aspiration. Endpoints of pulmonary inflammation and toxicity were evaluated three days following AgNP exposure. MetS mice that were exposed to AgNPs and received PBS treatment exhibited significantly exacerbated pulmonary inflammatory responses compared to healthy mice. In mice exposed to AgNPs and treated with RvE1, neutrophil infiltration was reduced in healthy mice and the exacerbated neutrophil levels were decreased in the MetS model. This decreased neutrophilia was associated with decreases in proinflammatory cytokines' gene and protein expression. Healthy mice treated with PD1 did not demonstrate alterations in AgNP-induced neutrophil levels compared to mice not receiving treat; however, exacerbated neutrophilia was reduced in the MetS model. These PD1 alterations were associated with decreases in proinflammatory cytokines, as well as elevated interleukin-10 (IL-10). Both mouse models receiving MaR1 treatment demonstrated reductions in AgNP-induced neutrophil influx. MaR1 treatment was associated with decreases in proinflammatory cytokines in both models and increases in the resolution inflammatory cytokine IL-10 in both models, which were enhanced in MetS mice. Inflammatory responses to particulate exposure may be treated using specific SPMs, some of which may benefit susceptible subpopulations.
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Affiliation(s)
| | | | | | | | - Jonathan H. Shannahan
- School of Health Sciences, College of Health and Human Sciences, Purdue University, West Lafayette, IN 47907, USA
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25
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Ouagueni A, Shi Z, Shraim M, Al-Zoubi RM, Zarour A, Al-Ansari A, Bawadi H. Omega-3 Supplementation in Coronary Artery Bypass Graft Patients: Impact on ICU Stay and Hospital Stay-A Systematic Review and Meta-Analysis. Nutrients 2024; 16:3298. [PMID: 39408265 PMCID: PMC11478518 DOI: 10.3390/nu16193298] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2024] [Revised: 09/17/2024] [Accepted: 09/20/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Coronary artery bypass graft (CABG) is associated with inflammation and complications, potentially leading to prolonged ICU and hospital stays. Omega-3 PUFA has anti-inflammatory properties, thought to potentially reduce complications in CABG patients. This study aims to systematically review and meta-analyze the impact of perioperative omega-3 PUFA supplementation on total ICU and total hospital stays in CABG patients; Methods: Randomized controlled trials examining the effects of omega-3 PUFA supplementation (IV/oral) on ICU and hospital stays in CABG patients were included. Studies were searched for in PubMed, EMBASE, PsychINFO, CINAHL, and the Cochrane Central Register of Controlled Trial databases, along with hand searching of reference lists. The quality and risk of bias of the included studies were evaluated by two independent reviewers using the revised Cochrane risk-of-bias tool. Meta-analysis was performed using fixed or random effects models according to the level of heterogeneity by mean difference with their 95% confidence intervals; Results: Twelve studies were included in the qualitative analysis and seven in the meta-analysis. Omega-3 PUFA was associated with a significant reduction in days of hospital stay (-0.58 (95% CI -1.13, -0.04)). Subgroup analysis showed that only oral omega-3 PUFA supplementation resulted in a statistically significant reduction in length of hospitalization after subgroup analysis with MD -0.6 (95% CI -1.17, -0.04); Conclusions: This study suggests that perioperative omega-3 PUFA supplementation may reduce the length of hospitalization in CABG patients, especially when administered orally. However, the findings should be interpreted cautiously due to the high level of heterogeneity.
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Affiliation(s)
- Asma Ouagueni
- Department of Human Nutrition, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar; (A.O.); (Z.S.)
| | - Zumin Shi
- Department of Human Nutrition, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar; (A.O.); (Z.S.)
| | - Mujahed Shraim
- Department of Public Health, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar;
| | - Raed M. Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar; (R.M.A.-Z.); (A.A.-A.)
- Department of Chemistry, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
- Department of Biomedical Sciences, College of Health Science, Qatar University, Doha 2713, Qatar
| | - Ahmad Zarour
- Acute Care Surgery Division, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar;
| | - Abdulla Al-Ansari
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar; (R.M.A.-Z.); (A.A.-A.)
- Department of Surgery, Division of Urology/Andrology, Hamad Medical Corporation, Doha 576214, Qatar
| | - Hiba Bawadi
- Department of Human Nutrition, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar; (A.O.); (Z.S.)
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26
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Gracia Aznar A, Moreno Egea F, Gracia Banzo R, Gutierrez R, Rizo JM, Rodriguez-Ledo P, Nerin I, Regidor PA. Pro-Resolving Inflammatory Effects of a Marine Oil Enriched in Specialized Pro-Resolving Mediators (SPMs) Supplement and Its Implication in Patients with Post-COVID Syndrome (PCS). Biomedicines 2024; 12:2221. [PMID: 39457534 PMCID: PMC11505212 DOI: 10.3390/biomedicines12102221] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 09/11/2024] [Accepted: 09/19/2024] [Indexed: 10/28/2024] Open
Abstract
OBJECTIVES This study aimed to evaluate the eicosanoid and pro-resolutive parameters in patients with Post-COVID Syndrome (PCS) during a 12-week supplementation with a marine oil enriched in specialized pro-resolving mediators (SPMs). PATIENT AND METHODS This study was conducted on 53 adult patients with PCS. The subjects included must have had a positive COVID-19 test (PCR, fast antigen test, or serologic test) and persistent symptoms related to COVID-19 at least 12 weeks before their enrolment in the study. The following parameters were evaluated: polyunsaturated fatty acids EPA, DHA, ARA, and DPA; specialized pro-resolving mediators (SPMs), 17-HDHA, 18-HEPE, 14-HDHA, resolvins, maresins, protectins, and lipoxins. The eicosanoids group included prostaglandins, thromboxanes, and leukotrienes. The development of the clinical symptoms of fatigue and dyspnea were evaluated using the Fatigue Severity Scale (FSS) and the Modified Medical Research Council (mMRC) Dyspnea Scale. Three groups with different intake amounts were evaluated (daily use of 500 mg, 1500 mg, and 3000 mg) and compared to a control group not using the product. RESULTS In the serum from patients with PCS, an increase in 17-HDHA, 18-HEPE, and 14-HDHA could be observed, and a decrease in the ratio between the pro-inflammatory and pro-resolutive lipid mediators was detected; both differences were significant (p < 0.05). There were no differences found between the three treatment groups. Fatigue and dyspnea showed a trend of improvement after supplementation in all groups. CONCLUSIONS A clear enrichment in the serum of the three monohydroxylated SPMs could be observed at a dosage of 500 mg per day. Similarly, a clear improvement in fatigue and dyspnea was observed with this dosage.
