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Chaim FHM, Pascoal LB, de Castro MM, Palma BB, Rodrigues BL, Fagundes JJ, Milanski M, Lopes LR, Leal RF. The resolvin D2 and omega-3 polyunsaturated fatty acid as a new possible therapeutic approach for inflammatory bowel diseases. Sci Rep 2024; 14:28698. [PMID: 39562789 PMCID: PMC11576872 DOI: 10.1038/s41598-024-80051-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2024] [Accepted: 11/14/2024] [Indexed: 11/21/2024] Open
Abstract
Inflammatory bowel diseases (IBD) are idiopathic disorders characterized by chronic gastrointestinal inflammation. Given conventional therapies' adverse effects and clinical failures, novel approaches are being investigated. Recent studies have highlighted the role of specialized pro-resolving lipid mediators (SPMs) in the active resolution of chronic inflammation. In this regard, omega-3 fatty acid-derived Resolvin D2 (RvD2) appears to play a protective role in the pathophysiology of IBD. Therefore, we characterized the RvD2 pathway and its receptor expression in the intestinal mucosa of experimental colitis induced by dextran sulfate sodium. We also evaluated the preventive impact of an omega-3-enriched diet and the therapeutic efficacy of RvD2 compared with anti-TNF-α treatment. We found an increase in TNFα and IL22 expression and decreased levels of enzymes involved in RvD2 biosynthesis, such as PLA2, 15-LOX, 5-LOX, and its receptor GPR18 in experimental colitis. Omega-3 supplementation reduced the Disease Activity Index (DAI), weight loss, colonic shortening, and inflammation. These results and the increased IL-10 transcriptional levels after RvD2 treatment suggest that this mediator attenuated experimental colitis. These results enhance our understanding of the molecular mechanisms involved in the exacerbated inflammatory response present in experimental colitis and suggest that RvD2 and its omega-3 precursor offer a promising therapeutic approach for IBD.
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Affiliation(s)
- Fabio Henrique Mendonça Chaim
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Lívia Bitencourt Pascoal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Marina Moreira de Castro
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Bruna Biazon Palma
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Bruno Lima Rodrigues
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - João José Fagundes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Marciane Milanski
- Laboratory of Metabolic Disorders, School of Applied Sciences, University of Campinas (Unicamp), Limeira, São Paulo, Brazil
| | - Luiz Roberto Lopes
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil
| | - Raquel Franco Leal
- Inflammatory Bowel Disease Research Laboratory, Gastrocenter, Colorectal Surgery Unit, School of Medical Sciences, University of Campinas (Unicamp), Carlos Chagas Street, 420, Cidade Universitária Zeferino Vaz, Campinas, São Paulo, 13083-878, Brazil.
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Desterke C, Fu Y, Francés R, Mata-Garrido J. Metabolic Transcriptional Activation in Ulcerative Colitis Identified Through scRNA-seq Analysis. Genes (Basel) 2024; 15:1412. [PMID: 39596612 PMCID: PMC11593927 DOI: 10.3390/genes15111412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2024] [Revised: 10/25/2024] [Accepted: 10/28/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND Ulcerative colitis is a chronic inflammatory disease affecting the colon. During chronic inflammation of epithelial cells, lipid metabolism via pro-inflammatory eicosanoids is known to modify the immune response. METHODS Starting from the Mammalian Metabolic Database, the expression of metabolic enzymes was investigated in two independent cohorts from transcriptome datasets GSE38713 and GSE11223, which analyzed ulcerative colitis tissue samples from the digestive tract. RESULTS In the first cohort, 145 differentially expressed enzymes were identified as significantly regulated between ulcerative colitis tissues and normal controls. Overexpressed enzymes were selected to tune an Elastic Net model in the second cohort. Using the best parameters, the model achieved a prediction accuracy for ulcerative colitis with an area under the curve (AUC) of 0.79. Twenty-two metabolic enzymes were found to be commonly overexpressed in both independent cohorts, with decreasing Elastic Net predictive coefficients as follows: LIPG (3.98), PSAT1 (3.69), PGM3 (2.74), CD38 (2.28), BLVRA (1.99), CBR3 (1.94), NT5DC2 (1.76), PHGDH (1.71), GPX7 (1.58), CASP1 (1.56), ASRGL1 (1.4), SOD3 (1.25), CHST2 (0.965), CHST11 (0.95), KYNU (0.94), PLAG2G7 (0.92), SRM (0.87), PTGS2 (0.80), LPIN1 (0.47), ME1 (0.31), PTGDS (0.14), and ADA (0.13). Functional enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the main implications of these enzymes in cysteine and methionine metabolism (adjusted p-value = 0.01), arachidonic acid and prostaglandin metabolism (adjusted p-value = 0.01), and carbon metabolism (adjusted p-value = 0.04). A metabolic score based on the transcriptional activation of the validated twenty-two enzymes was found to be significantly greater in Ulcerative colitis samples compared to healthy donor samples (p-value = 1.52 × 10-8). CONCLUSIONS A metabolic expression score was established and reflects the implications of heterogeneous metabolic pathway deregulations in the digestive tract of patients with ulcerative colitis.
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Affiliation(s)
- Christophe Desterke
- Faculté de Médecine du Kremlin Bicêtre, University Paris-Sud, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France;
| | - Yuanji Fu
- INSERM, CNRS, Institut Necker Enfants Malades, Université Paris Cité, 75015 Paris, France;
| | - Raquel Francés
- Energy & Memory, Brain Plasticity Unit, CNRS, ESPCI Paris, PSL Research University, 75006 Paris, France;
| | - Jorge Mata-Garrido
- INSERM U993, Unité Organisation Nucléaire et Oncogenèse, Institut Pasteur, Université Paris Cité, 75006 Paris, France
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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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Mirzapour-Kouhdasht A, Garcia-Vaquero M, Huang JY. Algae-derived compounds: Bioactivity, allergenicity and technologies enhancing their values. BIORESOURCE TECHNOLOGY 2024; 406:130963. [PMID: 38876282 DOI: 10.1016/j.biortech.2024.130963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2024] [Revised: 06/02/2024] [Accepted: 06/11/2024] [Indexed: 06/16/2024]
Abstract
As a rapidly growing source of human nutrients, algae biosynthesize diverse metabolites which have promising bioactivities. However, the potential allergenicity of algal components hinder their widespread adoption. This review provides a comprehensive review of various macro and micronutrients derived from algal biomass, with particular focus on bioactive compounds, including peptides, polyphenols, carotenoids, omega-3 fatty acids and phycocyanins. The approaches used to produce algal bioactive compounds and their health benefits (antioxidant, antidiabetic, cardioprotective, anti-inflammatory and immunomodulatory) are summarised. This review particularly focuses on the state-of-the-art of precision fermentation, encapsulation, cold plasma, high-pressure processing, pulsed electric field, and subcritical water to reduce the allergenicity of algal compounds while increasing their bioactivity and bioavailability. By providing insights into current challenges of algae-derived compounds and opportunities for advancement, this review contributes to the ongoing discourse on maximizing their application potential in the food nutraceuticals, and pharmaceuticals industries.
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Affiliation(s)
- Armin Mirzapour-Kouhdasht
- Department of Chemical Sciences, SSPC, Science Foundation Ireland Research Centre for Pharmaceuticals, Bernal Institute, University of Limerick, Castletroy, Limerick, V94 T9PX, Ireland
| | - Marco Garcia-Vaquero
- School of Agriculture and Food Science, University College Dublin, Belfield, D04V1W8 Dublin, Ireland
| | - Jen-Yi Huang
- Department of Food Science, Purdue University, West Lafayette, IN 47907, USA; Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA; Environmental and Ecological Engineering, Purdue University, West Lafayette, IN 47907, USA.
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5
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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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Ben-Mustapha Y, Rekik R, Ben-Fradj MK, Serghini M, Sanhaji H, Ben-Ahmed M, Boubaker J, Feki M. Abnormal expression of oxylipins and related synthesizing/signaling pathways in inflammatory bowel diseases. Prostaglandins Leukot Essent Fatty Acids 2024; 202:102628. [PMID: 38991597 DOI: 10.1016/j.plefa.2024.102628] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2024] [Revised: 06/11/2024] [Accepted: 06/30/2024] [Indexed: 07/13/2024]
Abstract
We investigated selected oxylipins and related synthesizing/signaling pathways in 28 patients with Crohn's disease (CD), 19 patients with ulcerative colitis (UC), and 39 controls. Plasma and mucosal PUFA/oxylipin profiles were analyzed by LC-MS/MS. mRNA expression of 5, 12 and 15-lipooxygenases, FPR2/ALXR, FFAR4/GPR120, annexin A1, and interleukin-10 were analyzed by qRT-PCR. Oxylipin profile and related metabolic pathways were altered in both CD and UC patients. The patterns were characterized by increased prostaglandins, leukotrienes, and lipoxins and overexpression of 5-lipoxygenase, FPR2/ALXR, annexin A1, and interleukin-10 genes, but decreased n-3 PUFAs and 18-hydroxyeisapentaenoic acid. The gene of 15-lipoxygenase was under-expressed mainly in UC patients. CD and UC are associated with unbalanced n-6 and n-3 derivatives and pro-inflammatory and anti-inflammatory/pro-resolving mediators favoring the former compounds. The findings suggest that oxylipins engage in the pathophysiology of the diseases. Targeting oxylipin's metabolic pathways would be a promising therapy for inflammatory bowel diseases.
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Affiliation(s)
- Yamina Ben-Mustapha
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia; Laboratory of Biochemistry & LR99ES11, Rabta Hospital, Tunis 1007, Tunisia
| | - Raja Rekik
- Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 2092, Tunisia; Institute Pasteur of Tunis, Laboratory of Clinical Immunology, Tunis 1002, Tunisia
| | - Mohamed K Ben-Fradj
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Laboratory of Biochemistry & LR99ES11, Rabta Hospital, Tunis 1007, Tunisia
| | - Meriem Serghini
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Rabta Hospital, Service of Gastroenterology A, Tunis 1007, Tunisia
| | - Haifa Sanhaji
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Laboratory of Biochemistry & LR99ES11, Rabta Hospital, Tunis 1007, Tunisia
| | - Melika Ben-Ahmed
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Institute Pasteur of Tunis, Laboratory of Clinical Immunology, Tunis 1002, Tunisia
| | - Jalel Boubaker
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Rabta Hospital, Service of Gastroenterology A, Tunis 1007, Tunisia
| | - Moncef Feki
- Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia; Laboratory of Biochemistry & LR99ES11, Rabta Hospital, Tunis 1007, Tunisia.
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Magisetty J, Gadiraju B, Kondreddy V. Genomic analysis in the colon tissues of omega-3 fatty acid-treated rats identifies novel gene signatures implicated in ulcerative colitis. Int J Biol Macromol 2024; 258:128867. [PMID: 38123036 DOI: 10.1016/j.ijbiomac.2023.128867] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/11/2023] [Accepted: 12/15/2023] [Indexed: 12/23/2023]
Abstract
Several long-term intervention trials only studied the ex vivo immunological function to elucidate the beneficial mechanisms of n-3 polyunsaturated fatty acids (PUFA) in the ulcerative colitis (UC). An unbiased whole-transcriptome analysis would be more valuable to obtain a comprehensive understanding of the processes and genes regulated by n-3 PUFA in vivo. In this study, we have performed microarray analysis in the colon tissues of dextran sulfate sodium (DSS)-induced UC in rats supplemented with n-6 PUFA, n-3PUFA and long-chain n-3PUFA (LC-n3PUFA). We have identified the novel gene signatures previously not linked to colitis such as Etv3, Clec4d, CD180, CD72, Megf11, and Angptl4 which are most downregulated in both n-3PUFA and LC-n3PUFA groups compared to the n-6PUFA group. The most upregulated genes were Nr1i3, Nptx2, and Zfp810 in both n-3PUFA and LC-n3PUFA groups. The RT-PCR analysis confirmed similar results. Interestingly, LPS treatment in macrophages upregulated the Megf11, Etv3, CD180, and Angptl4, and correlated with increased secretion of cytokines. Gene silencing of Etv3, Megf11, and CD180 in rats using intravascular delivery of siRNA-lipoparticles attenuated the DSS-induced ulceration and mucosal damage. Thus, our genome-wide microarray analysis identified novel genes regulated by omega-3 PUFA and offers new drug targets that could prevent or reduce UC.
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Affiliation(s)
- Jhansi Magisetty
- Department of Biochemistry, Central Food Technological Research Institute, Mysore 570020, India
| | - Bhavani Gadiraju
- Center for Lipid Science & Technology, The Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India
| | - Vijay Kondreddy
- Center for Lipid Science & Technology, The Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500007, India.
