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Ortega Á, Duran P, Garrido B, Manzano A, Navarro C, Silva A, Rojas M, De Sanctis JB, Radzioch D, Rivera-Porras D, Paredes CS, Bermúdez V. Specialized Pro-Resolving Lipid Mediators in Pulmonary Diseases: Molecular and Therapeutic Implications. Molecules 2025; 30:2212. [PMID: 40430385 PMCID: PMC12114278 DOI: 10.3390/molecules30102212] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 04/21/2025] [Accepted: 04/23/2025] [Indexed: 05/29/2025] Open
Abstract
Inflammatory lung diseases (ILDs) represent a global public health crisis characterized by escalating prevalence, significant morbidity, and substantial mortality. In response to the complex immunopathogenic mechanisms driving these conditions, novel pharmacological strategies targeting resolution pathways have emerged throughout the discovery of specialized pro-resolving lipid mediator (SPM; resolvins, maresins, and protectins) dysregulation across the ILD spectra, positioning these endogenous molecules as promising therapeutic candidates for modulating maladaptive inflammation and promoting tissue repair. Over the past decade, this paradigm has catalyzed extensive translational research into SPM-based interventions as precision therapeutics for respiratory inflammation. In asthma, they reduce mucus hypersecretion, bronchial hyperreactivity, and airway inflammation, with prenatal SPM exposure potentially lowering offspring disease risk. In COPD, SPMs attenuate amyloid A-driven inflammation, normalizing cytokine/chemokine imbalances and oxidative stress and mitigating COVID-19-associated cytokine storm, enhancing survival. This review synthesizes SPMs' pharmacotherapeutic mechanisms in ILDs and evaluates current preclinical and clinical evidence.
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Affiliation(s)
- Ángel Ortega
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Pablo Duran
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Bermary Garrido
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Alexander Manzano
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Carolina Navarro
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Aljadis Silva
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Milagros Rojas
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4001, Venezuela; (Á.O.); (P.D.); (B.G.); (A.M.); (C.N.); (A.S.); (M.R.)
| | - Juan Bautista De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacký University Olomouc, 77900 Olomouc, Czech Republic;
| | - Danuta Radzioch
- The Research Institute of the McGill, University Health Center, McGill University, Montreal, QC H0H H9Z, Canada;
| | - Diego Rivera-Porras
- Universidad de la Costa, Departamento de Productividad e Innovación, Barranquilla 080001, Atlántico, Colombia;
| | - Carlos Silva Paredes
- Universidad del Zulia, Facultad de Medicina, Departamento de Ciencias Fisiológicas, Maracaibo 4001, Venezuela;
| | - Valmore Bermúdez
- Universidad Simón Bolívar, Facultad de Ciencias de la Salud, Centro de Investigaciones en Ciencias de la Vida, Barranquilla 080001, Atlántico, Colombia
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Molfino A, Imbimbo G, Salerno G, Lionetto L, De Luca A, Simmaco M, Gallicchio C, Picconi O, Amabile MI, Muscaritoli M. Effects of DHA Oral Supplementation on Plasma Resolvin D1 and D2 Levels in Naïve Breast Cancer Patients. Cancers (Basel) 2025; 17:1694. [PMID: 40427191 PMCID: PMC12109739 DOI: 10.3390/cancers17101694] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 05/07/2025] [Accepted: 05/16/2025] [Indexed: 05/29/2025] Open
Abstract
Background/Objectives: Specialized pro-resolving lipid mediators, such as resolvins derived from omega-3 fatty acids, play a key role in resolving inflammation and restoring homeostasis. Resolvin D1 and D2, derived from docosahexaenoic acid (DHA), have demonstrated inflammation pro-resolving properties and potential anticancer effects. This study aimed to evaluate the effects of oral DHA supplementation on plasma resolvin D1 and D2 levels in breast cancer patients and in controls, and by stratifying the patients by disease presentation (sporadic, familial, BRCA1/2 mutated) and immunohistochemical characteristics. Methods: This is a single-center, interventional, controlled study conducted in women with breast cancer and women with benign breast disease, serving as controls. Participants consumed DHA (2 g/day) as algal oil syrup for 10 consecutive days. Plasma resolvin D1 and D2 levels were measured at baseline (T0) and after supplementation (T1) using ELISA kits. Results: At baseline, breast cancer patients exhibited higher plasma resolvin D1 levels compared to controls (median 21.3 vs. 7.3 pg/mL, p = 0.039), with no significant difference in resolvin D2. Following DHA supplementation, resolvin D1 and D2 significantly increased in BRCA1/2-mutated patients (+185.8% and +101.2%, p = 0.037, p = 0.028, respectively). Conversely, the familial breast cancer group showed a significant decrease in resolvin D1 (p = 0.015). Patients with low Ki67 expression showed greater increase over time of resolvin D2 levels compared to those with high Ki67 expression (p = 0.046). Conclusions: DHA supplementation modulated resolvin levels in breast cancer patients, with significant increase in BRCA1/2-mutated patients, suggesting enhanced inflammation pro-resolving responses. The reduction in resolvin D1 in the familial group highlights a potential dysregulated response. These findings indicate the potential of resolvins as biomarkers of resolution of inflammation and novel therapeutic targets in breast cancer.
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Affiliation(s)
- Alessio Molfino
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (G.I.); (C.G.); (M.M.)
| | - Giovanni Imbimbo
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (G.I.); (C.G.); (M.M.)
| | - Gerardo Salerno
- Analytical Laboratory Unit, Department NESMOS, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy; (G.S.); (L.L.); (M.S.)
| | - Luana Lionetto
- Analytical Laboratory Unit, Department NESMOS, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy; (G.S.); (L.L.); (M.S.)
| | - Alessandro De Luca
- Department of Surgical Sciences, Sapienza University of Rome, 00185 Rome, Italy; (A.D.L.); (M.I.A.)
| | - Maurizio Simmaco
- Analytical Laboratory Unit, Department NESMOS, Sant’Andrea Hospital, Sapienza University of Rome, 00185 Rome, Italy; (G.S.); (L.L.); (M.S.)
| | - Carmen Gallicchio
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (G.I.); (C.G.); (M.M.)
| | - Orietta Picconi
- National HIV/AIDS Center, Istituto Superiore Di Sanità, 00161 Rome, Italy;
| | - Maria Ida Amabile
- Department of Surgical Sciences, Sapienza University of Rome, 00185 Rome, Italy; (A.D.L.); (M.I.A.)
| | - Maurizio Muscaritoli
- Department of Translational and Precision Medicine, Sapienza University of Rome, 00185 Rome, Italy; (G.I.); (C.G.); (M.M.)
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Karakasis P, Theofilis P, Vlachakis PK, Ktenopoulos N, Patoulias D, Antoniadis AP, Fragakis N. Atrial Cardiomyopathy in Atrial Fibrillation: Mechanistic Pathways and Emerging Treatment Concepts. J Clin Med 2025; 14:3250. [PMID: 40364280 PMCID: PMC12072501 DOI: 10.3390/jcm14093250] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2025] [Revised: 05/01/2025] [Accepted: 05/07/2025] [Indexed: 05/15/2025] Open
Abstract
Atrial fibrillation (AF) is increasingly recognized not merely as an arrhythmia, but as a clinical manifestation of atrial cardiomyopathy (AtCM)-a progressive, multifaceted disease of the atrial myocardium involving structural, electrical, mechanical, and molecular remodeling. AtCM often precedes AF onset, sustains its perpetuation, and contributes to thromboembolic risk independently of rhythm status. Emerging evidence implicates diverse pathophysiological drivers of AtCM, including inflammation, epicardial adipose tissue, metabolic dysfunction, oxidative stress, ageing, and sex-specific remodeling. The NLRP3 inflammasome has emerged as a central effector in atrial inflammation and remodeling. Gut microbial dysbiosis, lipid dicarbonyl stress, and fibro-fatty infiltration are also increasingly recognized as contributors to arrhythmogenesis. AtCM is further linked to atrial functional valve regurgitation and adverse outcomes in AF. Therapeutically, substrate-directed strategies-ranging from metabolic modulation and immunomodulation to early rhythm control-offer promise for altering the disease trajectory. This review synthesizes mechanistic insights into AtCM and discusses emerging therapeutic paradigms that aim not merely to suppress arrhythmia but to modify the underlying substrate. Recognizing AF as a syndrome of atrial disease reframes management strategies and highlights the urgent need for precision medicine approaches targeting the atrial substrate.
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Affiliation(s)
- Paschalis Karakasis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece; (A.P.A.); (N.F.)
| | - Panagiotis Theofilis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (P.T.); (P.K.V.); (N.K.)
| | - Panayotis K. Vlachakis
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (P.T.); (P.K.V.); (N.K.)
| | - Nikolaos Ktenopoulos
- First Cardiology Department, School of Medicine, Hippokration General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece; (P.T.); (P.K.V.); (N.K.)
| | - Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Faculty of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Antonios P. Antoniadis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece; (A.P.A.); (N.F.)
| | - Nikolaos Fragakis
- Second Department of Cardiology, Hippokration General Hospital, Medical School, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece; (A.P.A.); (N.F.)
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Nieto Ramirez LM, Mehaffy C, Dobos KM. Systematic review of innate immune responses against Mycobacterium tuberculosis complex infection in animal models. Front Immunol 2025; 15:1467016. [PMID: 39949719 PMCID: PMC11821578 DOI: 10.3389/fimmu.2024.1467016] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2024] [Accepted: 12/27/2024] [Indexed: 02/16/2025] Open
Abstract
Background Mycobacterium tuberculosis (Mtb) complex (MTBC) includes ten species that affect mammals and pose a significant global health concern. Upon infection, Mtb induces various stages in the host, including early bacterial elimination, which may or may not involve memory responses. Deciphering the role of innate immune responses during MTBC infection is crucial for understanding disease progression or protection. Over the past decade, there has been growing interest in the innate immune response to Mtb, with new preclinical models emerging. Methods We conducted a systematic review following PRISMA guidelines, focused on innate immune mediators linked to protection or disease progression in animal models of MTBC infection. We searched two databases: National Library of Medicine and Web of Science. Two researchers independently extracted data based on specific inclusion and exclusion criteria. Results Eighty-three articles were reviewed. Results were categorized in four groups: MTBC species, animal models, soluble factors and innate pathways, and other molecules (metabolites and drugs). Mtb and M. bovis were the only species studied. P2X7R receptor's role in disease progression and higher macrophage recruitment were observed differentially after infection with hypervirulent Mtb strains. Mice and non-human primates (NHPs) were the most used mammals, with emerging models like Galleria mellonella and planarians also studied. NHPs provided insights into age-dependent immunity and markers for active tuberculosis (ATB). Key innate immune factors/pathways identified included TNF-α, neutrophil recruitment, ROS/RNS responses, autophagy, inflammasomes, and antimicrobial peptides, with homologous proteins identified in insects. Metabolites like vitamin B5 and prostaglandin E2 were associated with protection. Immunomodulatory drugs targeting autophagy and other mechanisms were studied, exhibiting their potential as therapeutic alternatives. Conclusion Simpler, physiologically relevant, and ethically sound models, such as G. mellonella, are needed for studying innate responses in MTBC infection. While insects lack adaptive immunity, they could provide insights into "pure" innate immune responses. The dissection of "pure," "sustained" (later than 7 days post-infection), and trained innate immunity presents additional challenges that require high-resolution temporospatial analytical methods. Identifying early innate immune mediators and targetable pathways in the blood and affected tissues could identify biomarkers for immunization efficiency, disease progression, and potential synergistic therapies for ATB.
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Affiliation(s)
- Luisa Maria Nieto Ramirez
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
| | | | - Karen Marie Dobos
- Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, United States
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Paduchová Z, Gajdošová L, Katrenčíková B, Horváthová M, Országhová Z, Andrezálová L, Muchová J. Synergistic Effects of Omega-3 Fatty Acids and Physical Activity on Oxidative Stress Markers and Antioxidant Mechanisms in Aged Rats. Nutrients 2024; 17:96. [PMID: 39796529 PMCID: PMC11723026 DOI: 10.3390/nu17010096] [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: 12/11/2024] [Revised: 12/20/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
BACKGROUND Aging induces degenerative processes in the body, contributing to the onset of various age-associated diseases that affect the population. Inadequate dietary habits and low physical activity are major contributors to increased morbidity during aging. This study aimed to investigate the combined effects of omega-3 fatty acid supplementation and physical activity on the markers of oxidative stress and antioxidant defense mechanisms in aged male Wistar rats (23-24 months). METHODS The rats were randomly divided into four experimental groups: a sedentary control (placebo, no exercise), a trained (placebo and moderate-intensity graded aerobic exercise; Ex), and two trained groups supplemented with low (160 mg/kg of body weight; O1 + Ex) and high (320 mg/kg of body weight; O2 + Ex) doses of omega-3 fatty acids. The biochemical and functional parameters related to sarcopenia and the markers of oxidative stress were measured in blood and gastrocnemius muscle. RESULTS The results demonstrated dose-dependent, synergistic effects of omega-3 fatty acid supplementation and physical activity. The higher dose (320 mg/kg of body weight) improved plasma antioxidant capacity (TEAC, +21.01%, p < 0.01) and GPx activity (+78.05%, p < 0.05) while reducing CAT activity in erythrocytes (-19.92%, p < 0.05), likely as an adaptive stress response. Combined interventions also normalized cholesterol levels, improved the functional parameters of sarcopenia (stride length, +14.82%, p < 0.001), and enhanced antioxidant protection in aged rats. CONCLUSIONS These findings highlight the potential of combining omega-3 fatty acid supplementation and physical activity to counteract aging-related degenerative changes. Further research is needed to elucidate the underlying mechanisms and evaluate the long-term benefits of these strategies in aging populations.