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Affiliation(s)
- Asun Gracia Aznar
- Sociedad Española de Médicos Generales y de Familia (SEMG), 28005 Madrid, Spain; (A.G.A.); (P.R.-L.)
| | | | - Rafael Gracia Banzo
- Solutex GC SL, Parque Empresarial Utebo, Avda. Miguel Servet nº 81, 50180 Utebo, Spain;
| | - Rocio Gutierrez
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain; (R.G.); (J.M.R.)
| | - Jose Miguel Rizo
- OTC Chemo, Manuel Pombo Angulo 28-4th Floor, 28050 Madrid, Spain; (R.G.); (J.M.R.)
| | - Pilar Rodriguez-Ledo
- Sociedad Española de Médicos Generales y de Familia (SEMG), 28005 Madrid, Spain; (A.G.A.); (P.R.-L.)
| | - Isabel Nerin
- Directora de la Cátedra SEMG-Estilos de Vida Unidad de Tabaquismo FMZ Profª Dpto. Medicina, Psiquiatría y Dermatología Facultad de Medicina, Universidad de Zaragoza, 50009 Zaragoza, Spain;
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27
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Wang YH, Lin CW, Huang CW. Polyunsaturated Fatty Acids as Potential Treatments for COVID-19-Induced Anosmia. Biomedicines 2024; 12:2085. [PMID: 39335598 PMCID: PMC11428228 DOI: 10.3390/biomedicines12092085] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2024] [Revised: 09/05/2024] [Accepted: 09/09/2024] [Indexed: 09/30/2024] Open
Abstract
Some individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) experience anosmia, or loss of smell. Although the prevalence of anosmia has decreased with the emergence of the Omicron variant, it remains a significant concern. This review examines the potential role of polyunsaturated fatty acids (PUFAs), particularly omega-3 PUFAs, in treating COVID-19-induced anosmia by focusing on the underlying mechanisms of the condition. Omega-3 PUFAs are known for their anti-inflammatory, neuroprotective, and neurotransmission-enhancing properties, which could potentially aid in olfactory recovery. However, study findings are inconsistent. For instance, a placebo-controlled randomized clinical trial found no significant effect of omega-3 PUFA supplementation on olfactory recovery in patients with COVID-19-induced anosmia. These mixed results highlight the limitations of existing research, including small sample sizes, lack of placebo controls, short follow-up periods, and combined treatments. Therefore, more rigorous, large-scale studies are urgently needed to definitively assess the therapeutic potential of omega-3 PUFAs for olfactory dysfunction. Further research is also crucial to explore the broader role of PUFAs in managing viral infections and promoting sensory recovery.
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Affiliation(s)
- Yu-Han Wang
- Department of Education, National Taiwan University Hospital, Taipei 100, Taiwan
| | - Chung-Wei Lin
- Department of Education, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
- Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, Taiwan
| | - Chiung-Wei Huang
- Department of Physiology, Kaohsiung Medical University, Kaohsiung 807, Taiwan
- Department of Post-Baccalaureate Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan
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28
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Kim N, Shin HY. Deciphering the Potential Role of Specialized Pro-Resolving Mediators in Obesity-Associated Metabolic Disorders. Int J Mol Sci 2024; 25:9598. [PMID: 39273541 PMCID: PMC11395256 DOI: 10.3390/ijms25179598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/15/2024] Open
Abstract
Obesity-related metabolic disorders, including diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease, increasingly threaten global health. Uncontrolled inflammation is a key pathophysiological factor in many of these conditions. In the human body, inflammatory responses generate specialized pro-resolving mediators (SPMs), which are crucial for resolving inflammation and restoring tissue balance. SPMs derived from omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as resolvins, protectins, and maresins hold promise in attenuating the chronic inflammatory diseases associated with lipid metabolism disorders. Recent research has highlighted the therapeutic potential of n-3 PUFA-derived metabolites in addressing these metabolic disorders. However, the understanding of the pharmacological aspects of SPMs, particularly in obesity-related metabolic disorders, remains limited. This review comprehensively summarizes recent advances in understanding the role of SPMs in resolving metabolic disorders, based on studies in animal models and humans. These studies indicate that SPMs have potential as therapeutic targets for combating obesity, as well as offering insights into their mechanisms of action.
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Affiliation(s)
- Nahyun Kim
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea
| | - Ha Youn Shin
- Department of Biomedical Science and Engineering, Konkuk University, Seoul 05029, Republic of Korea
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29
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Yu T, Chen D, Qi H, Lin L, Tang Y. Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway. Biofactors 2024; 50:967-979. [PMID: 38485285 DOI: 10.1002/biof.2049] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 12/26/2023] [Indexed: 10/04/2024]
Abstract
Diabetes is associated with increased oxidative stress, leading to altered tight junction formation and increased apoptosis in colonic epithelial cells. These changes may lead to intestinal barrier dysfunction and corresponding gastrointestinal symptoms in patients with diabetes, including diarrhea. The aim of this study was to characterize the effect and mechanism of Resolvin D1 (RvD1) on diabetes-induced oxidative stress and barrier disruption in the colon. Mice with streptozotocin-induced diabetes were treated with RvD1 for 2 weeks, then evaluated for stool frequency, stool water content, gut permeability, and colonic transepithelial electrical resistance as well as production of reactive oxygen species (ROS), apoptosis, and expression of tight junction proteins Zonula Occludens 1 (ZO-1) and occludin. The same parameters were assessed in human colonoid cultures subjected to elevated glucose. We found that RvD1 treatment did not affect blood glucose, but normalized stool water content and prevented intestinal barrier dysfunction, epithelial oxidative stress, and apoptosis. RvD1 also restored ZO-1 and occludin expression in diabetic mice. RvD1 treatment increased phosphorylation of Akt and was accompanied by a 3.5-fold increase in heme oxygenase-1 (HO-1) expression in the epithelial cells. The protective effects of RvD1 were blocked by ZnPP, a competitive inhibitor of HO-1. Similar findings were observed in RvD1-treated human colonoid cultures subjected to elevated glucose. In conclusion, Oxidative stress in diabetes results in mucosal barrier dysfunction, contributing to the development of diabetic diarrhea. Resolvins prevent ROS-mediated mucosal injury and protect gut barrier function by intracellular PI3K/Akt activation and subsequent HO-1 upregulation in intestinal epithelial cells. These actions result in normalizing stool frequency and stool water content in diabetic mice, suggesting that resolvins may be useful in the treatment of diabetic diarrhea.
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Affiliation(s)
- Ting Yu
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province, China
| | - Die Chen
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province, China
| | - Hongyan Qi
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province, China
| | - Lin Lin
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province, China
| | - Yurong Tang
- Department of Gastroenterology, The First Affiliated Hospital with Nanjing Medical University, Jiangsu Province, China
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30
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Tobin D, Vuckovic A, Sarris J. Targeting Divergent Pathways in the Nutritional Management of Depression. Nutrients 2024; 16:2806. [PMID: 39203943 PMCID: PMC11357244 DOI: 10.3390/nu16162806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Revised: 07/17/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024] Open
Abstract
The nutritional management of depression has long been discussed, due to the perceived benefit of a nutritional product having less side effects than pharmaceutical agents. Candidate nutrients for managing depression include vitamin D, B vitamins, tryptophan, branch chain amino acids, probiotics, omega-3 fatty acids, folate/methylfolate (also known as vitamin B9), and s-adenosylmethionine. This paper provides a narrative review of three nutrients which have significant scientific support for the management of depression. A deficiency in each nutrient is associated with depression, and interventional studies indicate that the correction of the nutritional deficiency may provide clinical benefit. We present epidemiological evidence, a mechanistic explanation and a review of interventional studies for these nutrients. Finally, relevant nutritional guidelines are presented with their conclusion for the role of each nutrient in the management of depression.
