LitCovid-sentences  

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T476 0-50 Sentence denotes 8.1 The anti-inflammatory properties of n-3 PUFAs
T477 51-242 Sentence denotes As mentioned earlier, an exacerbated immune system response and uncontrolled inflammation are fundamental mechanisms in the development of cardiovascular impairment in patients with COVID-19.
T478 243-508 Sentence denotes Accordingly, a plethora of experimental studies and clinical trials demonstrate that targeting different inflammatory components may be considered promising strategies to control cardiovascular impairment during the acute and remission phases of COVID-19 (Fig. 3 ).
T479 509-1027 Sentence denotes Fig. 3 A summary of the anti-inflammatory mechanisms of n-3 PUFAs. (A) N-3 PUFAs can regulate expression of inflammatory cytokines, chemokines and adhesion molecules, inhibit NLRP3 inflammasomes, activate anti-inflammatory transcription factors (PPARα/γ) and activate GPR120 receptors which inhibit TLR4-mediated activation of NF-κB. (B) N-3 PUFAs are metabolized by COX/5-LOX into 5-series LTs which exert anti-inflammatory effects. (C) N-3 PUFAs can replace n-6 PUFAs, such as AA, altering the inflammatory response.
T480 1028-1334 Sentence denotes N-3 PUFA will alter cell membrane composition, fluidity and mediated signaling. (D) N-3 PUFAs, DHA and EPA, are metabolized by CYP epoxygenases into bioactive epoxylipids with anti-inflammatory properties. (E) N-3 PUFAs are metabolized by COX/LOX into SPMs which act as potent anti-inflammatory modulators.
T481 1335-2027 Sentence denotes AA, Arachidonic acid; CCL, Chemokine ligand; COX, Cyclooxygenase; CYP, Cytochrome P450; DHA, Docosahexaenoic acid; EDP, Epoxydocosapentaenoic acid; EEQ, Epoxyeicosatetraenoic acid; EPA, Eicosapentaenoic acid; GRP, G-protein coupled receptor; IL, Interleukin; LOX, Lipoxygenase; LT, Leukotriene; PUFA, Poly unsaturated fatty acid; NFκB, Nuclear factor kappa-light-chain enhancer activated B-cells; NLRP3, NACHT, LRR and PYD domains-containing protein 3; PLA2, Phospholipase A2; PMN, Polymorphonuclear neutrophils; PPAR, Peroxisome proliferator-activated receptor; ROS, Reactive oxygen species; SPMs, Specialized pro-resolving mediators; TLR, Toll like receptor; TNF-α, Tumor necrosis factor-α.
T482 2029-2154 Sentence denotes 8.1.1 N-3 PUFAs regulate the expression of several proinflammatory innate immune components and modulate macrophage response
T483 2155-2401 Sentence denotes A ‘cytokine storm’ and activation of the central innate immune pathway linking the NLRP3 inflammasome, IL-1β, TNF-α and IL-6 response is a primary cause of excessive inflammation reported in COVID-19 that negatively impacts cardiovascular system.
T484 2402-2551 Sentence denotes Therefore, targeting the different components is a promising approach to ameliorate cardiac complications secondary to COVID-19 (Huang et al., 2020).
T485 2552-2857 Sentence denotes While there is no direct clinical evidence related to the use of n-3 PUFAs in COVID-19 patients, the application of n-3 PUFAs in several inflammatory settings, including cardiovascular disorders, has been demonstrated to ameliorate detrimental immune reactions by several mechanisms (Rogero et al., 2020).
T486 2858-3076 Sentence denotes The anti-inflammatory effect of n-3 PUFAs seems to be consistent across several previous clinical findings (Calder, Carr, Gombart, & Eggersdorfer, 2020; Fritsche, 2006; Kiecolt-Glaser et al., 2012; Vedin et al., 2008).
T487 3077-3514 Sentence denotes Intriguingly, Tan et al. recently demonstrated in a randomized controlled study that high-dose n-3 PUFA supplementation (1.5 g/day EPA and 1.0 g/day DHA) markedly reduces plasma levels of IL-6, IL-1β and TNF-α after 4 weeks of therapy in middle or late-aged patients with chronic venous leg ulcers suggesting n-3 PUFAs as an effective low-risk dietary intervention to modulate inflammation (Tan, Sullenbarger, Prakash, & McDaniel, 2018).
