LitCovid-sentences  

PMC:7781431 / 1570-39179 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T12 0-12 Sentence denotes Introduction
T13 13-269 Sentence denotes The unexpected emergence of deadly coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS- CoV) significantly affected human health, leading to increased mortality and life disruption.
T14 270-535 Sentence denotes Recently, a third highly pathogenic and infectious coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged as a deadly pandemic calling for intense research efforts on its pathogenicity mechanism and development of therapeutic strategies.
T15 536-904 Sentence denotes Among others, pro-resolving mediators have been investigated as a therapeutic opportunity for treatment and management of SARS-CoV-2; cytokine storm has been associated with severe illness and mortality, with many studies reporting higher concentrations of pro-inflammatory cytokines in severely ill SARS-CoV-2 patients as compared to those with less severe infection.
T16 905-1058 Sentence denotes Hence, resolution of inflammation through selective counter-regulation of cytokines has been identified as a potential therapeutic target for SARS-CoV-2.
T17 1059-1319 Sentence denotes In this review, we discussed the characteristics of specialized pro-resolving lipid mediators (SPMs) that induce the resolution of inflammation and reviewed evidence from recent studies on SPMs as therapeutic options for viral infections, including SARS-CoV-2.
T18 1320-1457 Sentence denotes We hope that this review will be of great help in guiding researchers who are exploring SPMs as therapeutic targets for viral infections.
T19 1459-1507 Sentence denotes Specialized pro-resolving lipid mediators (SPMs)
T20 1508-1780 Sentence denotes Inflammation is an extremely important, self-limiting immune response; however, uncontrolled or unresolved inflammation has been established as a pathophysiological mechanism for various diseases including viral infections, and a cause for prolonged homeostasis imbalance.
T21 1781-2022 Sentence denotes Resolution of inflammation occurs in an overlapping stage dominated by the spatial and temporal biosynthesis of pro-resolved mediators (Headland and Norling 2015), SPMs, from essential polyunsaturated fatty acids (PUFAs) during inflammation.
T22 2023-2351 Sentence denotes The SPMs initiate the process of resolution which include restriction or cessation of neutrophil infiltration, counter-regulation of chemokines and cytokines, induction of the neutrophils apoptosis and subsequent efferocytosis (the process by which apoptotic cells are removed by phagocytic cells) by macrophages (Reville et al.
T23 2352-2609 Sentence denotes 2006), the conversion of macrophages from classically activated (M1) to alternatively activated cells (M2), return of non-apoptotic cells to the vascular system or lymphatic vessels, and the start of the healing process (Fig. 1) (Headland and Norling 2015).
T24 2610-2693 Sentence denotes These events facilitate proper return homeostasis balance (Serhan and Savill 2005).
T25 2694-2789 Sentence denotes For a comprehensive review, including structural explanations of SPMs, see reviews (Park et al.
T26 2790-2830 Sentence denotes 2020; Chiang and Serhan 2017; Lee 2012).
T27 2832-2846 Sentence denotes Lipoxins (LXs)
T28 2847-3082 Sentence denotes Lipoxin A4 (LXA4; 5S, 6R, 15S-trihydroxy-7E, 9E, 11Z, 13E-eicosatetraenoic acid) and lipoxin B4 (LXB4; 5S, 14R, 15S-trihydroxy-6E, 8Z, 10E, 12E-eicosatetraenoic acid) were the first lipid SPMs to be discovered (Chiang and Serhan 2017).
T29 3083-3242 Sentence denotes They are produced from the conversion of omega-6 (ω-6) arachidonic acid (AA) by lipoxygenase (LOX) through unicellular and transcellular biosynthesis pathways.
T30 3243-3480 Sentence denotes In transcellular biosynthesis, LXs are synthesized by12-LOX derived through platelet-leukocyte interaction while unicellular biosynthesis pathways involve a series of LOXs-15-lipoxygenase, 5-lipoxygenase, and epoxide hydrolase reactions.
T31 3481-3649 Sentence denotes In addition to the lipoxygenase-initiated biosynthesis, two distinct lipoxins biosynthesis pathways have been elucidated; aspirin-triggered and statin-triggered routes.
T32 3650-3901 Sentence denotes Aspirin induces the production of a lipoxin named “aspirin-triggered " (AT) 15-epi-LX through acetylation of serine residue of cyclooxygenase-2 (COX-2), acetylated COX-2 transforms AA into 15R-HETE, which serves as a substrate for 5-LOX (Chiang et al.
T33 3902-3908 Sentence denotes 2005).
T34 3909-4062 Sentence denotes Statins, widely used as potent cholesterol-lowering agents, have also been found to enhance the conversion of arachidonate to 15-epi-LX (Planaguma et al.
T35 4063-4069 Sentence denotes 2010).
T36 4070-4229 Sentence denotes Epi-lipoxins, trihydroxy metabolites of arachidonic acid, are 15R-epimers of their respective lipoxins, 15-epi-LXA4, LXA4, and 15-epi-LXB4, LXB4 (Romano et al.
T37 4230-4236 Sentence denotes 2015).
T38 4237-4484 Sentence denotes In vivo biosynthesis of LXA4 is triggered in an acute inflammatory process in which Polymorphonuclear neutrophil (PMN)’s interaction with PGE2 and PGD2 activates 15-lipoxygenase subsequently facilitating LXA4 biosynthesis (Claria and Serhan 1995).
T39 4485-4638 Sentence denotes In a murine peritonitis model, the maximum level of LXA4 was achieved within 2 hours and gradually decreased during the first 24 hours (Bannenberg et al.
T40 4639-4645 Sentence denotes 2005).
T41 4646-4751 Sentence denotes The formation of LXs is preserved across a wide range of animal species, from fish to humans (Levy 2005).
T42 4752-4803 Sentence denotes This indicates the physiological importance of LXs.
T43 4805-4841 Sentence denotes E-, D-, and T-series resolvins (Rvs)
T44 4842-5080 Sentence denotes Resolvin (Rv) is a pro-resolving mediator that is derived from omega-3 fatty acids, primarily eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), docosapentaenoic acid (DPA), and clupanodonic acid (Duvall and Levy 2016; Serhan et al.
T45 5081-5087 Sentence denotes 2014).
T46 5088-5234 Sentence denotes Rvs are divided into several subclasses based on the unique aspects of their structure and/or the straight-chain PUFAs from which they are formed.
T47 5235-5293 Sentence denotes Resolvin Ds (RvDs) are metabolites of 22-carbon PUFA, DHA.
