3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells

3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human ker...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Molecular medicine reports 2021-07, Vol.24 (1), Article 509
Hauptverfasser: Park, Ji-Won, Oh, Jae-Hoon, Hwang, Daseul, Kim, Seong-Man, Min, Jae-Hong, Seo, Ji-Yun, Chun, Wanjoo, Lee, Hee Jae, Oh, Sei-Ryang, Lee, Jae-Won, Ahn, Kyung-Seop
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
container_end_page
container_issue 1
container_start_page
container_title Molecular medicine reports
container_volume 24
creator Park, Ji-Won
Oh, Jae-Hoon
Hwang, Daseul
Kim, Seong-Man
Min, Jae-Hong
Seo, Ji-Yun
Chun, Wanjoo
Lee, Hee Jae
Oh, Sei-Ryang
Lee, Jae-Won
Ahn, Kyung-Seop
description 3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.
doi_str_mv 10.3892/mmr.2021.12148
format Article
fullrecord <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8134876</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2536745802</sourcerecordid><originalsourceid>FETCH-LOGICAL-c418t-8fd67fe140bf694a64d00b4ecf1a01d57491a1b532d00267575a7e23f90d90673</originalsourceid><addsrcrecordid>eNpdkc9OVDEYxRuDEUS3LM1N2Lhghv7v7YaETBwhIbgZ102nt4WS23Zo7yXMzlfwUYzv4UP4JPbKSNRN-6Xn15Pv5ABwhOCctBKfhpDnGGI0RxjR9gU4QEKiGYGQ7u1mLKXYB69LuYOQM8zkK7BPiGyx4PgAbMgJPWE_v3xdZX-77XJ63Bofow7eNNr4rrGPNg-l0XHwlfLR9ToEPaS8baxz1lQtxWZ1vazqj2-nl8vrafhejzL4MPZ6sF1zoRd61Rjb9-UNeOl0X-zb3X0IPi8_rBYXs6tPHy8X51czQ1E7zFrXceEsonDtuKSa0w7CNbXGIQ1RxwSVSKM1I7i-Yy6YYFpYTJyEnYRckENw9uS7GdfBdsbGIetebbIPOm9V0l79q0R_q27Sg2oRoa3g1eD9ziCn-9GWQQVfpgg62jQWhRnmBDIucUWP_0Pv0phjjVcpwgVlLZyo-RNlciolW_e8DIJqKlPVMtVUpvpdZv3w7u8Iz_if9sgvvQOhNg</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2536745802</pqid></control><display><type>article</type><title>3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells</title><source>Spandidos Publications Journals</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Park, Ji-Won ; Oh, Jae-Hoon ; Hwang, Daseul ; Kim, Seong-Man ; Min, Jae-Hong ; Seo, Ji-Yun ; Chun, Wanjoo ; Lee, Hee Jae ; Oh, Sei-Ryang ; Lee, Jae-Won ; Ahn, Kyung-Seop</creator><creatorcontrib>Park, Ji-Won ; Oh, Jae-Hoon ; Hwang, Daseul ; Kim, Seong-Man ; Min, Jae-Hong ; Seo, Ji-Yun ; Chun, Wanjoo ; Lee, Hee Jae ; Oh, Sei-Ryang ; Lee, Jae-Won ; Ahn, Kyung-Seop</creatorcontrib><description>3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.</description><identifier>ISSN: 1791-2997</identifier><identifier>EISSN: 1791-3004</identifier><identifier>DOI: 10.3892/mmr.2021.12148</identifier><identifier>PMID: 33982762</identifier><language>eng</language><publisher>Greece: Spandidos Publications UK Ltd</publisher><subject>Acids ; AKT protein ; Anti-inflammatory agents ; Asthma ; CCL17 protein ; CCL22 protein ; Cell activation ; Cell culture ; Chemokines ; Cytokines ; Eczema ; Gene expression ; Heme ; Heme oxygenase (decyclizing) ; Inflammatory diseases ; Interleukin 8 ; Kinases ; Lymphocytes T ; Monocyte chemoattractant protein ; Monocyte chemoattractant protein 1 ; Monocytes ; NAD ; NADPH quinone oxidoreductase ; Oxygenase ; Phosphorylation ; Proteins ; Quinone oxidoreductase ; Reverse transcription ; Thymus ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α ; γ-Interferon</subject><ispartof>Molecular medicine reports, 2021-07, Vol.24 (1), Article 509</ispartof><rights>Copyright Spandidos Publications UK Ltd. 2021</rights><rights>Copyright: © Park et al. 2021</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c418t-8fd67fe140bf694a64d00b4ecf1a01d57491a1b532d00267575a7e23f90d90673</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33982762$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Park, Ji-Won</creatorcontrib><creatorcontrib>Oh, Jae-Hoon</creatorcontrib><creatorcontrib>Hwang, Daseul</creatorcontrib><creatorcontrib>Kim, Seong-Man</creatorcontrib><creatorcontrib>Min, Jae-Hong</creatorcontrib><creatorcontrib>Seo, Ji-Yun</creatorcontrib><creatorcontrib>Chun, Wanjoo</creatorcontrib><creatorcontrib>Lee, Hee Jae</creatorcontrib><creatorcontrib>Oh, Sei-Ryang</creatorcontrib><creatorcontrib>Lee, Jae-Won</creatorcontrib><creatorcontrib>Ahn, Kyung-Seop</creatorcontrib><title>3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells</title><title>Molecular medicine reports</title><addtitle>Mol Med Rep</addtitle><description>3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.