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Affiliation(s)
| | | | - Jerome Sarris
- NICM Health Research Institute, Western Sydney University, Westmead, NSW 2145, Australia
- The Florey Institute of Neuroscience and Mental Health, Melbourne University, Melbourne, VIC 3052, Australia
- Centre for Mental Health, Swinburne University of Technology, Melbourne, VIC 3122, Australia
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31
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Distefano A, Orlando L, Giallongo S, Tropea E, Spampinato M, Santisi A, Longhitano L, Parisi G, Leonardi S, Russo A, Caruso M, Di Rosa M, Tibullo D, Salamone M, Li Volti G, Barbagallo IA. Fish Oil Containing Pro-Resolving Mediators Enhances the Antioxidant System and Ameliorates LPS-Induced Inflammation in Human Bronchial Epithelial Cells. Pharmaceuticals (Basel) 2024; 17:1066. [PMID: 39204170 PMCID: PMC11360764 DOI: 10.3390/ph17081066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Revised: 08/01/2024] [Accepted: 08/12/2024] [Indexed: 09/03/2024] Open
Abstract
Fish oil, renowned for its high content of omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), has gained considerable attention for its potential health benefits. EPA and DHA exhibit anti-inflammatory effects by promoting the production of specialized pro-resolving mediators (SPMs), such as resolvins and protectins. Fish oil has been studied for its potential to reduce bronchial inflammation, a key feature of respiratory conditions like asthma and COPD. This study investigates the cellular mechanisms of fish oil in an in vitro model of lung inflammation using lipopolysaccharide (LPS) on a healthy human bronchial epithelium cell line. LPS exposure for 24 h reduced cell viability, elevated reactive oxygen species (ROS), depleted glutathione (GSH), and induced mitochondrial depolarization, indicating oxidative stress and inflammation. Fish oil administration significantly mitigated ROS production, prevented GSH depletion, and reduced mitochondrial depolarization. This was associated with the upregulation of the endogenous antioxidant system, evidenced by restored GSH levels and the increased gene expression of glutathione peroxidase (GPX), catalase (CAT), superoxide dismutase 1 (SOD1), and superoxide dismutase 2 (SOD2). Fish oil also suppressed IL-6 and IL-1β expression and increased anti-inflammatory cytokine IL-10 expression. Furthermore, fish oil upregulated the expression of pro-resolving mediator receptors, suggesting a role in inflammation resolution. These findings highlight the potential of fish oil supplementation as a preventive measure against pulmonary diseases characterized by unresolved inflammation such as lung inflammation.
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Affiliation(s)
- Alfio Distefano
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Laura Orlando
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Sebastiano Giallongo
- Department of Medical, Surgical Sciences and Advanced Technologies “G.F. Ingrassia”, University of Catania, 95123 Catania, Italy
| | - Emanuela Tropea
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Mariarita Spampinato
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Annalisa Santisi
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Lucia Longhitano
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Giuseppe Parisi
- Pediatric Respiratory Unit, AOUP “G. Rodolico-San Marco”, University of Catania, 95123 Catania, Italy; (G.P.); (S.L.)
| | - Salvatore Leonardi
- Pediatric Respiratory Unit, AOUP “G. Rodolico-San Marco”, University of Catania, 95123 Catania, Italy; (G.P.); (S.L.)
| | - Arcangelo Russo
- Department of Medicine, Kore University of Enna, 94100 Enna, Italy;
| | - Massimo Caruso
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Michelino Di Rosa
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Daniele Tibullo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Maurizio Salamone
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Giovanni Li Volti
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
| | - Ignazio Alberto Barbagallo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy; (A.D.); (L.O.); (E.T.); (M.S.); (A.S.); (L.L.); (M.C.); (M.D.R.); (D.T.); (M.S.); (G.L.V.); (I.A.B.)
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Chiluveru S, Gundelly M, Pusuluri SV, Tummanepally M, Chandaka M, Koduganti RR. Resolvins in Periodontitis and Possible Periodontal Regeneration: A Literature Review. Cureus 2024; 16:e68187. [PMID: 39347277 PMCID: PMC11439191 DOI: 10.7759/cureus.68187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/29/2024] [Indexed: 10/01/2024] Open
Abstract
Periodontitis is a rampant global disease with multifactorial etiology. The main harbinger of periodontitis is the plaque biofilm. The mature biofilm in turn interacts with the micro-organisms and the host, with environmental and genetic factors as additional initiators to cause disease. There are several strategies of preventive periodontics which include host modulation therapy to ameliorate the disease. Recently a lot of research has been done related to the role of resolvins in periodontitis. This article showcases the role of resolvins in periodontal health and disease.
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Affiliation(s)
- Sneha Chiluveru
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
| | - Mrunalini Gundelly
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
| | - Santosh V Pusuluri
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
| | - Manasa Tummanepally
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
| | - Meenakshi Chandaka
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
| | - Rekha R Koduganti
- Department of Periodontics, Panineeya Mahavidyalaya Institute of Dental Sciences, Hyderabad, IND
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Daneshfar N, Falahi S, Gorgin Karaji A, Rezaiemanesh A, Mortazavi SHR, Akbari B, Eivazi A, Salari F. Association of Single Nucleotide Polymorphisms (SNPs) of Chemoattractant Receptor23 (ChemR23) Gene with Susceptibility to Allergic Rhinitis. Biochem Genet 2024; 62:2587-2605. [PMID: 37993706 DOI: 10.1007/s10528-023-10561-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 10/23/2023] [Indexed: 11/24/2023]
Abstract
The chemoattractant Receptor23 (ChemR23) plays an essential role in triggering and resolving acute inflammation. This study aimed to evaluate the association between four potentially functional SNPs of the chemR23 gene (rs4373981 G > C, rs73201532 C > T, rs35121177 G > A, and rs4964676 G > A) with susceptibility to Allergic rhinitis (AR). 130 patients with allergic rhinitis and 130 healthy individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our findings showed that genotypes and alleles frequencies were not significantly different between patient and control groups (p > 0.05). Furthermore, haplotype analysis (rs4373981, rs73201532, and rs4964676, respectively) revealed a protective effect of CTG, GTA, and GTG haplotypes against AR (p = 0.009, p = 0.0001, p = 0.001, respectively), and CCG, GCA, and GCG haplotypes of ChemR23 polymorphisms were associated with increased risk of AR (p = 0.03, p = 0.02, p = 0.0002, respectively). These findings suggested a possible role for ChemR23 in the pathogenesis of AR.
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Affiliation(s)
- Niloofar Daneshfar
- School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sara Falahi
- School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Ali Gorgin Karaji
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran
| | - Alireza Rezaiemanesh
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran
| | - Seyed Hamid Reza Mortazavi
- Department of Pediatrics, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Bahman Akbari
- Department of Biotechnology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Atefeh Eivazi
- School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Farhad Salari
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, PO-Box: 6714869914, Kermanshah, Iran.