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8
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Mao X, Shen J. Potential roles of enteric glial cells in Crohn's disease: A critical review. Cell Prolif 2024; 57:e13536. [PMID: 37551711 PMCID: PMC10771111 DOI: 10.1111/cpr.13536] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2023] [Revised: 07/23/2023] [Accepted: 07/26/2023] [Indexed: 08/09/2023] Open
Abstract
Enteric glial cells in the enteric nervous system are critical for the regulation of gastrointestinal homeostasis. Increasing evidence suggests two-way communication between enteric glial cells and both enteric neurons and immune cells. These interactions may be important in the pathogenesis of Crohn's disease (CD), a chronic relapsing disease characterized by a dysregulated immune response. Structural abnormalities in glial cells have been identified in CD. Furthermore, classical inflammatory pathways associated with CD (e.g., the nuclear factor kappa-B pathway) function in enteric glial cells. However, the specific mechanisms by which enteric glial cells contribute to CD have not been summarized in detail. In this review, we describe the possible roles of enteric glial cells in the pathogenesis of CD, including the roles of glia-immune interactions, neuronal modulation, neural plasticity, and barrier integrity. Additionally, the implications for the development of therapeutic strategies for CD based on enteric glial cell-mediated pathogenic processes are discussed.
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Affiliation(s)
- Xinyi Mao
- Division of Gastroenterology and HepatologyBaoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and HepatologyMinistry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive DiseaseShanghaiChina
| | - Jun Shen
- Division of Gastroenterology and HepatologyBaoshan Branch, Renji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and HepatologyMinistry of Health, Inflammatory Bowel Disease Research Center, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive DiseaseShanghaiChina
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Wang C, Han D, Feng X, Hu L, Wu J. Docosahexaenoic acid alleviates LPS-induced cytotoxicity in HL-1 cardiac cells via improving stress-induced mitochondrial fragmentation. Heliyon 2023; 9:e22465. [PMID: 38107281 PMCID: PMC10724566 DOI: 10.1016/j.heliyon.2023.e22465] [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: 07/02/2023] [Revised: 11/11/2023] [Accepted: 11/13/2023] [Indexed: 12/19/2023] Open
Abstract
Sepsis-induced cardiac injury is associated with oxidative stress and mitochondrial dysfunction. Docosahexaenoic acid (DHA), an essential omega-3 fatty acid, protects the injured myocardium by modulating mitochondrial dysfunction. We aimed to confirm whether the cardioprotective effect of DHA is mediated via the alleviation of mitochondrial fragmentation in lipopolysaccharide (LPS)-induced cardiomyopathy in vitro. We found that DHA improved cell viability and alleviated cardiac cell apoptosis by reducing lactate dehydrogenase (LDH) release, expression levels of Cleaved caspase-3, and Caspase 3 activity. DHA attenuated oxidative stress as evidenced by decreased ROS production and increased superoxide dismutase activity. In addition, DHA ameliorated mitochondrial dysfunction by modulating mitochondrial respiratory chain injury and mitochondrial fragmentation, especially decreasing the mitochondrial fission-related protein p-Drp1(ser 616) but no effects on Drp1, p-Drp1(ser 637), and mitochondrial fusion-related protein. Our data suggest that DHA conferred cardioprotection by alleviating oxidative stress-induced apoptosis, which may be associated with alleviation of stress-induced mitochondrial fragmentation.
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Affiliation(s)
- Chenyang Wang
- Department of Pain Management, Zhongnan Hospital of Wuhan University, Wuhan, 430071, Hubei, China
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Dong Han
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Xiaojing Feng
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Li Hu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
| | - Jing Wu
- Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China
- Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, China
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10
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Immune regulation of poly unsaturated fatty acids and free fatty acid receptor 4. J Nutr Biochem 2023; 112:109222. [PMID: 36402250 DOI: 10.1016/j.jnutbio.2022.109222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2021] [Revised: 09/24/2022] [Accepted: 11/10/2022] [Indexed: 11/19/2022]
Abstract
Fatty acid metabolism contributes to energy supply and plays an important role in regulating immunity. Free fatty acids (FFAs) bind to free fatty acid receptors (FFARs) on the cell surface and mediate effects through the intra-cellular FFAR signaling pathways. FFAR4, also known as G-protein coupled receptor 120 (GPR120), has been identified as the primary receptor of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). FFAR4 is a promising target for treating metabolic and inflammatory disorders due to its immune regulatory functions and the discovery of highly selective and efficient agonists. This review summarizes the reported immune regulatory functions of ω-3 PUFAs and FFAR4 in immune cells and immune-related diseases. We also speculate possible involvements of ω-3 PUFAs and FFAR4 in other types of inflammatory disorders.
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Jayapala HPS, Lim SY. N-3 Polyunsaturated Fatty Acids and Gut Microbiota. Comb Chem High Throughput Screen 2023; 26:892-905. [PMID: 35786331 DOI: 10.2174/1386207325666220701121025] [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: 11/25/2021] [Revised: 03/09/2022] [Accepted: 04/07/2022] [Indexed: 11/22/2022]
Abstract
For several decades, studies have reported that n-3 polyunsaturated fatty acids (PUFAs) play a beneficial role in cardiovascular, immune, cognitive, visual, mental and metabolic health. The mammalian intestine is colonized by microbiota, including bacteria, archaea, viruses, protozoans, and fungi. The composition of the gut microbiota is influenced by long-term dietary habits, disease-associated dysbiosis, and the use of antibiotics. Accumulating evidence suggests a relationship between n-3 PUFAs and the gut microbiota. N-3 PUFAs can alter the diversity and abundance of the gut microbiome, and gut microbiota can also affect the metabolism and absorption of n-3 PUFAs. Changes in the populations of certain gut microbiota can lead to negative effects on inflammation, obesity, and metabolic diseases. An imbalanced consumption of n-3/n-6 PUFAs may lead to gut microbial dysbiosis, in particular, a significant increase in the ratio of Firmicutes to Bacteroidetes, which eventually results in being overweight and obesity. N-3 PUFA deficiency disrupts the microbiota community in metabolic disorders. In addition, accumulating evidence indicates that the interplay between n-3 PUFAs, gut microbiota, and immune reactions helps to maintain the integrity of the intestinal wall and interacts with host immune cells. Supplementation with n-3 PUFAs may be an effective therapeutic measure to restore gut microbiota homeostasis and correct metabolic disturbances associated with modern chronic diseases. In particular, marine extracts from seaweed contain a considerable dry weight of lipids, including n-3 PUFAs such as eicosapentaenoic acid (EPA, C20: 5) and docosahexaenoic acid (DHA, C22: 6). This review describes how gut microbiota function in intestinal health, how n-3 PUFAs interact with the gut microbiota, and the potential of n-3 PUFAs to influence the gut-brain axis, acting through gut microbiota composition.
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Affiliation(s)
| | - Sun Young Lim
- Division of Convergence on Marine Science, Korea Maritime & Ocean University, Busan, 49112, Korea
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Heterologous expression of antimicrobial peptides S-thanatin and bovine lactoferricin in the marine diatom Phaeodactylum tricornutum enhances native antimicrobial activity against Gram-negative bacteria. ALGAL RES 2022. [DOI: 10.1016/j.algal.2022.102927] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Lao L, Yang G, Zhang A, Liu L, Guo Y, Lian L, Pan D, Wu Z. Anti-inflammation and gut microbiota regulation properties of fatty acids derived from fermented milk in mice with dextran sulfate sodium-induced colitis. J Dairy Sci 2022; 105:7865-7877. [PMID: 36055856 DOI: 10.3168/jds.2022-21877] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 06/01/2022] [Indexed: 01/03/2024]
Abstract
The by-products of milk fermentation by lactic acid bacteria provide potential health benefits to the balance of host intestinal microflora. In this study, the anti-inflammatory properties of fatty acids from monoculture-strain (Lactiplantibacillusplantarum A3) and multiple-strain (Streptococcus thermophilus, Lactobacillus bulgaricus, and L. plantarum A3 1:1:2) fermented milk were evaluated in a mouse model of dextran sulfate sodium-induced colitis, and the gut microbiota regulation properties of the fatty acids were also investigated. Results showed that fatty acids can attenuate the inflammatory response by inhibiting the expression of inflammatory factors IL-6 and tumor necrosis factor-α, and blocking the phosphorylation of the JNK in MAPK signal pathway. In addition, the relative abundance of the taxa Akkermansia and Lactobacillus were both enriched after the fatty acid intervention. This finding suggests that fatty acids from the milk fermentation with mixed lactic acid bacteria starters can reduce the severity of dextran sulfate sodium-induced colitis and enhance the abundance of the probiotics in the mice intestinal tract.
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Affiliation(s)
- Lifeng Lao
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China
| | - Guo Yang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China
| | - Ao Zhang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China
| | - Lianliang Liu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China
| | - Yuxing Guo
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, P. R. China
| | - Liwei Lian
- Ningbo Dairy Group, Ningbo, 315211, Zhejiang, China
| | - Daodong Pan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China
| | - Zhen Wu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang, School of Food and Pharmaceutical Sciences, Ningbo University, Ningbo, 315211, Zhejiang, P. R. China.
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14
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Gurke R, Bendes A, Bowes J, Koehm M, Twyman RM, Barton A, Elewaut D, Goodyear C, Hahnefeld L, Hillenbrand R, Hunter E, Ibberson M, Ioannidis V, Kugler S, Lories RJ, Resch E, Rüping S, Scholich K, Schwenk JM, Waddington JC, Whitfield P, Geisslinger G, FitzGerald O, Behrens F, Pennington SR. Omics and Multi-Omics Analysis for the Early Identification and Improved Outcome of Patients with Psoriatic Arthritis. Biomedicines 2022; 10:2387. [PMID: 36289648 PMCID: PMC9598654 DOI: 10.3390/biomedicines10102387] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 09/15/2022] [Accepted: 09/17/2022] [Indexed: 11/17/2022] Open
Abstract
The definitive diagnosis and early treatment of many immune-mediated inflammatory diseases (IMIDs) is hindered by variable and overlapping clinical manifestations. Psoriatic arthritis (PsA), which develops in ~30% of people with psoriasis, is a key example. This mixed-pattern IMID is apparent in entheseal and synovial musculoskeletal structures, but a definitive diagnosis often can only be made by clinical experts or when an extensive progressive disease state is apparent. As with other IMIDs, the detection of multimodal molecular biomarkers offers some hope for the early diagnosis of PsA and the initiation of effective management and treatment strategies. However, specific biomarkers are not yet available for PsA. The assessment of new markers by genomic and epigenomic profiling, or the analysis of blood and synovial fluid/tissue samples using proteomics, metabolomics and lipidomics, provides hope that complex molecular biomarker profiles could be developed to diagnose PsA. Importantly, the integration of these markers with high-throughput histology, imaging and standardized clinical assessment data provides an important opportunity to develop molecular profiles that could improve the diagnosis of PsA, predict its occurrence in cohorts of individuals with psoriasis, differentiate PsA from other IMIDs, and improve therapeutic responses. In this review, we consider the technologies that are currently deployed in the EU IMI2 project HIPPOCRATES to define biomarker profiles specific for PsA and discuss the advantages of combining multi-omics data to improve the outcome of PsA patients.