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Affiliation(s)
| | | | | | | | | | | | - Jana Muchová
- Institute of Medical Chemistry, Biochemistry and Clinical Biochemistry, Comenius University, Faculty of Medicine, Sasinkova 2, 811 08 Bratislava, Slovakia; (Z.P.); (L.G.); (B.K.); (M.H.); (Z.O.); (L.A.)
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Rahi Roy D, Roy K, Panserat S, Stejskal V, Mraz J, Turchini GM. Long chain polyunsaturated fatty acid (LC-PUFA) composition of fish sperm: nexus of dietary, evolutionary, and biomechanical drivers. Prog Lipid Res 2024; 96:101305. [PMID: 39566856 DOI: 10.1016/j.plipres.2024.101305] [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: 07/31/2024] [Revised: 11/06/2024] [Accepted: 11/13/2024] [Indexed: 11/22/2024]
Abstract
Long-chain polyunsaturated fatty acids (LC-PUFA) like arachidonic acid (ARA, 20:4n-6), eicosapentaenoic acid (EPA, 20:5n-3), and docosahexaenoic acid (DHA, 22:6n-3) constitute one-third to half of fish sperm lipids. Fish sperm is rich in phospholipid (PL)-primarily phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin. DHA is generally the most abundant LC-PUFA in each PL class, followed by competition between ARA and EPA. While the total n-6: n-3 PUFA ratio does not correlate significantly with sperm biomechanics, LC-PUFA do. DHA positively influences sperm biomechanics, while ARA and EPA may be negatively associated. Fish sperm maintains lower (≤1) total n-6 PUFA per unit of n-3 PUFA but keep a higher (>1) ARA per unit EPA. A weak dietary influence on sperm EPA and DHA exists but not on ARA. The DHA: EPA ratio in fish sperm is often >1, though values <1 occur. Certain species cannot fortify DHA sufficiently during spermatogenesis, diverging through whole genome duplications. Fish sperm can show ARA: EPA ratios greater or less than 1, due to shifts in prostaglandin pathways in different evolutionary eras. DHA-rich PL bilayers provide unique packing and fusogenic properties, with ARA/EPA-derived eicosanoids guiding sperm rheotaxis/chemotaxis, modulated by DHA-derived resolvins. Docosapentaenoic acid (DPA, 22:5n-3) sometimes substitutes for DHA in fish sperm.
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Affiliation(s)
- Deepali Rahi Roy
- University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, České Budějovice 370 05, Czech Republic
| | - Koushik Roy
- University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, České Budějovice 370 05, Czech Republic.
| | - Stephane Panserat
- Université de Pau Et Des Pays de L'Adour, E2S UPPA, INRAE, NUMEA, 64310 Saint Pée sur Nivelle, France
| | - Vlastimil Stejskal
- University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, České Budějovice 370 05, Czech Republic
| | - Jan Mraz
- University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Institute of Aquaculture and Protection of Waters, České Budějovice 370 05, Czech Republic
| | - Giovanni M Turchini
- School of Agriculture, Food and Ecosystem Sciences, Faculty of Science, The University of Melbourne, VIC 3010, Australia
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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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Clare J, Lindley MR, Ratcliffe E. The Potential of Fish Oil Components and Manuka Honey in Tackling Chronic Wound Treatment. Microorganisms 2024; 12:1593. [PMID: 39203434 PMCID: PMC11356504 DOI: 10.3390/microorganisms12081593] [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: 06/27/2024] [Revised: 07/21/2024] [Accepted: 07/23/2024] [Indexed: 09/03/2024] Open
Abstract
Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution-marine based fatty acids (including their metabolites) and manuka honey-their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.
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Affiliation(s)
- Jenna Clare
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
| | - Martin R. Lindley
- School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney 2052, Australia;
| | - Elizabeth Ratcliffe
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
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Huang L, Wu J, Cao J, Sheng X, Wang M, Cheng T. Resolvin D1 inhibits T follicular helper cell expansion in systemic lupus erythematosus. Scand J Rheumatol 2024; 53:276-283. [PMID: 38742879 DOI: 10.1080/03009742.2024.2344906] [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: 02/14/2024] [Accepted: 04/16/2024] [Indexed: 05/16/2024]
Abstract
OBJECTIVE Resolvin D1 (RvD1) is one of the specialized pro-resolving lipid mediators, which control inflammation resolution and regulate immune responses. Previous research showed that RvD1 could block the progression of systemic lupus erythematosus (SLE). However, the detailed mechanism remains to be fully understood. METHOD Plasma RvD1 levels, and proportions of T follicular helper cells (Tfh cells) were measured in SLE patients and healthy controls. Plasma RvD1 levels and proportions of Tfh cells were quantitated in an MRL/lpr mouse model of lupus treated with RvD1. Naïve CD4+ T cells were purified from MRL/lpr mice to study the effect of RvD1 on Tfh cell differentiation in vitro. RESULTS In patients, there were significant negative correlations between plasma RvD1 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, as well as between plasma RvD1 and anti-double-stranded DNA antibody levels, and numbers of peripheral Tfh cells and plasma cells. In MRL/lpr mice, the expected amelioration of disease phenotype and inflammatory response with RvD1 treatment correlated with decreased percentages of Tfh cells and plasma cells. In addition, the differentiation and proliferation of Tfh cells were markedly suppressed by RvD1 in vitro. CONCLUSION RvD1 may control SLE progression through the suppression of Tfh cell differentiation and subsequent inhibition of B-cell responses.
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Affiliation(s)
- L Huang
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
| | - J Wu
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
| | - J Cao
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
| | - X Sheng
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
| | - M Wang
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
| | - T Cheng
- Department of Rheumatology, The First Affiliated Hospital of Soochow University, Su Zhou, PR China
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10
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Reed EK, Smith KA. Using our understanding of interactions between helminth metabolism and host immunity to target worm survival. Trends Parasitol 2024; 40:549-561. [PMID: 38853079 DOI: 10.1016/j.pt.2024.05.006] [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: 01/29/2024] [Revised: 05/10/2024] [Accepted: 05/12/2024] [Indexed: 06/11/2024]
Abstract
Helminths can adapt to environmental conditions in the host, utilising anaerobic processes like fermentation and malate dismutation to produce energy from carbohydrate. Although targeting carbohydrate metabolism is an established therapeutic strategy to combat helminth infection, questions remain over the metabolic pathways they employ as adults to survive and evade host immunity. Helminths also use amino acid, polyunsaturated fatty acid (PUFA), and cholesterol metabolism, a possible strategy favouring the production of immunomodulatory compounds that may influence survival in the host. Here, we discuss the significance of these differing metabolic pathways and whether targeting of helminth metabolic pathways may allow for the development of novel anthelmintics.
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Affiliation(s)
- Ella K Reed
- Cardiff School of Biosciences, Cardiff University, Cardiff, UK
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11
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Adiguzel E, Bozkurt NM, Unal G. Independent and combined effects of astaxanthin and omega-3 on behavioral deficits and molecular changes in a prenatal valproic acid model of autism in rats. Nutr Neurosci 2024; 27:590-606. [PMID: 37534957 DOI: 10.1080/1028415x.2023.2239575] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2023]
Abstract
Objectives: Autism is a devastating neurodevelopmental disorder and recent studies showed that omega-3 or astaxanthin might reduce autistic symptoms due to their anti-inflammatory properties. Therefore, we investigated the effects of omega-3 and astaxanthin on the VPA-induced autism model of rats.Material and Methods: Female Wistar albino pups (n = 40) were grouped as control, autistic, astaxanthin (2 mg/kg), omega-3 (200 mg/kg), and astaxanthin (2 mg/kg)+omega-3 (200 mg/kg). All groups except the control were prenatally exposed to VPA. Astaxanthin and omega-3 were orally administered from the postnatal day 41 to 68 and behavioral tests were performed between day 69 and 73. The rats were decapitated 24 h after the behavioral tests and hippocampal and prefrontal cytokines and 5-HT levels were analyzed by ELISA.Results: VPA rats have increased grooming behavior while decreased sociability (SI), social preference index (SPI), discrimination index (DI), and prepulse inhibition (PPI) compared to control. Additionally, IL-1β, IL-6, TNF-α, and IFN-γ levels increased while IL-10 and 5-HT levels decreased in both brain regions. Astaxanthin treatment raised SI, SPI, DI, PPI, and prefrontal IL-10 levels. It also raised 5-HT levels and decreased IL-6 levels in both brain regions. Omega-3 and astaxanthin + omega-3 increased the SI, SPI, DI, and PPI and decreased grooming behavior. Moreover, they increased IL-10 and 5-HT levels whereas decreased IL-1β, IL-6, TNF-α, IFN-γ levels in both brain regions.Conclusions: Our results showed that VPA administration mimicked the behavioral and molecular changes of autism in rats. Single and combined administration of astaxanthin and omega-3 improved the autistic-like behavioral and molecular changes in the VPA model of rats.
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Affiliation(s)
- Emre Adiguzel
- Faculty of Health Sciences, Department of Nutrition and Dietetics, Karamanoğlu Mehmetbey University, Karaman, Türkiye
| | - Nuh Mehmet Bozkurt
- Faculty of Pharmacy, Department of Pharmacology, Erciyes University, Kayseri, Türkiye
- Experimental Research and Application Center (DEKAM), Brain Research Unit, Erciyes University, Kayseri, Türkiye
- e-Neuro Lab, Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Türkiye
| | - Gokhan Unal
- Faculty of Pharmacy, Department of Pharmacology, Erciyes University, Kayseri, Türkiye
- Experimental Research and Application Center (DEKAM), Brain Research Unit, Erciyes University, Kayseri, Türkiye
- e-Neuro Lab, Drug Application and Research Center (ERFARMA), Erciyes University, Kayseri, Türkiye
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12
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Laursen ALS, Olesen MV, Folke J, Brudek T, Knecht LH, Sotty F, Lambertsen KL, Fog K, Dalgaard LT, Aznar S. Systemic inflammation activates coagulation and immune cell infiltration pathways in brains with propagating α-synuclein fibril aggregates. Mol Cell Neurosci 2024; 129:103931. [PMID: 38508542 DOI: 10.1016/j.mcn.2024.103931] [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: 01/04/2024] [Revised: 02/15/2024] [Accepted: 03/13/2024] [Indexed: 03/22/2024] Open
Abstract
Synucleinopathies are a group of diseases characterized by brain aggregates of α-synuclein (α-syn). The gradual accumulation of α-syn and the role of inflammation in early-stage pathogenesis remain poorly understood. We explored this interaction by inducing chronic inflammation in a common pre-clinical synucleinopathy mouse model. Three weeks post unilateral intra-striatal injections of human α-syn pre-formed fibrils (PFF), mice underwent repeated intraperitoneal injections of 1 mg/ml lipopolysaccharide (LPS) for 3 weeks. Histological examinations of the ipsilateral site showed phospho-α-syn regional spread and LPS-induced neutrophil recruitment to the brain vasculature. Biochemical assessment of the contralateral site confirmed spreading of α-syn aggregation to frontal cortex and a rise in intracerebral TNF-α, IL-1β, IL-10 and KC/GRO cytokines levels due to LPS. No LPS-induced exacerbation of α-syn pathology load was observed at this stage. Proteomic analysis was performed contralateral to the PFF injection site using LC-MS/MS. Subsequent downstream Reactome Gene-Set Analysis indicated that α-syn pathology alters mitochondrial metabolism and synaptic signaling. Chronic LPS-induced inflammation further lead to an overrepresentation of pathways related to fibrin clotting as well as integrin and B cell receptor signaling. Western blotting confirmed a PFF-induced increase in fibrinogen brain levels and a PFF + LPS increase in Iba1 levels, indicating activated microglia. Splenocyte profiling revealed changes in T and B cells, monocytes, and neutrophils populations due to LPS treatment in PFF injected animals. In summary, early α-syn pathology impacts energy homeostasis pathways, synaptic signaling and brain fibrinogen levels. Concurrent mild systemic inflammation may prime brain immune pathways in interaction with peripheral immunity.