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Peh HY, Nshimiyimana R, Brüggemann TR, Duvall MG, Nijmeh J, Serhan CN, Levy BD. 15-epi-lipoxin A 5 promotes neutrophil exit from exudates for clearance by splenic macrophages. FASEB J 2024; 38:e23807. [PMID: 38989570 PMCID: PMC11344644 DOI: 10.1096/fj.202400610r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2024] [Revised: 06/10/2024] [Accepted: 06/26/2024] [Indexed: 07/12/2024]
Abstract
Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates. Activated human neutrophils converted 15-HEPE to lipoxin A5 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), 15-epi-lipoxin A5 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), and resolvin E4 (RvE4; 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid). Exogenous 15-epi-lipoxin A5, 15-epi-lipoxin A4 and a structural lipoxin mimetic significantly decreased exudate neutrophils and increased local tissue macrophage efferocytosis, with comparison to naproxen. 15-epi-lipoxin A5 also cleared exudate neutrophils faster than the apparent local capacity for stimulated macrophage efferocytosis, so the fate of exudate neutrophils was tracked with CD45.1 variant neutrophils. 15-epi-lipoxin A5 augmented the exit of adoptively transferred neutrophils from the pouch exudate to the spleen, and significantly increased splenic SIRPa+ and MARCO+ macrophage efferocytosis. Together, these findings demonstrate new systemic resolution mechanisms for 15-epi-lipoxin A5 and RvE4 in localized tissue inflammation, which distally engage the spleen to activate macrophage efferocytosis for the clearance of tissue exudate neutrophils.
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Affiliation(s)
- Hong Yong Peh
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Robert Nshimiyimana
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Thayse R. Brüggemann
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Melody G. Duvall
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Julie Nijmeh
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Charles N. Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
| | - Bruce D. Levy
- Pulmonary and Critical Care Medicine Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
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Liu X, Tang Y, Luo Y, Gao Y, He L. Role and mechanism of specialized pro-resolving mediators in obesity-associated insulin resistance. Lipids Health Dis 2024; 23:234. [PMID: 39080624 PMCID: PMC11290132 DOI: 10.1186/s12944-024-02207-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Accepted: 07/07/2024] [Indexed: 08/02/2024] Open
Abstract
With the changing times, obesity has become a characteristic epidemic in the context of the current era. Insulin resistance (IR) is most commonly caused by obesity, and IR is a common basis of the pathogenesis of many diseases such as cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes, which seriously threaten human life, as well as health. A major pathogenetic mechanism of obesity-associated IR has been found to be chronic low-grade inflammation in adipose tissue. Specialized pro-resolving mediators (SPMs) are novel lipid mediators that both function as "stop signals" for inflammatory reaction and promote inflammation to subside. In this article, we summarize the pathogenesis of obesity-associated IR and its treatments and outline the classification and biosynthesis of SPMs and their mechanisms and roles in the treatment of obesity-associated IR in order to explore the potential of SPMs for treating metabolic diseases linked with obesity-associated IR.
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Affiliation(s)
- Xinru Liu
- College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yu Tang
- College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yuanyuan Luo
- College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yongxiang Gao
- College of International Education, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
| | - Lisha He
- College of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
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Zhou Y, Zhou Z. Unraveling the causal link: fatty acids and inflammatory bowel disease. Front Immunol 2024; 15:1405790. [PMID: 39119343 PMCID: PMC11306040 DOI: 10.3389/fimmu.2024.1405790] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2024] [Accepted: 07/12/2024] [Indexed: 08/10/2024] Open
Abstract
Background Previous observational studies have revealed the strong relationship between fatty acids (FA) and inflammatory bowel disease (IBD). Nonetheless, due to the inherent limitations of retrospective research, the causality between the two has not been clearly established. Methods Genetic variants associated with the 17 FA indicators were derived from genome-wide association studies. Summary statistics for the discovery cohort and testing cohort for IBD, including ulcerative colitis (UC) and Crohn's disease (CD), were available from IIBDGC and FinnGen, respectively. Bidirectional MR analysis and sensitivity analysis with multiple measures were applied to comprehensively investigate the causal link between FA and IBD. Results Combining the results of various MR methods, the validation of testing cohort, and the merging of meta-analysis, we demonstrated that genetically predicted Omega-3 FA levels, Ratio of Omega-3 FA to total FA, Docosahexaenoic acid (DHA) levels, and Ratio of DHA to total FA reduced the risk of IBD, UC, and CD. Meanwhile, multivariate MR suggested that the risk effects of Omega-3 FA and DHA for UC and CD were mainly affected by Saturated FA and Monounsaturated fatty acid (MUFA). Furthermore, although there was the causal association between Ratio of MUFA to total FA as well as Ratio of Polyunsaturated fatty acid (PUFA) to MUFA and CD, sensitivity analysis prompted that the findings were not robust. None of the above results had a reverse causal effect. Conclusion This MR investigation provided evidence of causality between diverse FA and IBD. These findings offered new insights into the treatment and prevention of IBD.
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Affiliation(s)
| | - Zhenhua Zhou
- Department of General Surgery, Medical Center of Digestive Disease, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, China
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Savran L, Sağlam M. Clinical effects of omega-3 fatty acids supplementation in the periodontal treatment of smokers and non-smokers with periodontitis: a retrospective study. Clin Oral Investig 2024; 28:437. [PMID: 39031219 PMCID: PMC11271343 DOI: 10.1007/s00784-024-05835-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 07/17/2024] [Indexed: 07/22/2024]
Abstract
OBJECTIVES Omega-3 supplementation as an adjunct to nonsurgical periodontal treatment has been reported to have a positive effect on healing in periodontitis patients. However, there is a lack of information on the effects of periodontal healing in smokers with periodontitis. The aim of this retrospective study was to investigate the effect of omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment on clinical parameters in smoker and non-smoker periodontitis patients. METHODS This study included a total of 80 periodontitis patients, 40 non-smokers and 40 smokers who were systemically healthy. In this study, patients were divided into 4 groups as follows: Group 1 (Subgingival instrumentation (SI) alone/nonsmoker), Group 2 (SI alone/smoker), Group 3 (SI + Omega-3/nonsmoker) and Group 4 (SI + Omega-3/smoker). Group 3 and 4 consumed 1320 mg Omega-3 capsule (640 mg EPA, 480 mg DHA) once a day for 3 months. Probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP %) were recorded at baseline, 1 month and 3 months after treatment. RESULTS Significant improvement of all clinical parameters at 1 and 3 months was observed in all groups. Whole mouth CAL, GI and BOP% were significantly reduced in group 4 compared to group 2 at 1 and 3 months postoperatively (p < 0.05). For moderately deep pockets (4-6 mm) and deep pockets (7 mm≤), PD and CAL reductions were significantly greater in groups taking omega - 3 (group 3 and group 4) compared to groups not taking omega-3 (group 1 and group 2) between baseline and 1 month and between baseline and 3 months (p ˂ 0.05). CONCLUSION Omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment provided significant benefit in the improvement of clinical parameters (especially for CAL and PD) in the short term in smokers and non-smokers with periodontitis. CLINICAL RELEVANCE Nonsurgical periodontal treatment with omega-3 supplementation resulted in significant improvements in clinical parameters in smokers and non-smokers with periodontitis.
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Affiliation(s)
- Levent Savran
- Department of Periodontology, Faculty of Dentistry, Izmir Katip Çelebi University, Izmir, Turkey
| | - Mehmet Sağlam
- Department of Periodontology, Faculty of Dentistry, Izmir Katip Çelebi University, Izmir, Turkey.