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Affiliation(s)
- Robert Gurke
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Annika Bendes
- Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 171 65 Solna, Sweden
| | - John Bowes
- NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WU, UK
- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK
| | - Michaela Koehm
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Division of Rheumatology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | | | - Anne Barton
- NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M13 9WU, UK
- Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK
| | - Dirk Elewaut
- VIB-UGent Center for Inflammation Research, Ghent University, 9052 Ghent, Belgium
| | - Carl Goodyear
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8QQ, UK
| | - Lisa Hahnefeld
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | | | - Ewan Hunter
- Oxford BioDynamics Limited, Oxford OX4 2JZ, UK
| | - Mark Ibberson
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
| | - Vassilios Ioannidis
- Vital-IT Group, SIB Swiss Institute of Bioinformatics, CH-1015 Lausanne, Switzerland
| | - Sabine Kugler
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer IAIS, Institute for Intelligent Analysis and Information Systems, Schloss Birlinghoven 1, 53757 Sankt Augustin, Germany
| | - Rik J. Lories
- Department of Development and Regeneration, KU Leuven, Skeletal Biology and Engineering Research Centre, P.O. Box 813 O&N, Herestraat 49, 3000 Leuven, Belgium
| | - Eduard Resch
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | - Stefan Rüping
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer IAIS, Institute for Intelligent Analysis and Information Systems, Schloss Birlinghoven 1, 53757 Sankt Augustin, Germany
| | - Klaus Scholich
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Jochen M. Schwenk
- Science for Life Laboratory, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH Royal Institute of Technology, 171 65 Solna, Sweden
| | - James C. Waddington
- Atturos Ltd., c/o UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland
| | - Phil Whitfield
- Glasgow Polyomics, College of Medical, Veterinary and Life Sciences, Garscube Campus, University of Glasgow, Glasgow G61 1QH, UK
| | - Gerd Geisslinger
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Pharmazentrum Frankfurt/ZAFES, Institute of Clinical Pharmacology, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
| | - Oliver FitzGerald
- UCD Conway Institute, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
| | - Frank Behrens
- Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Fraunhofer Cluster of Excellence Immune-Mediated Diseases CIMD, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
- Division of Rheumatology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany
| | - Stephen R. Pennington
- Atturos Ltd., c/o UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland
- UCD Conway Institute, School of Medicine, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
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15
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Suzuki T, Karayama M, Inoue Y, Hozumi H, Suzuki Y, Furuhashi K, Fujisawa T, Enomoto N, Nakamura Y, Inui N, Suda T. Associations of serum long-chain fatty acids with multiple organ involvement in patients with sarcoidosis. BMC Pulm Med 2022; 22:290. [PMID: 35902843 PMCID: PMC9335968 DOI: 10.1186/s12890-022-02084-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 07/19/2022] [Indexed: 11/17/2022] Open
Abstract
Background Fatty acids have diverse immunomodulatory functions and the potential to be associated with inflammatory responses in sarcoidosis. Methods The serum levels of multiple long-chain fatty acids (LCFAs) were compared between 63 patients with sarcoidosis and 38 healthy controls. The associations of LCFAs with clinical outcomes of sarcoidosis were also evaluated. Results The patients with sarcoidosis had significantly lower levels of n-3 poly-unsaturated fatty acids (PUFAs) (p < 0.001) and n-6 PUFAs (p < 0.001) than the healthy controls. However, there were no significant differences in the levels of saturated fatty acids (SFAs) and mono-unsaturated fatty acids (MUFAs) between the two groups. On multivariate logistic analysis, lower levels of n-3 PUFAs, n-6 PUFAs, and n-3/n-6 ratio were predictive of sarcoidosis. Among the patients with sarcoidosis, those with multiple organ involvement had significantly lower levels of n-3 PUFAs and n-3/n-6 ratio than those with single organ involvement. There were no significant differences in the levels of n-6 PUFAs, SFAs, and MUFAs between the patients with multiple and single organ involvement. On multivariate logistic analysis, lower levels of SFAs and n-3/n-6 ratio were predictive of multiple organ involvement. The levels of LCFAs had no significant association with radiographic stage or spontaneous remission. Conclusions Assessment of LCFA profiles may be useful for the diagnosis of sarcoidosis and evaluation of the disease activity. Supplementary Information The online version contains supplementary material available at 10.1186/s12890-022-02084-x.
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Affiliation(s)
- Takahito Suzuki
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Masato Karayama
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan. .,Department of Chemotherapy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.
| | - Yusuke Inoue
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan.,Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Hironao Hozumi
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Yuzo Suzuki
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Kazuki Furuhashi
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Tomoyuki Fujisawa
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Noriyuki Enomoto
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Yutaro Nakamura
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Naoki Inui
- Department of Clinical Pharmacology and Therapeutics, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu, 431-3192, Japan
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Kikut J, Drozd A, Mokrzycka M, Grzybowska-Chlebowczyk U, Ziętek M, Szczuko M. Are EPA and DHA Derivatives Involved in IBD Remission? J Clin Med 2022; 11:jcm11092388. [PMID: 35566515 PMCID: PMC9104684 DOI: 10.3390/jcm11092388] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2022] [Revised: 04/10/2022] [Accepted: 04/22/2022] [Indexed: 12/10/2022] Open
Abstract
Recently, an increase in the incidence of inflammatory bowel disease (IBD) has been observed among children and adolescents. Although the pathogenesis of IBD is not fully elucidated currently, actual research focuses on the occurrence of imbalance between pro- and anti-inflammatory molecules and future identification of the role of cytokines in IBD therapy. The purpose of this study was to compare the concentrations of eicosapentaenoic and docosahexaenoic acid derivatives during both phases of Crohn’s disease (CD) and ulcerative colitis (UC). The study included 64 adolescent patients with CD (n = 34) and UC (n = 30) aged 13.76 ± 2.69 and 14.15 ± 3.31, respectively. Biochemical analysis was performed on a liquid chromatography apparatus. A statistically significant lower concentration of resolvin E1 (RvE1) was observed in the CD group relative to UC. In the active phase of CD, a statistically significantly higher concentration of protectin DX (PDX) was observed relative to remission CD. Comparing the active phase of both diseases, a statistically significantly higher concentration of resolvin E1 (RvE1) was observed in UC relative to CD. Comparing the remission phase of both diseases showed statistically significantly higher PDX levels in CD relative to UC. Our study adds to the knowledge on the involvement of anti-inflammatory lipid mediators in both IBD entities. In conclusion, it seems that the marker differentiating both disease entities in the active phase may be RvE1, while in the remission phase, PDX. In CD remission, the greatest involvement was observed towards PDX, whereas in UC, MaR1, RvE1 and 18RS-HEPE seem to be the most involved in remission.
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Affiliation(s)
- Justyna Kikut
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (J.K.); (A.D.)
- Department of Pediatrics, Hemato-Oncology and Pediatric Gastroenterology, Independent Public Clinical Hospital No.1, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland;
| | - Arleta Drozd
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (J.K.); (A.D.)
| | - Małgorzata Mokrzycka
- Department of Pediatrics, Hemato-Oncology and Pediatric Gastroenterology, Independent Public Clinical Hospital No.1, Pomeranian Medical University in Szczecin, 71-252 Szczecin, Poland;
| | - Urszula Grzybowska-Chlebowczyk
- Department of Pediatrics, Faculty of Medical Sciences in Katowice, Medical University of Silesia in Katowice, 40-752 Katowice, Poland;
| | - Maciej Ziętek
- Department of Perinatology, Obstetrics and Gynecology, Pomeranian Medical University in Szczecin, 72-010 Police, Poland;
| | - Małgorzata Szczuko
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University in Szczecin, 71-460 Szczecin, Poland; (J.K.); (A.D.)
- Correspondence:
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de Oliveira Galassi T, Fernandes PF, Salgado ASI, Cidral-Filho FJ, Piovezan AP, Lüdtke DD, Mack JM, Weber KA, Reed WR, Bobinski F, Martins DF. Preventive Supplementation of Omega-3 Reduces Pain and Pro-inflammatory Cytokines in a Mouse Model of Complex Regional Pain Syndrome Type I. Front Integr Neurosci 2022; 16:840249. [PMID: 35431823 PMCID: PMC9005766 DOI: 10.3389/fnint.2022.840249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 03/04/2022] [Indexed: 01/14/2023] Open
Abstract
Complex regional pain syndrome type I (CRPS-I) is a condition that responds poorly to treatments. The role of omega-3 fatty acids in the treatment of inflammatory disorders is well described in the literature; however, few studies have evaluated its therapeutic benefits in different types of pain. We evaluated the potential antihyperalgesic and anti-inflammatory effects of preventive omega-3 supplementation in an animal model of CRPS-I. In experiment 1, Swiss female mice were supplemented for 30 days with omega-3 before the induction of the CRPS-I model and 14 days after. Mechanical hyperalgesia was evaluated at baseline and from the 4th to the 14th day after CPRS-I induction along with open field locomotor activity after 30 days of supplementation. In experiment 2, Swiss female mice were supplemented for 30 days with omega-3 and then subjected to the CRPS-I model. Twenty-four hours later the animals were euthanized, and tissue samples of the spinal cord and right posterior paw muscle were taken to measure pro-inflammatory cytokine TNF and IL-1β concentrations. Omega-3 supplementation produced antihyperalgesic and anti-inflammatory effects, as well as reducing pro-inflammatory cytokine concentrations, without altering the animals’ locomotion. No open field locomotor changes were found. The 30-day supplementation at the tested dose was effective in the CRPS-I model.
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Affiliation(s)
- Taynah de Oliveira Galassi
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Paula Franson Fernandes
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Afonso Shiguemi Inoue Salgado
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
- Natural Quanta Wellness Center, Windermere, FL, United States
| | - Francisco José Cidral-Filho
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Anna Paula Piovezan
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Daniela Dero Lüdtke
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Josiel Mileno Mack
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
- Department of Medical Clinic, Graduate Program in Medical Sciences, Federal University of Santa Catarina - UFSC, Florianopolis, Brazil
| | - Kenneth A. Weber
- Division of Pain Medicine, Stanford School of Medicine, Palo Alto, CA, United States
| | - William R. Reed
- Department of Physical Therapy, University of Alabama at Birmingham, Birmingham, AL, United States
| | - Franciane Bobinski
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
| | - Daniel F. Martins
- Experimental Neuroscience Laboratory (LaNEx), Postgraduate Program in Health Sciences, University of Southern Santa Catarina - UNISUL, Palhoça, Brazil
- *Correspondence: Daniel F. Martins,
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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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19
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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: 9] [Impact Index Per Article: 2.3] [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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20
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Derada Troletti C, Enzmann G, Chiurchiù V, Kamermans A, Tietz SM, Norris PC, Jahromi NH, Leuti A, van der Pol SMA, Schouten M, Serhan CN, de Vries HE, Engelhardt B, Kooij G. Pro-resolving lipid mediator lipoxin A 4 attenuates neuro-inflammation by modulating T cell responses and modifies the spinal cord lipidome. Cell Rep 2021; 35:109201. [PMID: 34077725 PMCID: PMC8491454 DOI: 10.1016/j.celrep.2021.109201] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2019] [Revised: 06/30/2020] [Accepted: 05/11/2021] [Indexed: 02/06/2023] Open
Abstract
The chronic neuro-inflammatory character of multiple sclerosis (MS) suggests that the natural process to resolve inflammation is impaired. This protective process is orchestrated by specialized pro-resolving lipid mediators (SPMs), but to date, the role of SPMs in MS remains largely unknown. Here, we provide in vivo evidence that treatment with the SPM lipoxin A4 (LXA4) ameliorates clinical symptoms of experimental autoimmune encephalomyelitis (EAE) and inhibits CD4+ and CD8+ T cell infiltration into the central nervous system (CNS). Moreover, we show that LXA4 potently reduces encephalitogenic Th1 and Th17 effector functions, both in vivo and in isolated human T cells from healthy donors and patients with relapsing-remitting MS. Finally, we demonstrate that LXA4 affects the spinal cord lipidome by significantly reducing the levels of pro-inflammatory lipid mediators during EAE. Collectively, our findings provide mechanistic insight into LXA4-mediated amelioration of neuro-inflammation and highlight the potential clinical application of LXA4 for MS.
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Affiliation(s)
- Claudio Derada Troletti
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands; Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland
| | - Gaby Enzmann
- Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland
| | - Valerio Chiurchiù
- Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy; Laboratory of Resolution of Neuroinflammation, European Center for Brain Research, IRCCS Santa Lucia Foundation, 00179 Rome, Italy
| | - Alwin Kamermans
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands
| | | | - Paul C Norris
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | | | - Alessandro Leuti
- Department of Medicine, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128 Rome, Italy
| | - Susanne M A van der Pol
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands
| | - Marijn Schouten
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Helga E de Vries
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands
| | - Britta Engelhardt
- Theodor Kocher Institute, University of Bern, 3012 Bern, Switzerland
| | - Gijs Kooij
- MS Center Amsterdam, Department of Molecular Cell Biology and Immunology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, De Boelelaan 1117, 1081 Amsterdam, the Netherlands; Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
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21
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Ripon MAR, Bhowmik DR, Amin MT, Hossain MS. Role of arachidonic cascade in COVID-19 infection: A review. Prostaglandins Other Lipid Mediat 2021; 154:106539. [PMID: 33592322 PMCID: PMC7882227 DOI: 10.1016/j.prostaglandins.2021.106539] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 02/01/2021] [Accepted: 02/08/2021] [Indexed: 02/06/2023]
Abstract
The World Health Organization has described the 2019 Coronavirus disease caused by an influenza-like virus called SARS-CoV-2 as a pandemic. Millions of people worldwide are already infected by this virus, and severe infection causes hyper inflammation, thus disrupting lung function, exacerbating breath difficulties, and death. Various inflammatory mediators bio-synthesized through the arachidonic acid pathway play roles in developing cytokine storms, injuring virus-infected cells. Since pro-inflammatory eicosanoids, including prostaglandins, and leukotrienes, are key brokers for physiological processes such as inflammation, fever, allergy, and pain but, their function in COVID-19 is not well defined. This study addresses eicosanoid's crucial role through the arachidonic pathway in inflammatory cascading and recommends using bioactive lipids, NSAIDs, steroids, cell phospholipase A2 (cPLA2) inhibitors, and specialized pro-resolving mediators (SPMs) to treat COVID-19 disease. The role of soluble epoxide hydrolase inhibitors (SEHIs) in promoting the activity of epoxyeicosatrienoic acids (EETs) and 17-hydroxide-docosahexaenoic acid (17-HDHA) is also discussed. Additional research that assesses the eicosanoid profile in COVID-19 patients or preclinical models generates novel insights into coronavirus-host interaction and inflammation regulation.