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Affiliation(s)
- Anne-Line Strange Laursen
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark; Department of Science and Environment, Roskilde University, Universitetsvej 1, DK-4000, Roskilde, Denmark.
| | - Mikkel Vestergaard Olesen
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark.
| | - Jonas Folke
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark.
| | - Tomasz Brudek
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark.
| | - Luisa Harriet Knecht
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark.
| | | | - Kate Lykke Lambertsen
- Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsløwsvej 21-25, DK-5000, Odense, Denmark; Department of Neurology, Odense University Hospital, J.B. Winsløwsvej 4, Odense, Denmark; BRIDGE - Brain-Research-Inter-Disciplinary Guided Excellence, Department of Clinical Institute, University of Southern Denmark, Winsløwparken 19, Odense, Denmark.
| | - Karina Fog
- H. Lundbeck A/S, Ottiliavej 9, DK-2500, Valby, Denmark.
| | - Louise Torp Dalgaard
- Department of Science and Environment, Roskilde University, Universitetsvej 1, DK-4000, Roskilde, Denmark.
| | - Susana Aznar
- Centre for Neuroscience & Stereology, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 6B, DK-2400, Copenhagen, NV, Denmark; Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Copenhagen University Hospital, Nielsine Nielsens Vej 4B, DK-2400, Copenhagen, NV, Denmark.
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13
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Ali AH, Hachem M, Ahmmed MK. Docosahexaenoic acid-loaded nanoparticles: A state-of-the-art of preparation methods, characterization, functionality, and therapeutic applications. Heliyon 2024; 10:e30946. [PMID: 38774069 PMCID: PMC11107210 DOI: 10.1016/j.heliyon.2024.e30946] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 05/08/2024] [Accepted: 05/08/2024] [Indexed: 05/24/2024] Open
Abstract
Docosahexaenoic acid (DHA, C22:6 n-3), an omega-3 polyunsaturated fatty acid, offers several beneficial effects. DHA helps in reducing depression, autoimmune diseases, rheumatoid arthritis, attention deficit hyperactivity syndrome, and cardiovascular diseases. It can stimulate the development of brain and nerve, alleviate lipids metabolism-related disorders, and enhance vision development. However, DHA susceptibility to chemical oxidation, poor water solubility, and unpleasant order could restrict its applications for nutritional and therapeutic purposes. To avoid these drawbacks and enhance its bioavailability, DHA can be encapsulated using an effective delivery system. Several encapsulation methods are recognized, and DHA-loaded nanoparticles have demonstrated numerous benefits. In clinical studies, positive influences on the development of several diseases have been reported, but some assumptions are conflicting and need more exploration, since DHA has a systemic and not a targeted release at the required level. This might cause the applications of nanoparticles that could allow DHA release at the required level and improve its efficiency, thus resulting in a better controlling of several diseases. In the current review, we focused on researches investigating the formulation and development of DHA-loaded nanoparticles using different delivery systems, including low-density lipoprotein, zinc oxide, silver, zein, and resveratrol-stearate. Silver-DHA nanoparticles presented a typical particle size of 24 nm with an incorporation level of 97.67 %, while the entrapment efficiency of zinc oxide-DHA nanoparticles represented 87.3 %. By using zein/Poly (lactic-co-glycolic acid) stabilized nanoparticles, DHA's encapsulation level reached 84.6 %. We have also highlighted the characteristics, functionality and medical implementation of these nanoparticles in the treatment of inflammations, brain disorders, diabetes as well as hepatocellular carcinoma.
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Affiliation(s)
- Abdelmoneim H. Ali
- Department of Chemical and Petroleum Engineering, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates
| | - Mayssa Hachem
- Department of Chemistry and Healthcare Engineering Innovation Group, Khalifa University of Sciences and Technology, Abu Dhabi, 127788, United Arab Emirates
| | - Mirja Kaizer Ahmmed
- Department of Fishing and Post-harvest Technology, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh
- Riddet Institute, Massey University, Palmerston North, New Zealand
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14
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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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Clare J, Lindley MR, Ratcliffe E. The Antimicrobial and Antibiofilm Abilities of Fish Oil Derived Polyunsaturated Fatty Acids and Manuka Honey. Microorganisms 2024; 12:778. [PMID: 38674722 PMCID: PMC11052219 DOI: 10.3390/microorganisms12040778] [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: 03/18/2024] [Revised: 04/04/2024] [Accepted: 04/09/2024] [Indexed: 04/28/2024] Open
Abstract
Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins.
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Affiliation(s)
- Jenna Clare
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
| | - Martin R. Lindley
- School of Health Sciences, Faculty of Medicine and Health, University of New South Wales, Sydney 2052, Australia;
| | - Elizabeth Ratcliffe
- Department of Chemical Engineering, Loughborough University, Loughborough LE11 3TU, UK
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16
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Luján-Amoraga L, Delgado-Martín B, Lourenço-Marques C, Gavaia PJ, Bravo J, Bandarra NM, Dominguez D, Izquierdo MS, Pousão-Ferreira P, Ribeiro L. Exploring Omega-3's Impact on the Expression of Bone-Related Genes in Meagre ( Argyrosomus regius). Biomolecules 2023; 14:56. [PMID: 38254657 PMCID: PMC10813611 DOI: 10.3390/biom14010056] [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: 10/31/2023] [Revised: 12/20/2023] [Accepted: 12/22/2023] [Indexed: 01/24/2024] Open
Abstract
Dietary supplementation with Omega-3 fatty acids seems to promote skeletal health. Therefore, their consumption at imbalanced or excessive levels has offered less beneficial or even prejudicial effects. Fish produced in aquaculture regimes are prone to develop abnormal skeletons. Although larval cultures are usually fed with diets supplemented with Omega-3 Long Chain Polyunsaturated fatty acids (LC-PUFAs), the lack of knowledge about the optimal requirements for fatty acids or about their impact on mechanisms that regulate skeletal development has impeded the design of diets that could improve bone formation during larval stages when the majority of skeletal anomalies appear. In this study, Argyrosomus regius larvae were fed different levels of Omega-3s (2.6% and 3.6% DW on diet) compared to a commercial diet. At 28 days after hatching (DAH), their transcriptomes were analyzed to study the modulation exerted in gene expression dynamics during larval development and identify impacted genes that can contribute to skeletal formation. Mainly, both levels of supplementation modulated bone-cell proliferation, the synthesis of bone components such as the extracellular matrix, and molecules involved in the interaction and signaling between bone components or in important cellular processes. The 2.6% level impacted several genes related to cartilage development, denoting a special impact on endochondral ossification, delaying this process. However, the 3.6% level seemed to accelerate this process by enhancing skeletal development. These results offered important insights into the impact of dietary Omega-3 LC-PUFAs on genes involved in the main molecular mechanism and cellular processes involved in skeletal development.
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Affiliation(s)
- Leticia Luján-Amoraga
- Aquaculture Research Station (EPPO), Portuguese Institute for the Ocean and Atmosphere (IPMA), 8700-194 Olhão, Portugal; (L.L.-A.); (C.L.-M.); (P.P.-F.)
| | - Belén Delgado-Martín
- Department of Microbiology and Crop Protection, Institute of Subtropical and Mediterranean Horticulture (IHSM-UMA-CSIC), 29010 Malaga, Spain;
| | - Cátia Lourenço-Marques
- Aquaculture Research Station (EPPO), Portuguese Institute for the Ocean and Atmosphere (IPMA), 8700-194 Olhão, Portugal; (L.L.-A.); (C.L.-M.); (P.P.-F.)
- Collaborative Laboratory on Sustainable and Smart Aquaculture (S2AQUACOLAB) Av. Parque Natural da Ria Formosa s/n, 8700-194 Olhão, Portugal
| | - Paulo J. Gavaia
- Centre of Marine Sciences (CCMAR), University of Algarve (UALG), 8005-139 Faro, Portugal;
| | - Jimena Bravo
- Aquaculture Research Group (GIA), University of Las Palmas de Gran Canaria (ULPGC) Crta. Taliarte s/n, 35214 Telde, Spain; (J.B.); (D.D.); (M.S.I.)
| | - Narcisa M. Bandarra
- Division of Aquaculture, Upgrading, and Bioprospection (DivAV), Portuguese Institute for the Sea and Atmosphere (IPMA, IP), Rua Alfredo Magalhães Ramalho, 7, 1495-006 Lisbon, Portugal;
- CIIMAR, Interdisciplinary Centre of Marine and Environmental Research, University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal
| | - David Dominguez
- Aquaculture Research Group (GIA), University of Las Palmas de Gran Canaria (ULPGC) Crta. Taliarte s/n, 35214 Telde, Spain; (J.B.); (D.D.); (M.S.I.)
| | - Marisol S. Izquierdo
- Aquaculture Research Group (GIA), University of Las Palmas de Gran Canaria (ULPGC) Crta. Taliarte s/n, 35214 Telde, Spain; (J.B.); (D.D.); (M.S.I.)
| | - Pedro Pousão-Ferreira
- Aquaculture Research Station (EPPO), Portuguese Institute for the Ocean and Atmosphere (IPMA), 8700-194 Olhão, Portugal; (L.L.-A.); (C.L.-M.); (P.P.-F.)
- Collaborative Laboratory on Sustainable and Smart Aquaculture (S2AQUACOLAB) Av. Parque Natural da Ria Formosa s/n, 8700-194 Olhão, Portugal
| | - Laura Ribeiro
- Aquaculture Research Station (EPPO), Portuguese Institute for the Ocean and Atmosphere (IPMA), 8700-194 Olhão, Portugal; (L.L.-A.); (C.L.-M.); (P.P.-F.)
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Wong R, Murphy A, Lira M, Sichmann MGDO, Kim AR, Saechee VD, Hermanson KD, Hawkins SS. Microneedling with a Novel, n-3-PUFA-Rich Formulation Accelerates Inflammation Resolution to Improve Skin Recovery Outcomes in Adults with Healthy Skin. Dermatol Ther (Heidelb) 2023; 13:3057-3069. [PMID: 37833618 PMCID: PMC10689607 DOI: 10.1007/s13555-023-01049-0] [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: 08/25/2023] [Accepted: 09/22/2023] [Indexed: 10/15/2023] Open
Abstract
INTRODUCTION Microneedling is a cosmetic procedure that leverages the skin's natural ability to heal in order to promote collagen formation and skin rejuvenation. To provide improved results, the technique can be combined with topical formulations. A new formulation of multiple actives, including omega-3 (n-3) polyunsaturated fatty acids (PUFAs), was designed to accelerate the resolution of inflammation and wound healing following micro-injury treatments, while enhancing the visible appearance of procedure results, including erythema, luminosity and skin texture. METHODS In this randomised, controlled, split-face study, we examined 32 healthy female participants aged 30-70 years for 4 weeks following microneedling treatment with a novel multiple-active-ingredient formulation or conventional microneedling protocol with a hyaluronic acid control serum. Changes in skin condition were assessed by blinded clinical photography and expert evaluation. Measurements were collected at baseline, 1 h, 1 day, 7 days and 28 days post treatment. RESULTS Significantly greater improvements in expert-assessed erythema, luminosity and skin texture were reported following application of the novel multiple-active-ingredient formulation than the hyaluronic acid control serum. This was confirmed by representative VISIA®-CR imaging. CONCLUSION These data provide new evidence for the role of a novel multiple-active-ingredient formulation for improving skin outcomes up to 28 days following microneedling in adults with healthy skin when compared with a hyaluronic acid serum. The n-3 PUFA content of this formulation may drive accelerated inflammation resolution and wound healing alongside the complementary action of the other active ingredients, leading to the observed improvements in erythema, luminosity and skin texture.
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Affiliation(s)
- Russell Wong
- Rejuvenation Medical Group, 5083 Windermere Blvd Unit 101, Edmonton, AB, T6W 0J5, Canada.
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18
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Joshi NP, Madiwale SD, Sundrani DP, Joshi SR. Fatty acids, inflammation and angiogenesis in women with gestational diabetes mellitus. Biochimie 2023; 212:31-40. [PMID: 37059350 DOI: 10.1016/j.biochi.2023.04.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/01/2023] [Accepted: 04/11/2023] [Indexed: 04/16/2023]
Abstract
Gestational diabetes mellitus (GDM) is a metabolic disorder in pregnancy whose prevalence is on the rise. Reports suggest a likely association between inflammation and maternal GDM. A balance between pro and anti-inflammatory cytokines is necessary for the regulation of maternal inflammation system throughout pregnancy. Along with various inflammatory markers, fatty acids also act as pro-inflammatory molecules. However, studies reporting the role of inflammatory markers in GDM are contradictory, suggesting the need of more studies to better understand the role of inflammation in pregnancies complicated by GDM. Inflammatory response can be regulated by angiopoietins suggesting a link between inflammation and angiogenesis. Placental angiogenesis is a normal physiological process which is tightly regulated during pregnancy. Various pro and anti-angiogenic factors influence the regulation of the feto-placental vascular development. Studies evaluating the levels of angiogenic markers in women with GDM are limited and the findings are inconsistent. This review summarizes the available literature on fatty acids, inflammatory markers and angiogenesis in women with GDM. We also discuss the possible link between them and their influence on placental development in GDM.
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Affiliation(s)
- Nikita P Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Shweta D Madiwale
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Deepali P Sundrani
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India
| | - Sadhana R Joshi
- Mother and Child Health, Interactive Research School for Health Affairs, Bharati Vidyapeeth University, Pune, India.