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Ghodsi A, Hidalgo A, Libreros S. Lipid mediators in neutrophil biology: inflammation, resolution and beyond. Curr Opin Hematol 2024; 31:175-192. [PMID: 38727155 PMCID: PMC11301784 DOI: 10.1097/moh.0000000000000822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/31/2024]
Abstract
PURPOSE OF REVIEW Acute inflammation is the body's first defense in response to pathogens or injury. Failure to efficiently resolve the inflammatory insult can severely affect tissue homeostasis, leading to chronic inflammation. Neutrophils play a pivotal role in eradicating infectious pathogens, orchestrating the initiation and resolution of acute inflammation, and maintaining physiological functions. The resolution of inflammation is a highly orchestrated biochemical process, partially modulated by a novel class of endogenous lipid mediators known as specialized pro-resolving mediators (SPMs). SPMs mediate their potent bioactions via activating specific cell-surface G protein-coupled receptors (GPCR). RECENT FINDINGS This review focuses on recent advances in understanding the multifaceted functions of SPMs, detailing their roles in expediting neutrophil apoptosis, promoting clearance by macrophages, regulating their excessive infiltration at inflammation sites, orchestrating bone marrow deployment, also enhances neutrophil phagocytosis and tissue repair mechanisms under both physiological and pathological conditions. We also focus on the novel role of SPMs in regulating bone marrow neutrophil functions, differentiation, and highlight open questions about SPMs' functions in neutrophil heterogeneity. SUMMARY SPMs play a pivotal role in mitigating excessive neutrophil infiltration and hyperactivity within pathological milieus, notably in conditions such as sepsis, cardiovascular disease, ischemic events, and cancer. This significant function highlights SPMs as promising therapeutic agents in the management of both acute and chronic inflammatory disorders.
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Affiliation(s)
- Anita Ghodsi
- Vascular Biology and Therapeutics Program and Department of Pathology, Yale University, New Haven, USA
| | - Andres Hidalgo
- Vascular Biology and Therapeutics Program and Department of Immunobiology, Yale University, New Haven, USA
| | - Stephania Libreros
- Vascular Biology and Therapeutics Program and Department of Pathology, Yale University, New Haven, USA
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Sánchez-Rosales AI, Posadas-Calleja JG, Serralde-Zúñiga AE, Quiroz-Olguín G. Nutritional interventions as modulators of the disease activity for idiopathic inflammatory myopathies: a scoping review. J Hum Nutr Diet 2024; 37:772-787. [PMID: 38324396 DOI: 10.1111/jhn.13287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2023] [Accepted: 01/17/2024] [Indexed: 02/09/2024]
Abstract
Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.
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Affiliation(s)
- Abril I Sánchez-Rosales
- School of Public Health, Instituto Nacional de Salud Pública, Universidad No. 655, Colonia Santa María Ahuacatitlán, Cerrada Los Pinos y Caminera, Cuernavaca, Morelos, Mexico
| | | | - Aurora E Serralde-Zúñiga
- Clinical Nutrition Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
| | - Gabriela Quiroz-Olguín
- Clinical Nutrition Service, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Ciudad de México, Mexico
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Costenbader KH, Cook NR, Lee IM, Hahn J, Walter J, Bubes V, Kotler G, Yang N, Friedman S, Alexander EK, Manson JE. Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial. Arthritis Rheumatol 2024; 76:973-983. [PMID: 38272846 PMCID: PMC11565399 DOI: 10.1002/art.42811] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 01/02/2024] [Accepted: 01/22/2024] [Indexed: 01/27/2024]
Abstract
OBJECTIVE In the 5.3-year randomized, 2 × 2 factorial, double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.61-0.99). Omega-3 (n-3) fatty acid supplementation showed a statistically nonsignificant reduction (HR 0.85, 95% CI 0.67-1.08). We aimed to confirm further AD cases arising during and after randomization and assess sustained effects with two years of postintervention observation. METHODS Of the 12,786 men aged ≥50 and 13,085 women aged ≥55 initially randomized, we observed surviving and willing participants for two more years. We continued to confirm annual participant-reported new AD by medical record review. Cox models calculated HRs for all confirmed incident AD, (and secondary endpoints, including probable cases, and individual ADs), during the observational and randomized periods. RESULTS A total of 21,592 participants (83.5%) were observed for two more years; 514 participants developed incident confirmed AD (236 since prior report), of whom 255 had been randomized to vitamin D versus 259 to vitamin D placebo (HR 0.98 [95% CI 0.83-1.17] at 7 years). AD was confirmed in 234 participants initially randomized to n-3 fatty acids versus 280 randomized to its placebo (HR 0.83 [95% CI 0.70-0.99] at 7 years). Of newly confirmed cases, 65 had onset during randomization; their inclusion changed randomized results as follows: HR 0.85 (95% CI 0.70-1.04) for vitamin D and HR 0.87 (95% CI 0.71-1.06) for n-3 fatty acids. CONCLUSION Two years after trial termination, the protective effects of 2000 IU/day of vitamin D dissipated, but 1,000 mg/day of n-3 fatty acids had a sustained effect in reducing AD incidence.
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Affiliation(s)
| | - Nancy R. Cook
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
| | - I-Min Lee
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
| | - Jill Hahn
- Harvard University, Boston, Massachusetts
| | | | - Vadim Bubes
- Brigham and Women’s Hospital, Boston, Massachusetts
| | | | - Nicole Yang
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
| | - Sonia Friedman
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
| | - Erik K. Alexander
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
| | - JoAnn E. Manson
- Brigham and Women’s Hospital and Harvard University, Boston, Massachusetts
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Mattè A, Federti E, Recchiuti A, Hamza M, Ferri G, Riccardi V, Ceolan J, Passarini A, Mazzi F, Siciliano A, Bhatt DL, Coughlan D, Climax J, Gremese E, Brugnara C, De Franceschi L. Epeleuton, a novel synthetic ω-3 fatty acid, reduces hypoxia/ reperfusion stress in a mouse model of sickle cell disease. Haematologica 2024; 109:1918-1932. [PMID: 38105727 PMCID: PMC11141675 DOI: 10.3324/haematol.2023.284028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2023] [Accepted: 12/07/2023] [Indexed: 12/19/2023] Open
Abstract
Inflammatory vasculopathy is critical in sickle cell disease (SCD)-associated organ damage. An imbalance between pro-inflammatory and pro-resolving mechanisms in response to different triggers such as hypoxia/reoxygenation or infections has been proposed to contribute to the progression of SCD. Administration of specialized pro-resolving lipid mediators may provide an effective therapeutic strategy to target inflammatory vasculopathy and to modulate inflammatory response. Epeleuton (15 hydroxy eicosapentaenoic acid ethyl ester) is a novel, orally administered, second-generation ω-3 fatty acid with a favorable clinical safety profile. In this study we show that epeleuton re-programs the lipidomic pattern of target organs for SCD towards a pro-resolving pattern. This protects against systemic and local inflammatory responses and improves red cell features, resulting in reduced hemolysis and sickling compared with that in vehicle-treated SCD mice. In addition, epeleuton prevents hypoxia/reoxygenation-induced activation of nuclear factor-κB with downregulation of the NLRP3 inflammasome in lung, kidney, and liver. This was associated with downregulation of markers of vascular activation in epeleuton-treated SCD mice when compared to vehicle-treated animals. Collectively our data support the potential therapeutic utility of epeleuton and provide the rationale for the design of clinical trials to evaluate the efficacy of epeleuton in patients with SCD.