T48 5294-5644 Sentence denotes Resolvin Es (RvE) are metabolites of 20 carbons PUFA, EPA; Resolvin Dn-6DPA (RvDn-6DPA) is a DPA isomer, a metabolite of osbond acids; Resolvin Dn-3DPA (RvDn-3DPA) is a DPA isomer, a metabolite of clupanodonic acid; Resolvin Ts (RvT) is a metabolite of clupanodonic acid with 17R-hydroxyl residues, unlike RvDsn-3DPA (all have 17S-hydroxyl residues).
T49 5645-5790 Sentence denotes AT-RvDs, RvD isomers are synthesized by the aspirin-modified COX-2 enzyme to form 17 (R)-hydroxyl rather than the 17 (S)-hydroxyl residue of RvE.
T50 5791-5942 Sentence denotes Cytochrome P450 enzymes that have not yet been characterized may also form this 17 (R)-hydroxy intermediate and contribute to the production of AT-RvE.
T51 5943-6032 Sentence denotes All mentioned Rvs except RvDsn-6DPA are metabolites of omega-3 fatty acids (Serhan et al.
T52 6033-6061 Sentence denotes 2014; Duvall and Levy 2016).
T53 6063-6081 Sentence denotes E-series resolvins
T54 6082-6129 Sentence denotes RvE is a di- or tri-hydroxyl metabolite of EPA.
T55 6130-6203 Sentence denotes To date, four RvEs (RvE1, 18S-RvE1, RvE2, and RvE3) have been discovered.
T56 6204-6345 Sentence denotes COX-2, acetylated by aspirin in hypoxic endothelial cells, introduces oxygen groups into 18R-hydro (peroxy)-eicosapentaenoic acid (18R-HEPE).
T57 6346-6467 Sentence denotes Activated PMN uses 5-LOX to convert 18R-HEPE to 5S (6)-epoxy-18R-HEPE, which is further hydrolyzed to RvE1 (Serhan et al.
T58 6468-6474 Sentence denotes 2000).
T59 6475-6594 Sentence denotes RvE2 is produced by reduction of 18R HEPE products by 5-LOX to 5S-hydroperoxy, 18-hydroxy-EPE in whole blood (Oh et al.
T60 6595-6601 Sentence denotes 2012).
T61 6602-6715 Sentence denotes Unlike RvE1, RvE2 and RvE3 are biosynthesized from 18-HEPE via the 12/15-LOX pathway in eosinophils (Isobe et al.
T62 6716-6723 Sentence denotes 2012b).
T63 6724-6856 Sentence denotes Endogenous RvE1 has been shown to accumulate for between 48 and 72 hours, which is a delayed time point of inflammation (Hong et al.
T64 6857-6863 Sentence denotes 2008).
T65 6864-7031 Sentence denotes RvE2 appeared at the time point corresponding to initial PMN infiltration in rat peritoneal exudate stimulated by zymosan A and decreased within 24 hours (Isobe et al.
T66 7032-7039 Sentence denotes 2012a).
T67 7040-7129 Sentence denotes 18S-RvE1 is produced by 5-LOX and LTA4 hydrolase using 18S-HEPE as a substrate (Oh et al.
T68 7130-7136 Sentence denotes 2011).
T69 7138-7156 Sentence denotes D-series resolvins
T70 7157-7196 Sentence denotes RvD is a polyhydroxy metabolite of DHA.
T71 7197-7354 Sentence denotes To date, six RvDs with different positions of cis-trans isomers, as well as the number, position and chirality of the hydroxyl residues have been discovered.
T72 7355-7456 Sentence denotes D-series Rvs (RvD1-RvD6) are biosynthesized from DHA by the LOX in PMN and macrophages (Serhan et al.
T73 7457-7463 Sentence denotes 2002).
T74 7464-7553 Sentence denotes Hydrolysis of peroxide intermediates derived from two LOXs in DHA produces RvD1 and RvD2.
T75 7554-7645 Sentence denotes On the other hand, the reduction of the peroxide intermediates produces RvD5 (Serhan et al.
T76 7646-7652 Sentence denotes 2002).
T77 7653-7853 Sentence denotes In hypoxic endothelial cells in the presence of aspirin, COX-2 converts DHA to 13-hydroxy-DHA or 17R-hydroxy-DHA and activated PMN converts these products to AT-RvD1, AT-RvD2, and other AT-RvD-series.
T78 7854-8014 Sentence denotes RvD3 and RvD4 are produced through hydrolysis of 4S-hydroperoxy-17S-hydroxy-docosahexaenoic acid, whereas RvD6 is derived from peroxidase of the same precursor.
T79 8015-8275 Sentence denotes In a peritonitis model, the in vivo RvD3 levels after zymosan A challenge increases significantly up to 48 hours after inflammation initiation, while RvD1, RvD2, and RvD5 peak at the early stages of the inflammation termination phase (6–24 hours) (Dalli et al.
T80 8276-8283 Sentence denotes 2013b).
T81 8284-8385 Sentence denotes RvD3 appears to be produced by a subpopulation of macrophages with high 15-LOX activity (Dalli et al.
T82 8386-8393 Sentence denotes 2013b).
T83 8394-8655 Sentence denotes In vivo production of RvD4 in an Staphylococcus aureus injected the dorsal pouch infection model continues for more than 72 hours after sustained release, suggesting that RvD is produced continuously and is under different control from other Rvs (Winkler et al.
T84 8656-8662 Sentence denotes 2016).
T85 8663-8704 Sentence denotes RvD6 kinetics have not been reported yet.
T86 8706-8724 Sentence denotes Resolvin Ts (RvTs)
T87 8725-8875 Sentence denotes In human platelets, COX-2 pre-treated with aspirin or atorvastatin metabolizes omega-3s, DPA and clupanodonic acid (DPAn-3), to 13S-hydroperoxy forms.
T88 8876-8982 Sentence denotes Aspirin and atorvastatin change the activity of COX-2 from cyclooxygenase to hydroperoxide-forming enzyme.
T89 8983-9159 Sentence denotes The intermediates formed are transported to the nearby human neutrophils and perhaps by the activity of the ALOX5 enzyme they are metabolized into four polyhydroxy metabolites:
T90 9160-9319 Sentence denotes RvT1 (7,13R, 20-trihydroxy-DPAn-3); RvT2 (7, 8,13R-trihydroxy-DPAn-3); RvT3 (7,12,13R-trihydroxy-8Z, 10E, 14E, 16Z, 19Z-DPAn-3); RvT4 (7,13R-dihydroxy-DPAn-3).
T91 9320-9469 Sentence denotes These four RvTs are formed by human neutrophils and vascular endothelial cells and are also found in rodents and human infected tissues (Dalli et al.
T92 9470-9483 Sentence denotes 2013a, 2015).