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Affiliation(s)
- Md Abdur Rahman Ripon
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Dipty Rani Bhowmik
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Mohammad Tohidul Amin
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh
| | - Mohammad Salim Hossain
- Department of Pharmacy, Noakhali Science and Technology University, Noakhali 3814, Bangladesh.
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22
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Kolobarić N, Drenjančević I, Matić A, Šušnjara P, Mihaljević Z, Mihalj M. Dietary Intake of n-3 PUFA-Enriched Hen Eggs Changes Inflammatory Markers' Concentration and Treg/Th17 Cells Distribution in Blood of Young Healthy Adults-A Randomised Study. Nutrients 2021; 13:nu13061851. [PMID: 34071714 PMCID: PMC8229500 DOI: 10.3390/nu13061851] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2021] [Revised: 05/25/2021] [Accepted: 05/26/2021] [Indexed: 12/28/2022] Open
Abstract
In the present study, we aimed to determine the effects of n-3 polyunsaturated acid (PUFA) supplementation (~1053 mg/per day), i.e., α-linolenic (~230 mg), eicosapentaenoic (~15 mg), and docosahexaenoic acid (~105 mg), through hen eggs, on pro- and anti-inflammatory parameters in healthy individuals (23.8 ± 2.57 years old). Here, we demonstrate differential effects of regular hen eggs (N = 21; W/M = 10/11) and n-3 PUFA-enriched hen eggs (N = 19; W/M = 10/9) consumption on the serum levels of lipid mediators, representation of peripheral T helper cell subsets (recently activated T-helper cells, nTreg, Th17 and non-Th17-IL-17A secreting T-helper lymphocytes) and their functional capacity for cytokine secretion. Both diets significantly altered systemic levels of pro-inflammatory and inflammation resolving lipid mediators; however, only the n-3 PUFAs group showed a significant shift towards anti-inflammatory prostanoids and increased levels of pro-resolving oxylipins. Both study groups showed reduced frequencies of peripheral nTreg lymphocytes and decreased rates of peripheral Th17 cells. Their functional capacity for cytokine secretion was significantly altered only in the n-3 PUFAs group in terms of increased transforming growth factor β-1 and reduced interleukin 6 secretion. Diet supplemented with n-3 PUFAs alters immune response towards inflammation resolving conditions through effects on lipid mediators and cytokine secretion by T lymphocytes in human model without underlying comorbidities.
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Affiliation(s)
- Nikolina Kolobarić
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Ines Drenjančević
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Anita Matić
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Petar Šušnjara
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Zrinka Mihaljević
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
| | - Martina Mihalj
- Department of Physiology and Immunology, Faculty of Medicine Osijek, Josip Juraj Strossmayer University of Osijek, J. Huttlera 4, 31000 Osijek, Croatia; (N.K.); (I.D.); (A.M.); (P.Š.); (Z.M.)
- Scientific Center of Excellence for Personalized Health Care, Josip Juraj Strossmayer University of Osijek, Trg Svetog Trojstva 3, 31000 Osijek, Croatia
- Department of Dermatology and Venereology, Osijek University Hospital, J. Huttlera 4, 31000 Osijek, Croatia
- Correspondence: ; Tel.: +385-3151-2800
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23
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Basson AR, Chen C, Sagl F, Trotter A, Bederman I, Gomez-Nguyen A, Sundrud MS, Ilic S, Cominelli F, Rodriguez-Palacios A. Regulation of Intestinal Inflammation by Dietary Fats. Front Immunol 2021; 11:604989. [PMID: 33603741 PMCID: PMC7884479 DOI: 10.3389/fimmu.2020.604989] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Accepted: 12/11/2020] [Indexed: 12/12/2022] Open
Abstract
With the epidemic of human obesity, dietary fats have increasingly become a focal point of biomedical research. Epidemiological studies indicate that high-fat diets (HFDs), especially those rich in long-chain saturated fatty acids (e.g., Western Diet, National Health Examination survey; NHANES 'What We Eat in America' report) have multi-organ pro-inflammatory effects. Experimental studies have confirmed some of these disease associations, and have begun to elaborate mechanisms of disease induction. However, many of the observed effects from epidemiological studies appear to be an over-simplification of the mechanistic complexity that depends on dynamic interactions between the host, the particular fatty acid, and the rather personalized genetics and variability of the gut microbiota. Of interest, experimental studies have shown that certain saturated fats (e.g., lauric and myristic fatty acid-rich coconut oil) could exert the opposite effect; that is, desirable anti-inflammatory and protective mechanisms promoting gut health by unanticipated pathways. Owing to the experimental advantages of laboratory animals for the study of mechanisms under well-controlled dietary settings, we focus this review on the current understanding of how dietary fatty acids impact intestinal biology. We center this discussion on studies from mice and rats, with validation in cell culture systems or human studies. We provide a scoping overview of the most studied diseases mechanisms associated with the induction or prevention of Inflammatory Bowel Disease in rodent models relevant to Crohn's Disease and Ulcerative Colitis after feeding either high-fat diet (HFD) or feed containing specific fatty acid or other target dietary molecule. Finally, we provide a general outlook on areas that have been largely or scarcely studied, and assess the effects of HFDs on acute and chronic forms of intestinal inflammation.
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Affiliation(s)
- Abigail R. Basson
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Christy Chen
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Filip Sagl
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Ashley Trotter
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Department of Hospital Medicine, Pritzker School of Medicine, NorthShore University Health System, Chicago, IL, United States
| | - Ilya Bederman
- Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH, United States
| | - Adrian Gomez-Nguyen
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
| | - Mark S. Sundrud
- Department of Immunology and Microbiology, The Scripps Research Institute, Jupiter, FL, United States
| | - Sanja Ilic
- Department of Human Sciences, Human Nutrition, College of Education and Human Ecology, The Ohio State University, Columbus, OH, United States
| | - Fabio Cominelli
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
| | - Alex Rodriguez-Palacios
- Division of Gastroenterology and Liver Diseases, School of Medicine, Case Western Reserve University School of Medicine, Cleveland, OH, United States
- Digestive Health Research Institute, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Cleveland Digestive Diseases Research Core, School of Medicine, Case Western Reserve University, Cleveland, OH, United States
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
- University Hospitals Research and Education Institute, University Hospitals Cleveland Medical Center, Cleveland, OH, United States
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24
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Ma QL, Zhu C, Morselli M, Su T, Pelligrini M, Lu Z, Jones M, Denver P, Castro D, Gu X, Relampagos F, Caoili K, Teter B, Frautschy SA, Cole GM. The Novel Omega-6 Fatty Acid Docosapentaenoic Acid Positively Modulates Brain Innate Immune Response for Resolving Neuroinflammation at Early and Late Stages of Humanized APOE-Based Alzheimer's Disease Models. Front Immunol 2020; 11:558036. [PMID: 33178186 PMCID: PMC7596305 DOI: 10.3389/fimmu.2020.558036] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 08/27/2020] [Indexed: 12/21/2022] Open
Abstract
Neuroinflammation plays a crucial role in the development and progression of Alzheimer's disease (AD), in which activated microglia are found to be associated with neurodegeneration. However, there is limited evidence showing how neuroinflammation and activated microglia are directly linked to neurodegeneration in vivo. Besides, there are currently no effective anti-inflammatory drugs for AD. In this study, we report on an effective anti-inflammatory lipid, linoleic acid (LA) metabolite docosapentaenoic acid (DPAn-6) treatment of aged humanized EFAD mice with advanced AD pathology. We also report the associations of neuroinflammatory and/or activated microglial markers with neurodegeneration in vivo. First, we found that dietary LA reduced proinflammatory cytokines of IL1-β, IL-6, as well as mRNA expression of COX2 toward resolving neuroinflammation with an increase of IL-10 in adult AD models E3FAD and E4FAD mice. Brain fatty acid assays showed a five to six-fold increase in DPAn-6 by dietary LA, especially more in E4FAD mice, when compared to standard diet. Thus, we tested DPAn-6 in aged E4FAD mice. After DPAn-6 was administered to the E4FAD mice by oral gavage for three weeks, we found that DPAn-6 reduced microgliosis and mRNA expressions of inflammatory, microglial, and caspase markers. Further, DPAn-6 increased mRNA expressions of ADCYAP1, VGF, and neuronal pentraxin 2 in parallel, all of which were inversely correlated with inflammatory and microglial markers. Finally, both LA and DPAn-6 directly reduced mRNA expression of COX2 in amyloid-beta42 oligomer-challenged BV2 microglial cells. Together, these data indicated that DPAn-6 modulated neuroinflammatory responses toward resolution and improvement of neurodegeneration in the late stages of AD models.
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Affiliation(s)
- Qiu-Lan Ma
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Cansheng Zhu
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States.,Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Marco Morselli
- Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, United States.,Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA, United States.,Institute for Quantitative and Computational Biology, University of California, Los Angeles, Los Angeles, CA, United States
| | - Trent Su
- Institute for Quantitative and Computational Biology, University of California, Los Angeles, Los Angeles, CA, United States.,Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, CA, United States
| | - Matteo Pelligrini
- Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA, United States.,Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA, United States.,Institute for Quantitative and Computational Biology, University of California, Los Angeles, Los Angeles, CA, United States.,Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, United States
| | - Zhengqi Lu
- Department of Neurology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China
| | - Mychica Jones
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Paul Denver
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Daniel Castro
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Xuelin Gu
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Frances Relampagos
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Kaitlin Caoili
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Bruce Teter
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States
| | - Sally A Frautschy
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States.,Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
| | - Gregory M Cole
- Department of Neurology, University of California, Los Angeles, Los Angeles, CA, United States.,Geriatric Research and Clinical Center, Greater Los Angeles Veterans Affairs Healthcare System, West Los Angeles VA Medical Center, Los Angeles, CA, United States.,Department of Medicine, University of California, Los Angeles, Los Angeles, CA, United States
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25
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Ho GT, Cartwright JA, Thompson EJ, Bain CC, Rossi AG. Resolution of Inflammation and Gut Repair in IBD: Translational Steps Towards Complete Mucosal Healing. Inflamm Bowel Dis 2020; 26:1131-1143. [PMID: 32232386 PMCID: PMC7365805 DOI: 10.1093/ibd/izaa045] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Indexed: 02/07/2023]
Abstract
Despite significant recent therapeutic advances, complete mucosal healing remains a difficult treatment target for many patients with inflammatory bowel diseases (IBD) to achieve. Our review focuses on the translational concept of promoting resolution of inflammation and repair as a necessary adjunctive step to reach this goal. We explore the roles of inflammatory cell apoptosis and efferocytosis to promote resolution, the new knowledge of gut monocyte-macrophage populations and their secreted prorepair mediators, and the processes of gut epithelial repair and regeneration to bridge this gap. We discuss the need and rationale for this vision and the tangible steps toward integrating proresolution therapies in IBD.
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Affiliation(s)
- Gwo-tzer Ho
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom,Address correspondence to: Gwo-tzer Ho, FRCP, PhD, Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh, EH16 4TJ, Scotland, United Kingdom ()
| | - Jennifer A Cartwright
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Emily J Thompson
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Calum C Bain
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
| | - Adriano G Rossi
- Edinburgh IBD Science Unit, Centre for Inflammation Research, Queen’s Medical Research Unit, University of Edinburgh, Scotland, United Kingdom
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26
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Leung HH, Leung KS, Durand T, Galano JM, Lee JCY. Measurement of Enzymatic and Nonenzymatic Polyunsaturated Fatty Acid Oxidation Products in Plasma and Urine of Macular Degeneration Using LC-QTOF-MS/MS. Lipids 2020; 55:693-706. [PMID: 32602621 DOI: 10.1002/lipd.12264] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2019] [Revised: 05/21/2020] [Accepted: 05/22/2020] [Indexed: 11/09/2022]
Abstract
Oxidized polyunsaturated fatty acids (PUFA) are associated to pathogenesis of diseases including cardiovascular and neurodegeneration. The novel products are not only biomarkers but also lipid mediators in gene regulation and signaling pathways. Herein, simultaneous quantitation of 28 products derived from nonenzymatic and enzymatic oxidation of PUFA i.e. 5-, 15-F2t -isoprostanes, 7-, 17-F2t -dihomo-isoprostanes, 7-, 17-F2t -dihomo-isofurans, 5-, 8-, 18-F3t -isoprostanes, 4-, 10-, 13-, 14-, 20-F4t -neuroprostanes, 5-, 8-, 9-, 11-,12-, 15-, 20-HETE, 4-, 7-, 11-, 14-, 17-HDHA, RvE1, and NPD1 using LC-(ESI)-QTOF-MS/MS was developed. These products were measurable in a single sample and the analytical time was relative short (~15 min). Furthermore, we showed that the use of internal standards is a requisite to normalize matrix effects and preparation loss for the quantitation. Validation assays indicated the method to be robust for plasma and mid-stream urine sample analysis in particular from those of age-related macular degeneration subjects, where the accuracy of quantitation displayed good repeatability.