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Mishra G, Singh P, Pottoo FH, Javed MN, Zeleke MM, Yimer YS. Nutraceuticals for Fibromyalgia and Neuropathic Pain. ADVANCES IN MEDICAL DIAGNOSIS, TREATMENT, AND CARE 2023:133-191. [DOI: 10.4018/978-1-7998-4120-3.ch007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/16/2024]
Abstract
Both neuropathic pain and fibromyalgia are horrific painful conditions arising due to impairment in the somatosensory nervous system and the musculoskeletal system, respectively. They share some common symptoms like hyperalgesia, allodynia, insomnia, cognitive deficits, and mood disturbances. It is believed that fibromyalgia is the consequence of dysfunction of the central nervous system, autonomic nervous system, imbalance in neurotransmitters, and psychological and emotional stress. Henceforth, these pain syndromes have become a major challenge for healthcare professionals due to their complex etiology and poor availability and effectiveness of the drugs. Notably, the available synthetic drugs possess serious side effects including physical dependence and tolerance. Therefore, researchers are now seeking natural-based therapy for modulating chronic pain conditions. This chapter has been written with the intention of exploring the beneficial effects of various nutraceuticals including herbal dietary supplements in neuropathic pain and fibromyalgia.
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Affiliation(s)
- Garima Mishra
- Department of Pharmacy, College of Health Sciences, Debre Tabor University, Ethiopia
| | - Pradeep Singh
- Department of Pharmacy, College of Health Sciences, Debre Tabor University, Ethiopia
| | - Faheem Hyder Pottoo
- College of Clinical Pharmacy, Imam Abdulrahman Bin Faisal University, Saudi Arabia
| | - Md Noushad Javed
- School of Pharmaceutical Sciences and Research, Jamia Hamdard, India
| | - Mulugeta Molla Zeleke
- Department of Pharmacy, College of Health Sciences, Debre Tabor University, Ethiopia
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Kousparou C, Fyrilla M, Stephanou A, Patrikios I. DHA/EPA (Omega-3) and LA/GLA (Omega-6) as Bioactive Molecules in Neurodegenerative Diseases. Int J Mol Sci 2023; 24:10717. [PMID: 37445890 DOI: 10.3390/ijms241310717] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 06/22/2023] [Accepted: 06/25/2023] [Indexed: 07/15/2023] Open
Abstract
Neurodegenerative diseases are characterized by neuroinflammation, neuronal depletion and oxidative stress. They coincide with subtle chronic or flaring inflammation, sometimes escalating with infiltrations of the immune system cells in the inflamed parts causing mild to severe or even lethal damage. Thus, neurodegenerative diseases show all features of autoimmune diseases. Prevalence of neurodegenerative diseases has dramatically increased in recent decades and unfortunately, the therapeutic efficacy and safety profile of available drugs is moderate. The beneficial effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) polyunsaturated fatty acids (omega-3 PUFAs) are nowadays highlighted by a plethora of studies. They play a role in suppression of inflammation, gene expression, cellular membrane fluidity/permeability, immune functionality and intracellular/exocellular signaling. The role of omega-6 polyunsaturated fatty acids, such as linoleic acid (LA), gamma linolenic acid (GLA), and arachidonic acid (AA), on neuroprotection is controversial, as some of these agents, specifically AA, are proinflammatory, whilst current data suggest that they may have neuroprotective properties as well. This review provides an overview of the existing recent clinical studies with respect to the role of omega-3 and omega-6 PUFAs as therapeutic agents in chronic, inflammatory, autoimmune neurodegenerative diseases as well as the dosages and the period used for testing.
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Affiliation(s)
- Christina Kousparou
- School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus
| | - Maria Fyrilla
- School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus
| | - Anastasis Stephanou
- School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus
| | - Ioannis Patrikios
- School of Medicine, European University Cyprus, 6 Diogenous Str., 2404 Nicosia, Cyprus
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21
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Wu J, Gao J, Yi L, Gao N, Wang L, Zhu J, Dai C, Sun L, Guo H, Yu FSX, Wu X. Protective effects of resolvin D1 in Pseudomonas aeruginosa keratitis. Mol Immunol 2023; 158:35-42. [PMID: 37104999 DOI: 10.1016/j.molimm.2023.04.007] [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: 08/06/2022] [Revised: 03/31/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023]
Abstract
PURPOSE Here, we explored the protective effects of resolvin D1 (RvD1) in Pseudomonas aeruginosa (PA) keratitis. METHODS C57BL/6 (B6) mice were used as an animal model of PA keratitis. Plate counting and clinical scores were used to assess the severity of the infection and the therapeutic effects of RvD1 in the model. Myeloperoxidase assay was used to detect neutrophil infiltration and activity. Quantitative PCR (qPCR) was used to examine the expression of proflammatory and anti-inflammatory mediators. Immunofluorescence staining and qPCR were performed to identify macrophage polarization. RESULTS RvD1 treatment alleviated PA keratitis severity by decreasing corneal bacterial load and inhibiting neutrophil infiltration in the mouse model. Furthermore, RvD1 treatment decreased mRNA levels of TNF-α, IFN-γ, IL-1β, CXCL1, and S100A8/9 while increasing those of IL-1RA, IL-10, and TGF-β1. RvD1 treatment also reduced the aggregation of M1 macrophages and increased that of M2 macrophages. RvD1 provided an auxiliary effect in gatifloxacin-treated mice with PA keratitis. CONCLUSION Based on these findings, RvD1 may improve the prognosis of PA keratitis by inhibiting neutrophil recruitment and activity, dampening the inflammatory response, and promoting M2 macrophage polarization. Thus, RvD1 may be a potential complementary therapy for PA keratitis.
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Affiliation(s)
- Jiayin Wu
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China; Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
| | - Jianlu Gao
- Department of Ophthalmology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China
| | - Lili Yi
- Joint Laboratory for Translational Medicine Research, Liaocheng People's Hospital, Liaocheng 252000, China
| | - Nan Gao
- Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Leyi Wang
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China
| | - Jing Zhu
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China
| | - Chenyang Dai
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China
| | - Lin Sun
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China
| | - Hui Guo
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China
| | - Fu-Shin X Yu
- Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine, Detroit, MI 48201, USA
| | - Xinyi Wu
- Department of Ophthalmology, Qilu Hospital of Shandong University, Jinan, Shandong 250014, China.
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22
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Yasmeen N, Selvaraj H, Lakhawat SS, Datta M, Sharma PK, Jain A, Khanna R, Srinivasan J, Kumar V. Possibility of averting cytokine storm in SARS-COV 2 patients using specialized pro-resolving lipid mediators. Biochem Pharmacol 2023; 209:115437. [PMID: 36731803 PMCID: PMC9884647 DOI: 10.1016/j.bcp.2023.115437] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 01/31/2023]
Abstract
Fatal "cytokine storms (CS)" observed in critically ill COVID-19 patients are consequences of dysregulated host immune system and over-exuberant inflammatory response. Acute respiratory distress syndrome (ARDS), multi-system organ failure, and eventual death are distinctive symptoms, attributed to higher morbidity and mortality rates among these patients. Consequent efforts to save critical COVID-19 patients via the usage of several novel therapeutic options are put in force. Strategically, drugs being used in such patients are dexamethasone, remdesivir, hydroxychloroquine, etc. along with the approved vaccines. Moreover, it is certain that activation of the resolution process is important for the prevention of chronic diseases. Until recently Inflammation resolution was considered a passive process, rather it's an active biochemical process that can be achieved by the use of specialized pro-resolving mediators (SPMs). These endogenous mediators are an array of atypical lipid metabolites that include Resolvins, lipoxins, maresins, protectins, considered as immunoresolvents, but their role in COVID-19 is ambiguous. Recent evidence from studies such as the randomized clinical trial, in which omega 3 fatty acid was used as supplement to resolve inflammation in COVID-19, suggests that direct supplementation of SPMs or the use of synthetic SPM mimetics (which are still being explored) could enhance the process of resolution by regulating the aberrant inflammatory process and can be useful in pain relief and tissue remodeling. Here we discussed the biosynthesis of SPMs, & their mechanistic pathways contributing to inflammation resolution along with sequence of events leading to CS in COVID-19, with a focus on therapeutic potential of SPMs.
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Affiliation(s)
- Nusrath Yasmeen
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Harikrishnan Selvaraj
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Sudarshan S Lakhawat
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Manali Datta
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Pushpender K Sharma
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Ajay Jain
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India
| | - Rakhi Khanna
- Rajasthan State Regional Forensic Science Laboratory, Kota, Rajasthan, India
| | | | - Vikram Kumar
- Amity Institute of Biotechnology, Amity University Rajasthan, Jaipur, Rajasthan, India.
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23
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da Silva BPM, Fanalli SL, Gomes JD, de Almeida VV, Fukumasu H, Freitas FAO, Moreira GCM, Silva-Vignato B, Reecy JM, Koltes JE, Koltes D, de Carvalho Balieiro JC, de Alencar SM, da Silva JPM, Coutinho LL, Afonso J, Regitano LCDA, Mourão GB, Luchiari Filho A, Cesar ASM. Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil. BMC Genomics 2023; 24:91. [PMID: 36855067 PMCID: PMC9976441 DOI: 10.1186/s12864-023-09188-6] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2022] [Accepted: 02/15/2023] [Indexed: 03/02/2023] Open
Abstract
BACKGROUND The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.
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Affiliation(s)
- Bruna Pereira Martins da Silva
- grid.11899.380000 0004 1937 0722Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo, Brazil
| | - Simara Larissa Fanalli
- grid.11899.380000 0004 1937 0722Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo, Brazil
| | - Julia Dezen Gomes
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Vivian Vezzoni de Almeida
- grid.411195.90000 0001 2192 5801College of Veterinary Medicine and Animal Science, Federal University of Goiás, Goiânia, Goiás Brazil
| | - Heidge Fukumasu
- grid.11899.380000 0004 1937 0722Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo, Brazil
| | - Felipe André Oliveira Freitas
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | | | - Bárbara Silva-Vignato
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - James Mark Reecy
- grid.34421.300000 0004 1936 7312College of Agriculture and Life Sciences, Iowa State University, Ames, IA USA
| | - James Eugene Koltes
- grid.34421.300000 0004 1936 7312College of Agriculture and Life Sciences, Iowa State University, Ames, IA USA
| | - Dawn Koltes
- grid.34421.300000 0004 1936 7312College of Agriculture and Life Sciences, Iowa State University, Ames, IA USA
| | - Júlio Cesar de Carvalho Balieiro
- grid.11899.380000 0004 1937 0722School of Veterinary Medicine and Animal Science, University of São Paulo, Pirassununga, São Paulo, Brazil
| | - Severino Matias de Alencar
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Julia Pereira Martins da Silva
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Luiz Lehmann Coutinho
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Juliana Afonso
- grid.460200.00000 0004 0541 873XEmbrapa Pecuária Sudeste, São Carlos, São Paulo, Brazil
| | | | - Gerson Barreto Mourão
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Albino Luchiari Filho
- grid.11899.380000 0004 1937 0722Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil
| | - Aline Silva Mello Cesar
- Faculty of Animal Science and Food Engineering, University of São Paulo, Pirassununga, São Paulo, Brazil. .,Luiz de Queiroz College of Agriculture, University of São Paulo, Piracicaba, São Paulo, Brazil.
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24
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Hirbo JB, Pasutto F, Gamazon ER, Evans P, Pawar P, Berner D, Sealock J, Tao R, Straub PS, Konkashbaev AI, Breyer MA, Schlötzer-Schrehardt U, Reis A, Brantley MA, Khor CC, Joos KM, Cox NJ. Analysis of genetically determined gene expression suggests role of inflammatory processes in exfoliation syndrome. BMC Genomics 2023; 24:75. [PMID: 36797672 PMCID: PMC9936777 DOI: 10.1186/s12864-023-09179-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 02/09/2023] [Indexed: 02/18/2023] Open
Abstract
BACKGROUND Exfoliation syndrome (XFS) is an age-related systemic disorder characterized by excessive production and progressive accumulation of abnormal extracellular material, with pathognomonic ocular manifestations. It is the most common cause of secondary glaucoma, resulting in widespread global blindness. The largest global meta-analysis of XFS in 123,457 multi-ethnic individuals from 24 countries identified seven loci with the strongest association signal in chr15q22-25 region near LOXL1. Expression analysis have so far correlated coding and a few non-coding variants in the region with LOXL1 expression levels, but functional effects of these variants is unclear. We hypothesize that analysis of the contribution of the genetically determined component of gene expression to XFS risk can provide a powerful method to elucidate potential roles of additional genes and clarify biology that underlie XFS. RESULTS Transcriptomic Wide Association Studies (TWAS) using PrediXcan models trained in 48 GTEx tissues leveraging on results from the multi-ethnic and European ancestry GWAS were performed. To eliminate the possibility of false-positive results due to Linkage Disequilibrium (LD) contamination, we i) performed PrediXcan analysis in reduced models removing variants in LD with LOXL1 missense variants associated with XFS, and variants in LOXL1 models in both multiethnic and European ancestry individuals, ii) conducted conditional analysis of the significant signals in European ancestry individuals, and iii) filtered signals based on correlated gene expression, LD and shared eQTLs, iv) conducted expression validation analysis in human iris tissues. We observed twenty-eight genes in chr15q22-25 region that showed statistically significant associations, which were whittled down to ten genes after statistical validations. In experimental analysis, mRNA transcript levels for ARID3B, CD276, LOXL1, NEO1, SCAMP2, and UBL7 were significantly decreased in iris tissues from XFS patients compared to control samples. TWAS genes for XFS were significantly enriched for genes associated with inflammatory conditions. We also observed a higher incidence of XFS comorbidity with inflammatory and connective tissue diseases. CONCLUSION Our results implicate a role for connective tissues and inflammation pathways in the etiology of XFS. Targeting the inflammatory pathway may be a potential therapeutic option to reduce progression in XFS.