T488 3515-3655 Sentence denotes This study indicates that n-3 PUFAs could have direct modulatory effects on the main components of the cytokine storm IL-6, IL-1β and TNF-α.
T489 3656-4044 Sentence denotes N-3 PUFAs can modulate the transcription and expression of inflammatory genes including cytokines, chemokines and adhesion molecules in cardiomyocytes, fibroblasts, endothelial cells, monocytes and macrophages (Collie-Duguid & Wahle, 1996; De Caterina, Cybulsky, Clinton, Gimbrone, & Libby, 1994; Hughes, Southon, & Pinder, 1996; Miles, Wallace, & Calder, 2000; Sanderson & Calder, 1998).
T490 4045-4433 Sentence denotes This is primarily achieved through the regulation of key transcription factors, such as inhibiting NF-κB (Kumar, Takada, Boriek, & Aggarwal, 2004; Lo, Chiu, Fu, Lo, & Helton, 1999; Novak, Babcock, Jho, Helton, & Espat, 2003; Zhao, Joshi-Barve, Barve, & Chen, 2004) or activating peroxisome proliferator-activated receptors-α/γ (PPARα/γ) (Gani & Sylte, 2008; Zapata-Gonzalez et al., 2008).
T491 4434-4729 Sentence denotes Activation of PPARα/γ can directly interfere with the activation of NF-κB and prevent its shuttling to the nucleus reducing the inflammatory burst (Matsumoto et al., 2008; Mishra, Chaudhary, & Sethi, 2004; Poynter & Daynes, 1998; Ricote, Huang, Welch, & Glass, 1999; Vanden Berghe et al., 2003).
T492 4730-4995 Sentence denotes Interestingly, direct activation of PPAR, using PPAR agonists, was proposed as a therapeutic target for blunting and regulating cytokine storm in COVID-19 patients suggesting n-3 PUFAs could have a promising effect (Ciavarella, Motta, Valente, & Pasquinelli, 2020).
T493 4996-5191 Sentence denotes Another important immunomodulatory mechanism induced by n-3 PUFAs involves activation of G protein-coupled receptor 120 (GPR120), which mediates strong and wide-ranging anti-inflammatory effects.
T494 5192-5375 Sentence denotes Research from Oh et al. indicates n-3 PUFAs stimulate GPR120 in both monocytic RAW 264.7 cells and primary intraperitoneal macrophages inhibiting TLR4-mediated inflammatory responses.
T495 5376-5483 Sentence denotes Knockdown of GPR120 attenuates the protective effects attributed to n-3 PUFA consumption (Oh et al., 2010).
T496 5484-5612 Sentence denotes These studies together provide evidence that n-3 PUFAs mediate anti-inflammatory effects through different mechanistic pathways.
T497 5613-5772 Sentence denotes Cardiac macrophages are primarily derived and replenished from inflammatory monocytes in response to an infection with resident macrophages also having a role.
T498 5773-5909 Sentence denotes Briefly, macrophages will differentiate into classical M1 inflammatory cells to clean cellular and matrix debris (Epelman et al., 2014).
T499 5910-6144 Sentence denotes Subsequently, M1 macrophages may undergo polarization and transformation to the alternatively activated or reparatory M2 stage which secrete IL-10 to promote resolution and contribute to wound healing and tissue repair (Murray, 2017).
T500 6145-6443 Sentence denotes Controlling the migration and the polarization of macrophages to the myocardium in the context of COVID-19 is a tentative approach to limit cardiac injury (Frantz & Nahrendorf, 2014; Fujiu, Wang, & Nagai, 2014; Leblond et al., 2015; van Amerongen, Harmsen, van Rooijen, Petersen, & van Luyn, 2007).
T501 6444-6587 Sentence denotes In COVID-19, an excessive cardiac recruitment and accumulation of pro-inflammatory M1 macrophages potentially aggravates cardiovascular injury.
T502 6588-6786 Sentence denotes Notably, as M1 macrophages secrete a large variety of chemokines and cytokines such as TNF-α and IL-1β to recruit and activate other immune cells from both the innate and the adaptive immune system.