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Affiliation(s)
- Ho Hang Leung
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Pokfulam Road, Hong Kong, Hong Kong SAR
| | - Kin Sum Leung
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Pokfulam Road, Hong Kong, Hong Kong SAR
| | - Thierry Durand
- Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, ENSCM, Université de Montpellier, 5 Av. Charles Flahault, Montpellier, Cedex 05, F34093, France
| | - Jean-Marie Galano
- Institut des Biomolécules Max Mousseron, UMR 5247 CNRS, ENSCM, Université de Montpellier, 5 Av. Charles Flahault, Montpellier, Cedex 05, F34093, France
| | - Jetty Chung-Yung Lee
- School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Pokfulam Road, Hong Kong, Hong Kong SAR
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27
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Mariqueo TA, Zúñiga-Hernández J. Omega-3 derivatives, specialized pro-resolving mediators: Promising therapeutic tools for the treatment of pain in chronic liver disease. Prostaglandins Leukot Essent Fatty Acids 2020; 158:102095. [PMID: 32450460 DOI: 10.1016/j.plefa.2020.102095] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 02/02/2020] [Accepted: 03/23/2020] [Indexed: 12/12/2022]
Abstract
The main causes of liver injury are associated with inflammation and permanent damage. They can cause chronic liver disease (CLD), which is mainly related to viral hepatitis, alcohol consumption and non-alcoholic steatohepatitis, leading to fibrosis, cirrhosis and hepatocellular carcinoma. These conditions prevent the liver from working normally and make it begin to fail, which in turn may prompt a liver transplant. CLD and cirrhosis are the eleventh cause of death worldwide. At present, there are no approved pharmacological treatments to prevent, treat or resolve liver fibrosis. The prevalence of pain in the hepatic disease is elevated with ranges between 30% and 40%. Most of the pain drugs require hepatic function; therefore, the suitable control of pain is still a clinical challenge. Specialized pro-resolving mediators (SPM): lipoxins, resolvins, protectins and maresins, are potent endogenous molecules (nM concentrations) that modulate inflammatory body responses by reducing neutrophil infiltration, macrophage activity and pain sensitization. SPM have anti-inflammatory properties, stimulate tissue resolution, repair and regeneration, and exhibit anti-nociceptive actions. Furthermore, SPM were tried on different cellular, animal models and human observational data of liver injury, improving the pathogenesis of inflammation and fibrosis. In the present work, we will describe recent evidence that suggests that SPM can be used as a therapeutic option for CLD. Additionally, we will examine the role of SPM in the control of pain in pathologies associated with liver injury.
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Affiliation(s)
- T A Mariqueo
- Centro de Investigaciones Medicas, Escuela de Medicina, Universidad de Talca, Talca, Chile
| | - J Zúñiga-Hernández
- Centro de Investigaciones Medicas, Escuela de Medicina, Universidad de Talca, Talca, Chile.
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28
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Yamazaki A, Nakamura T, Miyabe-Nishiwaki T, Hirata A, Inoue R, Kobayashi K, Miyazaki Y, Hamasaki Y, Ishigami A, Nagata N, Kaneko A, Koizumi M, Ohta H, Okano HJ, Murata T. The profile of lipid metabolites in urine of marmoset wasting syndrome. PLoS One 2020; 15:e0234634. [PMID: 32574169 PMCID: PMC7310677 DOI: 10.1371/journal.pone.0234634] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2020] [Accepted: 05/29/2020] [Indexed: 01/25/2023] Open
Abstract
Marmoset wasting syndrome (MWS) is clinically characterized by progressive weight loss. Although morbidity and mortality of MWS are relatively high in captive marmosets, its causes remain unknown. Lipid mediators are bioactive metabolites which are produced from polyunsaturated fatty acids, such as arachidonic acid (AA) and eicosapentaenoic acid. These lipid metabolites regulate a wide range of inflammatory responses and they are excreted into the urine. As urinary lipid profiles reflect systemic inflammatory conditions, we comprehensively measured the levels of 141 types of lipid metabolites in the urines obtained from healthy common marmoset (Callithrix jacchus) (N = 7) or marmosets with MWS (N = 7). We found that 41 types of metabolites were detected in all urine samples of both groups. Among them, AA-derived metabolites accounted for 63% (26/41 types) of all detected metabolites. Notably, the levels of AA-derived prostaglandin (PG) E2, PGF2α, thromboxane (TX) B2 and F2-isoprostanes significantly increased in the urine samples of marmosets with MWS. In this study, we found some urinary lipid metabolites which may be involved in the development of MWS. Although the cause of MWS remains unclear, our findings may provide some insight into understanding the mechanisms of development of MWS.
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Affiliation(s)
- Arisa Yamazaki
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Tatsuro Nakamura
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | | | - Akihiro Hirata
- Department of Animal Experiment, Life Science Research Center, Gifu University, Gifu, Japan
| | - Rikako Inoue
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Koji Kobayashi
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Yusuke Miyazaki
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Yuta Hamasaki
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Akiyo Ishigami
- Department of Primate Research Institute, Kyoto University, Aichi, Japan
| | - Nanae Nagata
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
| | - Akihisa Kaneko
- Department of Primate Research Institute, Kyoto University, Aichi, Japan
| | - Makoto Koizumi
- Department of Laboratory Animal Facilities, The Jikei University School of Medicine, Tokyo, Japan
| | - Hiroki Ohta
- Department of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Hirotaka James Okano
- Department of Regenerative Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Takahisa Murata
- Department of Animal Radiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan
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29
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Avanoǧlu Güler A, Rossi FW, Bellando-Randone S, Prevete N, Tufan A, Manetti M, de Paulis A, Matucci-Cerinic M. The Role of Endogenous Eicosapentaenoic Acid and Docosahexaenoic Acid-Derived Resolvins in Systemic Sclerosis. Front Immunol 2020; 11:1249. [PMID: 32636845 PMCID: PMC7318896 DOI: 10.3389/fimmu.2020.01249] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2020] [Accepted: 05/18/2020] [Indexed: 12/19/2022] Open
Abstract
Resolvins, the member of specialized pro-resolving mediators, are produced from omega-3 polyunsaturated fatty acids as a response to an acute inflammatory process in that termination and resolution of inflammation. In the acute inflammation, these lipid mediators limit polymorphonuclear cells infiltration, proinflammatory cytokine production; promote efferocytosis, and regulate several cell types being important roles in innate and adaptive immunity. Any dysregulation or defect of the resolution phase result in prolonged, persistent inflammation and eventually fibrosis. Resolvins are implicated in the development of various chronic autoimmune diseases. Systemic sclerosis (SSc) is a very complicated, chronic autoimmune disorder proceeding with vasculopathy, inflammation, and fibrosis. Dysregulation of innate and adaptive immunity is another important contributing factor in the pathogenesis of SSc. In this review, we will focus on the different roles of this new family of lipid mediators, characterized by the ability to prevent the spread of inflammation and its chronicity in various ways and how they can control the development of fibrotic diseases like SSc.
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Affiliation(s)
- Aslıhan Avanoǧlu Güler
- Department of Experimental and Clinical Medicine, University of Florence and Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
- Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Francesca Wanda Rossi
- Department of Internal Medicine, Clinical Immunology and Rheumatology, University of Naples Federico II, Naples, Italy
| | - Silvia Bellando-Randone
- Department of Experimental and Clinical Medicine, University of Florence and Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
| | - Nella Prevete
- Department of Internal Medicine, Clinical Immunology and Rheumatology, University of Naples Federico II, Naples, Italy
| | - Abdurrahman Tufan
- Department of Internal Medicine, Division of Rheumatology, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Mirko Manetti
- Department of Experimental and Clinical Medicine, University of Florence and Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
| | - Amato de Paulis
- Department of Internal Medicine, Clinical Immunology and Rheumatology, University of Naples Federico II, Naples, Italy
| | - Marco Matucci-Cerinic
- Department of Experimental and Clinical Medicine, University of Florence and Department of Geriatric Medicine, Division of Rheumatology AOUC, Florence, Italy
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30
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Zahoor I, Giri S. Specialized Pro-Resolving Lipid Mediators: Emerging Therapeutic Candidates for Multiple Sclerosis. Clin Rev Allergy Immunol 2020; 60:147-163. [PMID: 32495237 DOI: 10.1007/s12016-020-08796-4] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Multiple sclerosis (MS) is a neuroinflammatory disease in which unresolved and uncontrolled inflammation disrupts normal cellular homeostasis and leads to a pathological disease state. It has long been recognized that endogenously derived metabolic by-products of omega fatty acids, known as specialized pro-resolving lipid mediators (SPMs), are instrumental in resolving the pathologic inflammation. However, there is minimal data available on the functional status of SPMs in MS, despite the fact that MS presents a classical model of chronic inflammation. Studies to date indicate that dysfunction of the SPM biosynthetic pathway is responsible for their altered levels in patient-derived biofluids, which contributes to heightened inflammation and disease severity. Collectively, current findings suggest the contentious role of SPMs in MS due to variable outcomes in biological matrices across studies conducted so far, which could, in part, also be attributed to differences in population characteristics. It seems that SPMs have neuroprotective action on MS by exerting proresolving effects on brain microglia in its preclinical model; however, there are no reports demonstrating the direct effect of SPMs on oligodendrocytes or neurons. This reveals that "one size does not fit all" notion holds significance for MS in terms of the status of SPMs in other inflammatory conditions. The lack of clarity served as the impetus for this review, which is the first of its kind to summarize the relevant data regarding the role of SPMs in MS and the potential to target them for biomarker development and future alternative therapies for this disease. Understanding the mechanisms behind biological actions of SPMs as resolution mediators may prevent or even cure MS and other neurodegenerative pathologies.
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Affiliation(s)
- Insha Zahoor
- Department of Neurology, Research Division, Education & Research Building, Henry Ford Hospital, Room 4023, 2799 W Grand Blvd, Detroit, MI, 48202, USA.
| | - Shailendra Giri
- Department of Neurology, Research Division, Education & Research Building, Henry Ford Hospital, Room 4051, 2799 W Grand Blvd, Detroit, MI, 48202, USA.
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31
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Wasserman AH, Venkatesan M, Aguirre A. Bioactive Lipid Signaling in Cardiovascular Disease, Development, and Regeneration. Cells 2020; 9:E1391. [PMID: 32503253 PMCID: PMC7349721 DOI: 10.3390/cells9061391] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 05/23/2020] [Accepted: 06/01/2020] [Indexed: 12/13/2022] Open
Abstract
Cardiovascular disease (CVD) remains a leading cause of death globally. Understanding and characterizing the biochemical context of the cardiovascular system in health and disease is a necessary preliminary step for developing novel therapeutic strategies aimed at restoring cardiovascular function. Bioactive lipids are a class of dietary-dependent, chemically heterogeneous lipids with potent biological signaling functions. They have been intensively studied for their roles in immunity, inflammation, and reproduction, among others. Recent advances in liquid chromatography-mass spectrometry techniques have revealed a staggering number of novel bioactive lipids, most of them unknown or very poorly characterized in a biological context. Some of these new bioactive lipids play important roles in cardiovascular biology, including development, inflammation, regeneration, stem cell differentiation, and regulation of cell proliferation. Identifying the lipid signaling pathways underlying these effects and uncovering their novel biological functions could pave the way for new therapeutic strategies aimed at CVD and cardiovascular regeneration.
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Affiliation(s)
- Aaron H. Wasserman
- Regenerative Biology and Cell Reprogramming Laboratory, Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI 48824, USA; (A.H.W.); (M.V.)
- Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA
| | - Manigandan Venkatesan
- Regenerative Biology and Cell Reprogramming Laboratory, Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI 48824, USA; (A.H.W.); (M.V.)
- Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA
| | - Aitor Aguirre
- Regenerative Biology and Cell Reprogramming Laboratory, Institute for Quantitative Health Science and Engineering (IQ), Michigan State University, East Lansing, MI 48824, USA; (A.H.W.); (M.V.)
- Department of Biomedical Engineering, College of Engineering, Michigan State University, East Lansing, MI 48824, USA
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32
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Lucchinetti E, Lou PH, Wawrzyniak P, Wawrzyniak M, Scharl M, Holtzhauer GA, Krämer SD, Hersberger M, Rogler G, Zaugg M. Novel Strategies to Prevent Total Parenteral Nutrition-Induced Gut and Liver Inflammation, and Adverse Metabolic Outcomes. Mol Nutr Food Res 2020; 65:e1901270. [PMID: 32359213 DOI: 10.1002/mnfr.201901270] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 04/09/2020] [Indexed: 12/15/2022]
Abstract
Total parenteral nutrition (TPN) is a life-saving therapy administered to millions of patients. However, it is associated with significant adverse effects, namely liver injury, risk of infections, and metabolic derangements. In this review, the underlying causes of TPN-associated adverse effects, specifically gut atrophy, dysbiosis of the intestinal microbiome, leakage of the epithelial barrier with bacterial invasion, and inflammation are first described. The role of the bile acid receptors farnesoid X receptor and Takeda G protein-coupled receptor, of pleiotropic hormones, and growth factors is highlighted, and the mechanisms of insulin resistance, namely the lack of insulinotropic and insulinomimetic signaling of gut-originating incretins as well as the potentially toxicity of phytosterols and pro-inflammatory fatty acids mainly released from soybean oil-based lipid emulsions, are discussed. Finally, novel approaches in the design of next generation lipid delivery systems are proposed. Propositions include modifying the physicochemical properties of lipid emulsions, the use of lipid emulsions generated from sustainable oils with favorable ratios of anti-inflammatory n-3 to pro-inflammatory n-6 fatty acids, beneficial adjuncts to TPN, and concomitant pharmacotherapies to mitigate TPN-associated adverse effects.