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Affiliation(s)
- Alessandro Mattè
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Enrica Federti
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Antonio Recchiuti
- Department of Medical, Oral, and Biotechnology Science, "G. d'Annunzio"University Chieti - Pescara
| | | | - Giulia Ferri
- Department of Medical, Oral, and Biotechnology Science, "G. d'Annunzio"University Chieti - Pescara
| | - Veronica Riccardi
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Jacopo Ceolan
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Alice Passarini
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Filippo Mazzi
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Angela Siciliano
- Department of Medicine, University of Verona and AOUI Verona, Verona
| | - Deepak L Bhatt
- Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | | | - Elisa Gremese
- Division of Clinical Immunology, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy; Immunology Core Facility, Fondazione Policlinico Universitario A. Gemelli-IRCCS, Rome
| | - Carlo Brugnara
- Department of Laboratory Medicine, Boston Children's Hospital, Department of Pathology, Harvard Medical School, Boston, MA, USA.
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Serhan CN, Bäck M, Chiurchiù V, Hersberger M, Mittendorfer B, Calder PC, Waitzberg DL, Stoppe C, Klek S, Martindale RG. Expert consensus report on lipid mediators: Role in resolution of inflammation and muscle preservation. FASEB J 2024; 38:e23699. [PMID: 38805158 DOI: 10.1096/fj.202400619r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Revised: 04/22/2024] [Accepted: 05/13/2024] [Indexed: 05/29/2024]
Abstract
This meeting report presents a consensus on the biological aspects of lipid emulsions in parenteral nutrition, emphasizing the unanimous support for the integration of lipid emulsions, particularly those containing fish oil, owing to their many potential benefits beyond caloric provision. Lipid emulsions have evolved from simple energy sources to complex formulations designed to improve safety profiles and offer therapeutic benefits. The consensus highlights the critical role of omega-3 polyunsaturated fatty acids (PUFAs), notably eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), found in fish oil and other marine oils, for their anti-inflammatory properties, muscle mass preservation, and as precursors to the specialized pro-resolving mediators (SPMs). SPMs play a significant role in immune modulation, tissue repair, and the active resolution of inflammation without impairing host defense mechanisms. The panel's agreement underscores the importance of incorporating fish oil within clinical practices to facilitate recovery in conditions like surgery, critical illness, or immobility, while cautioning against therapies that might disrupt natural inflammation resolution processes. This consensus not only reaffirms the role of specific lipid components in enhancing patient outcomes, but also suggests a shift towards nutrition-based therapeutic strategies in clinical settings, advocating for the proactive evidence-based use of lipid emulsions enriched with omega-3 PUFAs. Furthermore, we should seek to apply our knowledge concerning DHA, EPA, and their SPM derivatives, to produce more informative randomized controlled trial protocols, thus allowing more authoritative clinical recommendations.
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Affiliation(s)
- Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Hale Building for Transformative Medicine, Boston, Massachusetts, USA
| | - Magnus Bäck
- Department of Medicine Solna, Karolinska Institute, Solna, Sweden
- Department of Cardiology, Karolinska University Hospital, Stockholm, Sweden
- INSERM U1116, Université de Lorraine, Nancy University Hospital, Vandoeuvre les Nancy, France
| | - Valerio Chiurchiù
- Institute of Translational Pharmacology, National Research Council of Rome, Rome, Italy
- Laboratory of Resolution of Neuroinflammation, European Center for Brain Research, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Santa Lucia Foundation, Rome, Italy
| | - Martin Hersberger
- Division of Clinical Chemistry and Biochemistry, University Children's Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Bettina Mittendorfer
- Department of Medicine, University of Missouri School of Medicine, Columbia, Missouri, USA
- Department of Nutrition & Exercise Physiology, University of Missouri School of Medicine, Columbia, Missouri, USA
| | - Philip C Calder
- Faculty of Medicine, University of Southampton and NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK
| | - Dan L Waitzberg
- Department of Gastroenterology, School of Medicine, University of Sao Paulo, Hospital das Clínicas LIM 35, Ganep-Human Nutrition, Sao Paulo, Brazil
| | - Christian Stoppe
- Department of Anesthesiology, Intensive Care, Emergency, and Pain Medicine, University Hospital Wuerzburg, Wuerzburg, Germany
- Department of Cardiac Anesthesiology and Intensive Care Medicine, Charité Berlin, Berlin, Germany
| | - Stanislaw Klek
- Surgical Oncology Clinic, The Maria Sklodowska-Curie National Cancer Institute, Krakow, Poland
| | - Robert G Martindale
- Department of Surgery, Oregon Health and Science University, Portland, Oregon, USA
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Babar MU, Nassar AF, Nie X, Zhang T, He J, Yeung J, Norris P, Ogura H, Muldoon A, Chen L, Libreros S. Is Lipid Metabolism of Value in Cancer Research and Treatment? Part II: Role of Specialized Pro-Resolving Mediators in Inflammation, Infections, and Cancer. Metabolites 2024; 14:314. [PMID: 38921449 PMCID: PMC11205484 DOI: 10.3390/metabo14060314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 05/17/2024] [Accepted: 05/22/2024] [Indexed: 06/27/2024] Open
Abstract
Acute inflammation is the body's first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor's microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.
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Affiliation(s)
- Muhammad Usman Babar
- Department of Pathology, Yale University, New Haven, CT 06520, USA
- Vascular Biology and Therapeutic Program, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Ala F. Nassar
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Xinxin Nie
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Tianxiang Zhang
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Jianwei He
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Jacky Yeung
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Paul Norris
- Sciex, 500 Old Connecticut Path, Framingham, MA 01701, USA
| | - Hideki Ogura
- Department of Microbiology, Hyogo Medical University, Kobe 678-1297, Japan
| | - Anne Muldoon
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Lieping Chen
- Department of Immunobiology, Yale University, West Haven, CT 06520, USA
| | - Stephania Libreros
- Department of Pathology, Yale University, New Haven, CT 06520, USA
- Vascular Biology and Therapeutic Program, Yale University School of Medicine, New Haven, CT 06520, USA
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Jain SK, Bansal S, Bansal S, Singh B, Klotzbier W, Mehta KY, Cheema AK. An Optimized Method for LC-MS-Based Quantification of Endogenous Organic Acids: Metabolic Perturbations in Pancreatic Cancer. Int J Mol Sci 2024; 25:5901. [PMID: 38892088 PMCID: PMC11172734 DOI: 10.3390/ijms25115901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2024] [Revised: 05/23/2024] [Accepted: 05/25/2024] [Indexed: 06/21/2024] Open
Abstract
Accurate and reliable quantification of organic acids with carboxylic acid functional groups in complex biological samples remains a major analytical challenge in clinical chemistry. Issues such as spontaneous decarboxylation during ionization, poor chromatographic resolution, and retention on a reverse-phase column hinder sensitivity, specificity, and reproducibility in multiple-reaction monitoring (MRM)-based LC-MS assays. We report a targeted metabolomics method using phenylenediamine derivatization for quantifying carboxylic acid-containing metabolites (CCMs). This method achieves accurate and sensitive quantification in various biological matrices, with recovery rates from 90% to 105% and CVs ≤ 10%. It shows linearity from 0.1 ng/mL to 10 µg/mL with linear regression coefficients of 0.99 and LODs as low as 0.01 ng/mL. The library included a wide variety of structurally variant CCMs such as amino acids/conjugates, short- to medium-chain organic acids, di/tri-carboxylic acids/conjugates, fatty acids, and some ring-containing CCMs. Comparing CCM profiles of pancreatic cancer cells to normal pancreatic cells identified potential biomarkers and their correlation with key metabolic pathways. This method enables sensitive, specific, and high-throughput quantification of CCMs from small samples, supporting a wide range of applications in basic, clinical, and translational research.