</description><subject>Acids</subject><subject>AKT protein</subject><subject>Anti-inflammatory agents</subject><subject>Asthma</subject><subject>CCL17 protein</subject><subject>CCL22 protein</subject><subject>Cell activation</subject><subject>Cell culture</subject><subject>Chemokines</subject><subject>Cytokines</subject><subject>Eczema</subject><subject>Gene expression</subject><subject>Heme</subject><subject>Heme oxygenase (decyclizing)</subject><subject>Inflammatory diseases</subject><subject>Interleukin 8</subject><subject>Kinases</subject><subject>Lymphocytes T</subject><subject>Monocyte chemoattractant protein</subject><subject>Monocyte chemoattractant protein 1</subject><subject>Monocytes</subject><subject>NAD</subject><subject>NADPH quinone oxidoreductase</subject><subject>Oxygenase</subject><subject>Phosphorylation</subject><subject>Proteins</subject><subject>Quinone oxidoreductase</subject><subject>Reverse transcription</subject><subject>Thymus</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor necrosis factor-α</subject><subject>γ-Interferon</subject><issn>1791-2997</issn><issn>1791-3004</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkc9OVDEYxRuDEUS3LM1N2Lhghv7v7YaETBwhIbgZ102nt4WS23Zo7yXMzlfwUYzv4UP4JPbKSNRN-6Xn15Pv5ABwhOCctBKfhpDnGGI0RxjR9gU4QEKiGYGQ7u1mLKXYB69LuYOQM8zkK7BPiGyx4PgAbMgJPWE_v3xdZX-77XJ63Bofow7eNNr4rrGPNg-l0XHwlfLR9ToEPaS8baxz1lQtxWZ1vazqj2-nl8vrafhejzL4MPZ6sF1zoRd61Rjb9-UNeOl0X-zb3X0IPi8_rBYXs6tPHy8X51czQ1E7zFrXceEsonDtuKSa0w7CNbXGIQ1RxwSVSKM1I7i-Yy6YYFpYTJyEnYRckENw9uS7GdfBdsbGIetebbIPOm9V0l79q0R_q27Sg2oRoa3g1eD9ziCn-9GWQQVfpgg62jQWhRnmBDIucUWP_0Pv0phjjVcpwgVlLZyo-RNlciolW_e8DIJqKlPVMtVUpvpdZv3w7u8Iz_if9sgvvQOhNg</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Park, Ji-Won</creator><creator>Oh, Jae-Hoon</creator><creator>Hwang, Daseul</creator><creator>Kim, Seong-Man</creator><creator>Min, Jae-Hong</creator><creator>Seo, Ji-Yun</creator><creator>Chun, Wanjoo</creator><creator>Lee, Hee Jae</creator><creator>Oh, Sei-Ryang</creator><creator>Lee, Jae-Won</creator><creator>Ahn, Kyung-Seop</creator><general>Spandidos Publications UK Ltd</general><general>D.A. Spandidos</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210701</creationdate><title>3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells</title><author>Park, Ji-Won ; Oh, Jae-Hoon ; Hwang, Daseul ; Kim, Seong-Man ; Min, Jae-Hong ; Seo, Ji-Yun ; Chun, Wanjoo ; Lee, Hee Jae ; Oh, Sei-Ryang ; Lee, Jae-Won ; Ahn, Kyung-Seop</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c418t-8fd67fe140bf694a64d00b4ecf1a01d57491a1b532d00267575a7e23f90d90673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acids</topic><topic>AKT protein</topic><topic>Anti-inflammatory agents</topic><topic>Asthma</topic><topic>CCL17 protein</topic><topic>CCL22 protein</topic><topic>Cell activation</topic><topic>Cell culture</topic><topic>Chemokines</topic><topic>Cytokines</topic><topic>Eczema</topic><topic>Gene expression</topic><topic>Heme</topic><topic>Heme oxygenase (decyclizing)</topic><topic>Inflammatory diseases</topic><topic>Interleukin 8</topic><topic>Kinases</topic><topic>Lymphocytes T</topic><topic>Monocyte chemoattractant protein</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Monocytes</topic><topic>NAD</topic><topic>NADPH quinone oxidoreductase</topic><topic>Oxygenase</topic><topic>Phosphorylation</topic><topic>Proteins</topic><topic>Quinone oxidoreductase</topic><topic>Reverse transcription</topic><topic>Thymus</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor necrosis