T503 6787-7018 Sentence denotes The effect will impede the reparative phase mediated by M2 macrophages and thus aggravates adverse cardiac remodeling (Dewald et al., 2005; Gordon, Pluddemann, & Martinez Estrada, 2014; Murray & Wynn, 2011; ter Horst et al., 2015).
T504 7019-7311 Sentence denotes Interestingly, evidence demonstrates n-3 PUFAs and/or their biologically active metabolites have the ability to blunt the expression, production and release of IL-1β, TNF-α, and IL-6 by M1 macrophages (Allam-Ndoul, Guenard, Barbier, & Vohl, 2017; Liu et al., 2014; Mildenberger et al., 2017).
T505 7312-7607 Sentence denotes Schoeniger et al., showed n-3 PUFAs have the ability to down-regulate inflammatory processes and reduce the production and secretion of pro-inflammatory cytokines from RAW 264.7 macrophages infected with microorganisms, R. equi and P. aeruginosa (Schoeniger, Adolph, Fuhrmann, & Schumann, 2011).
T506 7608-7855 Sentence denotes Moreover, the inhibitory effects of EPA and DHA on the pro-inflammatory NLRP3 inflammasome pathway has also been well-documented in macrophage cell lines as well as in primary human and mouse macrophages (Iverson et al., 2018; Kumar et al., 2016).
T507 7856-8035 Sentence denotes Kumar et al., investigated the effects of 15-lipoxygenase (LOX) metabolites of ALA on lipopolysaccharide (LPS) -induced inflammation in RAW 264.7 cells and peritoneal macrophages.
T508 8036-8212 Sentence denotes The findings revealed the anti-inflammatory effects of these metabolites involve inactivation of the NLRP3 inflammasome complex through the PPAR-γ pathway (Kumar et al., 2016).
T509 8213-8540 Sentence denotes N-3 PUFAs can increase the phagocytic capacity of macrophages, which has been shown through the engulfment of zymosan particles (Chang, Lee, Kim, & Surh, 2015), Pseudomonas aeruginosa, Rhodococcus equi (Adolph, Fuhrmann, & Schumann, 2012), E.coli (Davidson, Kerr, Guy, & Rotondo, 1998) and apoptotic cells (Chang et al., 2015).
T510 8541-8867 Sentence denotes It has been suggested the increase in phagocytic capacity of macrophages upon n-3 PUFA treatment could be attributed to changes in the cellular membrane composition and structure caused by the incorporation of the n-3 PUFAs (Hellwing, Tigistu-Sahle, Fuhrmann, Kakela, & Schumann, 2018; Schoeniger, Fuhrmann, & Schumann, 2016).
T511 8868-9107 Sentence denotes Importantly, n-3 PUFAs have been found to promote M2 polarization in macrophage cell lines and primary mouse macrophages enhancing resolution of inflammation and tissue repair after infection (Chang et al., 2015; Ohue-Kitano et al., 2018).
T512 9108-9367 Sentence denotes Collectively, the modulatory properties of n-3 PUFAs on the immune system could impart a promising beneficial effect on the cardiovascular system in the context of COVID-19, an effect which needs further exploration and confirmation in larger clinical trials.
T513 9369-9455 Sentence denotes 8.1.2 Shifting to the anti-inflammatory COX- and LOX-derived metabolites of n-3 PUFAs
T514 9456-9723 Sentence denotes Accumulating literature demonstrates potent immunomodulatory properties of metabolites generated from n-3 PUFAs and consequently their impact on cardiovascular health (Jamieson, Endo, Darwesh, Samokhvalov, & Seubert, 2017; Schunck, Konkel, Fischer, & Weylandt, 2018).
T515 9724-9938 Sentence denotes The metabolism of n-3 and n-6 PUFAs is closely interconnected as parent compounds compete for the same metabolic enzymes but result in the production of a wide array of either pro- or anti-inflammatory metabolites.
T516 9939-10215 Sentence denotes For example, cyclooxygenase (COX) converts the n-6 PUFA arachidonic acid (AA) to the 2-series of prostaglandins (PGs) and the 2-series of thromboxanes (TX), while lipoxygenase (LOX) enzymes metabolize AA to the 4-series leukotrienes (LTs) and the hydroxyicosatetraenoic acids.
