Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats
ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-i...
Gespeichert in:
Veröffentlicht in: | Indian journal of pharmacology 2022-09, Vol.54 (5), p.329-337 |
---|---|
Hauptverfasser: | , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 337 |
---|---|
container_issue | 5 |
container_start_page | 329 |
container_title | Indian journal of pharmacology |
container_volume | 54 |
creator | Lagariya, Labhu Soni, Kinal Shah, Jigna |
description | ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO).
MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment.
RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone.
CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis. |
doi_str_mv | 10.4103/ijp.ijp_802_21 |
format | Article |
fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9846918</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A730768542</galeid><sourcerecordid>A730768542</sourcerecordid><originalsourceid>FETCH-LOGICAL-c495o-d2f7e98d478dc11fcac89dc50ebdfadaf1613df6443ddc755774034e255b4b2b3</originalsourceid><addsrcrecordid>eNp9kk1v1DAQhiMEokvhyhFF4pwlieN8XBBVVT6kSlzgbDn2OPHWsYPtdLt_k1_ERP1ipYIiK4nnmXfG4zdJ3hb5tipy8kHv5i0u1uYlK4tnyaboujYjDS2eJ5u8pCRr6oKcJK9C2OX4X3X1y-SE1JQ0VV5skt9nNuq4TM6noBSIGFKn0tmZwzyCdSbzWowp3ETPRVxDF8s8Oq95apwduOVpAJBpf0iveRCL4ahjpYsjGM1NOni3j2OqMBkrcCtTFLJBOT9pOxyHsx4iyunBcrMGtR11r6N2Fj-xhRm8nsBGbswBd-QisLDzWEVwK8CvlOcxvE5eKG4CvLl7nyY_P1_8OP-aXX7_8u387DITVUddJkvVQNfKqmmlKAoluGg7KWgOvVRcclXg4KSqq4pIKRpKG5wYqaCktK_6sienycdb3XnpJ5ACW8Nm2Ixdcn9gjmt2HLF6ZIO7Zl1b1V3RosD7OwHvfi0QItu5xePpAysbWud5Swh9pAZugGmr3HoXkw6CnTUkb-qWViVS2RPUABawsrOgNG4f8dsneHwkTFr8L0F4F4IH9XDQImerFdlqw0crYsK7v8fzgN97D4FPt8DemQg-XJllD54he2Xd_h-yjJQdu_cs-QOqSvll</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2756008335</pqid></control><display><type>article</type><title>Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats</title><source>MEDLINE</source><source>PubMed Central Open Access</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Lagariya, Labhu ; Soni, Kinal ; Shah, Jigna</creator><creatorcontrib>Lagariya, Labhu ; Soni, Kinal ; Shah, Jigna</creatorcontrib><description>ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO).
MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment.
RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone.
CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis.</description><identifier>ISSN: 0253-7613</identifier><identifier>EISSN: 1998-3751</identifier><identifier>DOI: 10.4103/ijp.ijp_802_21</identifier><identifier>PMID: 36537401</identifier><language>eng</language><publisher>India: Wolters Kluwer India Pvt. Ltd</publisher><subject>Animals ; Antioxidants ; Care and treatment ; Disease control ; Fluorouracil ; Health aspects ; Materia medica, Vegetable ; Mouth cancer ; Mouth Neoplasms ; Oral cancer ; Plant extracts ; Plant Extracts - pharmacology ; Polyphenols ; Polyphenols - pharmacology ; Rats ; Rats, Sprague-Dawley ; Sapindaceae - chemistry ; Seeds - chemistry ; Soapberries ; Testing ; Transforming Growth Factor beta - metabolism ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A</subject><ispartof>Indian journal of pharmacology, 2022-09, Vol.54 (5), p.329-337</ispartof><rights>COPYRIGHT 2022 Medknow Publications and Media Pvt. Ltd.</rights><rights>2022. This article is published under (http://creativecommons.org/licenses/by-nc-sa/3.0/) (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Copyright: © 2022 Indian Journal of Pharmacology 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c495o-d2f7e98d478dc11fcac89dc50ebdfadaf1613df6443ddc755774034e255b4b2b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846918/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9846918/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36537401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lagariya, Labhu</creatorcontrib><creatorcontrib>Soni, Kinal</creatorcontrib><creatorcontrib>Shah, Jigna</creatorcontrib><title>Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats</title><title>Indian journal of pharmacology</title><addtitle>Indian J Pharmacol</addtitle><description>ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO).
MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment.
RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone.
CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis.</description><subject>Animals</subject><subject>Antioxidants</subject><subject>Care and treatment</subject><subject>Disease control</subject><subject>Fluorouracil</subject><subject>Health aspects</subject><subject>Materia medica, Vegetable</subject><subject>Mouth cancer</subject><subject>Mouth Neoplasms</subject><subject>Oral cancer</subject><subject>Plant extracts</subject><subject>Plant Extracts - pharmacology</subject><subject>Polyphenols</subject><subject>Polyphenols - pharmacology</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Sapindaceae - chemistry</subject><subject>Seeds - chemistry</subject><subject>Soapberries</subject><subject>Testing</subject><subject>Transforming Growth Factor beta - metabolism</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A</subject><issn>0253-7613</issn><issn>1998-3751</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kk1v1DAQhiMEokvhyhFF4pwlieN8XBBVVT6kSlzgbDn2OPHWsYPtdLt_k1_ERP1ipYIiK4nnmXfG4zdJ3hb5tipy8kHv5i0u1uYlK4tnyaboujYjDS2eJ5u8pCRr6oKcJK9C2OX4X3X1y-SE1JQ0VV5skt9nNuq4TM6noBSIGFKn0tmZwzyCdSbzWowp3ETPRVxDF8s8Oq95apwduOVpAJBpf0iveRCL4ahjpYsjGM1NOni3j2OqMBkrcCtTFLJBOT9pOxyHsx4iyunBcrMGtR11r6N2Fj-xhRm8nsBGbswBd-QisLDzWEVwK8CvlOcxvE5eKG4CvLl7nyY_P1_8OP-aXX7_8u387DITVUddJkvVQNfKqmmlKAoluGg7KWgOvVRcclXg4KSqq4pIKRpKG5wYqaCktK_6sienycdb3XnpJ5ACW8Nm2Ixdcn9gjmt2HLF6ZIO7Zl1b1V3RosD7OwHvfi0QItu5xePpAysbWud5Swh9pAZugGmr3HoXkw6CnTUkb-qWViVS2RPUABawsrOgNG4f8dsneHwkTFr8L0F4F4IH9XDQImerFdlqw0crYsK7v8fzgN97D4FPt8DemQg-XJllD54he2Xd_h-yjJQdu_cs-QOqSvll</recordid><startdate>20220901</startdate><enddate>20220901</enddate><creator>Lagariya, Labhu</creator><creator>Soni, Kinal</creator><creator>Shah, Jigna</creator><general>Wolters Kluwer India Pvt. Ltd</general><general>Medknow Publications and Media Pvt. Ltd</general><general>Medknow Publications & Media Pvt. Ltd</general><general>Wolters Kluwer - Medknow</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20220901</creationdate><title>Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats</title><author>Lagariya, Labhu ; Soni, Kinal ; Shah, Jigna</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c495o-d2f7e98d478dc11fcac89dc50ebdfadaf1613df6443ddc755774034e255b4b2b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antioxidants</topic><topic>Care and treatment</topic><topic>Disease control</topic><topic>Fluorouracil</topic><topic>Health aspects</topic><topic>Materia medica, Vegetable</topic><topic>Mouth cancer</topic><topic>Mouth Neoplasms</topic><topic>Oral cancer</topic><topic>Plant extracts</topic><topic>Plant Extracts - pharmacology</topic><topic>Polyphenols</topic><topic>Polyphenols - pharmacology</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Sapindaceae - chemistry</topic><topic>Seeds - chemistry</topic><topic>Soapberries</topic><topic>Testing</topic><topic>Transforming Growth Factor beta - metabolism</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lagariya, Labhu</creatorcontrib><creatorcontrib>Soni, Kinal</creatorcontrib><creatorcontrib>Shah, Jigna</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</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>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</collection><collection>Publicly Available Content 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>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Indian journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lagariya, Labhu</au><au>Soni, Kinal</au><au>Shah, Jigna</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats</atitle><jtitle>Indian journal of pharmacology</jtitle><addtitle>Indian J Pharmacol</addtitle><date>2022-09-01</date><risdate>2022</risdate><volume>54</volume><issue>5</issue><spage>329</spage><epage>337</epage><pages>329-337</pages><issn>0253-7613</issn><eissn>1998-3751</eissn><abstract>ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO).
MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment.
RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-β) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone.
CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-β signaling axis.</abstract><cop>India</cop><pub>Wolters Kluwer India Pvt. Ltd</pub><pmid>36537401</pmid><doi>10.4103/ijp.ijp_802_21</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0253-7613 |
ispartof | Indian journal of pharmacology, 2022-09, Vol.54 (5), p.329-337 |
issn | 0253-7613 1998-3751 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9846918 |
source | MEDLINE; PubMed Central Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Animals Antioxidants Care and treatment Disease control Fluorouracil Health aspects Materia medica, Vegetable Mouth cancer Mouth Neoplasms Oral cancer Plant extracts Plant Extracts - pharmacology Polyphenols Polyphenols - pharmacology Rats Rats, Sprague-Dawley Sapindaceae - chemistry Seeds - chemistry Soapberries Testing Transforming Growth Factor beta - metabolism Vascular endothelial growth factor Vascular Endothelial Growth Factor A |
title | Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-26T16%3A46%3A20IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Antitumor%20effects%20of%20polyphenol-rich%20extract%20of%20Euphoria%20longana%20seed%20by%20vascular%20endothelial%20growth%20factor%20and%20transforming%20growth%20factor-beta%20signaling%20inhibition%20in%20experimentally%20induced%20oral%20cancer%20in%20rats&rft.jtitle=Indian%20journal%20of%20pharmacology&rft.au=Lagariya,%20Labhu&rft.date=2022-09-01&rft.volume=54&rft.issue=5&rft.spage=329&rft.epage=337&rft.pages=329-337&rft.issn=0253-7613&rft.eissn=1998-3751&rft_id=info:doi/10.4103/ijp.ijp_802_21&rft_dat=%3Cgale_pubme%3EA730768542%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2756008335&rft_id=info:pmid/36537401&rft_galeid=A730768542&rfr_iscdi=true |