T93 9484-9620 Sentence denotes Recently, the total synthesis of RvT1, RvT2, and its 13R-epimer RvT2, and RvT4 were successfully achieved (Rodriguez and Spur 2020a, b).
T94 9621-9736 Sentence denotes Therefore, it is expected that there will be many physiological and pharmacological research on RvTs in the future.
T95 9738-9746 Sentence denotes Maresins
T96 9747-9951 Sentence denotes Maresins (MaRs) are biosynthesized from DHA by macrophages through the action of 12-LOX, which catalyzes the oxygenation of DHA to 14-hydroperoxidocosahexaenoic acid (14-HpDHA) (Rodriguez and Spur 2020a).
T97 9952-10084 Sentence denotes This is followed by reduction to 13S, 14S-epoxy-maresin, which is further modified in human macrophages to produce MaR1 (Deng et al.
T98 10085-10189 Sentence denotes 2014) and conversion of 13S, 14S-epoxy-maresin by soluble epoxide hydrolase to produce MaR2 (Deng et al.
T99 10190-10196 Sentence denotes 2014).
T100 10197-10318 Sentence denotes Maresins, like the many other SPM members mentioned, have anti-inflammatory, protective and healing-promoting properties.
T101 10319-10567 Sentence denotes In a study using a murine model of respiratory distress syndrome, and initial in vivo production of MaR1was detected during platelet-neutrophil interactions, and its levels increased significantly within 2 hours and peaked at 24 hours (Dalli et al.
T102 10568-10575 Sentence denotes 2013c).
T103 10576-10699 Sentence denotes Measurement of 17-HDHA in tissue is used as a marker for the level of activation of the MaR production pathway (Wang et al.
T104 10700-10706 Sentence denotes 2015).
T105 10707-10884 Sentence denotes Maresin-like lipid mediators MaR-L1 and MaR-L2 are produced by white blood cells and platelets and rescue the reparative function of macrophages damaged by diabetes (Hong et al.
T106 10885-10891 Sentence denotes 2014).
T107 10892-10942 Sentence denotes Total synthesis of MaRs has not yet been reported.
T108 10944-10960 Sentence denotes Protectins (PDs)
T109 10961-11041 Sentence denotes Protectin D1 (PD1), also known as neuroprotectin D1 (NPD1), is derived from DHA.
T110 11042-11109 Sentence denotes DHA is a component of fish oil and the most important omega-3 PUFA.
T111 11110-11297 Sentence denotes Like other members of PUFA metabolites specialized pro-resolving mediators class, PD1 exerts potent anti-inflammatory and anti-apoptotic/neuroprotective biological activities (Hong et al.
T112 11298-11316 Sentence denotes 2003; Bazan 2007).
T113 11317-11466 Sentence denotes PD1 accumulates in the ipsilateral hemisphere of the brain after focal ischemia and has been shown to take part in wound healing and neuroprotection.
T114 11467-11586 Sentence denotes 15-LOX can acts 17S-HpDHA to produce the isomers of PD1, 10S, 17S-diHDHA (PDx), which also have pro-resolving activity.
T115 11587-11683 Sentence denotes PD1 production peaks at 12 hours in a zymosan A-induced rat peritonitis model (Bannenberg et al.
T116 11684-11690 Sentence denotes 2005).
T117 11691-11784 Sentence denotes Other PDs with similar activity include PDX; 20-hydroxy-PD1; and 10-epi-PD1 (Shinohara et al.
T118 11785-11814 Sentence denotes 2012; Balas and Durand 2016).
T119 11815-11888 Sentence denotes The activity of 17-epi-PD1, a PD1-like metabolite, has not been reported.
T120 11889-12032 Sentence denotes It should be noted that Neuroprotectin A and B, the bicyclohexapeptides, are structurally and mechanically different from PDs (Kobayashi et al.
T121 12033-12039 Sentence denotes 2001).
T122 12040-12125 Sentence denotes The total synthesis of PDX and PD1 methyl ester epimer was successful (Dayaker et al.
T123 12126-12146 Sentence denotes 2014; Sanceau et al.
T124 12147-12153 Sentence denotes 2019).
T125 12155-12169 Sentence denotes SPMs receptors
T126 12170-12233 Sentence denotes Herein, we briefly describe each known SPMs receptors (Fig. 2).
T127 12234-12458 Sentence denotes Previous studies have demonstrated that pro-resolving activities of SPMs occur through activation of one or more G protein-coupled receptors (GPCRs), suitable receptors for several types of SPMs have not yet been identified.
T128 12459-12661 Sentence denotes Four GPCRs have been reported as receptors for RvD1 and RvE1; however, it has not been determined whether other Rvs and PDs such as RvE2, RvE4, RvD2, RvD3, PDs, and MaRs act on these GPCRs (Arita et al.
T129 12662-12695 Sentence denotes 2005, 2007; Krishnamoorthy et al.
T130 12696-12702 Sentence denotes 2010).
T131 12703-12871 Sentence denotes For recent and specific physiological actions of these receptors and research data in KO mice, we would like to refer to other reviews and references there (Park et al.
T132 12872-12887 Sentence denotes 2020; Im 2012).
T133 12889-12908 Sentence denotes Chemerin receptor 1
T134 12909-13100 Sentence denotes Chemerin receptor 1 (chemerin1, ChemR23, or ERV1) is expressed on a wide range of immune cells, including monocytes, macrophages, natural killer cells, bone marrow cells, and dendritic cells.
T135 13101-13187 Sentence denotes Besides, ERV1 has been identified in adipocytes and endothelial cells (Luangsay et al.
T136 13188-13194 Sentence denotes 2009).
T137 13195-13301 Sentence denotes ERV1 was initially classified as an orphan GPCR with homology to the formyl peptide receptor (Gantz et al.
T138 13302-13366 Sentence denotes 1996) and the anaphylatoxin C3a and C5a receptors (Samson et al.
T139 13367-13478 Sentence denotes 1998) until recently when it was discovered to be a receptor for the chemotactic protein chemerin (Meder et al.
T140 13479-13485 Sentence denotes 2003).
T141 13486-13626 Sentence denotes In addition to chemerin, RvE1 was identified as a second endogenous agonist through a screening program against the GPCR panel (Arita et al.
T142 13627-13633 Sentence denotes 2007).
T143 13634-13802 Sentence denotes ERV1 (chemokine like receptor 1, also known as CMKLR1) is a receptor for RvE1, which has been shown to bind more strongly than chemerin (a peptide ligand) (Arita et al.
T144 13803-13824 Sentence denotes 2005; Wittamer et al.
T145 13825-13831 Sentence denotes 2004).