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Affiliation(s)
- Jibril B Hirbo
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA.
- Vanderbilt Genetics Institute, Nashville, TN, 37232, USA.
| | - Francesca Pasutto
- Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg FAU, 91054, Erlangen, Germany
| | - Eric R Gamazon
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
- Vanderbilt Genetics Institute, Nashville, TN, 37232, USA
- Clare Hall and MRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0SL, UK
| | - Patrick Evans
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Priyanka Pawar
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Daniel Berner
- Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany
| | - Julia Sealock
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Ran Tao
- Biostatistics, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Peter S Straub
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Anuar I Konkashbaev
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Max A Breyer
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
| | - Ursula Schlötzer-Schrehardt
- Department of Ophthalmology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054, Erlangen, Germany
| | - André Reis
- Institute of Human Genetics, Friedrich-Alexander-Universität Erlangen-Nürnberg FAU, 91054, Erlangen, Germany
| | - Milam A Brantley
- Clare Hall and MRC Epidemiology Unit, University of Cambridge, Cambridge, CB2 0SL, UK
| | - Chiea C Khor
- Genome Institute of Singapore, 60 Biopolis St, Singapore, 138672, Singapore
| | - Karen M Joos
- Vanderbilt Eye Institute, Vanderbilt University Medical Center, Nashville, TN, 37232, USA
| | - Nancy J Cox
- Genetic Medicine, Vanderbilt University School of Medicine, Nashville, TN, 37232, USA
- Vanderbilt Genetics Institute, Nashville, TN, 37232, USA
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25
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Fang XX, Zhai MN, Zhu M, He C, Wang H, Wang J, Zhang ZJ. Inflammation in pathogenesis of chronic pain: Foe and friend. Mol Pain 2023; 19:17448069231178176. [PMID: 37220667 DOI: 10.1177/17448069231178176] [Citation(s) in RCA: 40] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/25/2023] Open
Abstract
Chronic pain is a refractory health disease worldwide causing an enormous economic burden on individuals and society. Accumulating evidence suggests that inflammation in the peripheral nervous system (PNS) and central nervous system (CNS) is the major factor in the pathogenesis of chronic pain. The inflammation in the early- and late phase may have distinctive effects on the initiation and resolution of pain, which can be viewed as friend or foe. On the one hand, painful injuries lead to the activation of glial cells and immune cells in the PNS, releasing pro-inflammatory mediators, which contribute to the sensitization of nociceptors, leading to chronic pain; neuroinflammation in the CNS drives central sensitization and promotes the development of chronic pain. On the other hand, macrophages and glial cells of PNS and CNS promote pain resolution via anti-inflammatory mediators and specialized pro-resolving mediators (SPMs). In this review, we provide an overview of the current understanding of inflammation in the deterioration and resolution of pain. Further, we summarize a number of novel strategies that can be used to prevent and treat chronic pain by controlling inflammation. This comprehensive view of the relationship between inflammation and chronic pain and its specific mechanism will provide novel targets for the treatment of chronic pain.
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Affiliation(s)
- Xiao-Xia Fang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Meng-Nan Zhai
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Meixuan Zhu
- Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA
| | - Cheng He
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Heng Wang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Juan Wang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
| | - Zhi-Jun Zhang
- Department of Human Anatomy, School of Medicine, Nantong University, Nantong, China
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26
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Chung KW, Kim DH, Jung HJ, Arulkumar R, Chung HY, Yu BP. Chronic Inflammation as an Underlying Mechanism of Ageing and Ageing-Related Diseases. Subcell Biochem 2023; 103:31-44. [PMID: 37120463 DOI: 10.1007/978-3-031-26576-1_3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/01/2023]
Abstract
Age-related chronic inflammation is characterized as the unresolved low-grade inflammatory process underlying the ageing process and various age-related diseases. In this chapter, we review the age-related changes in the oxidative stress-sensitive pro-inflammatory NF-κB signaling pathways causally linked with chronic inflammation during ageing based on senoinflammation schema. We describe various age-related dysregulated pro- and anti-inflammatory cytokines, chemokines, and senescence-associated secretory phenotype (SASP), and alterations of inflammasome, specialized pro-resolving lipid mediators (SPM), and autophagy as major players in the chronic inflammatory intracellular signaling network. A better understanding of the molecular, cellular, and systemic mechanisms involved in chronic inflammation in the ageing process would provide further insights into the potential anti-inflammatory strategies.
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Affiliation(s)
- Ki Wung Chung
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Dae Hyun Kim
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Hee Jin Jung
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Radha Arulkumar
- Interdisciplinary Research Program of Bioinformatics and Longevity Science, Pusan National University, Busan, Republic of Korea
| | - Hae Young Chung
- Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, Republic of Korea
| | - Byung Pal Yu
- Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
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27
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Zhang Y, Zhang A, Wang L, Yang T, Dong B, Wang Z, Bi Y, Chen G, Chang G. Metabolomics and Proteomics Characterizing Hepatic Reactions to Dietary Linseed Oil in Duck. Int J Mol Sci 2022; 23:ijms232415690. [PMID: 36555340 PMCID: PMC9778787 DOI: 10.3390/ijms232415690] [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: 11/08/2022] [Revised: 12/03/2022] [Accepted: 12/05/2022] [Indexed: 12/14/2022] Open
Abstract
The imbalance in polyunsaturated fatty acid (PUFA) composition in human food is ubiquitous and closely related to obesity and cardiovascular diseases. The development of n-3 PUFA-enriched poultry products is of great significance for optimizing fatty acid composition. This study aimed to improve our understanding of the effects of dietary linseed oil on hepatic metabolism using untargeted metabolomics and 4D label-free proteome analysis. A total of 91 metabolites and 63 proteins showed differences in abundance in duck livers between the high linseed oil and control groups. Pathway analysis revealed that the biosynthesis of unsaturated fatty acids, linoleic acid, glycerophospholipid, and pyrimidine metabolisms were significantly enriched in ducks fed with linseed oil. Meanwhile, dietary linseed oil changed liver fatty acid composition, which was reflected in the increase in the abundance of downstream metabolites, such as α-linolenic acid (ALA; 18:3n-3) as a substrate, including n-3 PUFA and its related glycerophospholipids, and a decrease in downstream n-6 PUFA synthesis using linoleic acid (LA; 18:2n-6) as a substrate. Moreover, the anabolism of PUFA in duck livers showed substrate-dependent effects, and the expression of related proteins in the process of fatty acid anabolism, such as FADS2, LPIN2, and PLA2G4A, were significantly regulated by linseed oil. Collectively, our work highlights the ALA substrate dependence during n-3 PUFA synthesis in duck livers. The present study expands our knowledge of the process products of PUFA metabolism and provides some potential biomarkers for liver health.
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28
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Zanesco S, Hall W, Gibson R, Griffiths C, Maruthappu T. Approaches to nutrition intervention in plaque psoriasis, a multi-system inflammatory disease-The Diet and Psoriasis Project (DIEPP). NUTR BULL 2022; 47:524-537. [PMID: 36082746 DOI: 10.1111/nbu.12580] [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: 04/30/2022] [Revised: 08/16/2022] [Accepted: 08/17/2022] [Indexed: 01/04/2023]
Abstract
Psoriasis is an immune-mediated inflammatory skin disease affecting approximately 2% of the UK population. Its pathogenesis is suggested to be an outcome of genetic and environmental interplay. People with psoriasis have an increased likelihood of developing other conditions such as type 2 diabetes and cardiovascular disease. Systemic inflammation is hypothesised to be the common link between psoriasis and cardio-metabolic diseases. Emerging evidence shows diet as a potential therapeutic adjunct in the management of psoriasis. The Diet and Psoriasis Project (DIEPP) aims to investigate whether dietary factors are related to psoriasis severity by conducting an observational study followed by a dietary intervention trial, to assess the effect of the Mediterranean diet (MedD) and time-restricted eating (TRE) on psoriasis. This review article will explore the potential mechanisms by which the MedD and TRE may exert protective effects on psoriasis, evaluate the current evidence, and outline the design of the DIEPP. Given the early-stage evidence, we hope to be able to build knowledge to derive medically approved dietary recommendations and contribute to the research gaps exploring the role of diet and psoriasis.
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Affiliation(s)
- Sylvia Zanesco
- Department of Nutritional Sciences, King's College London, London, UK
| | - Wendy Hall
- Department of Nutritional Sciences, King's College London, London, UK
| | - Rachel Gibson
- Department of Nutritional Sciences, King's College London, London, UK
| | - Christopher Griffiths
- Division of Musculoskeletal & Dermatological Sciences, The University of Manchester, Manchester, UK
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Nutraceuticals: A source of benefaction for neuropathic pain and fibromyalgia. J Funct Foods 2022. [DOI: 10.1016/j.jff.2022.105260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Fatty Acid Levels and Their Inflammatory Metabolites Are Associated with the Nondipping Status and Risk of Obstructive Sleep Apnea Syndrome in Stroke Patients. Biomedicines 2022; 10:biomedicines10092200. [PMID: 36140306 PMCID: PMC9496373 DOI: 10.3390/biomedicines10092200] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2022] [Revised: 09/02/2022] [Accepted: 09/04/2022] [Indexed: 11/17/2022] Open
Abstract
Background: This paper discusses the role of inflammation in the pathogenesis of nondipping blood pressure and its role in the pathogenesis of obstructive sleep apnea syndrome. The aim of the study was to assess the impact of free fatty acids (FAs) and their inflammatory metabolites on the nondipping phenomenon and the risk of sleep apnea in stroke patients. Methods: Sixty-four ischemic stroke patients were included in the prospective study. Group I consisted of 33 patients with a preserved physiological dipping effect (DIP), while group II included 31 patients with the nondipping phenomenon (NDIP). All subjects had FA gas chromatography and inflammatory metabolite measurements performed with the use of liquid chromatography, their 24 h blood pressure was recorded, and they were assessed with the Epworth sleepiness scale (ESS). Results: In the nondipping group a higher level of C16:0 palmitic acid was observed, while lower levels were observed in regard to C20:0 arachidic acid, C22:0 behenic acid and C24:1 nervonic acid. A decreased leukotriene B4 level was recorded in the nondipping group. None of the FAs and derivatives correlated with the ESS scale in the group of patients after stroke. Correlations were observed after dividing into the DIP and NDIP groups. In the DIP group, a higher score of ESS was correlated with numerous FAs and derivatives. Inflammation of a lower degree and a higher level of anti-inflammatory mediators from EPA and DHA acids favored the occurrence of the DIP. A high level of C18: 3n6 gamma linoleic acid indicating advanced inflammation, intensified the NDIP effect. Conclusions: We demonstrated potential novel associations between the FA levels and eicosanoids in the pathogenesis of the nondipping phenomenon. There are common connections between fatty acids, their metabolites, inflammation, obstructive sleep apnea syndrome and nondipping in stroke patients.
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Roohbakhsh A, Etemad L, Karimi G. Resolvin D1: A key endogenous inhibitor of neuroinflammation. Biofactors 2022; 48:1005-1026. [PMID: 36176016 DOI: 10.1002/biof.1891] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/05/2022] [Accepted: 08/08/2022] [Indexed: 12/14/2022]
Abstract
After the initiation of inflammation, a series of processes start to resolve the inflammation. A group of endogenous lipid mediators, namely specialized pro-resolving lipid mediators is at the top list of inflammation resolution. Resolvin D1 (RvD1), is one of the lipid mediators with significant anti-inflammatory properties. It is produced from docosahexaenoic acid (omega-3 polyunsaturated fatty acid) in the body. In this article, we aimed to review the most recent findings concerning the pharmacological effects of RvD1 in the central nervous system with a focus on major neurological diseases and dysfunctions. A literature review of the past studies demonstrated that RvD1 plasma level changes during mania, depression, and Parkinson's disease. Furthermore, RVD1 and its epimer, aspirin-triggered RvD1 (AT-RvD1), have significant therapeutic effects on experimental models of ischemic and traumatic brain injuries, memory dysfunction, pain, depression, amyotrophic lateral sclerosis, and Alzheimer's and Parkinson's diseases. Interestingly, the beneficial effects of RvD1 and AT-RvD1 were mostly induced at nanomolar and micromolar concentrations implying the significant potency of these lipid mediators in treating diseases with inflammation.