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Affiliation(s)
- Eliana Lucchinetti
- Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre, University of Alberta, Edmonton, T6G 2R3, Canada
| | - Phing-How Lou
- Department of Pharmacology, University of Alberta, Edmonton, T6G 2R3, Canada
| | - Paulina Wawrzyniak
- Division of Clinical Chemistry and Biochemistry, Children's Hospital Zurich, Zurich, 8032, Switzerland
| | - Marcin Wawrzyniak
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, 8091, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, 8091, Switzerland
| | - Gregory A Holtzhauer
- Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 8093, Switzerland
| | - Stefanie D Krämer
- Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 8093, Switzerland
| | - Martin Hersberger
- Division of Clinical Chemistry and Biochemistry, Children's Hospital Zurich, Zurich, 8032, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, 8091, Switzerland
| | - Michael Zaugg
- Department of Anesthesiology and Pain Medicine and Cardiovascular Research Centre, University of Alberta, Edmonton, T6G 2R3, Canada.,Department of Pharmacology, University of Alberta, Edmonton, T6G 2R3, Canada
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33
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Lock JY, Carlson TL, Yu Y, Lu J, Claud EC, Carrier RL. Impact of Developmental Age, Necrotizing Enterocolitis Associated Stress, and Oral Therapeutic Intervention on Mucus Barrier Properties. Sci Rep 2020; 10:6692. [PMID: 32317678 PMCID: PMC7174379 DOI: 10.1038/s41598-020-63593-5] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2019] [Accepted: 02/24/2020] [Indexed: 12/12/2022] Open
Abstract
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease of incompletely understood pathophysiology predominantly affecting premature infants. While NEC is associated with microbial invasion of intestinal tissues, and mucus modulates interactions between microbes and underlying tissues, variations in mucus barrier properties with NEC-associated risk factors have not been investigated. This study explored differences in mucus composition (total protein, DNA, mucin content, sialic acid, and immunoregulatory proteins), as well as structural and transport properties, assessed by tracking of particles and bacteria (E. coli and E. cloacae) with developmental age and exposure to NEC stressors in Sprague Dawley rats. Early developmental age (5 day old) was characterized by a more permeable mucus layer relative to 21 day old pups, suggesting immaturity may contribute to exposure of the epithelium to microbes. Exposure to NEC stressors was associated with reduced mucus permeability, which may aid in survival. Feeding with breastmilk as opposed to formula reduces incidence of NEC. Thus, NEC-stressed (N-S) rat pups were orally dosed with breastmilk components lysozyme (N-S-LYS) or docosahexaenoic acid (N-S-DHA). N-S-LYS and N-S-DHA pups had a less permeable mucus barrier relative to N-S pups, which suggests the potential of these factors to strengthen the mucus barrier and thus protect against disease.
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Affiliation(s)
- Jaclyn Y Lock
- Department of Bioengineering, Northeastern University, Boston, Massachusetts, USA
| | - Taylor L Carlson
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA
| | - Yueyue Yu
- Department of Pediatrics, Section of Neonatology, University of Chicago, Chicago, Illinois, USA
| | - Jing Lu
- Department of Pediatrics, Section of Neonatology, University of Chicago, Chicago, Illinois, USA
| | - Erika C Claud
- Department of Pediatrics, Section of Neonatology, University of Chicago, Chicago, Illinois, USA
- Department of Medicine, Section of Gastroenterology, University of Chicago, Chicago, Illinois, USA
| | - Rebecca L Carrier
- Department of Chemical Engineering, Northeastern University, Boston, Massachusetts, USA.
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34
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Nagatake T, Kunisawa J. Emerging roles of metabolites of ω3 and ω6 essential fatty acids in the control of intestinal inflammation. Int Immunol 2020; 31:569-577. [PMID: 30722032 PMCID: PMC6736389 DOI: 10.1093/intimm/dxy086] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2018] [Accepted: 01/25/2019] [Indexed: 02/07/2023] Open
Abstract
The gastrointestinal tract is continuously exposed to the external environment, which contains numerous non-self antigens, including food materials and commensal micro-organisms. For the maintenance of mucosal homeostasis, the intestinal epithelial layer and mucosal immune system simultaneously provide the first line of defense against pathogens and are tightly regulated to prevent their induction of inflammatory responses to non-pathogenic antigens. Defects in mucosal homeostasis lead to the development of inflammatory and associated intestinal diseases, such as Crohn’s disease, ulcerative colitis, food allergy and colorectal cancer. The recent discovery of novel dietary ω3 and ω6 lipid-derived metabolites—such as resolvin, protectin, maresin, 17,18-epoxy-eicosatetraenoic acid and microbe-dependent 10-hydroxy-cis-12-octadecenoic acid—and their potent biologic effects on the regulation of inflammation have initiated a new era of nutritional immunology. In this review, we update our understanding of the role of lipid metabolites in intestinal inflammation.
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Affiliation(s)
- Takahiro Nagatake
- Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Asagi Saito, Ibaraki, Osaka, Japan
| | - Jun Kunisawa
- Laboratory of Vaccine Materials, Center for Vaccine and Adjuvant Research, and Laboratory of Gut Environmental System, National Institutes of Biomedical Innovation, Health and Nutrition (NIBIOHN), Asagi Saito, Ibaraki, Osaka, Japan.,Department of Microbiology and Immunology, Kobe University Graduate School of Medicine, Kusunoki-cho, Chuo-ku, Kobe, Hyogo, Japan.,International Research and Development Center for Mucosal Vaccine, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo, Japan.,Graduate School of Medicine, Graduate School of Pharmaceutical Sciences, Graduate School of Dentistry, Osaka University, Yamadaoka, Suita, Osaka, Japan
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35
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Davinelli S, Intrieri M, Corbi G, Scapagnini G. Metabolic indices of polyunsaturated fatty acids: current evidence, research controversies, and clinical utility. Crit Rev Food Sci Nutr 2020; 61:259-274. [PMID: 32056443 DOI: 10.1080/10408398.2020.1724871] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The n-3 and n-6 polyunsaturated fatty acids (PUFA) are among the most studied nutrients in human metabolism. In the past few decades, prospective studies and controlled trials have supported the view that the effects of these essential fatty acids are clinically relevant. PUFA profiles in different blood compartments are reflections of both diet and metabolism, and their levels may be related to disease risk. Despite widespread interest, there is no consensus regarding which biomarkers best reflect PUFA status in the body. The measurement of PUFA levels is not straight-forward, and a wide variety of indices have been used in clinical studies, producing conflicting results. A major source of heterogeneity among studies is associated with research design, sampling, and laboratory analyses. To date, the n-3 index, n-6/n-3 ratio, and arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio are the most promising biomarkers associated with PUFA metabolism. Although hotly debated, these indices may be considered at least markers, if not risk factors, for several diseases, especially cardiovascular events and brain disorders. Here, we summarize the most updated evidence of n-3 and n-6 PUFA effects on human health, reviewing current controversies on the aforementioned indices and whether they can be considered valuable predictors of clinical outcomes.
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Affiliation(s)
- Sergio Davinelli
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Mariano Intrieri
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Graziamaria Corbi
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
| | - Giovanni Scapagnini
- Department of Medicine and Health Sciences "V. Tiberio", University of Molise, Campobasso, Italy
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36
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Lopes Kubitza FM, Anthony JMG. Topical oral 1-tetradecanol complex in the treatment of periodontal diseases in cats. J Feline Med Surg 2019; 21:1141-1148. [PMID: 30652935 PMCID: PMC10814267 DOI: 10.1177/1098612x18820734] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/12/2024]
Abstract
OBJECTIVES The aim of this study was to evaluate the outcomes of the treatment of chronic periodontal disease with an oral application of tetradecanol complex (1-TDC) in cats. METHODS The test group (n = 9) received 1-TDC (525 mg per gel capsule/day) and the placebo group (n = 4) received olive oil (0.25 ml per gel capsule/day) for 6 weeks. RESULTS Oral treatment with 1-TDC resulted in significant reductions in all parameters of clinical periodontal disease except tooth mobility at 6 weeks. The 1-TDC group exhibited a statistically significant reduction in pocket depth, clinical attachment loss, gingival index and bleeding on probing after treatment at 6 weeks, whereas the placebo group did not show any significant change. CONCLUSIONS AND RELEVANCE Chronic inflammation associated with periodontal diseases leads to periodontal tissue destruction. As a result, modulation of the host response has been included in the treatment protocol for periodontal diseases. Fatty acids present anti-inflammatory properties and are being investigated for use in the treatment and prevention of progressive periodontal diseases.
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37
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Warner DR, Warner JB, Hardesty JE, Song YL, King TN, Kang JX, Chen CY, Xie S, Yuan F, Prodhan MAI, Ma X, Zhang X, Rouchka EC, Maddipati KR, Whitlock J, Li EC, Wang GP, McClain CJ, Kirpich IA. Decreased ω-6:ω-3 PUFA ratio attenuates ethanol-induced alterations in intestinal homeostasis, microbiota, and liver injury. J Lipid Res 2019; 60:2034-2049. [PMID: 31586017 PMCID: PMC6889711 DOI: 10.1194/jlr.ra119000200] [Citation(s) in RCA: 46] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2019] [Revised: 09/22/2019] [Indexed: 02/07/2023] Open
Abstract
Ethanol (EtOH)-induced alterations in intestinal homeostasis lead to multi-system pathologies, including liver injury. ω-6 PUFAs exert pro-inflammatory activity, while ω-3 PUFAs promote anti-inflammatory activity that is mediated, in part, through specialized pro-resolving mediators [e.g., resolvin D1 (RvD1)]. We tested the hypothesis that a decrease in the ω-6:ω-3 PUFA ratio would attenuate EtOH-mediated alterations in the gut-liver axis. ω-3 FA desaturase-1 (fat-1) mice, which endogenously increase ω-3 PUFA levels, were protected against EtOH-mediated downregulation of intestinal tight junction proteins in organoid cultures and in vivo. EtOH- and lipopolysaccharide-induced expression of INF-γ, Il-6, and Cxcl1 was attenuated in fat-1 and WT RvD1-treated mice. RNA-seq of ileum tissue revealed upregulation of several genes involved in cell proliferation, stem cell renewal, and antimicrobial defense (including Alpi and Leap2) in fat-1 versus WT mice fed EtOH. fat-1 mice were also resistant to EtOH-mediated downregulation of genes important for xenobiotic/bile acid detoxification. Further, gut microbiome and plasma metabolomics revealed several changes in fat-1 versus WT mice that may contribute to a reduced inflammatory response. Finally, these data correlated with a significant reduction in liver injury. Our study suggests that ω-3 PUFA enrichment or treatment with resolvins can attenuate the disruption in intestinal homeostasis caused by EtOH consumption and systemic inflammation with a concomitant reduction in liver injury.