T146 13832-13987 Sentence denotes ERV1 overexpressing mice showed a large increase in phagocytosis upon decreased neutrophil inhibition and decreased neutrophil infiltration (Herrera et al.
T147 13988-13994 Sentence denotes 2015).
T148 13995-14097 Sentence denotes Also, RvE2 is a partial agonist compared to RvE1 in CHO-chemerin1 β-arrestin recruitment (Isobe et al.
T149 14098-14105 Sentence denotes 2012a).
T150 14106-14241 Sentence denotes However, since there is no additional information on this ligand, further investigation of potential ligand-receptor pairs is required.
T151 14243-14296 Sentence denotes N-formyl peptide receptor 2/LX A4 receptor (FPR2/ALX)
T152 14297-14452 Sentence denotes Originally FPR2 was classified as an FPR receptor due to its activation by the low-affinity endogenous agonist N-formyl methionyl peptide (fMLP) (Ye et al.
T153 14453-14459 Sentence denotes 1992).
T154 14460-14698 Sentence denotes The receptor was reclassified as FPR2/ALX, as LXA4 exhibited the highest affinity of all FPR2/ALX endogenous agonists through screening of various receptor ligands using radiolabelled [3H]-LXA4 and subsequent GTPase activity (Fiore et al.
T155 14699-14717 Sentence denotes 1994; Brink et al.
T156 14718-14724 Sentence denotes 2003).
T157 14725-14851 Sentence denotes Binding of LXA4 leads to the stimulation of monocyte chemotaxis, macrophage differentiation, and efferocytosis (Maderna et al.
T158 14852-14882 Sentence denotes 2010; Maddox and Serhan 1996).
T159 14883-15007 Sentence denotes LXA4 also reduces the adaptive immune response by reducing memory B cell antibody production and proliferation (Ramon et al.
T160 15008-15014 Sentence denotes 2014).
T161 15015-15185 Sentence denotes Endogenous and exogenous lipids, peptides, and proteins have been shown to bind and activate FPR2/ALX to produce inflammatory and anti-inflammatory effects (Takano et al.
T162 15186-15205 Sentence denotes 1997; Cooray et al.
T163 15206-15212 Sentence denotes 2013).
T164 15213-15372 Sentence denotes Both the LXs and Rvs families, including LXA4, AT-LXA4 (15-epi-LXA4), RvD1, AT-RvD1 (17-epi-RvD1), and Annexin A1 (ANXA1) activate receptors with high potency.
T165 15373-15512 Sentence denotes On the other hand, endogenous antagonists, including serum amyloid A (SAA) and cathelicidin (LL-37) have been identified (Bozinovski et al.
T166 15513-15529 Sentence denotes 2012; Wan et al.
T167 15530-15536 Sentence denotes 2011).
T168 15538-15543 Sentence denotes GPR18
T169 15544-15642 Sentence denotes GPR18 was discovered as a receptor for RvD2 through GPCR-β-arrestin-based screening (Chiang et al.
T170 15643-15711 Sentence denotes 2015), and the receptor was referred to as DRV2/GPR18 (Chiang et al.
T171 15712-15725 Sentence denotes 2017, 2019a).
T172 15726-15777 Sentence denotes Besides, several other ligands activate DRV2/GPR18.
T173 15778-16093 Sentence denotes These include endogenous ligands such as N-arachidonylglycine (NAGly), anandamide, a metabolite of the endocannabinoid anandamide, synthetic ligands such as abnormal-cannabidiol (Abn-CBD), and O-1918, a partial agonist, which can be used as a pharmacological tool to inhibit DRV2/GPR18 signalling (Offertaler et al.
T174 16094-16112 Sentence denotes 2003; Kohno et al.
T175 16113-16119 Sentence denotes 2006).
T176 16120-16197 Sentence denotes GPR18 is abundantly expressed in PMNs, monocytes and macrophages (Wang et al.
T177 16198-16204 Sentence denotes 2014).
T178 16205-16571 Sentence denotes In addition to the resolution of inflammation, while GPR18 has low structural similarity to the cannabinoid receptors CB1, CB2, and GPR55, it responds to endogenous and synthetic cannabinoid ligands including n-arachidonoyl ethanolamine (AEA), 2-arachidonoyl glycerol (2-AG), Δ9-tetrahydrocannabinol (Δ9-THC), and, arachidonoylcyclopropylamide (ACPA) (McHugh, 2012).
T179 16572-16835 Sentence denotes Also interestingly, GPR18 is structurally very similar to EBV-induced receptor 2 (EBI2), whose expression is increased more than 20 times in Epstein-Barr virus (EBV) infected cells, and is a GPCR receptor clustered together in the 13q32 (Rosenkilde et al., 2006).
T180 16837-16842 Sentence denotes GPR32
T181 16843-16969 Sentence denotes GPR32 is primarily expressed in human PMN, monocytes, adipose tissue and vascular endothelial cells (Sansbury and Spite 2016).
T182 16970-17198 Sentence denotes RvD1 was identified as a potential agonist due to the activation of GPR32, where [3H]-RvD1 binds to human leukocytes and significantly lowers TNF-α-stimulated NF-κB signalling in GPR32 overexpressing cells (Krishnamoorthy et al.
T183 17199-17205 Sentence denotes 2010).
T184 17206-17342 Sentence denotes Although RvD1 has a higher affinity for GPR32 than FPR2/ALX, its interaction with GPR32 has not been extensively studied (Norling et al.
T185 17343-17349 Sentence denotes 2012).
T186 17350-17465 Sentence denotes This could be since GPR32 exists as a pseudogene in rodents, which makes animal testing in principle inappropriate.
T187 17466-17660 Sentence denotes Treatment of inflammatory macrophages expressing GPR32 with RvD1 enhanced the pro-resolving phenotype to increase phagocytosis and decrease the secretion of inflammatory cytokines (Schmid et al.
T188 17661-17667 Sentence denotes 2016).
T189 17668-17792 Sentence denotes Also, GPR32 was also involved when during the inhibition of the EMT phenomenon of lung cancer cell lines by RvD1 (Lee et al.
T190 17793-17799 Sentence denotes 2013).
T191 17800-17939 Sentence denotes Additionally, RvD3, AT-RvD3, and RvD5 have all been shown to activate GPR32 in a recombinant system of β-arrestin recruitment (Dalli et al.
T192 17940-17960 Sentence denotes 2013b; Chiang et al.
T193 17961-17967 Sentence denotes 2012).
T194 17968-18040 Sentence denotes These facts suggest the potential redundancy of ligands acting on GPCRs.
T195 18042-18047 Sentence denotes GPR37
T196 18048-18218 Sentence denotes GPR37 or Parkin-related endothelin-like receptor (Pael-R) was originally discovered through genomic library screening to find new neuropeptide receptors (Marazziti et al.
