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LitCovid-PD-FMA-UBERON

LitCovid-PD-UBERON

{"project":"LitCovid-PD-UBERON","denotations":[{"id":"T67","span":{"begin":805,"end":819},"obj":"Body_part"},{"id":"T68","span":{"begin":813,"end":819},"obj":"Body_part"},{"id":"T69","span":{"begin":823,"end":828},"obj":"Body_part"},{"id":"T70","span":{"begin":3818,"end":3823},"obj":"Body_part"}],"attributes":[{"id":"A67","pred":"uberon_id","subj":"T67","obj":"http://purl.obolibrary.org/obo/UBERON_0001013"},{"id":"A68","pred":"uberon_id","subj":"T68","obj":"http://purl.obolibrary.org/obo/UBERON_0000479"},{"id":"A69","pred":"uberon_id","subj":"T69","obj":"http://purl.obolibrary.org/obo/UBERON_0000948"},{"id":"A70","pred":"uberon_id","subj":"T70","obj":"http://purl.obolibrary.org/obo/UBERON_0000178"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

LitCovid-PD-MONDO

{"project":"LitCovid-PD-MONDO","denotations":[{"id":"T163","span":{"begin":187,"end":199},"obj":"Disease"},{"id":"T164","span":{"begin":688,"end":700},"obj":"Disease"},{"id":"T165","span":{"begin":1099,"end":1111},"obj":"Disease"},{"id":"T166","span":{"begin":1294,"end":1306},"obj":"Disease"},{"id":"T167","span":{"begin":1360,"end":1372},"obj":"Disease"},{"id":"T168","span":{"begin":1591,"end":1603},"obj":"Disease"}],"attributes":[{"id":"A163","pred":"mondo_id","subj":"T163","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A164","pred":"mondo_id","subj":"T164","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A165","pred":"mondo_id","subj":"T165","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A166","pred":"mondo_id","subj":"T166","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A167","pred":"mondo_id","subj":"T167","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"},{"id":"A168","pred":"mondo_id","subj":"T168","obj":"http://purl.obolibrary.org/obo/MONDO_0021166"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

LitCovid-PD-CLO

LitCovid-PD-CHEBI

LitCovid-PD-GO-BP

LitCovid-sentences

{"project":"LitCovid-sentences","denotations":[{"id":"T308","span":{"begin":0,"end":52},"obj":"Sentence"},{"id":"T309","span":{"begin":53,"end":167},"obj":"Sentence"},{"id":"T310","span":{"begin":168,"end":527},"obj":"Sentence"},{"id":"T311","span":{"begin":528,"end":905},"obj":"Sentence"},{"id":"T312","span":{"begin":906,"end":1010},"obj":"Sentence"},{"id":"T313","span":{"begin":1011,"end":1254},"obj":"Sentence"},{"id":"T314","span":{"begin":1255,"end":1373},"obj":"Sentence"},{"id":"T315","span":{"begin":1374,"end":1467},"obj":"Sentence"},{"id":"T316","span":{"begin":1468,"end":2083},"obj":"Sentence"},{"id":"T317","span":{"begin":2084,"end":2210},"obj":"Sentence"},{"id":"T318","span":{"begin":2211,"end":2328},"obj":"Sentence"},{"id":"T319","span":{"begin":2329,"end":2524},"obj":"Sentence"},{"id":"T320","span":{"begin":2525,"end":2734},"obj":"Sentence"},{"id":"T321","span":{"begin":2735,"end":2835},"obj":"Sentence"},{"id":"T322","span":{"begin":2836,"end":2959},"obj":"Sentence"},{"id":"T323","span":{"begin":2960,"end":3288},"obj":"Sentence"},{"id":"T324","span":{"begin":3289,"end":3436},"obj":"Sentence"},{"id":"T325","span":{"begin":3437,"end":3531},"obj":"Sentence"},{"id":"T326","span":{"begin":3532,"end":3699},"obj":"Sentence"},{"id":"T327","span":{"begin":3700,"end":3857},"obj":"Sentence"}],"namespaces":[{"prefix":"_base","uri":"http://pubannotation.org/ontology/tao.owl#"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

LitCovid-PD-HP

{"project":"LitCovid-PD-HP","denotations":[{"id":"T94","span":{"begin":1990,"end":1996},"obj":"Phenotype"}],"attributes":[{"id":"A94","pred":"hp_id","subj":"T94","obj":"http://purl.obolibrary.org/obo/HP_0002664"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

MyTest

{"project":"MyTest","denotations":[{"id":"32640331-21762726-30720915","span":{"begin":521,"end":525},"obj":"21762726"},{"id":"32640331-28900017-30720916","span":{"begin":736,"end":740},"obj":"28900017"},{"id":"32640331-25149823-30720917","span":{"begin":889,"end":893},"obj":"25149823"},{"id":"32640331-28900017-30720918","span":{"begin":2518,"end":2522},"obj":"28900017"},{"id":"32640331-16469992-30720919","span":{"begin":2953,"end":2957},"obj":"16469992"},{"id":"32640331-25149823-30720920","span":{"begin":3282,"end":3286},"obj":"25149823"},{"id":"32640331-28900017-30720921","span":{"begin":3430,"end":3434},"obj":"28900017"},{"id":"32640331-17519235-30720922","span":{"begin":3693,"end":3697},"obj":"17519235"},{"id":"32640331-12225374-30720923","span":{"begin":3851,"end":3855},"obj":"12225374"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