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Affiliation(s)
- Dennis R Warner
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
| | - Jeffrey B Warner
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
- Department of Medicine Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL
| | - Josiah E Hardesty
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
| | - Ying L Song
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
| | - Taylor N King
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
| | - Jing X Kang
- Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Chih-Yu Chen
- Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Shanfu Xie
- Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA
| | - Fang Yuan
- Department of Chemistry, University of Louisville, Louisville, KY
| | | | - Xipeng Ma
- Department of Chemistry, University of Louisville, Louisville, KY
| | - Xiang Zhang
- Department of Chemistry, University of Louisville, Louisville, KY
| | - Eric C Rouchka
- Department of Computer Engineering and Computer Science, Speed School of Engineering, University of Louisville, Louisville, KY
| | | | - Joan Whitlock
- Department of Medicine Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL
| | - Eric C Li
- Department of Medicine Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL
| | - Gary P Wang
- Department of Medicine Division of Infectious Diseases and Global Medicine, College of Medicine, University of Florida, Gainesville, FL
| | - Craig J McClain
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
- Department of Pharmacology and Toxicology and University of Louisville Alcohol Center, University of Louisville School of Medicine, Louisville, KY
- Robley Rex Veterans Medical Center, Louisville, KY
| | - Irina A Kirpich
- Department of Medicine, Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville, Louisville, KY
- Department of Pharmacology and Toxicology and University of Louisville Alcohol Center, University of Louisville School of Medicine, Louisville, KY
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38
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Kooij G, Troletti CD, Leuti A, Norris PC, Riley I, Albanese M, Ruggieri S, Libreros S, van der Pol SMA, van Het Hof B, Schell Y, Guerrera G, Buttari F, Mercuri NB, Centonze D, Gasperini C, Battistini L, de Vries HE, Serhan CN, Chiurchiù V. Specialized pro-resolving lipid mediators are differentially altered in peripheral blood of patients with multiple sclerosis and attenuate monocyte and blood-brain barrier dysfunction. Haematologica 2019; 105:2056-2070. [PMID: 31780628 PMCID: PMC7395264 DOI: 10.3324/haematol.2019.219519] [Citation(s) in RCA: 77] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 11/21/2019] [Indexed: 12/11/2022] Open
Abstract
Chronic inflammation is a key pathological hallmark of multiple sclerosis (MS) and suggests that resolution of inflammation, orchestrated by specialized pro-resolving lipid mediators (LM), is impaired. Here, through targeted-metabololipidomics in peripheral blood of patients with MS, we revealed that each disease form was associated with distinct LM profiles that significantly correlated with disease severity. In particular, relapsing and progressive MS patients were associated with high eicosanoids levels, whereas the majority of pro-resolving LM were significantly reduced or below limits of detection and correlated with disease progression. Furthermore, we found impaired expression of several pro-resolving LM biosynthetic enzymes and receptors in blood-derived leukocytes of MS patients. Mechanistically, differentially expressed mediators like LXA4, LXB4, RvD1 and PD1 reduced MS-derived monocyte activation and cytokine production, and inhibited inflammation-induced blood-brain barrier dysfunction and monocyte transendothelial migration. Altogether, these findings reveal peripheral defects in the resolution pathway in MS, suggesting pro-resolving LM as novel diagnostic biomarkers and potentially safe therapeutics.
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Affiliation(s)
- Gijs Kooij
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands.,Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Claudio Derada Troletti
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Alessandro Leuti
- Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy.,European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Paul C Norris
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Ian Riley
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Maria Albanese
- Neurology Unit, Department of Neurosciences, University of Rome Tor Vergata, Rome, Italy
| | | | - Stephania Libreros
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Susanne M A van der Pol
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Bert van Het Hof
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Yoëlle Schell
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Gisella Guerrera
- European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Fabio Buttari
- Unit of Neurology and Unit of Neurorehabilitation, IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, IS, Italy
| | - Nicola Biagio Mercuri
- European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy.,Neurology Unit, Department of Neurosciences, University of Rome Tor Vergata, Rome, Italy
| | - Diego Centonze
- Neurology Unit, Department of Neurosciences, University of Rome Tor Vergata, Rome, Italy.,Unit of Neurology and Unit of Neurorehabilitation, IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, IS, Italy
| | | | - Luca Battistini
- European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy
| | - Helga E de Vries
- Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Molecular Cell Biology and Immunology, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam, the Netherlands
| | - Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Valerio Chiurchiù
- Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy .,European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy
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39
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Rodríguez M, G Rebollar P, Mattioli S, Castellini C. n-3 PUFA Sources (Precursor/Products): A Review of Current Knowledge on Rabbit. Animals (Basel) 2019; 9:ani9100806. [PMID: 31618904 PMCID: PMC6827073 DOI: 10.3390/ani9100806] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Revised: 09/27/2019] [Accepted: 10/09/2019] [Indexed: 01/01/2023] Open
Abstract
This review compares the effects of different n-3 polyunsaturated fatty acid (PUFA) sources on biological activity, physiological/reproductive endpoints, and health implications with a special emphasis on a rabbit case study. Linoleic acid (LA) and α-linolenic acid (ALA) are members of two classes of PUFAs, namely the n-6 and n-3 series, which are required for normal human health. Both are considered precursors of a cascade of molecules (eicosanoids), which take part in many biological processes (inflammation, vasoconstriction/vasodilation, thromboregulation, etc.). However, their biological functions are opposite and are mainly related to the form (precursor or long-chain products) in which they were administered and to the enzyme-substrate preference. ALA is widely present in common vegetable oils and foods, marine algae, and natural herbs, whereas its long-chain PUFA derivatives are available mainly in fish and animal product origins. Recent studies have shown that the accumulation of n-3 PUFAs seems mostly to be tissue-dependent and acts in a tissue-selective manner. Furthermore, dietary n-3 PUFAs widely affect the lipid oxidation susceptibility of all tissues. In conclusion, sustainable sources of n-3 PUFAs are limited and exert a different effect about (1) the form in which they are administered, precursor or derivatives; (2) their antioxidant protections; and (3) the purpose to be achieved (health improvement, physiological and reproductive traits, metabolic pathways, etc.).
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Affiliation(s)
- María Rodríguez
- Departamento de Producción Agraria, Escuela Técnica Superior de Ingeniería Agronómica Alimentaria y de Biosistemas, Universidad Politécnica de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
| | - Pilar G Rebollar
- Departamento de Producción Agraria, Escuela Técnica Superior de Ingeniería Agronómica Alimentaria y de Biosistemas, Universidad Politécnica de Madrid, Ciudad Universitaria s/n, 28040 Madrid, Spain.
| | - Simona Mattioli
- Department of Agricultural, Environmental and Food Science, University of Perugia, Borgo XX Giugno, 74, 06121 Perugia, Italy.
| | - Cesare Castellini
- Department of Agricultural, Environmental and Food Science, University of Perugia, Borgo XX Giugno, 74, 06121 Perugia, Italy.
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Rod-In W, Monmai C, Lee SM, Jung SK, You S, Park WJ. Anti-Inflammatory Effects of Lipids Extracted from Arctoscopus japonicus Eggs on LPS-Stimulated RAW264.7 Cells. Mar Drugs 2019; 17:md17100580. [PMID: 31614594 PMCID: PMC6836062 DOI: 10.3390/md17100580] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2019] [Revised: 10/06/2019] [Accepted: 10/08/2019] [Indexed: 12/12/2022] Open
Abstract
Arctoscopus japonicus is a cold-water marine fish. The present study investigated the fatty acid composition of A. japonicus egg lipids and their anti-inflammatory effects on LPS-stimulated RAW246.7 macrophages. The results showed that A. japonicus egg lipids contained primarily polyunsaturated fatty acids (52.9% of the total fatty acid content; mostly eicosapentaenoic acid [EPA, 21.2 ± 0.5%] and docosahexaenoic acid [DHA, 25.9 ± 0.1%]), followed by monounsaturated fatty acids and saturated fatty acids (23.7% and 23.4%, respectively). A. japonicus egg lipids significantly decreased nitric oxide (NO) production and suppressed the expression of immune-associated genes such as iNOS, COX-2, IL-1β, IL-6, and TNF-α LPS-stimulated RAW246.7 macrophages in dose-dependent manner. A. japonicus egg lipids also reduced the phosphorylation levels of NF-κB p-65, p38, ERK1/2, and JNK, key components of the NF-κB and MAPK pathways, suggesting that the lipid-induced anti-inflammatory activity is related to these signaling pathways. These results indicate that the lipids extracted from A. japonicus eggs have potential biofunctions and might be useful for regulating inflammation in macrophages.
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Affiliation(s)
- Weerawan Rod-In
- Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea.
| | - Chaiwat Monmai
- Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea.
| | - Sang-Min Lee
- Department of Marine Biotechnology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea.
| | - Seok-Kyu Jung
- Department of Horticulture, Daegu Catholic University, Gyeongsan, Gyeongbuk 38430, Korea.
| | - SangGuan You
- Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea.
| | - Woo Jung Park
- Department of Marine Food Science and Technology, Gangneung-Wonju National University, Gangneung, Gangwon 25457, Korea.
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41
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Mosińska P, Martín-Ruiz M, González A, López-Miranda V, Herradón E, Uranga JA, Vera G, Sánchez-Yáñez A, Martín-Fontelles MI, Fichna J, Abalo R. Changes in the diet composition of fatty acids and fiber affect the lower gastrointestinal motility but have no impact on cardiovascular parameters: In vivo and in vitro studies. Neurogastroenterol Motil 2019; 31:e13651. [PMID: 31145538 DOI: 10.1111/nmo.13651] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 04/30/2019] [Accepted: 05/17/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Food and diet are central issues for proper functioning of the cardiovascular (CV) system and gastrointestinal (GI) tract. We hypothesize that different types of dietary FAs affect CV parameters as well as GI motor function and visceral sensitivity. METHODS Male Wistar rats were fed with control diet (CTRL), diet supplemented with 7% soybean oil (SOY), SOY + 3.5% virgin coconut oil (COCO), and SOY + 3.5% evening primrose oil (EP) for 4 weeks. The content of insoluble fiber in CTRL was higher than in SOY, COCO, or EP. Body weight gain and food/water intake were measured. At day 28, biometric, biochemical, CV parameters, GI motor function (X-ray and colon bead expulsion test), and visceral sensitivity were evaluated. Changes in propulsive colonic activity were determined in vitro. The colon and adipose tissue were histologically studied; the number of mast cells (MCs) in the colon was calculated. RESULTS SOY, COCO, and EP had increased body weight gain but decreased food intake vs CTRL. Water consumption, biometric, biochemical, and CV parameters were comparable between groups. SOY increased the sensitivity to colonic distention. All groups maintained regular propulsive neurogenic contractions; EP delayed colonic motility (P < 0.01). SOY, COCO, and EP displayed decreased size of the cecum, lower number and size of fecal pellets, and higher infiltration of MCs to the colon (P < 0.001). CONCLUSIONS AND INFERENCES Dietary FAs supplementation and lower intake of insoluble fiber can induce changes in the motility of the lower GI tract, in vivo and in vitro, but CV function and visceral sensitivity are not generally affected.
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Affiliation(s)
- Paula Mosińska
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Marta Martín-Ruiz
- Departamento de Biología, Facultad de Ciencias, Universidad Autónoma de Madrid, Madrid, Spain
| | - Antonio González
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Visitación López-Miranda
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.,Unidad Asociada al Instituto de Química Medica (IQM) del Consejo Superior de Investigaciones Científicas (CSIC), Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Esperanza Herradón
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.,Unidad Asociada al Instituto de Química Medica (IQM) del Consejo Superior de Investigaciones Científicas (CSIC), Universidad Rey Juan Carlos, Alcorcón, Spain
| | - José A Uranga
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Gema Vera
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.,Unidad Asociada al Instituto de Química Medica (IQM) del Consejo Superior de Investigaciones Científicas (CSIC), Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Adrián Sánchez-Yáñez
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Mª Isabel Martín-Fontelles
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.,Unidad Asociada al Instituto de Química Medica (IQM) del Consejo Superior de Investigaciones Científicas (CSIC), Universidad Rey Juan Carlos, Alcorcón, Spain
| | - Jakub Fichna
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, Lodz, Poland
| | - Raquel Abalo
- Departamento de Ciencias Básicas de la Salud, Facultad de Ciencias de la Salud, Universidad Rey Juan Carlos, Alcorcón, Spain.,Unidad Asociada al Instituto de Química Medica (IQM) del Consejo Superior de Investigaciones Científicas (CSIC), Universidad Rey Juan Carlos, Alcorcón, Spain
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42
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Barnig C, Bezema T, Calder PC, Charloux A, Frossard N, Garssen J, Haworth O, Dilevskaya K, Levi-Schaffer F, Lonsdorfer E, Wauben M, Kraneveld AD, Te Velde AA. Activation of Resolution Pathways to Prevent and Fight Chronic Inflammation: Lessons From Asthma and Inflammatory Bowel Disease. Front Immunol 2019; 10:1699. [PMID: 31396220 PMCID: PMC6664683 DOI: 10.3389/fimmu.2019.01699] [Citation(s) in RCA: 57] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Accepted: 07/08/2019] [Indexed: 12/15/2022] Open
Abstract
Formerly considered as a passive process, the resolution of acute inflammation is now recognized as an active host response, with a cascade of coordinated cellular and molecular events that promotes termination of the inflammatory response and initiates tissue repair and healing. In a state of immune fitness, the resolution of inflammation is contained in time and space enabling the restoration of tissue homeostasis. There is increasing evidence that poor and/or inappropriate resolution of inflammation participates in the pathogenesis of chronic inflammatory diseases, extending in time the actions of pro-inflammatory mechanisms, and responsible in the long run for excessive tissue damage and pathology. In this review, we will focus on how resolution can be the target for therapy in "Th1/Th17 cell-driven" immune diseases and "Th2 cell-driven" immune diseases, with inflammatory bowel diseases (IBD) and asthma, as relevant examples. We describe the main cells and mediators stimulating the resolution of inflammation and discuss how pharmacological and dietary interventions but also life style factors, physical and psychological conditions, might influence the resolution phase. A better understanding of the impact of endogenous and exogenous factors on the resolution of inflammation might open a whole area in the development of personalized therapies in non-resolving chronic inflammatory diseases.
