Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities
Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiologic...
Gespeichert in:
Veröffentlicht in: | Fundamental & clinical pharmacology 2022-06, Vol.36 (3), p.468-485 |
---|---|
Hauptverfasser: | , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 485 |
---|---|
container_issue | 3 |
container_start_page | 468 |
container_title | Fundamental & clinical pharmacology |
container_volume | 36 |
creator | Chupradit, Supat Bokov, Dmitry Zamanian, Mohammad Yassin Heidari, Mahsa Hakimizadeh, Elham |
description | Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti‐inflammatory, anti‐apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro‐inflammatory cytokines like TNF‐α, IL‐1α, IL‐1β, and IL‐6. It also inhibits the transcription factor nuclear NF‐κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti‐inflammatory, and anti‐fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals. |
doi_str_mv | 10.1111/fcp.12746 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2612733928</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2662359074</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4196-d60b0ab3f95e9bef769e31e5387d8025e3d0240e87b3c34a246038d7fc6edec63</originalsourceid><addsrcrecordid>eNp1kc9O3DAQhy0EKtttD7xAFYkLPWTxn8SOuaFVYZGQ4EDPkeOMhVdJnNoO7d54hD5jn6ReAj1UwhdLM58_jeeH0AnBK5LOudHjilBR8AO0IIWgeUUxP0QLLLjImazIMfoYwhZjIjDhH9AxKyQriWQLFDcwquhG7yLoaJ8gU0ObxUfwaoQpWp2BMakTMmcyD-EpNaJ33UV2mRmnp1Qf0pNo_zz_toPpVN8nnd-9aPZ198u2ahbv_TZaCJ_QkVFdgM-v9xJ9v_r2sN7kt3fXN-vL21wXRPK85bjBqmFGliAbMIJLYARKVom2wrQE1mJaYKhEwzQrFC04ZlUrjObQguZsic5mb_rejwlCrHsbNHSdGsBNoaY8bY0xSauEnv6Hbt3khzRdojhlpcSiSNTXmdLeheDB1KO3vfK7muB6H0Wdoqhfokjsl1fj1PTQ_iPfdp-A8xn4aTvYvW-qr9b3s_IvHJuVXQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2662359074</pqid></control><display><type>article</type><title>Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities</title><source>Wiley-Blackwell Journals</source><source>MEDLINE</source><creator>Chupradit, Supat ; Bokov, Dmitry ; Zamanian, Mohammad Yassin ; Heidari, Mahsa ; Hakimizadeh, Elham</creator><creatorcontrib>Chupradit, Supat ; Bokov, Dmitry ; Zamanian, Mohammad Yassin ; Heidari, Mahsa ; Hakimizadeh, Elham</creatorcontrib><description>Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti‐inflammatory, anti‐apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro‐inflammatory cytokines like TNF‐α, IL‐1α, IL‐1β, and IL‐6. It also inhibits the transcription factor nuclear NF‐κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti‐inflammatory, and anti‐fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.</description><identifier>ISSN: 0767-3981</identifier><identifier>EISSN: 1472-8206</identifier><identifier>DOI: 10.1111/fcp.12746</identifier><identifier>PMID: 34935193</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>1-Phosphatidylinositol 3-kinase ; AKT protein ; Alanine ; Alanine transaminase ; Anti-Inflammatory Agents - pharmacology ; antioxidant activity ; Antioxidants ; Antioxidants - pharmacology ; anti‐inflammatory activity ; Apoptosis ; Aspartate aminotransferase ; Catalase ; chemical toxins ; Chemicals ; Cytokines ; Fatty liver ; Fibrosis ; Flavones ; Flavonoids ; Glutathione ; Glutathione - metabolism ; Hepatitis ; Hepatocellular carcinoma ; Humans ; Inflammation ; Injury prevention ; Interleukin 6 ; Liver ; Liver cancer ; Liver diseases ; Liver Diseases - drug therapy ; Nitric oxide ; Oxidative Stress ; Pharmacology ; Phosphatidylinositol 3-Kinases - metabolism ; Resveratrol ; Resveratrol - pharmacology ; Steatosis ; Subgroups ; Superoxide dismutase ; TOR protein ; Transaminases ; Wines</subject><ispartof>Fundamental & clinical pharmacology, 2022-06, Vol.36 (3), p.468-485</ispartof><rights>2021 Société Française de Pharmacologie et de Thérapeutique</rights><rights>2021 Société Française de Pharmacologie et de Thérapeutique.