T197 18219-18225 Sentence denotes 1997).
T198 18226-18376 Sentence denotes The GPR37 receptor is primarily expressed in the brain and is associated with neurological disorders such as Parkin’s disease and autism (Lopes et al.
T199 18377-18383 Sentence denotes 2015).
T200 18384-18537 Sentence denotes Mutations within GPR37 affect various autism spectrum disorders, regulation of dopamine reuptake and oligodendrocyte differentiation (Fujita-Jimbo et al.
T201 18538-18560 Sentence denotes 2012; Marazziti et al.
T202 18561-18578 Sentence denotes 2007; Yang et al.
T203 18579-18585 Sentence denotes 2016).
T204 18586-18784 Sentence denotes PD1 is considered as a ligand for GPR37 because it induced a significant increase in intracellular calcium in HEK293 cells overexpressing GPR37 and murine peritoneal-derived macrophages (Bang et al.
T205 18785-18791 Sentence denotes 2018).
T206 18792-19024 Sentence denotes Based on the fact that Gpr37-/- mice exhibited increased apoptosis and infarct size, it has recently been suggested that GPR37 is also involved in cell damage protection and inflammation after ischemic stroke (McCrary et al., 2019).
T207 19025-19241 Sentence denotes However, due to its clear role in the central nervous system (CNS), the development of a therapeutic agent targeting GPR37 requires a balance between the effect on the central nervous system and therapeutic benefits.
T208 19243-19259 Sentence denotes Leukotriene BLT1
T209 19260-19516 Sentence denotes BLT1 has also been shown to be a receptor for RvE1 although its clone, high-affinity leukotriene B4 (LTB4) is a potent lipid inflammatory chemoattractant, inducing T helper cell chemotaxis and early effector T cell recruitment through BLT1 (Yokomizo et al.
T210 19517-19535 Sentence denotes 1997; Arita et al.
T211 19536-19542 Sentence denotes 2007).
T212 19543-19761 Sentence denotes BLT1 shares 21% sequence identity with chemerin1; while this value is relatively low, selective BLT1 antagonist U-75,302 has been demonstrated to replace the binding of [3H]-RvE1 to the human PMN membrane (Arita et al.
T213 19762-19768 Sentence denotes 2007).
T214 19769-19951 Sentence denotes Besides, although RvE1 is 100 times less potent than LTB4, it inhibited adenylate cyclase activity and induced intracellular calcium mobilization in HEK293 cells overexpressing BLT1.
T215 19952-20151 Sentence denotes These data indicate the role of RvE1 in reducing BLT1-induced inflammation by RvE1 acting as a partial agonist that competes with LTB4-mediated NF-κB activation and calcium mobilization (Arita et al.
T216 20152-20158 Sentence denotes 2007).
T217 20159-20363 Sentence denotes Activation of BLT1 by RvE1 also serves as a feedback mechanism for other SPMs, including increased production of LXA4 in the FPR2/ALX-mediated resolution of allergic pulmonary inflammation (Haworth et al.
T218 20364-20370 Sentence denotes 2008).
T219 20371-20589 Sentence denotes RvE2 was identified as an additional BLT1 agonist, and the β-arrestin assay showed that RvE2 blocked LTB4-mediated β-arrestin signalling with similar efficacy to RvE1, indicating direct competition with LTB4 (Oh et al.
T220 20590-20596 Sentence denotes 2012).
T221 20597-20725 Sentence denotes Various pro-resolving roles of RvE2 have been proposed, including regulation of PMN infiltration and IL-10 production (Oh et al.
T222 20726-20732 Sentence denotes 2012).
T223 20733-20871 Sentence denotes However, while RvE1 promotes NADPH oxidase-mediated ROS production through the BLT1, RvE2 and RvE3 do not exhibit this effect (Unno et al.
T224 20872-20878 Sentence denotes 2018).
T225 20880-20917 Sentence denotes Activation of other receptors by SPMs
T226 20918-20988 Sentence denotes A few studies have reported the possibility of other GPCR involvement.
T227 20989-21097 Sentence denotes Among them, GPR101 mediates the pro-resolving effects of RvD5n-3 DPA in arthritis and infection (Flak et al.
T228 21098-21104 Sentence denotes 2020).
T229 21105-21197 Sentence denotes Besides, SPMs have been reported to activate non-GPCRs receptors, such as nuclear receptors.
T230 21198-21384 Sentence denotes In a dose-dependent manner, PD1 enhances PPARγ transcriptional activation reporter activity in human neuron-glia (HNG) cells co-transfected with hPPARγ-GAL4 and MH100-tk-Luc (Zhao et al.
T231 21385-21391 Sentence denotes 2011).
T232 21392-21509 Sentence denotes This suggests that PD1 is capable of enhancing the peroxisome proliferator-activated receptor gamma (PPARγ) (Fig. 2).
T233 21510-21608 Sentence denotes The transcriptional activity of PPARγ was significantly increased after treatment with 100 nM PD1.
T234 21609-21840 Sentence denotes RvD1 was also assumed to be a ligand for PPARγ and inhibited IκBα degradation and NF-κB p65 nuclear translocation in an LPS-induced lung injury model, which was partially reversed by the PPARγ inhibitor GW9662 (Fig. 2) (Liao et al.
T235 21841-21847 Sentence denotes 2012).
T236 21848-21963 Sentence denotes Recently, it has been reported that LXA4 binds to the nuclear aryl hydrocarbon receptor (AhR) (Fig. 2) (Asha et al.
T237 21964-21970 Sentence denotes 2020).
T238 21971-22033 Sentence denotes A GPCR that acts directly on MaR1 has not yet been identified.
T239 22034-22356 Sentence denotes However, MaR1 blocks TRPV1-mediated currents in neurons, acts as a ligand for the retinoid-associated orphan receptor α (RORα), and inhibits TLR4 signalling (Fig. 2) (Park 2015), Chiang et al. found that MaR1 can activate LGR6, a member of the glycoprotein hormone receptor subfamily of rhodopsin-like GPCRs (Chiang et al.
T240 22357-22500 Sentence denotes 2019b), which initiates cAMP, impedance changes, and stimulate an innate immune response against PMNs, monocytes and macrophages (Chiang et al.
T241 22501-22508 Sentence denotes 2019b).
T242 22510-22562 Sentence denotes Role of SPMs and Their Receptors in Virus Infections
T243 22563-22726 Sentence denotes Because viruses are obligate intracellular parasites, viruses must enter target cells and multiply using host cell machinery to produce progeny viruses (Ryu 2017).