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Affiliation(s)
- Cindy Barnig
- Department of Chest Disease, Strasbourg University Hospital, Strasbourg, France.,Equipe d'accueil 3072, University of Strasbourg, Strasbourg, France
| | | | - Philip C Calder
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.,National Institute for Health Research Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, United Kingdom
| | - Anne Charloux
- Department of Chest Disease, Strasbourg University Hospital, Strasbourg, France.,Equipe d'accueil 3072, University of Strasbourg, Strasbourg, France
| | - Nelly Frossard
- UMR 7200 CNRS/Université de Strasbourg, Laboratoire d'Innovation Thérapeutique and LabEx MEDALIS, Faculté de Pharmacie, Strasbourg, France
| | - Johan Garssen
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.,Nutricia Research, Utrecht, Netherlands
| | - Oliver Haworth
- Biochemical Pharmacology, William Harvey Research Institute, Bart's School of Medicine and Queen Mary University of London, London, United Kingdom
| | - Ksenia Dilevskaya
- Division of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
| | - Francesca Levi-Schaffer
- Pharmacology and Experimental Therapeutics Unit, Faculty of Medicine, School of Pharmacy, Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel
| | - Evelyne Lonsdorfer
- Department of Chest Disease, Strasbourg University Hospital, Strasbourg, France.,Equipe d'accueil 3072, University of Strasbourg, Strasbourg, France
| | - Marca Wauben
- Department of Biochemistry & Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
| | - Aletta D Kraneveld
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, Netherlands.,Institute for Risk Assessment Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, Netherlands
| | - Anje A Te Velde
- Amsterdam UMC, Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, AGEM, Amsterdam, Netherlands
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The Lipid Status in Patients with Ulcerative Colitis: Sphingolipids are Disease-Dependent Regulated. J Clin Med 2019; 8:jcm8070971. [PMID: 31277430 PMCID: PMC6678307 DOI: 10.3390/jcm8070971] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2019] [Revised: 06/13/2019] [Accepted: 07/02/2019] [Indexed: 02/06/2023] Open
Abstract
The factors that contribute to the development of ulcerative colitis (UC), are still not fully identified. Disruption of the colon barrier is one of the first events leading to invasion of bacteria and activation of the immune system. The colon barrier is strongly influenced by sphingolipids. Sphingolipids impact cell-cell contacts and function as second messengers. We collected blood and colon tissue samples from UC patients and healthy controls and investigated the sphingolipids and other lipids by LC-MS/MS or LC-QTOFMS. The expression of enzymes of the sphingolipid pathway were determined by RT-PCR and immunohistochemistry. In inflamed colon tissue, the de novo-synthesis of sphingolipids is reduced, whereas lactosylceramides are increased. Reduction of dihydroceramides was due to posttranslational inhibition rather than altered serine palmitoyl transferase or ceramide synthase expression in inflamed colon tissue. Furthermore, in human plasma from UC-patients, several sphinglipids change significantly in comparison to healthy controls. Beside sphingolipids free fatty acids, lysophosphatidylcholines and triglycerides changed significantly in the blood of colitis patients dependent on the disease severity. Our data indicate that detraction of the sphingolipid de novo synthesis in colon tissue might be an important trigger for UC. Several lipids changed significantly in the blood, which might be used as biomarkers for disease control; however, diet-related variabilities need to be considered.
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Serum Resolvin E1 Levels and Its Relationship with Disease Activity in Ulcerative Colitis. Gastroenterol Res Pract 2019; 2019:6258327. [PMID: 30906319 PMCID: PMC6393930 DOI: 10.1155/2019/6258327] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2018] [Accepted: 01/08/2019] [Indexed: 01/11/2023] Open
Abstract
Background Resolvins originate from ω-3 PUFA (polyunsaturated fatty acid) precursors and play a role in the resolution of inflammation. The aim of this study was to determine the serum Resolvin E1 levels in patients with ulcerative colitis (UC) and to evaluate the relationship between the serum Resolvin E1 levels and ulcerative colitis disease activity. Methods In this observational study, serum samples were collected from 51 patients with UC and 30 healthy controls for the determination of Resolvin E1 levels. Firstly, we compared the serum Resolvin E1 levels between the UC patients and the control group. Subsequently, Resolvin E1 levels were analyzed in patients with active UC and UC in remission. Finally, the correlation between Resolvin E1 and C-reactive protein (CRP) and partial Mayo score (p-MS) was analyzed to determine the efficacy of Resolvin E1 in predicting disease activity. Results Serum Resolvin E1 level was determined in the UC group (3126 ± 1413 ng/ml) and in the control group (2758 ± 1065 ng/ml) (p = 0.187). Serum Resolvin E1 levels were determined in patients with active UC (3114 ± 1166 ng/ml) and patients in remission (3132 ± 1520 ng/ml) (p = 0.749). In the UC group, a low-grade positive significant association was found between Resolvin E1 and CRP (r = 0.303, p = 0.031). There was no significant association between Resolvin E1 and partial Mayo score (r = −0.207, p = 0.146). Conclusions There was no sufficient evidence that Resolvin E1 was an appropriate inflammatory marker to determine disease activity in UC.
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45
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Manfredi M, Conte E, Barberis E, Buzzi A, Robotti E, Caneparo V, Cecconi D, Brandi J, Vanni E, Finocchiaro M, Astegiano M, Gariglio M, Marengo E, De Andrea M. Integrated serum proteins and fatty acids analysis for putative biomarker discovery in inflammatory bowel disease. J Proteomics 2019; 195:138-149. [DOI: 10.1016/j.jprot.2018.10.017] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2018] [Revised: 10/19/2018] [Accepted: 10/31/2018] [Indexed: 12/30/2022]
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46
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Kiss B, Németh Á. High-throughput microalgae cultivation with adjustable LED-module applying different colours for Nannochloropsis and Chlorella microcultures. ACTA ALIMENTARIA 2019. [DOI: 10.1556/066.2019.48.1.13] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Affiliation(s)
- B. Kiss
- Fermentation Pilot Plant Laboratory, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rkp. 3. Hungary
| | - Á. Németh
- Fermentation Pilot Plant Laboratory, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, H-1111 Budapest, Műegyetem rkp. 3. Hungary
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47
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Scoville EA, Allaman MM, Adams DW, Motley AK, Peyton SC, Ferguson SL, Horst SN, Williams CS, Beaulieu DB, Schwartz DA, Wilson KT, Coburn LA. Serum Polyunsaturated Fatty Acids Correlate with Serum Cytokines and Clinical Disease Activity in Crohn's Disease. Sci Rep 2019; 9:2882. [PMID: 30814550 PMCID: PMC6393448 DOI: 10.1038/s41598-019-39232-z] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2018] [Accepted: 01/18/2019] [Indexed: 12/19/2022] Open
Abstract
Crohn's disease (CD) has been associated with an increased consumption of n-6 polyunsaturated fatty acid (PUFA), while greater intake of n-3 PUFA has been associated with a reduced risk. We sought to investigate serum fatty acid composition in CD, and associations of fatty acids with disease activity, cytokines, and adipokines. Serum was prospectively collected from 116 CD subjects and 27 non-IBD controls. Clinical disease activity was assessed by the Harvey Bradshaw Index (HBI). Serum fatty acids were measured by gas chromatography. Serum cytokines and adipokines were measured by Luminex assay. Dietary histories were obtained from a subset of patients. Nine serum cytokines and adipokines were increased in CD versus controls. CD subjects had increased percentage serum monounsaturated fatty acids (MUFA), dihomo-gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and oleic acid, but decreased arachidonic acid (AA) versus controls. The % total n-3 fatty acids and % EPA directly correlated with pro-inflammatory cytokine levels and HBI, whereas the % total n-6 fatty acids were inversely correlated with pro-inflammatory cytokine levels and HBI. CD subjects had increased caloric intake versus controls, but no alterations in total fat or PUFA intake. We found differences in serum fatty acids, most notably PUFA, in CD that correlated both with clinical disease activity and inflammatory cytokines. Our findings indicate that altered fatty acid metabolism or utilization is present in CD and is related to disease activity.
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Affiliation(s)
- Elizabeth A Scoville
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Margaret M Allaman
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Dawn W Adams
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
| | - Amy K Motley
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Shannon C Peyton
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah L Ferguson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sara N Horst
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Christopher S Williams
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Center for Mucosal Inflammation and Cancer, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
- Vanderbilt Center for Stem Cell Biology, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Dawn B Beaulieu
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - David A Schwartz
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Keith T Wilson
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
- Vanderbilt Center for Mucosal Inflammation and Cancer, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA
- Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Lori A Coburn
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Vanderbilt Center for Mucosal Inflammation and Cancer, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
- Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN, USA.
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48
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Zheng Z, Dai Z, Cao Y, Shen Q, Zhang Y. Docosapentaenoic acid (DPA, 22:5n-3) ameliorates inflammation in an ulcerative colitis model. Food Funct 2019; 10:4199-4209. [DOI: 10.1039/c8fo02338g] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
DPA showed an anti-inflammatory profile by competing with AA to decrease the synthesis of pro-inflammatory eicosanoids (LTB4 and PGE2).
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Affiliation(s)
- Zhenxiao Zheng
- Institute of Seafood
- Zhejiang Gongshang University
- Hangzhou 310012
- China
| | - Zhiyuan Dai
- Institute of Seafood
- Zhejiang Gongshang University
- Hangzhou 310012
- China
- State Key Laboratory of Aquatic Products Processing of Zhejiang Province
| | - Yalun Cao
- Institute of Seafood
- Zhejiang Gongshang University
- Hangzhou 310012
- China
| | - Qing Shen
- Institute of Seafood
- Zhejiang Gongshang University
- Hangzhou 310012
- China
- State Key Laboratory of Aquatic Products Processing of Zhejiang Province
| | - Yiqi Zhang
- Institute of Seafood
- Zhejiang Gongshang University
- Hangzhou 310012
- China
- State Key Laboratory of Aquatic Products Processing of Zhejiang Province
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Vinogradov IV, Zhivulko AR, Vinogradova LM, Korolev SV. Docosahexaenoic acid in the treatment of male infertility. ANDROLOGY AND GENITAL SURGERY 2018. [DOI: 10.17650/2070-9781-2018-19-4-21-27] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Literature review is devoted to the analysis of modern data on the use of docosahexaenoic acid in the treatment of male infertility. A brief description of modern ideas about the possible causes of male infertility (a disturbance of function of the cell membrane and genetic damage of sperm) was conducted. The data on the anti-inflammatory properties of omega-3 polyunsaturated fatty acids are described in detail. The bioavailability of docosahexaenoic acid and the choice of drugs containing it for the treatment of male infertility are discussed. Increasing the content of polyunsaturated fatty acids, in particular docosahexaenoic acid, in the sperm membrane was associated with higher ejaculate quality. Therapy with the use of these substances led to the improvement of standard indicators of semen and a decrease in the proportion of sperm with fragmented DNA.
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50
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Serhan CN, Chiang N, Dalli J. New pro-resolving n-3 mediators bridge resolution of infectious inflammation to tissue regeneration. Mol Aspects Med 2018; 64:1-17. [PMID: 28802833 PMCID: PMC5832503 DOI: 10.1016/j.mam.2017.08.002] [Citation(s) in RCA: 181] [Impact Index Per Article: 25.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Accepted: 08/07/2017] [Indexed: 12/16/2022]
Abstract
While protective, the acute inflammatory response when uncontrolled can lead to further tissue damage and chronic inflammation that is now widely recognized to play important roles in many commonly occurring diseases, such as cardiovascular disease, neurodegenerative diseases, metabolic syndrome, and many other diseases of significant public health concern. The ideal response to initial challenges of the host is complete resolution of the acute inflammatory response, which is now recognized to be a biosynthetically active process governed by specialized pro-resolving mediators (SPM). These chemically distinct families include lipoxins, resolvins, protectins and maresins that are biosynthesized from essential fatty acids. The biosynthesis and complete stereochemical assignments of the major SPM are established, and new profiling procedures have recently been introduced to document the activation of these pathways in vivo with isolated cells and in human tissues. The active resolution phase leads to tissue regeneration, where we've recently identified new molecules that communicate during resolution of inflammation to activate tissue regeneration in model organisms. This review presents an update on the documentation of the roles of SPMs and the biosynthesis and structural elucidation of novel mediators that stimulate tissue regeneration, coined conjugates in tissue regeneration. The identification and actions of the three families, maresin conjugates in tissue regeneration (MCTR), protectin conjugates in tissue regeneration (PCTR), and resolvin conjugates in tissue regeneration (RCTR), are reviewed here. The identification, structural elucidation and the pathways and biosynthesis of these new mediators in tissue regeneration demonstrate the host capacity to protect from collateral tissue damage, stimulate clearance of bacteria and debris, and promote tissue regeneration via endogenous pathways and molecules in the resolution metabolome.
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Affiliation(s)
- Charles N Serhan
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
| | - Nan Chiang
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Jesmond Dalli
- Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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