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Affiliation(s)
- Ali Roohbakhsh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Leila Etemad
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Gholamreza Karimi
- Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Livshits G, Kalinkovich A. Targeting chronic inflammation as a potential adjuvant therapy for osteoporosis. Life Sci 2022; 306:120847. [PMID: 35908619 DOI: 10.1016/j.lfs.2022.120847] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/07/2022] [Accepted: 07/26/2022] [Indexed: 11/16/2022]
Abstract
Systemic, chronic, low-grade inflammation (SCLGI) underlies the pathogenesis of various widespread diseases. It is often associated with bone loss, thus connecting chronic inflammation to the pathogenesis of osteoporosis. In postmenopausal women, osteoporosis is accompanied by SCLGI development, likely owing to estrogen deficiency. We propose that SCGLI persistence in osteoporosis results from failed inflammation resolution, which is mainly mediated by specialized, pro-resolving mediators (SPMs). In corroboration, SPMs demonstrate encouraging therapeutic effects in various preclinical models of inflammatory disorders, including bone pathology. Since numerous data implicate gut dysbiosis in osteoporosis-associated chronic inflammation, restoring balanced microbiota by supplementing probiotics and prebiotics could contribute to the efficient resolution of SCGLI. In the present review, we provide evidence for this hypothesis and argue that efficient SCGLI resolution may serve as a novel approach for treating osteoporosis, complementary to traditional anti-osteoporotic medications.
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Affiliation(s)
- Gregory Livshits
- Adelson School of Medicine, Ariel University, Ariel 4077625, Israel; Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6905126, Israel.
| | - Alexander Kalinkovich
- Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv 6905126, Israel
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Hall DCN, Benndorf RA. Aspirin sensitivity of PIK3CA-mutated Colorectal Cancer: potential mechanisms revisited. Cell Mol Life Sci 2022; 79:393. [PMID: 35780223 PMCID: PMC9250486 DOI: 10.1007/s00018-022-04430-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 06/01/2022] [Accepted: 06/14/2022] [Indexed: 11/30/2022]
Abstract
PIK3CA mutations are amongst the most prevalent somatic mutations in cancer and are associated with resistance to first-line treatment along with low survival rates in a variety of malignancies. There is evidence that patients carrying PIK3CA mutations may benefit from treatment with acetylsalicylic acid, commonly known as aspirin, particularly in the setting of colorectal cancer. In this regard, it has been clarified that Class IA Phosphatidylinositol 3-kinases (PI3K), whose catalytic subunit p110α is encoded by the PIK3CA gene, are involved in signal transduction that regulates cell cycle, cell growth, and metabolism and, if disturbed, induces carcinogenic effects. Although PI3K is associated with pro-inflammatory cyclooxygenase-2 (COX-2) expression and signaling, and COX-2 is among the best-studied targets of aspirin, the mechanisms behind this clinically relevant phenomenon are still unclear. Indeed, there is further evidence that the protective, anti-carcinogenic effect of aspirin in this setting may be mediated in a COX-independent manner. However, until now the understanding of aspirin's prostaglandin-independent mode of action is poor. This review will provide an overview of the current literature on this topic and aims to analyze possible mechanisms and targets behind the aspirin sensitivity of PIK3CA-mutated cancers.
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Affiliation(s)
- Daniella C N Hall
- Department of Clinical Pharmacy and Pharmacotherapy, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120, Halle (Saale), Germany
| | - Ralf A Benndorf
- Department of Clinical Pharmacy and Pharmacotherapy, Institute of Pharmacy, Martin-Luther-University Halle-Wittenberg, Kurt-Mothes-Str. 3, 06120, Halle (Saale), Germany.
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Liang N, Emami S, Patten KT, Valenzuela AE, Wallis CD, Wexler AS, Bein KJ, Lein PJ, Taha AY. Chronic exposure to traffic-related air pollution reduces lipid mediators of linoleic acid and soluble epoxide hydrolase in serum of female rats. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2022; 93:103875. [PMID: 35550873 PMCID: PMC9353974 DOI: 10.1016/j.etap.2022.103875] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Revised: 05/02/2022] [Accepted: 05/04/2022] [Indexed: 06/15/2023]
Abstract
Chronic exposure to traffic-related air pollution (TRAP) is known to promote systemic inflammation, which is thought to underlie respiratory, cardiovascular, metabolic and neurological disorders. It is not known whether chronic TRAP exposure dampens inflammation resolution, the homeostatic process for stopping inflammation and repairing damaged cells. In vivo, inflammation resolution is facilitated by bioactive lipid mediators known as oxylipins, which are derived from the oxidation of polyunsaturated fatty acids. To understand the effects of chronic TRAP exposure on lipid-mediated inflammation resolution pathways, we measured total (i.e. free+bound) pro-inflammatory and pro-resolving lipid mediators in serum of female rats exposed to TRAP or filtered air (FA) for 14 months. Compared to rats exposed to FA, TRAP-exposed rats showed a significant 36-48% reduction in fatty acid alcohols, specifically, 9-hydroxyoctadecadienoic acid (9-HODE), 11,12-dihydroxyeicosatetraenoic acid (11,12-DiHETE) and 16,17-dihydroxydocosapentaenoic acid (16, 17-DiHDPA). The decrease in fatty acid diols (11,12-DiHETE and 16, 17-DiHDPA) corresponded to a significant 34-39% reduction in the diol to epoxide ratio, a marker of soluble epoxide hydrolase activity; this enzyme is typically upregulated during inflammation. The findings demonstrate that 14 months exposure to TRAP reduced pro-inflammatory 9-HODE concentration and dampened soluble epoxide hydrolase activation, suggesting adaptive immune changes in lipid mediator pathways involved in inflammation resolution.
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Affiliation(s)
- Nuanyi Liang
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, USA
| | - Shiva Emami
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, USA
| | - Kelley T Patten
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA
| | - Anthony E Valenzuela
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA
| | | | - Anthony S Wexler
- Mechanical and Aerospace Engineering, University of California, Davis, CA 95616, USA; Air Quality Research Center, University of California, Davis, Davis, CA, USA
| | - Keith J Bein
- Air Quality Research Center, University of California, Davis, Davis, CA, USA; Center for Health and the Environment, University of California, Davis, Davis, CA, USA
| | - Pamela J Lein
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA, USA
| | - Ameer Y Taha
- Department of Food Science and Technology, College of Agriculture and Environmental Sciences, University of California Davis, Davis, CA, USA; West Coast Metabolomics Center, Genome Center, University of California Davis, Davis, CA, USA.
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Xiao H, Yan Y, Gu Y, Zhang Y. Strategy for sodium-salt substitution: On the relationship between hypertension and dietary intake of cations. Food Res Int 2022; 156:110822. [PMID: 35650987 DOI: 10.1016/j.foodres.2021.110822] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2021] [Revised: 10/28/2021] [Accepted: 11/22/2021] [Indexed: 11/04/2022]
Abstract
Chronic diseases, especially cardiovascular diseases (CVD), have become one of the main causes affecting human health. Hypertension is a prominent representative of CVD. The formation and development of hypertension is closely related to people's daily diet. A large number of studies have shown that excessive intake of salt (NaCl) could increase the risk of hypertension. In recent years, more and more investigations have focused on other cations that may be contained in edible salt, exploring whether they have an effect on hypertension and the underlying mechanism. This article focuses on the relationship between four metal elements (potassium, calcium, magnesium, and zinc) and hypertension, by discussing the main metabolic pathway, the impact of diet intake on blood pressure, and especially the regulation mechanisms on blood pressure in detail. At the same time, some opinions and suggestions are put forward, combined with the current hot topics "salt reduction" and "salt substitution".
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Affiliation(s)
- Hongrui Xiao
- College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Yali Yan
- College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Yanpei Gu
- College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou 310058, Zhejiang, China
| | - Ying Zhang
- College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing, Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou 310058, Zhejiang, China.
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36
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Centorame A, Dumut DC, Youssef M, Ondra M, Kianicka I, Shah J, Paun RA, Ozdian T, Hanrahan JW, Gusev E, Petrof B, Hajduch M, Pislariu R, De Sanctis JB, Radzioch D. Treatment With LAU-7b Complements CFTR Modulator Therapy by Improving Lung Physiology and Normalizing Lipid Imbalance Associated With CF Lung Disease. Front Pharmacol 2022; 13:876842. [PMID: 35668939 PMCID: PMC9163687 DOI: 10.3389/fphar.2022.876842] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 04/08/2022] [Indexed: 11/13/2022] Open
Abstract
Cystic fibrosis (CF) is the most common autosomal recessive genetic disease in Caucasians, affecting more than 100,000 individuals worldwide. It is caused by pathogenic variants in the gene encoding CFTR, an anion channel at the plasma membrane of epithelial and other cells. Many CF pathogenic variants disrupt the biosynthesis and trafficking of CFTR or reduce its ion channel function. The most frequent mutation, loss of a phenylalanine at position 508 (F508del), leads to misfolding, retention in the endoplasmic reticulum, and premature degradation of the protein. The therapeutics available for treating CF lung disease include antibiotics, mucolytics, bronchodilators, physiotherapy, and most recently CFTR modulators. To date, no cure for this life shortening disease has been found. Treatment with the Triple combination drug therapy, TRIKAFTA®, is composed of three drugs: Elexacaftor (VX-445), Tezacaftor (VX-661) and Ivacaftor (VX-770). This therapy, benefits persons with CF, improving their weight, lung function, energy levels (as defined by reduced fatigue), and overall quality of life. We examined the effect of combining LAU-7b oral treatment and Triple therapy combination on lung function in a F508deltm1EUR mouse model that displays lung abnormalities relevant to human CF. We assessed lung function, lung histopathology, protein oxidation, lipid oxidation, and fatty acid and lipid profiles in F508deltm1EUR mice.
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Affiliation(s)
- Amanda Centorame
- Faculty of Medicine, McGill University, Montreal, QC, Canada
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Daciana Catalina Dumut
- Faculty of Medicine, McGill University, Montreal, QC, Canada
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Mina Youssef
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Martin Ondra
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia
- Czech Advanced Technology and Research Institute, Palacky University, Olomouc, Czechia
| | | | - Juhi Shah
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Radu Alexandru Paun
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Department of Biomedical Engineering, McGill University, Montreal, QC, Canada
| | - Tomas Ozdian
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia
| | - John W. Hanrahan
- Department of Physiology, McGill University, Montreal, QC, Canada
| | - Ekaterina Gusev
- Meakins-Christie Laboratories, The Centre for Respiratory Research at McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Basil Petrof
- Meakins-Christie Laboratories, The Centre for Respiratory Research at McGill University and the Research Institute of the McGill University Health Centre, Montreal, QC, Canada
| | - Marian Hajduch
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia
- Czech Advanced Technology and Research Institute, Palacky University, Olomouc, Czechia
| | | | - Juan Bautista De Sanctis
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia
- Czech Advanced Technology and Research Institute, Palacky University, Olomouc, Czechia
| | - Danuta Radzioch
- Faculty of Medicine, McGill University, Montreal, QC, Canada
- Infectious Diseases and Immunity in Global Health, Research Institute of the McGill University Health Centre, Montreal, QC, Canada
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, Olomouc, Czechia
- Laurent Pharmaceuticals, Montreal, QC, Canada
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37
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Kotlyarov S, Kotlyarova A. Molecular Pharmacology of Inflammation Resolution in Atherosclerosis. Int J Mol Sci 2022; 23:4808. [PMID: 35563200 PMCID: PMC9104781 DOI: 10.3390/ijms23094808] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2022] [Revised: 04/18/2022] [Accepted: 04/25/2022] [Indexed: 02/01/2023] Open
Abstract
Atherosclerosis is one of the most important problems of modern medicine as it is the leading cause of hospitalizations, disability, and mortality. The key role in the development and progression of atherosclerosis is the imbalance between the activation of inflammation in the vascular wall and the mechanisms of its control. The resolution of inflammation is the most important physiological mechanism that is impaired in atherosclerosis. The resolution of inflammation has complex, not fully known mechanisms, in which lipid mediators derived from polyunsaturated fatty acids (PUFAs) play an important role. Specialized pro-resolving mediators (SPMs) represent a group of substances that carry out inflammation resolution and may play an important role in the pathogenesis of atherosclerosis. SPMs include lipoxins, resolvins, maresins, and protectins, which are formed from PUFAs and regulate many processes related to the active resolution of inflammation. Given the physiological importance of these substances, studies examining the possibility of pharmacological effects on inflammation resolution are of interest.