T517 10216-10428 Sentence denotes These lipid mediators are considered pro-inflammatory and are involved in various pathological processes including cardiovascular disorders (Innes & Calder, 2018; Kalinski, 2012; Lewis, Austen, & Soberman, 1990).
T518 10429-10565 Sentence denotes The synthesis and production of PGE2 occurs in several cells, including dendritic cells, macrophages, fibroblasts and endothelial cells.
T519 10566-10832 Sentence denotes PGE2 not only mediates vasodilation, endothelial permeability and increase of pain (Ricciotti & FitzGerald, 2011) but also contributes to the tissue influx of neutrophils, mast cells and macrophages and can affect the differentiation of these cells (Kalinski, 2012).
T520 10833-11172 Sentence denotes N-3 PUFAs can also act as a substrate for COX and 5-LOX enzymes resulting in production of the 3-series of PGs and TxAs as well as 5-series LTs, which are a set of less inflammatory or even anti-inflammatory metabolites in comparison to the metabolite family derived from AA (Corey, Shih, & Cashman, 1983; Lee et al., 1984; Surette, 2008).
T521 11173-11371 Sentence denotes These eicosanoids are responsible for producing several physiological responses related to inflammation, and their imbalance has been observed in several diseases (Calder, 2006; Falck et al., 2011).
T522 11372-11639 Sentence denotes For example, the production of PGE2 and LTB4 by human inflammatory cells was significantly decreased in a diet rich in fish oil (Caughey, Mantzioris, Gibson, Cleland, & James, 1996; Lee et al., 1985; Prescott, 1984; von Schacky, Kiefl, Jendraschak, & Kaminski, 1993).
T523 11640-11947 Sentence denotes Therefore, the metabolism of n-3 PUFAs by COX and LOX enzymes not only reduce the AA-derived pro-inflammatory metabolites but also alter the metabolic profile towards more biologically active anti-inflammatory mediators (Goldman, Pickett, & Goetzl, 1983; Lee et al., 1984; Lee, Mencia-Huerta, et al., 1984).
T524 11948-12117 Sentence denotes This may represent one of the central anti-inflammatory and consequently cardioprotective mechanisms of n-3 PUFAs against cardiac complications associated with COVID-19.
T525 12119-12220 Sentence denotes 8.1.3 Anti-inflammatory features of the n-3 PUFAs-derived specialized pro-resolving mediators (SPMs)
T526 12221-12569 Sentence denotes Metabolism of n-3 PUFAs also generates another group of highly specialized pro-resolving mediators (SPMs) which include resolvins ‘resolution phase interaction products’ produced from both EPA (E-series, RvE1-2) and DHA (D-series, RvD1-6) as well as protectins and maresins produced from DHA (Serhan et al., 2002; Serhan, Chiang, & Van Dyke, 2008).
T527 12570-12769 Sentence denotes Both the COX and LOX pathways are involved in the synthesis of these metabolites with distinct epimers being produced in the presence and absence of aspirin (Mas, Croft, Zahra, Barden, & Mori, 2012).
T528 12770-13112 Sentence denotes SPMs possess potent anti-inflammatory and inflammation resolving properties which is essential to terminate ongoing inflammatory processes, accelerate the cleaning process and aid in tissue regeneration and wound healing allowing tissue homeostasis to return (Serhan et al., 2000; Serhan et al., 2002; Spite et al., 2009; Titos et al., 2011).
T529 13113-13224 Sentence denotes Several mechanistic pathways contribute to the anti-inflammatory effects of resolvins, protectins and maresins.
T530 13225-13483 Sentence denotes This includes preventing the migration of neutrophils and monocytes across epithelial cells and promoting clearance of polymorphonuclear (PMNs) leukocytes, apoptotic cells and debris from the site of inflammation (Campbell et al., 2007; Serhan et al., 2002).
T531 13484-13739 Sentence denotes Krishnamoorthy et al. showed resolvins inhibit tissue migration of neutrophils by lowering the expression of surface adhesion receptors on neutrophils, such as CD11b or CD18, and reducing the production of the chemokine IL-8 (Krishnamoorthy et al., 2010).
T532 13740-14009 Sentence denotes Additionally, the partial agonist/antagonist activity of RvE1 toward LTB4 receptors on PMNs will inhibit NF-κB activation, abolish pro-inflammatory cytokine production and reduce PMN leukocyte infiltration (Arita et al., 2007; Serhan et al., 2002; Serhan et al., 2008).