T244 22727-22827 Sentence denotes The various stages involved in viral growth that occur inside cells are called the viral life cycle.
T245 22828-22919 Sentence denotes The viral life cycle can be divided into three stages: entry, genome replication, and exit.
T246 22920-23048 Sentence denotes Entry can be subdivided into attachment, penetration and uncoating, and exit can be subdivided into virion assembly and release.
T247 23049-23090 Sentence denotes Genome replication differs by virus type.
T248 23091-23276 Sentence denotes Many studies are showing that SPMs regulate the inflammatory response caused by viral infections, but studies on the effects of SPMs on the viral life cycle have been difficult to find.
T249 23277-23311 Sentence denotes There have a few reports recently.
T250 23312-23646 Sentence denotes For example, among SPMs, LXA4 modulates Kaposi’s Sarcoma-Associated Herpesvirus (KSHV) life cycle through chromatin modulation and hedgehog signalling to destabilize the latency of herpes virus and decreases the expression of programmed death-ligand 1 (PD-L1) in Kaposi’s Sarcoma, thereby reducing immune evasion (Fig. 3) (Asha et al.
T251 23647-23653 Sentence denotes 2020).
T252 23654-23793 Sentence denotes On the other hand, there are not a few reports that the receptors mentioned above for SPMs act as receptors in virus infection (see below).
T253 23794-23990 Sentence denotes So, in this section, we will discuss the effect of SPMs on the virus and the viral infection-induced inflammation and mention how the receptors of SPMs affect the life cycle of the virus (Fig. 3).
T254 23992-24001 Sentence denotes Influenza
T255 24002-24146 Sentence denotes Influenza viruses are a well-studied model for understanding the role of inflammation resolution mediators and the mechanism of viral infection.
T256 24147-24233 Sentence denotes This is because different viruses elicit different host immune responses and outcomes.
T257 24234-24457 Sentence denotes From studies comparing more virulent influenza virus strains to less virulent strains, it has been reported that pro-resolving mediators have an inverse correlation with the biological activity of the virus (Cilloniz et al.
T258 24458-24464 Sentence denotes 2010).
T259 24465-24567 Sentence denotes The more toxic strains of influenza induced reduction of LXs, which increased the spread of the virus.
T260 24568-24718 Sentence denotes LXB4 recently improved IgG production in B cells from donors vaccinated against influenza virus, suggesting potential as a novel adjuvant. (Kim et al.
T261 24719-24725 Sentence denotes 2018).
T262 24726-24870 Sentence denotes Annexin is the most abundant host cell protein in the virion, and annexin A1 (ANXA1) contributes to influenza-induced toxicity (Tcherniuk et al.
T263 24871-24877 Sentence denotes 2016).
T264 24878-25089 Sentence denotes That is, during virus entry into the host cell, viral hemagglutinin (HA) not only binds sialic acid but also ANXA1 binds to FPR2, resulting in activation of ERK2 and increased viral replication (Tcherniuk et al.
T265 25090-25096 Sentence denotes 2016).
T266 25097-25130 Sentence denotes RvD1 and LXA4 also activate FPR2.
T267 25131-25303 Sentence denotes It is still unknown whether RvD1 and LXA4 compete with viral annexin at the receptors site leads to the prevention of viral infection or the promotion of viral replication.
T268 25304-25405 Sentence denotes However, it is reported that AT-RvD1 reduces inflammation caused by the viral infection. (Wang et al.
T269 25406-25412 Sentence denotes 2017).
T270 25413-25683 Sentence denotes Increased SAA in recurrent acute exacerbations of COPD caused by bacterial and virus coinfection acts as a functional agonist of FPR2/ALX, antagonizing the protective action of FPR2/ALX by AT-RvD1, promoting chemotaxis of neutrophils and prolonging survival (Wang et al.
T271 25684-25690 Sentence denotes 2018).
T272 25691-25805 Sentence denotes There are no reports of direct research on whether RvD1, the same family as AT-RvD1, inhibits the influenza virus.
T273 25806-25896 Sentence denotes However, it promotes inflammation and removal of bacteria caused by a bacterial infection.
T274 25897-26024 Sentence denotes For example, RvD1 relieves lung inflammation and promotes the elimination of untypeable Haemophilus influenza (Croasdell et al.
T275 26025-26031 Sentence denotes 2016).
T276 26032-26185 Sentence denotes ChemR23, a receptor for RvE1, relieves lung inflammation and enhances antiviral immunity in a mouse model of acute viral pneumonia (Bondue et al., 2011).
T277 26186-26299 Sentence denotes Therefore, it would be fascinating to study whether RvE1 is effective in pneumonia caused by the influenza virus.
T278 26300-26369 Sentence denotes PD1 has pivotal and multiple roles in regulating viral pathogenicity.
T279 26370-26443 Sentence denotes Influenza strains, such as the lethal H5N1, down-regulate PD1 (Tam et al.
T280 26444-26450 Sentence denotes 2013).
T281 26451-26565 Sentence denotes There is an inverse correlation between the level of PD1 and the level of pathogenicity of various virus isolates.
T282 26566-26667 Sentence denotes In addition to the host’s inflammatory response, PD1 has a direct antiviral action against influenza.
T283 26668-26850 Sentence denotes Both PD1 and its isomer PDX (LOX-mediated double oxygenation) limit viral replication by interfering with the viral RNA nuclear transport mechanism (Fig. 3) (Imai 2015; Morita et al.
T284 26851-26882 Sentence denotes 2013; Baillie and Digard 2013).
T285 26883-27092 Sentence denotes Treatment of infected mice with PD1 improves survival, even if administered 48 hours after the onset of infection when the current antiviral therapy is no longer significantly effective (Fig. 4) (Morita et al.
T286 27093-27108 Sentence denotes 2013; Ng et al.
T287 27109-27115 Sentence denotes 2010).
T288 27117-27137 Sentence denotes Herpes simplex virus
T289 27138-27387 Sentence denotes Herpesviruses 1 and 2 (HSV-1 and HSV-2), with the taxonomic names human alphaherpesvirus 1 and human alphaherpesvirus 2, are the most common causes of human viral infections among the members of the human Herpesviridae family (Chayavichitsilp et al.
T290 27388-27394 Sentence denotes 2009).
T291 27395-27734 Sentence denotes Herpes simplex virus (HSV) ocular infection represents another example in which local control of the virus stems from a robust inflammatory response with long-term consequences of chronic inflammation, including the possibility of final blindness due to interstitial keratitis that persists even after the viral infection has been cleared.