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Affiliation(s)
- Shreyans K. Jain
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - Shivani Bansal
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - Sunil Bansal
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - Baldev Singh
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - William Klotzbier
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - Khyati Y. Mehta
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
| | - Amrita K. Cheema
- Department of Oncology, Lombardi Comprehensive Cancer Centre, Georgetown University Medical Center, E-415, New Research Building, 3900 Reservoir Road NW, Washington, DC 20057, USA; (S.K.J.); (S.B.); (S.B.); (B.S.); (W.K.); (K.Y.M.)
- Department of Biochemistry, Molecular and Cellular Biology, Georgetown University Medical Centre, Washington, DC 20057, USA
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Barden A, Shinde S, Beilin LJ, Phillips M, Adams L, Bollmann S, Mori TA. Adiposity associates with lower plasma resolvin E1 (Rve1): a population study. Int J Obes (Lond) 2024; 48:725-732. [PMID: 38347128 PMCID: PMC11058310 DOI: 10.1038/s41366-024-01482-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Revised: 01/16/2024] [Accepted: 01/19/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND Inadequate inflammation resolution may contribute to persistent low-grade inflammation that accompanies many chronic conditions. Resolution of inflammation is an active process driven by Specialized Pro-resolving Mediators (SPM) that derive from long chain n-3 and n-6 fatty acids. This study examined plasma SPM in relation to sex differences, lifestyle and a broad range cardiovascular disease (CVD) risk factors in 978, 27-year olds from the Australian Raine Study. METHODS Plasma SPM pathway intermediates (18-HEPE, 17-HDHA and 14-HDHA), and SPM (E- and D-series resolvins, PD1, MaR1) and LTB4 were measured by liquid chromatography-tandem mass spectrometry (LCMSMS). Pearson correlations and multiple regression analyses assessed relationships between SPM and CVD risk factors. Unpaired t-tests or ANOVA assessed the effect of sex, smoking, unhealthy alcohol consumption and obesity on SPM. RESULTS Women had higher 17-HDHA (p = 0.01) and lower RvE1 (p < 0.0001) and RvD1 (p = 0.05) levels compared with men. In univariate analysis, obesity associated with lower RvE1 (p = 0.002), whereas smoking (p < 0.001) and higher alcohol consumption (p < 0.001) associated with increased RvE1. In multiple regression analysis, plasma RvE1 was negatively associated with a range of measures of adiposity including BMI, waist circumference, waist-to-height ratio, abdominal subcutaneous fat volume, and skinfold thicknesses in both men and women. CONCLUSION This population study suggests that a deficiency in plasma RvE1 may occur in response to increasing adiposity. This observation could be relevant to ongoing inflammation that associates with CVD and other chronic diseases.
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Affiliation(s)
- Anne Barden
- Medical School, University of Western Australia, Perth, WA, Australia.
| | - Sujata Shinde
- Medical School, University of Western Australia, Perth, WA, Australia
| | - Lawrence J Beilin
- Medical School, University of Western Australia, Perth, WA, Australia
| | - Michael Phillips
- Centre for Medical Research, University of Western Australia, Perth, WA, Australia
- Royal Perth Hospital Research Foundation, Perth, WA, Australia
| | - Leon Adams
- Medical School, University of Western Australia, Perth, WA, Australia
| | - Steffen Bollmann
- School of Information Technology and Electrical Engineering, Centre for Advanced Imaging, The University of Queensland, Brisbane, QLD, Australia
| | - Trevor A Mori
- Medical School, University of Western Australia, Perth, WA, Australia
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Zhao Z, Liu S, Qian B, Zhou L, Shi J, Liu J, Xu L, Yang Z. CMKLR1 senses chemerin/resolvin E1 to control adipose thermogenesis and modulate metabolic homeostasis. FUNDAMENTAL RESEARCH 2024; 4:575-588. [PMID: 38933207 PMCID: PMC11197767 DOI: 10.1016/j.fmre.2022.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 06/01/2022] [Accepted: 06/22/2022] [Indexed: 11/18/2022] Open
Abstract
Induction of beige fat for thermogenesis is a potential therapy to improve homeostasis against obesity. β3-adrenoceptor (β3-AR), a type of G protein-coupled receptor (GPCR), is believed to mediate the thermogenesis of brown fat in mice. However, β3-AR has low expression in human adipose tissue, precluding its activation as a standalone clinical modality. This study aimed at identifying a potential GPCR target to induce beige fat. We found that chemerin chemokine-like receptor 1 (CMKLR1), one of the novel GPCRs, mediated the development of beige fat via its two ligands, chemerin and resolvin E1 (RvE1). The RvE1 levels were decreased in the obese mice, and RvE1 treatment led to a substantial improvement in obese features and augmented beige fat markers. Inversely, despite sharing the same receptor as RvE1, the chemerin levels were increased in obesogenic conditions, and chemerin treatment led to an augmented obese phenotype and a decline of beige fat markers. Moreover, RvE1 and chemerin induced or restrained the development of beige fat, respectively, via the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. We further showed that RvE1 and chemerin regulated mTORC1 signaling differentially by forming hydrogen bonds with different binding sites of CMKLR1. In conclusion, our study showed that RvE1 and chemerin affected metabolic homeostasis differentially, suggesting that selectively modulating CMKLR1 may be a potential therapeutic target for restoring metabolic homeostasis.
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Affiliation(s)
- Zewei Zhao
- Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University; Shenzhen, Guangdong 518107, China
| | - Siqi Liu
- Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University; Shenzhen, Guangdong 518107, China
| | - Bingxiu Qian
- Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University; Shenzhen, Guangdong 518107, China
| | - Lin Zhou
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University; Guangzhou, Guangdong 510080, China
| | - Jianglin Shi
- Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University; Shenzhen, Guangdong 518107, China
| | - Junxi Liu
- Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University; Guangzhou, Guangdong 510080, China
| | - Lin Xu
- School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong 510080, China
| | - Zhonghan Yang
- Department of Biochemistry, Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University; Shenzhen, Guangdong 518107, China
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Ouagueni A, Al-Zoubi RM, Zarour A, Al-Ansari A, Bawadi H. Effects of Omega-3 Polyunsaturated Fatty Acids, Docosahexaenoic Acid and Eicosapentaenoic Acid, on Post-Surgical Complications in Surgical Trauma Patients: Mechanisms, Nutrition, and Challenges. Mar Drugs 2024; 22:207. [PMID: 38786598 PMCID: PMC11123418 DOI: 10.3390/md22050207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Revised: 01/23/2024] [Accepted: 01/25/2024] [Indexed: 05/25/2024] Open
Abstract
This paper aims to provide an in-depth review of the specific outcomes associated with omega-3 polyunsaturated fatty acids (PUFAs), focusing on their purported effects on post-surgical complications in trauma patients. A comprehensive investigation of omega-3 polyunsaturated fatty acids was conducted until February 2023 using the PubMed database. Surgical trauma is characterized by a disruption in immune response post surgery, known to induce systemic inflammation. Omega-3 PUFAs are believed to offer potential improvements in multiple post-surgical complications because of their anti-inflammatory and antioxidant properties. Inconsistent findings have emerged in the context of cardiac surgeries, with the route of administration playing a mediating role in these outcomes. The effects of omega-3 PUFAs on post-operative atrial fibrillation have exhibited variability across various studies. Omega-3 PUFAs have demonstrated positive effects in liver surgery outcomes and in patients with acute respiratory distress syndrome. Omega-3 is suggested to offer potential benefits, particularly in the perioperative care of patients undergoing traumatic procedures. Incorporating omega-3 in such cases is hypothesized to contribute to a reduction in certain surgical outcomes, such as hospitalization duration and length of stay in the intensive care unit. Therefore, comprehensive assessments of adverse effects can aid in identifying the presence of subtle or inconspicuous side effects associated with omega-3.