2_test

{"project":"2_test","denotations":[{"id":"32640331-21762726-30720915","span":{"begin":521,"end":525},"obj":"21762726"},{"id":"32640331-28900017-30720916","span":{"begin":736,"end":740},"obj":"28900017"},{"id":"32640331-25149823-30720917","span":{"begin":889,"end":893},"obj":"25149823"},{"id":"32640331-28900017-30720918","span":{"begin":2518,"end":2522},"obj":"28900017"},{"id":"32640331-16469992-30720919","span":{"begin":2953,"end":2957},"obj":"16469992"},{"id":"32640331-25149823-30720920","span":{"begin":3282,"end":3286},"obj":"25149823"},{"id":"32640331-28900017-30720921","span":{"begin":3430,"end":3434},"obj":"28900017"},{"id":"32640331-17519235-30720922","span":{"begin":3693,"end":3697},"obj":"17519235"},{"id":"32640331-12225374-30720923","span":{"begin":3851,"end":3855},"obj":"12225374"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

LitCovid-PMC-OGER-BB

{"project":"LitCovid-PMC-OGER-BB","denotations":[{"id":"T25","span":{"begin":1374,"end":1385},"obj":"CHEBI:26195;CHEBI:26195"}],"text":"6.1 Inflammatory-resolving effects induced by PUFAs\nNowadays, the mechanisms of action by which n-3 PUFAs regulate the inflammatory processes are widely investigated. The suppression of inflammation by n-3 PUFAs is associated with one of the following mechanisms (1) competitive inhibition of n-6 PUFA pathway; (2) modification of cell membrane composition; (3) affecting the formation of rafts or (4) direct anti-inflammatory effect of their bioactive metabolites (resolvins, protectins, and maresins) (Poudyal et al., 2011).\nIt has been demonstrated that the dietary supplementation with DHA and EPA from fish increases in a dose-response manner the content of DHA and EPA in the cell inflammation-responsible phospholipids (Calder, 2017); increased content of DHA or EPA in different tissues, such as adipose tissue or heart was also observed in correlation with their intake (Calder, 2015) (Fig. 3 ).\nFig. 3 The effect of omega-3 fatty acids and polyphenols in the regulation of the inflammatory response. Omega-3 fatty acids inhibit the inflammatory response by inhibiting PGE2 which promotes inflammation and NF-κB either directly, via the interaction with the transcriptional factors PPARs, or by inhibiting TLR2/4 which normally activates NF-κB. Moreover, omega-3 fatty acids regulate inflammation by activating MAPK and GPR120 which in turn inhibits inflammation. Polyphenols inhibit the inflammatory response by directly inhibiting NF-κB, or via the PPARs. They also promote fatty acid b-oxidation and inhibit VCAM-1, ICAM-1, MAPK pathway, PGE2 and COX-2 that all promote chronic inflammation (PGE2 –prostaglandin 2; NF-κB – nuclear factor kappa-light-chain-enhancer of activated B cells; PPARs – peroxisome proliferator-activated receptors; TLR2/4– toll-like receptor; MAPK – mitogen-activated protein kinase; GPR120 – G-protein coupled receptor 120; VCAM-1 – vascular cell adhesion molecule 1; ICAM-1 – intracellular cell adhesion molecule 1; COX-2 – cyclooxygenase 2; TNF-α – tumour necrosis factor alpha; MCP-1 – monocyte chemoattractant protein 1; AMPK – AMP kinase).\nThese n-3 PUFAs frequently substitute n-6 PUFAs like ARA, resulting in decreased availability of ARA for eicosanoid synthesis. EPA also inhibits ARA metabolism as a competitive substrate for COX-2, decreasing prostaglandin E2 (PGE2) production. In rats, dietary supplementation with ALA inhibits PG biosynthesis from ARA, while equivalent quantities of ALA and LA decreased up to 40% n-6 PUFAs incorporation in phospholipids (Calder, 2017). Furthermore, Rees et al. observed that a daily EPA intake of 2.7 g or 4.05 g for 3 months decreases the PGE2 production by lipopolysaccharide-stimulated mononuclear cells, while a lower dose of 1.35 g did not. EPA was integrated in a linear dose-dependent manner into mononuclear cell phospholipids and plasma. This study suggested a daily threshold in the range of 1.35–2.7 g EPA for the anti-inflammatory action (Rees et al., 2006).\nBesides decreasing production of PGE2, DHA and EPA are also substrates for the biosynthesis of lipid derivatives, but the EPA-derived mediators as series-3 prostaglandins (PGD3) or series-5 leukotrienes are typically less biologically potent, having a lower ability to interact with relevant eicosanoid receptors (Calder, 2015). For example, EPA-derived leukotriene B5 (LTB5) is almost 100 times less active as a leukocyte chemoattractant than ARA-derived LTB4 (Calder, 2017). However, in some cases, EPA-derived mediators have similar potency with ARA-derived mediators. It appears that EPA-derived PGD3 inhibits the effect of the ARA-derived PGD2, due to a stronger interaction with the DP1 receptor compared to PGD2 (Wada et al., 2007). In other cases, EPA-derived mediators exhibited a similar magnitude of effect (e.g. inhibition of TNF-α production by blood monocytes) (Dooper et al., 2002)."}

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