T292 27735-28029 Sentence denotes In animals with HSV, topical administration of RvE1 reduced the influx of CD4+ T cells (both TH1 cells and TH17 cells) and neutrophils, decreased production of inflammatory cytokines including IFNγ and IL-6, and increased levels of the anti-inflammatory cytokine IL-10 (Fig. 4) (Rajasagi et al.
T293 28030-28036 Sentence denotes 2011).
T294 28037-28091 Sentence denotes Overall, RvE1 significantly reduced stromal keratitis.
T295 28092-28160 Sentence denotes Similar results were demonstrated with PD1 (Fig. 4) (Rajasagi et al.
T296 28161-28167 Sentence denotes 2013).
T297 28168-28468 Sentence denotes Besides, AT-RvD1 treatment significantly reduced the degree of corneal angiogenesis and the severity of stromal keratitis lesions, and AT-RvD1 treated mice had fewer Th1 and Th17 cells in the infected cornea, as well as the reduced number of inflammatory cells, including neutrophils (Rajasagi et al.
T298 28469-28475 Sentence denotes 2017).
T299 28477-28557 Sentence denotes Respiratory syncytial virus, human immunodeficiency virus, and hepatitis C virus
T300 28558-28811 Sentence denotes Respiratory syncytial virus (RSV), also known as human respiratory cell fusion virus (HRSV) and human orthopneumovirus, is a virus that causes respiratory infections in which infected mucosal cells fuse to form a syncytium (Schweitzer and Justice 2020).
T301 28812-28941 Sentence denotes It is the leading cause of lower respiratory tract infections and hospital visits in infancy and childhood (Read and Bosco 2020).
T302 28942-29112 Sentence denotes RSV infection results in bronchiolitis, which is classically caused by activated macrophages and eventually resolved by alternatively activated macrophages (Shirey et al.
T303 29113-29119 Sentence denotes 2010).
T304 29120-29293 Sentence denotes The promotion of these two alternative macrophage fates appears to be related to RSV-induced COX-2 and LXA4 and RvE1-mediated protective measures (Fig. 4) (Richardson et al.
T305 29294-29313 Sentence denotes 2005; Shirey et al.
T306 29314-29320 Sentence denotes 2014).
T307 29321-29594 Sentence denotes Also, although it does not directly act on the virus, RvD1 inhibits inflammatory signal transduction by polyinosinic-polycytidylic acid, an analogue of RNAs derived from respiratory viruses such as RSV, and the action of RvD1 is mediated by FPR2/ALX and GPR32 (Hsiao et al.
T308 29595-29601 Sentence denotes 2014).
T309 29602-29764 Sentence denotes These reports suggest the critical role of SPMs and lipid mediator class shift in the host’s response to RSV in the initial control and final infection clearance.
T310 29765-29945 Sentence denotes Human immunodeficiency virus (HIV) is a lentivirus (a subgroup of retroviruses) and are classified into two based on the genetic characteristics and viral antigen, HIV-1 and HIV-2.
T311 29946-30062 Sentence denotes HIV infection may progress to acquired immunodeficiency syndrome (AIDS), a progressive failure of the immune system.
T312 30063-30181 Sentence denotes Over time, AIDS causes life-threatening opportunistic infections and a condition in which cancer thrives (Douek et al.
T313 30182-30201 Sentence denotes 2009; Powell et al.
T314 30202-30208 Sentence denotes 2016).
T315 30209-30522 Sentence denotes When co-cultured with HIV-1 infected mononuclear cells and human glial cells (astrocytoma, glial and primary human astrocyte), tumour necrosis factor alpha (TNF-α) and interleukin-1β are produced, and large amounts of LTB4, LTD4, LXA4, and PAF, were also found in media from this co-culture (Fig. 4) (Genis et al.
T316 30523-30529 Sentence denotes 1992).
T317 30530-30640 Sentence denotes So far, this is the only in vitro study to prove, that LXs are produced in direct response to viral infection.
T318 30641-30716 Sentence denotes However, the role of LXs in this infection model has not been investigated.
T319 30717-30942 Sentence denotes Synthetic peptides derived from human immunodeficiency virus type 1 gp120 activate the 7-transmembrane GPCR FPR2/ALX, down-regulating the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes (Deng et al.
T320 30943-30949 Sentence denotes 1999).
T321 30950-31040 Sentence denotes FPR2/ALX acts as an efficient core receptor for the primary isolate of HIV (Shimizu et al.
T322 31041-31047 Sentence denotes 2008).
T323 31048-31158 Sentence denotes Viral entries through the alternative core receptors (CoR) CCR3 and FPR2/ALX depend on the HIV type 1 subtype.
T324 31159-31304 Sentence denotes Viruses pseudotyped with subtype A and C Env proteins use the recently described alternative CoR FPR2 more efficiently than CCR3 (Nedellec et al.
T325 31305-31311 Sentence denotes 2009).
T326 31312-31347 Sentence denotes ChemR23 also acts as a CoR for HIV.
T327 31348-31487 Sentence denotes At this time, HIV-1 and HIV-2 appear to use the N-terminus and the second extracellular loop of ChemR23 during infection (Martensson et al.
T328 31488-31494 Sentence denotes 2006).
T329 31495-31622 Sentence denotes As mentioned above, research is needed to determine the role of SPMs that act as ligands for FPR2 and ChemR23 in HIV infection.
T330 31623-31769 Sentence denotes Hepatitis C virus (HCV) is a positive-sense single-stranded RNA virus of the family Flaviviridae with a small (55–65 nm size) envelope (Lee et al.
T331 31770-31776 Sentence denotes 2017).
T332 31777-31931 Sentence denotes The HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma, abbreviated HCC) and lymphoma in humans (Ferri et al.
T333 31932-31960 Sentence denotes 2015; Rusyn and Lemon 2014).
T334 31961-32041 Sentence denotes To date, there appears to be no report on the effectiveness of SPMs against HCV.
T335 32042-32189 Sentence denotes However, HCV peptide (C5A), an amphiphilic α-helix peptide of HCV, is an activator of the N-formyl peptide receptor in human phagocytes (Lin et al.
T336 32190-32196 Sentence denotes 2011).
T337 32197-32287 Sentence denotes This suggests the possibility of interaction between RvD1 and LXA4, FPR families, and HCV.
T338 32288-32410 Sentence denotes Vitamin D metabolites inhibit HCV and upregulate GPR37 gene expression, which induces cellular autophagy (Gutierrez et al.
T339 32411-32417 Sentence denotes 2014).
T340 32418-32549 Sentence denotes PD1 was recently proposed as a new ligand for GPR37, and some studies suggest a possible relationship between PD1 and HCV (Fig. 4).
T341 32550-32700 Sentence denotes SAA also has antiviral effects against HCV, however, it induces chronic inflammation through FPR2/ALX, causing liver damage (Abouelasrar Salama et al.