factor-α</topic><topic>γ-Interferon</topic><toplevel>online_resources</toplevel><creatorcontrib>Park, Ji-Won</creatorcontrib><creatorcontrib>Oh, Jae-Hoon</creatorcontrib><creatorcontrib>Hwang, Daseul</creatorcontrib><creatorcontrib>Kim, Seong-Man</creatorcontrib><creatorcontrib>Min, Jae-Hong</creatorcontrib><creatorcontrib>Seo, Ji-Yun</creatorcontrib><creatorcontrib>Chun, Wanjoo</creatorcontrib><creatorcontrib>Lee, Hee Jae</creatorcontrib><creatorcontrib>Oh, Sei-Ryang</creatorcontrib><creatorcontrib>Lee, Jae-Won</creatorcontrib><creatorcontrib>Ahn, Kyung-Seop</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Biological Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecular medicine reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Park, Ji-Won</au><au>Oh, Jae-Hoon</au><au>Hwang, Daseul</au><au>Kim, Seong-Man</au><au>Min, Jae-Hong</au><au>Seo, Ji-Yun</au><au>Chun, Wanjoo</au><au>Lee, Hee Jae</au><au>Oh, Sei-Ryang</au><au>Lee, Jae-Won</au><au>Ahn, Kyung-Seop</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells</atitle><jtitle>Molecular medicine reports</jtitle><addtitle>Mol Med Rep</addtitle><date>2021-07-01</date><risdate>2021</risdate><volume>24</volume><issue>1</issue><artnum>509</artnum><issn>1791-2997</issn><eissn>1791-3004</eissn><abstract>3,4,5‑Trihydroxycinnamic acid (THCA) exhibits anti‑inflammatory activity in acute or chronic inflammatory disorders, such as acute lung injury and asthma. The present study investigated the anti‑inflammatory activity of THCA in a tumor necrosis factor‑α/interferon‑γ (TI) mixture‑stimulated human keratinocyte cell line. The results of ELISA and reverse transcription‑quantitative PCR revealed that THCA reduced the secretion and mRNA expression levels of interleukin (IL)‑6; IL‑8; thymus and activation‑regulated chemokine; macrophage‑derived chemokine; regulated upon activation, normal T cell expressed and secreted; and monocyte chemoattractant protein‑1 in TI mixture‑stimulated HaCaT cells. In addition, the results of western blot analysis demonstrated that THCA exerted inhibitory activity on the activation of AKT, ERK and nuclear factor‑κB in TI mixture‑stimulated HaCaT cells. Furthermore, THCA upregulated the expression levels of heme oxygenase‑1 and NAD(P)H:quinone oxidoreductase 1, and the activation of nuclear factor erythroid 2‑related factor 2 in HaCaT cells. These results demonstrated that THCA may exhibit anti‑inflammatory activity in activated HaCaT cells.</abstract><cop>Greece</cop><pub>Spandidos Publications UK Ltd</pub><pmid>33982762</pmid><doi>10.3892/mmr.2021.12148</doi><oa>free_for_read</oa></addata></record>
fulltext fulltext
identifier ISSN: 1791-2997
ispartof Molecular medicine reports, 2021-07, Vol.24 (1), Article 509
issn 1791-2997
1791-3004
language eng
recordid cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8134876
source Spandidos Publications Journals; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection
subjects Acids
AKT protein
Anti-inflammatory agents
Asthma
CCL17 protein
CCL22 protein
Cell activation
Cell culture
Chemokines
Cytokines
Eczema
Gene expression
Heme
Heme oxygenase (decyclizing)
Inflammatory diseases
Interleukin 8
Kinases
Lymphocytes T
Monocyte chemoattractant protein
Monocyte chemoattractant protein 1
Monocytes
NAD
NADPH quinone oxidoreductase
Oxygenase
Phosphorylation
Proteins
Quinone oxidoreductase
Reverse transcription
Thymus
Tumor necrosis factor-TNF
Tumor necrosis factor-α
γ-Interferon
title 3,4,5‑Trihydroxycinnamic acid exerts anti‑inflammatory effects on TNF‑α/IFN‑γ‑stimulated HaCaT cells
url https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-29T11%3A32%3A09IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=3,4,5%E2%80%91Trihydroxycinnamic%20acid%20exerts%20anti%E2%80%91inflammatory%20effects%20on%20TNF%E2%80%91%CE%B1/IFN%E2%80%91%CE%B3%E2%80%91stimulated%20HaCaT%20cells&rft.jtitle=Molecular%20medicine%20reports&rft.au=Park,%20Ji-Won&rft.date=2021-07-01&rft.volume=24&rft.issue=1&rft.artnum=509&rft.issn=1791-2997&rft.eissn=1791-3004&rft_id=info:doi/10.3892/mmr.2021.12148&rft_dat=%3Cproquest_pubme%3E2536745802%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2536745802&rft_id=info:pmid/33982762&rfr_iscdi=true