</rights><rights>2022 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4196-d60b0ab3f95e9bef769e31e5387d8025e3d0240e87b3c34a246038d7fc6edec63</citedby><cites>FETCH-LOGICAL-c4196-d60b0ab3f95e9bef769e31e5387d8025e3d0240e87b3c34a246038d7fc6edec63</cites><orcidid>0000-0002-9814-9297 ; 0000-0003-0944-0320</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Ffcp.12746$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Ffcp.12746$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34935193$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chupradit, Supat</creatorcontrib><creatorcontrib>Bokov, Dmitry</creatorcontrib><creatorcontrib>Zamanian, Mohammad Yassin</creatorcontrib><creatorcontrib>Heidari, Mahsa</creatorcontrib><creatorcontrib>Hakimizadeh, Elham</creatorcontrib><title>Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities</title><title>Fundamental & clinical pharmacology</title><addtitle>Fundam Clin Pharmacol</addtitle><description>Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti‐inflammatory, anti‐apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro‐inflammatory cytokines like TNF‐α, IL‐1α, IL‐1β, and IL‐6. It also inhibits the transcription factor nuclear NF‐κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti‐inflammatory, and anti‐fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>AKT protein</subject><subject>Alanine</subject><subject>Alanine transaminase</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>antioxidant activity</subject><subject>Antioxidants</subject><subject>Antioxidants - pharmacology</subject><subject>anti‐inflammatory activity</subject><subject>Apoptosis</subject><subject>Aspartate aminotransferase</subject><subject>Catalase</subject><subject>chemical toxins</subject><subject>Chemicals</subject><subject>Cytokines</subject><subject>Fatty liver</subject><subject>Fibrosis</subject><subject>Flavones</subject><subject>Flavonoids</subject><subject>Glutathione</subject><subject>Glutathione - metabolism</subject><subject>Hepatitis</subject><subject>Hepatocellular carcinoma</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Injury prevention</subject><subject>Interleukin 6</subject><subject>Liver</subject><subject>Liver cancer</subject><subject>Liver diseases</subject><subject>Liver Diseases - drug therapy</subject><subject>Nitric oxide</subject><subject>Oxidative Stress</subject><subject>Pharmacology</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Resveratrol</subject><subject>Resveratrol - pharmacology</subject><subject>Steatosis</subject><subject>Subgroups</subject><subject>Superoxide dismutase</subject><subject>TOR protein</subject><subject>Transaminases</subject><subject>Wines</subject><issn>0767-3981</issn><issn>1472-8206</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kc9O3DAQhy0EKtttD7xAFYkLPWTxn8SOuaFVYZGQ4EDPkeOMhVdJnNoO7d54hD5jn6ReAj1UwhdLM58_jeeH0AnBK5LOudHjilBR8AO0IIWgeUUxP0QLLLjImazIMfoYwhZjIjDhH9AxKyQriWQLFDcwquhG7yLoaJ8gU0ObxUfwaoQpWp2BMakTMmcyD-EpNaJ33UV2mRmnp1Qf0pNo_zz_toPpVN8nnd-9aPZ198u2ahbv_TZaCJ_QkVFdgM-v9xJ9v_r2sN7kt3fXN-vL21wXRPK85bjBqmFGliAbMIJLYARKVom2wrQE1mJaYKhEwzQrFC04ZlUrjObQguZsic5mb_rejwlCrHsbNHSdGsBNoaY8bY0xSauEnv6Hbt3khzRdojhlpcSiSNTXmdLeheDB1KO3vfK7muB6H0Wdoqhfokjsl1fj1PTQ_iPfdp-A8xn4aTvYvW-qr9b3s_IvHJuVXQ</recordid><startdate>202206</startdate><enddate>202206</enddate><creator>Chupradit, Supat</creator><creator>Bokov, Dmitry</creator><creator>Zamanian, Mohammad Yassin</creator><creator>Heidari, Mahsa</creator><creator>Hakimizadeh, Elham</creator><general>Wiley Subscription Services, Inc</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>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-9814-9297</orcidid><orcidid>https://orcid.org/0000-0003-0944-0320</orcidid></search><sort><creationdate>202206</creationdate><title>Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities</title><author>Chupradit, Supat ; Bokov, Dmitry ; Zamanian, Mohammad Yassin ; Heidari, Mahsa ; Hakimizadeh, Elham</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4196-d60b0ab3f95e9bef769e31e5387d8025e3d0240e87b3c34a246038d7fc6edec63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>AKT protein</topic><topic>Alanine</topic><topic>Alanine transaminase</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>antioxidant activity</topic><topic>Antioxidants</topic><topic>Antioxidants - pharmacology</topic><topic>anti‐inflammatory activity</topic><topic>Apoptosis</topic><topic>Aspartate