T533 14010-14283 Sentence denotes Resolvins can blunt reactive oxygen species (ROS) production from neutrophils, induce neutrophil apoptosis and clearance by macrophages, as well contribute to inhibiting chemokine signaling (Ariel et al., 2006; Schwab, Chiang, Arita, & Serhan, 2007; Serhan & Chiang, 2004).
T534 14284-14588 Sentence denotes Furthermore, Morin et al. demonstrated a diet enriched with DHA and monoglycerides can significantly increase the levels of RvD2 and RvD3, which correlate with reduced levels of proinflammatory mediators CRP, IL-6, TNF-α, and IL-1β in a rat model of hypertension (Morin, Rousseau, Blier, & Fortin, 2015).
T535 14589-14690 Sentence denotes Additionally, there is growing evidence for a role of SPMs in regulating the humoral immune response.
T536 14691-15016 Sentence denotes A study conducted by Ramon et al., showed 17-hydroxydocosahexaenoic acid (17-HDHA), the precursor of the D-series SPMs (RvD1, 17R-RvD1, RvD2), can reduce IL-6 secretion in human B cells, increase B cell antibody production and promote B cell differentiation to an antibody secreting cell (Ramon, Gao, Serhan, & Phipps, 2012).
T537 15017-15220 Sentence denotes These new findings highlight the potential applications of SPMs as non-toxic, supportive adjuvants and as anti-inflammatory therapeutic molecules particularly during infection as in the case of COVID-19.
T538 15221-15315 Sentence denotes Resolvins, protectins and maresins play a pivotal role regulating the function of macrophages.
T539 15316-15493 Sentence denotes Sulciner et al. demonstrates RvD1, RvD2 or RvE1 can inhibit debris-stimulated cancer progression by enhancing clearance of debris via macrophage phagocytosis in multiple tumors.
T540 15494-15729 Sentence denotes These resolvins suppressed the release of the proinflammatory cytokines/chemokines, including TNFα, IL-6, IL-8, chemokine ligand 4, and chemokine ligand 5, by human macrophages cocultured with tumor cell debris (Sulciner et al., 2018).
T541 15730-15917 Sentence denotes Maresins are conjugates of sulfides synthetized by macrophages, which are also participants in acute inflammation resolution and seem to promote tissue regeneration (Serhan et al., 2009).
T542 15918-16140 Sentence denotes Maresin-1 biosynthesis involves an active intermediate (13S,14S-epoxi-DHA) that stimulates macrophage conversion from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype (Dalli, Ramon, Norris, Colas, & Serhan, 2015).
T543 16141-16568 Sentence denotes It is noteworthy that M2 macrophages secrete resolvins, protectins and maresins to dampen inflammation and restore homeostasis (Bouchery & Harris, 2017; Ramon et al., 2016) and at the same time augment phagocytic capacity of macrophages and other cells to remove debris from the site(s) of infection and injury and enhance microbial clearance (Dalli et al., 2013; Norris et al., 2018; Poorani, Bhatt, Dwarakanath, & Das, 2016).
T544 16569-16776 Sentence denotes The role of resolvins in the resolution of inflammation has been demonstrated in several animal models of ALI and ARDS (Gao et al., 2017; Uddin & Levy, 2011; Wang, Yan, Hao, & Jin, 2018; Zhang et al., 2019).
T545 16777-17141 Sentence denotes These studies carried out using rat and mouse models infected with the E.coli endotoxin, LPS, suggested the pro-resolving effects of these molecules could be attributed, for example, to the suppression of neutrophil infiltration due to reduced expression and release of pro-inflammatory cytokines from alveolar macrophages (Uddin & Levy, 2011; Zhang et al., 2019).
T546 17142-17361 Sentence denotes Further, it has been demonstrated protectins may reduce the replication of influenza (Morita et al., 2013) and potentially affect the inflammatory manifestations of respiratory viral diseases (Russell & Schwarze, 2014).
T547 17362-17566 Sentence denotes Importantly, pro-inflammatory cytokines, TNF-α and IL-6, will inhibit the activities of desaturases, which are essential for the generation of AA, EPA and DHA from their precursors LA and ALA (Das, 2013).