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Affiliation(s)
- Stanislav Kotlyarov
- Department of Nursing, Ryazan State Medical University, 390026 Ryazan, Russia
| | - Anna Kotlyarova
- Department of Pharmacology and Pharmacy, Ryazan State Medical University, 390026 Ryazan, Russia;
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Di Filippo L, De Lorenzo R, Giustina A, Rovere-Querini P, Conte C. Vitamin D in Osteosarcopenic Obesity. Nutrients 2022; 14:1816. [PMID: 35565781 PMCID: PMC9100750 DOI: 10.3390/nu14091816] [Citation(s) in RCA: 41] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2022] [Revised: 04/24/2022] [Accepted: 04/25/2022] [Indexed: 02/07/2023] Open
Abstract
Osteosarcopenic obesity is a unique clinical condition where low bone and muscle mass coexist in individuals with obesity. Alterations in adipose tissue, skeletal muscle and bone are strictly interconnected, and vitamin D plays key roles in several metabolic pathways that are involved in maintaining musculoskeletal health and glucose homeostasis. We reviewed the available literature on mechanisms underlying osteosarcopenic obesity, with a focus on the role of vitamin D in the pathogenesis and treatment of the condition. We found that, although evidence from large observational studies and pre-clinical experiments strongly supports a role of vitamin D deficiency in the pathogenesis of osteosarcopenic obesity, the common belief that vitamin D improves musculoskeletal health lacks solid clinical evidence, as trials specifically aimed at assessing the effects of vitamin D supplementation in patients with osteosarcopenic obesity are not available, and trials that investigated the role of vitamin D on muscle and bone health in other patient populations either showed no or even detrimental effects. We conclude that large observational and interventional studies including individuals with osteosarcopenic obesity representative of different sex, age and race are needed to better define the role of vitamin D in the pathogenesis and treatment of this condition.
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Affiliation(s)
- Luigi Di Filippo
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 00132 Milan, Italy; (L.D.F.); (R.D.L.); (A.G.); (P.R.-Q.)
- Institute of Endocrine and Metabolic Sciences, IRCCS San Raffaele Hospital, Via Olgettina 60, 00132 Milan, Italy
| | - Rebecca De Lorenzo
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 00132 Milan, Italy; (L.D.F.); (R.D.L.); (A.G.); (P.R.-Q.)
- Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Hospital, Via Olgettina 60, 00132 Milan, Italy
| | - Andrea Giustina
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 00132 Milan, Italy; (L.D.F.); (R.D.L.); (A.G.); (P.R.-Q.)
- Institute of Endocrine and Metabolic Sciences, IRCCS San Raffaele Hospital, Via Olgettina 60, 00132 Milan, Italy
| | - Patrizia Rovere-Querini
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina 58, 00132 Milan, Italy; (L.D.F.); (R.D.L.); (A.G.); (P.R.-Q.)
- Division of Immunology, Transplantation and Infectious Diseases, IRCCS San Raffaele Hospital, Via Olgettina 60, 00132 Milan, Italy
| | - Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta 247, 00166 Rome, Italy
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, Via Milanese 300, Sesto San Giovanni, 20900 Milan, Italy
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Trotta MC, Gesualdo C, Petrillo F, Lepre CC, Della Corte A, Cavasso G, Maggiore G, Hermenean A, Simonelli F, D’Amico M, Rossi S. Resolution of Inflammation in Retinal Disorders: Briefly the State. Int J Mol Sci 2022; 23:4501. [PMID: 35562891 PMCID: PMC9100636 DOI: 10.3390/ijms23094501] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/13/2022] [Accepted: 04/16/2022] [Indexed: 12/24/2022] Open
Abstract
The most frequent retinal diseases, such as diabetic retinopathy, age-related macular degeneration and posterior uveitis, are underlined by oxidative stress or aging-induced retinal inflammation, which contributes to vision impairing or loss. Resolution of inflammation is emerging as a critical phase able to counteract the inflammatory process leading to the progression of retinal damage. Particularly, pro-resolving mediators (PMs) play a key role in the modulation of inflammatory exudates and could be considered a new target to be investigated in different inflammatory-autoimmune pathologies. Here, we highlight the most recent studies concerning the role of the main PMs (lipoxins, resolvins, prtectins, maresins and annexins) in retinal inflammation, in order to collect the best evidence in the field of inflammatory retinal damage resolution and to propose novel pharmacological approaches in the management of the most common retinal diseases.
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Affiliation(s)
- Maria Consiglia Trotta
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (M.C.T.); (F.P.); (C.C.L.); (M.D.)
| | - Carlo Gesualdo
- Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 6, 80131 Naples, Italy; (C.G.); (A.D.C.); (G.C.); (F.S.)
| | - Francesco Petrillo
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (M.C.T.); (F.P.); (C.C.L.); (M.D.)
| | - Caterina Claudia Lepre
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (M.C.T.); (F.P.); (C.C.L.); (M.D.)
| | - Alberto Della Corte
- Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 6, 80131 Naples, Italy; (C.G.); (A.D.C.); (G.C.); (F.S.)
| | - Giancuomo Cavasso
- Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 6, 80131 Naples, Italy; (C.G.); (A.D.C.); (G.C.); (F.S.)
| | - Giulia Maggiore
- Department of Ophthalmology, University of Foggia, Viale Luigi Pinto 1, 71122 Foggia, Italy;
| | - Anca Hermenean
- “Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei Av., 310414 Arad, Romania;
| | - Francesca Simonelli
- Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 6, 80131 Naples, Italy; (C.G.); (A.D.C.); (G.C.); (F.S.)
| | - Michele D’Amico
- Department of Experimental Medicine, University of Campania “Luigi Vanvitelli”, Via Santa Maria di Costantinopoli 16, 80138 Naples, Italy; (M.C.T.); (F.P.); (C.C.L.); (M.D.)
| | - Settimio Rossi
- Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 6, 80131 Naples, Italy; (C.G.); (A.D.C.); (G.C.); (F.S.)
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40
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Ferreira I, Falcato F, Bandarra N, Rauter AP. Resolvins, Protectins, and Maresins: DHA-Derived Specialized Pro-Resolving Mediators, Biosynthetic Pathways, Synthetic Approaches, and Their Role in Inflammation. Molecules 2022; 27:1677. [PMID: 35268778 PMCID: PMC8912121 DOI: 10.3390/molecules27051677] [Citation(s) in RCA: 46] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2022] [Revised: 02/11/2022] [Accepted: 02/16/2022] [Indexed: 12/31/2022] Open
Abstract
Marine organisms are an important source of natural products with unique and diverse chemical structures that may hold the key for the development of novel drugs. Docosahexaenoic acid (DHA) is an omega-3 fatty acid marine natural product playing a crucial regulatory role in the resolution of inflammation and acting as a precursor for the biosynthesis of the anti-inflammatory specialized pro-resolving mediators (SPMs) resolvins, protectins, and maresins. These metabolites exert many beneficial actions including neuroprotection, anti-hypertension, or anti-tumorigenesis. As dysregulation of SPMs is associated with diseases of prolonged inflammation, the disclosure of their bioactivities may be correlated with anti-inflammatory and pro-resolving capabilities, offering new targets for drug design. The availability of these SPMs from natural resources is very low, but the evaluation of their pharmacological properties requires their access in larger amounts, as achieved by synthetic routes. In this report, the first review of the total organic syntheses carried out for resolvins, protectins, and maresins is presented. Recently, it was proposed that DHA-derived pro-resolving mediators play a key role in the treatment of COVID-19. In this work we also review the current evidence on the structures, biosynthesis, and functional and new-found roles of these novel lipid mediators of disease resolution.
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Affiliation(s)
- Inês Ferreira
- Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Piso 5, Campo Grande, 1749-016 Lisboa, Portugal;
- Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalhães Ramalho, 6, 1495-006 Lisboa, Portugal;
| | - Filipa Falcato
- Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalhães Ramalho, 6, 1495-006 Lisboa, Portugal;
| | - Narcisa Bandarra
- Division of Aquaculture, Upgrading and Bioprospecting, Portuguese Institute of the Sea and Atmosphere, Rua Alfredo Magalhães Ramalho, 6, 1495-006 Lisboa, Portugal;
- Interdisciplinary Centre of Marine and Environmental Research (CIIMAR), University of Porto, Rua dos Bragas 289, 4050-123 Porto, Portugal
| | - Amélia P. Rauter
- Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Ed. C8, Piso 5, Campo Grande, 1749-016 Lisboa, Portugal;
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Pascoal LB, Palma BB, Chaim FHM, de Castro MM, Damázio TA, Franceschini APMDF, Milanski M, Velloso LA, Leal RF. New translational and experimental insights into the role of pro-resolving lipid mediators in inflammatory bowel disease. World J Exp Med 2022; 12:1-15. [PMID: 35096550 PMCID: PMC8771592 DOI: 10.5493/wjem.v12.i1.1] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/21/2021] [Accepted: 01/08/2022] [Indexed: 02/06/2023] Open
Abstract
The resolution of inflammation is an active process, guided by specialized pro-resolution lipid mediators (SPMs). These mediators originate from polyunsaturated fatty acids, such as omega-3. Sufficient evidence suggests that the beneficial effects attributed to omega-3 are, at least in part, the result of the immunomodulatory action of the SPMs, which act systemically by overcoming inflammation and repairing tissue damage, without suppressing the immune response. Recent studies suggest that an imbalance in the synthesis and/or activity of these compounds may be associated with the pathogenesis of several inflammatory conditions, such as inflammatory bowel disease (IBD). Thus, this review highlights the advances made in recent years with regard to the endo-genous synthesis and the biological role of lipoxins, resolvins, protectins, and maresins, as well as their precursors, in the regulation of inflammation; and provides an update on the participation of these mediators in the development and evolution of IBD and the therapeutic approaches that these immunomodulating substances are involved in this context.
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Affiliation(s)
- Lívia Bitencourt Pascoal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Bruna Biazon Palma
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Fabio Henrique Mendonça Chaim
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Marina Moreira de Castro
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Tiago Andrade Damázio
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Ana Paula Menezes de Freitas Franceschini
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Marciane Milanski
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
| | - Lício Augusto Velloso
- Laboratory of Cell Signaling, School of Medical Sciences, University of Campinas, Campinas 13083-864, São Paulo, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Colorectal Surgery Unit, Department of Surgery, School of Medical Sciences, University of Campinas, Campinas 13083-878, São Paulo, Brazil
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Menon D, Lewis EJH, Perkins BA, Bril V. Omega-3 Nutrition Therapy for the Treatment of Diabetic Sensorimotor Polyneuropathy. Curr Diabetes Rev 2022; 18:e010921196028. [PMID: 34488588 DOI: 10.2174/1573399817666210901121111] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 04/06/2021] [Accepted: 05/06/2021] [Indexed: 11/22/2022]
Abstract
Despite advances in clinical and translational research, an effective therapeutic option for diabetic sensorimotor polyneuropathy (DSP) has remained elusive. The pathomechanisms of DSP are diverse, and along with hyperglycemia, the roles of inflammatory mediators and lipotoxicity in the development of microangiopathy have been well elucidated. Omega-3 (n-3) polyunsaturated fatty acids (PUFA) are essential fatty acids with a vital role in a number of physiological processes, including neural health, membrane structure integrity, anti-inflammatory processes, and lipid metabolism. Identification of n-3 PUFA derived specialised proresolving mediators (SPM), namely resolvins, neuroprotectin, and maresins which also favour nerve regeneration, have positioned n-3 PUFA as potential treatment options in DSP. Studies in n-3 PUFA treated animal models of DSP showed positive nerve benefits in functional, electrophysiological, and pathological indices. Clinical trials in humans are limited, but recent proof-of-concept evidence suggests n-3 PUFA has a positive effect on small nerve fibre regeneration with an increase in the small nerve fiber measure of corneal nerve fibre length (CNFL). Further randomized control trials with a longer duration of treatment, higher n-3 PUFA doses, and more rigorous neuropathy measures are needed to provide a definitive understanding of the benefits of n-3 PUFA supplementation in DSP.
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Affiliation(s)
- Deepak Menon
- Ellen and Martin Prosserman Centre for Neuromuscular Disorders. Division of Neurology, University Health Network, University of Toronto, Toronto, Canada
| | - Evan J H Lewis
- Lunenfeld-Tanenbaum Research Institute, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada
| | - Bruce A Perkins
- Lunenfeld-Tanenbaum Research Institute, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Canada
| | - Vera Bril
- Ellen and Martin Prosserman Centre for Neuromuscular Disorders. Division of Neurology, University Health Network, University of Toronto, Toronto, Canada
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Molaei E, Molaei A, Hayes AW, Karimi G. Resolvin D1, therapeutic target in acute respiratory distress syndrome. Eur J Pharmacol 2021; 911:174527. [PMID: 34582846 PMCID: PMC8464084 DOI: 10.1016/j.ejphar.2021.174527] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 09/09/2021] [Accepted: 09/23/2021] [Indexed: 12/25/2022]
Abstract
Acute lung injury (ALI), or its more severe form, acute respiratory distress syndrome (ARDS), is a disease with high mortality and is a serious challenge facing the World Health Organization because there is no specific treatment. The excessive and prolonged immune response is the hallmark of this disorder, so modulating and regulating inflammation plays an important role in its prevention and treatment. Resolvin D1 (RvD1) as a specialized pro-resolving mediator has the potential to suppress the expression of inflammatory cytokines and to facilitate the production of antioxidant proteins by stimulating lipoxin A4 receptor/formyl peptide receptor 2 (ALX/FPR2). These changes limit the invasion of immune cells into the lung tissue, inhibit coagulation, and enhance cell protection against oxidative stress (OS). In particular, this biomolecule reduces the generation of reactive oxygen species (ROS) by blocking the activation of inflammatory transcription factors, especially nuclear factor-κB (NF-κB), and accelerating the synthesis of antioxidant compounds such as heme oxygenase 1 (HO-1) and superoxide dismutase (SOD). Therefore, the destruction and dysfunction of important cell components such as cytoplasmic membrane, mitochondria, Na+/k + adenosine triphosphatase (ATPase) and proteins involved in the phagocytic activity of scavenger macrophages are attenuated. Numerous studies on the effect of RvD1 over inflammation using animal models revealed that Rvs have both anti-inflammatory and pro-resolving capabilities and therefore, might have potential therapeutic value in treating ALI. Here, we review the current knowledge on the classification, biosynthesis, receptors, mechanisms of action, and role of Rvs in ALI/ARDS.