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Affiliation(s)
- Asma Ouagueni
- Department of Human Nutrition, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar;
| | - Raed M. Al-Zoubi
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar; (R.M.A.-Z.); (A.A.-A.)
- Department of Chemistry, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan
- Department of Biomedical Sciences, College of Health Science, Qatar University, Doha 2713, Qatar
| | - Ahmad Zarour
- Acute Care Surgery Division, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar;
| | - Abdulla Al-Ansari
- Surgical Research Section, Department of Surgery, Hamad Medical Corporation, Doha 576214, Qatar; (R.M.A.-Z.); (A.A.-A.)
- Department of Surgery, Division of Urology/Andrology, Hamad Medical Corporation, Doha 576214, Qatar
| | - Hiba Bawadi
- Department of Human Nutrition, College of Health Science, QU-Health, Qatar University, Doha 2713, Qatar;
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48
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Costa VV, Resende F, Melo EM, Teixeira MM. Resolution pharmacology and the treatment of infectious diseases. Br J Pharmacol 2024; 181:917-937. [PMID: 38355144 DOI: 10.1111/bph.16323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 12/06/2023] [Accepted: 12/28/2023] [Indexed: 02/16/2024] Open
Abstract
Inflammation is elicited by the host in response to microbes, and is believed to be essential for protection against infection. However, we have previously hypothesized that excessive or misplaced inflammation may be a major contributor to tissue dysfunction and death associated with viral and bacterial infections. The resolutive phase of inflammation is a necessary condition to achieve homeostasis after acute inflammation. It is possible that targeting inflammation resolution may be beneficial for the host during infection. In this review, we summarize the evidence demonstrating the expression, roles and effects of the best described pro-resolving molecules in the context of bacterial and viral infections. Pro-resolving molecules play a pivotal role in modulating a spectrum of pathways associated with tissue inflammation and damage during both viral and bacterial infections. These molecules offer a blend of anti-inflammatory, pro-resolving and sometimes anti-infective benefits, all the while circumventing the undesired and immune-suppressive unwanted effects associated with glucocorticoids. Whether these beneficial effects will translate into benefits to patients clearly deserve further investigation.
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Affiliation(s)
- Vivian Vasconcelos Costa
- Centro de Pesquisa e Desenvolvimento de Fármacos, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Filipe Resende
- Centro de Pesquisa e Desenvolvimento de Fármacos, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Eliza Mathias Melo
- Centro de Pesquisa e Desenvolvimento de Fármacos, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
| | - Mauro Martins Teixeira
- Centro de Pesquisa e Desenvolvimento de Fármacos, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil
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So J, Yao JH, Magadmi R, Matthan NR, Lamon-Fava S. Sex differences in lipid mediators derived from omega-3 fatty acids in older individuals with low-grade chronic inflammation. Prostaglandins Leukot Essent Fatty Acids 2024; 203:102655. [PMID: 39488904 PMCID: PMC11624983 DOI: 10.1016/j.plefa.2024.102655] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 10/16/2024] [Accepted: 10/25/2024] [Indexed: 11/05/2024]
Abstract
The rate of cardiovascular disease (CVD) death is higher in men than women before age 50 y, but the gap between sexes significantly narrows after menopause. Lipid mediators derived from EPA, DHA and AA play a role in inflammation and CVD. The aim of our study was to assess whether plasma concentrations of these lipid mediators differ between postmenopausal women and men. Twelve postmenopausal women and 9 men with low-grade chronic inflammation completed a randomized, double-blind, crossover study consisting of a 4-week lead-in placebo phase (3 g/d high-oleic acid sunflower oil) followed by randomization to either 3 g/d DHA or 3 g/d EPA for 10 weeks and crossover for additional 10 weeks, separated by a washout phase. Plasma phospholipid content of EPA, DHA and AA and plasma concentrations of their derived lipid mediators were measured at the end of the placebo lead-in phase (baseline) and the DHA and EPA supplementation phases. There were no sex differences in plasma phospholipid EPA, DHA and AA at baseline and after DHA and EPA supplementation. However, plasma concentrations of lipid mediators derived from EPA, DHA and AA via 15-lipoxygenase were lower in postmenopausal women than men, especially after supplementation. Sex differences in EPA- and DHA-derived lipid mediators with anti-inflammatory and pro-resolving actions may partly explain the faster rise in CVD in postmenopausal women than age-matched men.
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Affiliation(s)
- Jisun So
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Jonathan H Yao
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Rozana Magadmi
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Nirupa R Matthan
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA
| | - Stefania Lamon-Fava
- Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, USA; Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, USA.
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50
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Mohammad-Rafiei F, Negahdari S, Tahershamsi Z, Gheibihayat SM. Interface between Resolvins and Efferocytosis in Health and Disease. Cell Biochem Biophys 2024; 82:53-65. [PMID: 37794303 DOI: 10.1007/s12013-023-01187-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 09/25/2023] [Indexed: 10/06/2023]
Abstract
Acute inflammation resolution acts as a vital process for active host response, tissue support, and homeostasis maintenance, during which resolvin D (RvD) and E (RvE) as mediators derived from omega-3 polyunsaturated fatty acids display specific and stereoselective anti-inflammations like restricting neutrophil infiltration and pro-resolving activities. On the other side of the coin, potent macrophage-mediated apoptotic cell clearance, namely efferocytosis, is essential for successful inflammation resolution. Further studies mentioned a linkage between efferocytosis and resolvins. For instance, resolvin D1 (RvD1), which is endogenously formed from docosahexaenoic acid within the inflammation resolution, thereby provoking efferocytosis. There is still limited information regarding the mechanism of action of RvD1-related efferocytosis enhancement at the molecular level. The current review article was conducted to explore recent data on how the efferocytosis process and resolvins relate to each other during the inflammation resolution in illness and health. Understanding different aspects of this connection sheds light on new curative approaches for medical conditions caused by defective efferocytosis and disrupted inflammation resolution.
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Affiliation(s)
- Fatemeh Mohammad-Rafiei
- Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
| | - Samira Negahdari
- Legal Medicine Research Center, Legal Medicine Organization, Tehran, Iran
| | - Zahra Tahershamsi
- Department of Biophysics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Seyed Mohammad Gheibihayat
- Department of Medical Biotechnology, School of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
- Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Universal Scientific Education and Research Network (USERN), Munich, Germany.
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