T548 17567-17839 Sentence denotes Hence, in instances where there is a substantial degree of inflammation due to high levels of IL-6 and TNF-α, such as following COVID-19 infection, a deficiency of EPA and DHA and subsequent decreased generation of resolvins, protectins and maresins can occur (Das, 2018).
T549 17840-18078 Sentence denotes Thus, administration of PUFAs and/or their metabolites, resolvins, protectins and maresins can suppress inappropriate production of IL-6 and TNF-α to resolve inflammation, enhance recovery and limit cytokine storm (Das, 2019) in COVID-19.
T550 18079-18256 Sentence denotes Together, the studies imply administration of n-3 PUFA may enhance recovery from infections and further, if present in adequate amounts, may modulate the response to infections.
T551 18258-18326 Sentence denotes 8.1.4 Role of CYP-mediated metabolites in ameliorating inflammation
T552 18327-18743 Sentence denotes CYP2J and CYP2C isoforms, the constitutively expressed cytochrome P450 (CYP) epoxygenases found in the cardiovascular system, metabolize EPA into 5 regioisomeric epoxyeicosatetraenoic acids (5,6-, 8,9-, 11,12-, 14,15-, 17,18-EEQ) and DHA into 6 regioisomeric epoxydocosapentaenoic acids (4,5-, 7,8-, 10,11-, 13,14-, 16,17-, 19,20-EDP) (Arnold et al., 2010; Konkel & Schunck, 2011; Westphal, Konkel, & Schunck, 2015).
T553 18744-18957 Sentence denotes Recent evidence suggests that 17,18-EEQ and 19,20-EDP mediate several anti-inflammatory effects of n-3 PUFAs in various models of tissue injury (Arnold et al., 2010; Ulu et al., 2014; Wang, Chai, Lu, & Lee, 2011).
T554 18958-19292 Sentence denotes For example, Fang et al. demonstrated a n-3 PUFA-rich diet attenuates MI injury in mice by producing a protective eicosanoid pattern, which results in shifting the metabolite profile to a more anti-inflammatory state by increasing the levels of the 19,20-EDP and 17,18-EEQ and decreasing the pro-inflammatory PGE2 (Fang et al., 2018).
T555 19293-19480 Sentence denotes The cardioprotective effects of n-3 PUFAs are also attributed to their ability to attenuate the NLRP3 inflammasome complex cascade (Darwesh, Jamieson, Wang, Samokhvalov, & Seubert, 2019).
T556 19481-19596 Sentence denotes Importantly, the anti-inflammatory features of CYP-derived epoxy metabolites have been reported in numerous models.
T557 19597-19916 Sentence denotes For example, in TNFα-induced retinal vascular inflammation, Capozzi et al. demonstrated 19,20-EDP can ameliorate vascular adhesion molecule and intracellular adhesion molecule expression and reduce leukocyte adherence to human retinal microvascular endothelial cell monolayers (Capozzi, Hammer, McCollum, & Penn, 2016).
T558 19917-20150 Sentence denotes Additionally, evidence demonstrates intraperitoneal infusions of 17,18-EEQ and 19,20-EDP protect against allergic intestinal inflammation and kidney fibrosis in corresponding mouse models (Kunisawa et al., 2015; Sharma et al., 2016).
T559 20151-20415 Sentence denotes 17,18-EEQ was able to inhibit TNFα-induced inflammation in human lung tissue obtained from patients undergoing surgery for lung carcinoma via inhibition of NF-κB and activation of the transcription factor PPAR-γ (Morin, Sirois, Echave, Albadine, & Rousseau, 2010).
T560 20416-20534 Sentence denotes The anti-inflammatory properties of DHA epoxides were also well demonstrated using animal models of inflammatory pain.
T561 20535-20780 Sentence denotes For example, Morisseau et al. demonstrated that direct injection of the DHA epoxides, EDPs, together with the pro-inflammatory carrageenan into the paw or spinal cord of male Sprague-Dawley rats resulted in significant antihyperalgesic activity.
T562 20781-21009 Sentence denotes Surprisingly, both the parent free fatty acid DHA and the corresponding diols were inactive, supporting the hypothesis that the epoxylipids mediate many of the beneficial effects of the parent compounds (Morisseau et al., 2010).