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Affiliation(s)
- Emad Molaei
- Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Molaei
- Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - A Wallace Hayes
- University of South Florida College of Public Health, Tampa, FL, USA
| | - Gholamreza Karimi
- Pharmaceutical Research Center, Institute of Pharmaceutical Technology, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Cockcroft S. Mammalian lipids: structure, synthesis and function. Essays Biochem 2021; 65:813-845. [PMID: 34415021 PMCID: PMC8578989 DOI: 10.1042/ebc20200067] [Citation(s) in RCA: 76] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 07/05/2021] [Accepted: 08/04/2021] [Indexed: 12/13/2022]
Abstract
Lipids are essential constituents of cellular membranes. Once regarded merely as structural components, lipids have taken centre stage with the discovery of their roles in cell signalling and in the generation of bioactive metabolites. Lipids regulate many physiological functions of cells and alterations in membrane lipid metabolism are associated with major diseases including cancer, Type II diabetes, cardiovascular disease and immune disorders. Understanding lipid diversity, their synthesis and metabolism to generate signalling molecules will provide insight into the fundamental function of the cell. This review summarises the biosynthesis of the lipids of the mammalian cell; phospholipids, sphingolipids and cholesterol and how lipid diversity is achieved. The fatty acids (FAs) are the main building blocks of lipids and contribute to the diversity. Lipid synthesis is intimately connected to their transport within cells; the contribution by proteins that transport lipids, lipid transport proteins will be described. Cellular lipids are metabolised by phospholipases, lipid kinases and phosphatases to make new bioactive metabolites. These transient bioactive metabolites allow cells to respond to the external environment to maintain cellular health. The function of individual metabolites is also highlighted. Bioactive metabolites can be second messengers, or released to the external medium to regulate other cells. Alternatively, bioactive lipids also provide a platform for reversible recruitment of proteins to membranes using their lipid-binding domains. The wide range of physiological processes in which a specific involvement of lipids has been identified explains the need for lipid diversity present in mammalian cells.
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Affiliation(s)
- Shamshad Cockcroft
- Department of Neuroscience, Physiology and Pharmacology, Division of Biosciences, University College London, 21 University Street, London WC1E 6JJ, U.K
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Chávez-Castillo M, Ortega Á, Cudris-Torres L, Duran P, Rojas M, Manzano A, Garrido B, Salazar J, Silva A, Rojas-Gomez DM, De Sanctis JB, Bermúdez V. Specialized Pro-Resolving Lipid Mediators: The Future of Chronic Pain Therapy? Int J Mol Sci 2021; 22:ijms221910370. [PMID: 34638711 PMCID: PMC8509014 DOI: 10.3390/ijms221910370] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/15/2022] Open
Abstract
Chronic pain (CP) is a severe clinical entity with devastating physical and emotional consequences for patients, which can occur in a myriad of diseases. Often, conventional treatment approaches appear to be insufficient for its management. Moreover, considering the adverse effects of traditional analgesic treatments, specialized pro-resolving lipid mediators (SPMs) have emerged as a promising alternative for CP. These include various bioactive molecules such as resolvins, maresins, and protectins, derived from ω-3 polyunsaturated fatty acids (PUFAs); and lipoxins, produced from ω-6 PUFAs. Indeed, SPMs have been demonstrated to play a central role in the regulation and resolution of the inflammation associated with CP. Furthermore, these molecules can modulate neuroinflammation and thus inhibit central and peripheral sensitizations, as well as long-term potentiation, via immunomodulation and regulation of nociceptor activity and neuronal pathways. In this context, preclinical and clinical studies have evidenced that the use of SPMs is beneficial in CP-related disorders, including rheumatic diseases, migraine, neuropathies, and others. This review integrates current preclinical and clinical knowledge on the role of SPMs as a potential therapeutic tool for the management of patients with CP.
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Affiliation(s)
- Mervin Chávez-Castillo
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Ángel Ortega
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Lorena Cudris-Torres
- Programa de Psicología, Fundación Universitaria del Área Andina sede Valledupar, Valledupar 200001, Colombia;
| | - Pablo Duran
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Milagros Rojas
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Alexander Manzano
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Bermary Garrido
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Juan Salazar
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Aljadis Silva
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo 4004, Venezuela; (M.C.-C.); (Á.O.); (P.D.); (M.R.); (A.M.); (B.G.); (J.S.); (A.S.)
| | - Diana Marcela Rojas-Gomez
- Escuela de Nutrición y Dietética, Facultad de Medicina, Universidad Andres Bello, Santiago 8370035, Chile;
| | - Juan B. De Sanctis
- Institute of Molecular and Translational Medicine, Palacký University Olomouc, 77900 Olomouc, Czech Republic;
| | - Valmore Bermúdez
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla 080002, Colombia
- Correspondence:
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Ferrari I, Vagnozzi RJ. Mechanisms and strategies for a therapeutic cardiac immune response. J Mol Cell Cardiol 2021; 158:82-88. [PMID: 34051237 PMCID: PMC11964415 DOI: 10.1016/j.yjmcc.2021.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 05/13/2021] [Accepted: 05/21/2021] [Indexed: 10/21/2022]
Affiliation(s)
- Ilaria Ferrari
- Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Ronald J Vagnozzi
- Department of Medicine, Division of Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Gates Center for Regenerative Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
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Molecular Mechanisms of Neuroimmune Crosstalk in the Pathogenesis of Stroke. Int J Mol Sci 2021; 22:ijms22179486. [PMID: 34502395 PMCID: PMC8431165 DOI: 10.3390/ijms22179486] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/26/2021] [Accepted: 08/28/2021] [Indexed: 12/21/2022] Open
Abstract
Stroke disrupts the homeostatic balance within the brain and is associated with a significant accumulation of necrotic cellular debris, fluid, and peripheral immune cells in the central nervous system (CNS). Additionally, cells, antigens, and other factors exit the brain into the periphery via damaged blood–brain barrier cells, glymphatic transport mechanisms, and lymphatic vessels, which dramatically influence the systemic immune response and lead to complex neuroimmune communication. As a result, the immunological response after stroke is a highly dynamic event that involves communication between multiple organ systems and cell types, with significant consequences on not only the initial stroke tissue injury but long-term recovery in the CNS. In this review, we discuss the complex immunological and physiological interactions that occur after stroke with a focus on how the peripheral immune system and CNS communicate to regulate post-stroke brain homeostasis. First, we discuss the post-stroke immune cascade across different contexts as well as homeostatic regulation within the brain. Then, we focus on the lymphatic vessels surrounding the brain and their ability to coordinate both immune response and fluid homeostasis within the brain after stroke. Finally, we discuss how therapeutic manipulation of peripheral systems may provide new mechanisms to treat stroke injury.
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Mavrommatis A, Theodorou G, Politis I, Tsiplakou E. Schizochytrium sp. Dietary supplementation modify Toll-like receptor 4 (TLR4) transcriptional regulation in monocytes and neutrophils of dairy goats. Cytokine 2021; 148:155588. [PMID: 34403896 DOI: 10.1016/j.cyto.2021.155588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 04/26/2021] [Accepted: 05/17/2021] [Indexed: 12/29/2022]
Abstract
Animals protect themselves against pathogens or abiotic factors by innate or adaptive mechanisms. Long-chain polyunsaturated fatty acids (ω3) of microalgae modify both human and mice' immune systems resulting in a beneficial balance between pro-inflammatory and anti-inflammatory pathways. However, scarce information exists on their impact on lactating animals' immunity. The objective of this study was to investigate the impact of dietary inclusion of Schizochytrium sp. (rich in docosapentaenoic and docosahexaenoic acid), on the expression of several genes involved in the innate immunity of goats. Twenty-four dairy goats were divided into four homogeneous sub-groups (n = 6). All goats were fed individually with alfalfa hay and concentrate. The concentrate of the control group (CON) had no microalgae while those of the treated groups were supplemented daily with 20 (ALG20), 40 (ALG40), and 60 (ALG60) g Schizochytrium sp. Monocytes and neutrophils were isolated from goats' blood in the 20th, 40th, and 60th days from the beginning of the experimental period. The relative transcript levels of TLR4, MYD88, MAPK, IRF3, IFNG, and pro-inflammatory cytokines (IL1B, IL2, IL8, TNF), and chemokines (CCL5 and CXCL16) were decreased in monocytes of microalgae treated goats compared to the CON. In contrast, MAPK and IL1B relative transcript levels were increased in neutrophils of ALG40 and ALG60 groups. In conclusion, the supplementation of goats' diet with 20 g Schizochytrium sp. resulted in a downregulation of the pro-inflammatory transcriptions, and following further research could be considered as a sustainable alternative strategy to improve immune function.
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Affiliation(s)
- Alexandros Mavrommatis
- Department of Animal Science, Laboratory of Nutritional Physiology and Feeding, Agricultural University of Athens, Iera Odos 75, Athens GR-11855, Greece
| | - Georgios Theodorou
- Department of Animal Science, Laboratory of Animal Breeding & Husbandry, Agricultural University of Athens, Greece, Iera Odos 75, Athens GR-11855, Greece
| | - Ioannis Politis
- Department of Animal Science, Laboratory of Animal Breeding & Husbandry, Agricultural University of Athens, Greece, Iera Odos 75, Athens GR-11855, Greece
| | - Eleni Tsiplakou
- Department of Animal Science, Laboratory of Nutritional Physiology and Feeding, Agricultural University of Athens, Iera Odos 75, Athens GR-11855, Greece.
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Garcia Corrales AV, Haidar M, Bogie JFJ, Hendriks JJA. Fatty Acid Synthesis in Glial Cells of the CNS. Int J Mol Sci 2021; 22:ijms22158159. [PMID: 34360931 PMCID: PMC8348209 DOI: 10.3390/ijms22158159] [Citation(s) in RCA: 37] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2021] [Revised: 07/22/2021] [Accepted: 07/26/2021] [Indexed: 12/12/2022] Open
Abstract
Fatty acids (FAs) are of crucial importance for brain homeostasis and neural function. Glia cells support the high demand of FAs that the central nervous system (CNS) needs for its proper functioning. Additionally, FAs can modulate inflammation and direct CNS repair, thereby contributing to brain pathologies such Alzheimer’s disease or multiple sclerosis. Intervention strategies targeting FA synthesis in glia represents a potential therapeutic opportunity for several CNS diseases.
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Affiliation(s)
- Aida V Garcia Corrales
- Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium
| | - Mansour Haidar
- Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium
| | - Jeroen F J Bogie
- Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium
| | - Jerome J A Hendriks
- Department of Immunology and Infection, Biomedical Research Institute, Hasselt University, 3590 Diepenbeek, Belgium
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50
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Inflammation and tumor progression: signaling pathways and targeted intervention. Signal Transduct Target Ther 2021; 6:263. [PMID: 34248142 PMCID: PMC8273155 DOI: 10.1038/s41392-021-00658-5] [Citation(s) in RCA: 1298] [Impact Index Per Article: 324.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 05/11/2021] [Accepted: 05/23/2021] [Indexed: 02/06/2023] Open
Abstract
Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses tumor progression, potentially displaying opposing effects on therapeutic outcomes. Chronic inflammation facilitates tumor progression and treatment resistance, whereas induction of acute inflammatory reactions often stimulates the maturation of dendritic cells (DCs) and antigen presentation, leading to anti-tumor immune responses. In addition, multiple signaling pathways, such as nuclear factor kappa B (NF-kB), Janus kinase/signal transducers and activators of transcription (JAK-STAT), toll-like receptor (TLR) pathways, cGAS/STING, and mitogen-activated protein kinase (MAPK); inflammatory factors, including cytokines (e.g., interleukin (IL), interferon (IFN), and tumor necrosis factor (TNF)-α), chemokines (e.g., C-C motif chemokine ligands (CCLs) and C-X-C motif chemokine ligands (CXCLs)), growth factors (e.g., vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β), and inflammasome; as well as inflammatory metabolites including prostaglandins, leukotrienes, thromboxane, and specialized proresolving mediators (SPM), have been identified as pivotal regulators of the initiation and resolution of inflammation. Nowadays, local irradiation, recombinant cytokines, neutralizing antibodies, small-molecule inhibitors, DC vaccines, oncolytic viruses, TLR agonists, and SPM have been developed to specifically modulate inflammation in cancer therapy, with some of these factors already undergoing clinical trials. Herein, we discuss the initiation and resolution of inflammation, the crosstalk between tumor development and inflammatory processes. We also highlight potential targets for harnessing inflammation in the treatment of cancer.
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