T342 32701-32707 Sentence denotes 2019).
T343 32708-32873 Sentence denotes Although research has not been conducted yet, RvD1 and LXA4, which inhibit the action of SAA, are likely to suppress liver damage caused by SAA during HCV infection.
T344 32875-32885 Sentence denotes SARS-CoV-2
T345 32886-33172 Sentence denotes Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) refers to a coronavirus strain that causes 2019 coronavirus disease (COVID-19), a respiratory disease that is the cause of the COVID-19 pandemic (Coronaviridae Study Group of the International Committee on Taxonomy of, 2020).
T346 33173-33301 Sentence denotes SARS-CoV-2 is an RNA virus that infects the lungs and causes deaths through complications such as cytokine storms (Goldin et al.
T347 33302-33308 Sentence denotes 2020).
T348 33309-33487 Sentence denotes The anti-inflammatory action of mesenchymal stem cells is well known, and it is believed that these mesenchymal stem cells exhibit anti-inflammatory action through PGE2 and LXA4.
T349 33488-33670 Sentence denotes These lipids mediators alleviate the SARS-CoV-2 cytokine storm, while arachidonic acid, dihomo-gamma-linolenic acid, and gamma-linolenic acid inactivate enveloped viruses (Das 2020).
T350 33671-33805 Sentence denotes Obesity is a risk factor for SARS-CoV-2 infection, and a BMI of 30 kg/m2 increases the risk of infection by 61% (Bello-Chavolla et al.
T351 33806-33812 Sentence denotes 2020).
T352 33813-33961 Sentence denotes This is likely due to a deficiency of SPMs in obese patients, and this deficiency promotes adverse reactions during SARS-CoV-2 infection (Pal et al.
T353 33962-33968 Sentence denotes 2020).
T354 33969-34094 Sentence denotes LXA4, Elovanoid-N32 or RvD6 isomers reduced expression of angiotensin-converting enzyme 2 (ACE2), but NDP1 did not reduce it.
T355 34095-34265 Sentence denotes These lipids mediators also counteract the binding of the receptor-binding domain (RBD) of SARS-CoV-2 spike (S) protein to the injured cornea (Figs. 3 and 4) (Pham et al.
T356 34266-34272 Sentence denotes 2020).
T357 34273-34398 Sentence denotes Elovanoid-N32 or RvD6 isomers also attenuated the expression of cytokines involved in a cytokine storm and hyperinflammation.
T358 34399-34629 Sentence denotes Based on previous study results that have demonstrated SPMs as potential therapeutic targets for SARS-CoV-2 infection, studies and review on the use of fish oil, an SPMs precursor, as an adjuvant are in progress. (Torrinhas et al.
T359 34630-34649 Sentence denotes 2020; Rogero et al.
T360 34650-34656 Sentence denotes 2020).
T361 34657-34929 Sentence denotes SPMs and soluble epoxide hydrolase inhibitors are currently in clinical trials for other inflammatory diseases and can be quickly converted and used for SARS-CoV-2 management through the removal of cellular debris and inhibition of inflammatory cytokines (Panigrahy et al.
T362 34930-34936 Sentence denotes 2020).
T363 34938-34949 Sentence denotes Conclusions
T364 34950-35039 Sentence denotes Recently, a new group of molecules, named SPMs that resolve inflammation were elucidated.
T365 35040-35162 Sentence denotes Further, in efforts to investigate and demonstrate their mechanism of action, their receptors are slowly being discovered.
T366 35163-35240 Sentence denotes As an additional milestone, SPMs were detected in several biological samples.
T367 35241-35414 Sentence denotes However, the investigation of the pharmacological principle based on GPCR for SPMs under various physiological and pathological conditions is insufficient (Psychogios et al.
T368 35415-35433 Sentence denotes 2011; Lukiw et al.
T369 35434-35440 Sentence denotes 2005).
T370 35441-35555 Sentence denotes Further research is needed on specific molecular targets of omega-3 fatty acids such as RvE2, RvD2, PDs, and MaRs.
T371 35556-35830 Sentence denotes The interaction between the host immune system and infectious viral attacks represents new opportunities for the utilization of SPMs. The use of SPMs is likely to help regulate abnormal viral-mediated inflammation and prevent complications such as SARS-CoV-2 cytokine storm.
T372 35831-35913 Sentence denotes Besides, SPMs play parts in restoring tissue homeostasis, including wound healing.
T373 35914-36019 Sentence denotes Therefore, they are very likely to have therapeutic effects against the sequelae of SARS-CoV-2 infection.
T374 36020-36110 Sentence denotes Both inflammation and resolution of inflammation are vital processes of the immune system.
T375 36111-36339 Sentence denotes Therefore, a balance between the need for a sufficient immune response to clear the infection and the rapid decline of immune response to prevent host damage presents a novel opportunity for therapeutic exploitation of the SPMs.
T376 36340-36445 Sentence denotes Further research is needed to identify opportunities to optimize this balance in human viral infectivity.
T377 36446-36625 Sentence denotes Among them, it will be exciting to study how the receptors of SPMs, which act as coreceptors during virus infection, play a role in virus infection and virus-induced inflammation.
T378 36626-36774 Sentence denotes Finally, although not mentioned in this review, the author would like to emphasize that SPMs are effective in treating bacterial infections as well.
T379 36775-36949 Sentence denotes In nutshell, SPMs shows excellent potential as novel therapeutic options for severe inflammation and tissue damage caused by viral infections, including SARS-CoV-2 infection.
T380 36950-36989 Sentence denotes Fig. 1 Inflammation-resolution process.
T381 36990-37079 Sentence denotes Modified from Fullerton and Gilroy (Fullerton and Gilroy 2016), and Lee et al. (Lee 2018)
T382 37080-37112 Sentence denotes Fig. 2 SPMS and their receptors.
T383 37113-37205 Sentence denotes Blue dotted lines mean activation of receptors, and red dotted lines inhibition of receptors
T384 37206-37253 Sentence denotes Fig. 3 Effects of SPMS on the virus life cycle.
T385 37254-37291 Sentence denotes Please refer to the text for details.
T386 37292-37343 Sentence denotes RTA: replication and transcription activator, KSHV:
T387 37344-37383 Sentence denotes Kaposi’s sarcoma-associated herpesvirus
T388 37384-37463 Sentence denotes Fig. 4 Effects of SPMS on the viruses and viral infection-induced inflammation.
T389 37464-37506 Sentence denotes Green lines mean direct antiviral effects.
T390 37507-37609 Sentence denotes Blue dotted lines mean indirect effects on virus and purple dotted lines possible effects (not proved)