T563 21010-21149 Sentence denotes The bacterial endotoxin, LPS, has a marked role in triggering inflammatory injury which can result in several cardiovascular complications.
T564 21150-21427 Sentence denotes In a study using HL-1 cardiac cells, 19,20-EDP protected against LPS-stimulated inflammatory injury by activating the histone deacetylase Sirtuin-1 inhibiting the activation the pro-inflammatory transcription factor NF-κB (Samokhvalov, Jamieson, Vriend, Quan, & Seubert, 2015).
T565 21428-21634 Sentence denotes The accumulating evidence suggests the anti-inflammatory properties of CYP-epoxygenase metabolites of n-3 PUFAs have a substantial role in activating protective responses in models of cardiovascular injury.
T566 21635-21785 Sentence denotes However, further investigation is required to elucidate whether the protective properties limit cardiovascular injury secondary to COVID-19 infection.
T567 21787-21877 Sentence denotes 8.1.5 N-3 PUFAs alter cell membrane structure and function - modulation of the lipid raft
T568 21878-22118 Sentence denotes Within a cell, n-3 PUFAs can be found incorporated into phospholipid membranes where elevating levels will replace existing n-6 PUFAs thereby altering the composition and properties of lipid rafts (Lordan et al., 2017; Lordan et al., 2020).
T569 22119-22293 Sentence denotes The increased incorporation of n-3 PUFAs into membrane bilayers can have a role in mediating immunomodulatory effects by altering membrane composition, fluidity and function.
T570 22294-22486 Sentence denotes These changes will impact membrane-mediated signaling, protein trafficking, generation of bioactive lipids, cytokine secretion and gene activation in both innate and adaptive immune responses.
T571 22487-22697 Sentence denotes For example, a change in fluidity can interfere with the dimerization and expression of the TLR4 subunits, blocking the downstream inflammatory reaction (Ciesielska & Kwiatkowska, 2015; Takashima et al., 2016).
T572 22698-23063 Sentence denotes Evidence of these effects by n-3 PUFAs have been demonstrated to impact the maturation of dendritic cells, macrophage function and T and B cell polarization/activation (Katagiri, Kiyokawa, & Fujimoto, 2001; Kim et al., 2010; McMurray, Bonilla, & Chapkin, 2011; Rockett, Salameh, Carraway, Morrison, & Shaikh, 2010; Shaikh and Edidin, 2006, Shaikh and Edidin, 2008).
T573 23064-23309 Sentence denotes Interestingly, DHA appears to be better than EPA in replacing n-6 PUFAs and cholesterol in plasma membranes of aortic endothelial cells enhancing the fluidity of the phospholipid membrane (Hashimoto, Hossain, Yamasaki, Yazawa, & Masumura, 1999).
T574 23310-23444 Sentence denotes In most cell types, AA is the predominant n-6 PUFA in membrane phospholipids (Yaqoob, Pala, Cortina-Borja, Newsholme, & Calder, 2000).
T575 23445-23584 Sentence denotes Inflammatory immune cells such as monocytes, neutrophils, macrophages and lymphocytes often contain a large amount of AA in their membrane.
T576 23585-23668 Sentence denotes The high membrane AA composition is important during normal inflammatory responses.
T577 23669-23936 Sentence denotes Under stress conditions activation of phospholipase A2 liberates AA from the cell membrane leading to metabolism and production of many pro-inflammatory metabolites (Ford, Hazen, Saffitz, & Gross, 1991; Hazen, Ford, & Gross, 1991; Leslie, 2015; Mancuso et al., 2003).
T578 23937-24303 Sentence denotes Supplementation with n-3 PUFAs leads to the substitution of AA with EPA and DHA in the cell membrane which can alter immune cell reaction in response to stress stimuli by shifting the metabolic profile to less proinflammatory or even anti-inflammatory metabolite predominance (Brouard & Pascaud, 1990; Faber et al., 2011; Gibney & Hunter, 1993; Grando et al., 2009).
T579 24304-24504 Sentence denotes Therefore, increasing n-3 PUFAs, such as EPA and DHA, in the phospholipids has a potential benefit of ameliorating detrimental effects during uncontrolled inflammatory responses (Lordan et al., 2020).