aminotransferase</topic><topic>Catalase</topic><topic>chemical toxins</topic><topic>Chemicals</topic><topic>Cytokines</topic><topic>Fatty liver</topic><topic>Fibrosis</topic><topic>Flavones</topic><topic>Flavonoids</topic><topic>Glutathione</topic><topic>Glutathione - metabolism</topic><topic>Hepatitis</topic><topic>Hepatocellular carcinoma</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Injury prevention</topic><topic>Interleukin 6</topic><topic>Liver</topic><topic>Liver cancer</topic><topic>Liver diseases</topic><topic>Liver Diseases - drug therapy</topic><topic>Nitric oxide</topic><topic>Oxidative Stress</topic><topic>Pharmacology</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Resveratrol</topic><topic>Resveratrol - pharmacology</topic><topic>Steatosis</topic><topic>Subgroups</topic><topic>Superoxide dismutase</topic><topic>TOR protein</topic><topic>Transaminases</topic><topic>Wines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chupradit, Supat</creatorcontrib><creatorcontrib>Bokov, Dmitry</creatorcontrib><creatorcontrib>Zamanian, Mohammad Yassin</creatorcontrib><creatorcontrib>Heidari, Mahsa</creatorcontrib><creatorcontrib>Hakimizadeh, Elham</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Fundamental & clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chupradit, Supat</au><au>Bokov, Dmitry</au><au>Zamanian, Mohammad Yassin</au><au>Heidari, Mahsa</au><au>Hakimizadeh, Elham</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities</atitle><jtitle>Fundamental & clinical pharmacology</jtitle><addtitle>Fundam Clin Pharmacol</addtitle><date>2022-06</date><risdate>2022</risdate><volume>36</volume><issue>3</issue><spage>468</spage><epage>485</epage><pages>468-485</pages><issn>0767-3981</issn><eissn>1472-8206</eissn><abstract>Being the most essential organ in the body, the liver performs critical functions. Hepatic disorders, such as alcoholic liver disease, hepatic steatosis, liver fibrosis, nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic failure, have an impact on the biochemical and physiological functions of the body. The main representative of the flavonoid subgroup of flavones, resveratrol (RES), exhibits suitable pharmacological activities for treating various liver diseases, such as fatty hepatitis, liver steatosis, liver cancer, and liver fibrosis. According to various studies, grapes and red wine are good sources of RES. RES has various health properties; it is anti‐inflammatory, anti‐apoptotic, antioxidative, and hepatoprotective against several hepatic diseases and hepatoxicity. Therefore, we performed a thorough research and created a summary of the distinct targets of RES in various stages of liver diseases. We concluded that RES inhibited liver inflammation essentially by causing a significant decrease in the expression of various pro‐inflammatory cytokines like TNF‐α, IL‐1α, IL‐1β, and IL‐6. It also inhibits the transcription factor nuclear NF‐κB that brings about the inflammatory cascade. RES also inhibits the PI3K/Akt/mTOR pathway to induce apoptosis. Additionally, it reduces oxidative stress in hepatic tissue by markedly reducing malondialdehyde (MDA) and nitric oxide (NO) contents and significantly increasing the levels of catalase (CAT), superoxide dismutase (SOD), and reduced hepatic glutathione (GSH), in addition to aspartate aminotransferase (AST) and alanine aminotransferase (ALT), against toxic chemicals like CC14, As2O3, and TTA. Due to its antioxidant, anti‐inflammatory, and anti‐fibrotic properties, RES reduces liver injury markers. RES is safe natural antioxidant that provides pharmacological rectification of the hepatoxicity of toxic chemicals.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34935193</pmid><doi>10.1111/fcp.12746</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-9814-9297</orcidid><orcidid>https://orcid.org/0000-0003-0944-0320</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0767-3981 |
ispartof | Fundamental & clinical pharmacology, 2022-06, Vol.36 (3), p.468-485 |
issn | 0767-3981 1472-8206 |
language | eng |
recordid | cdi_proquest_miscellaneous_2612733928 |
source | Wiley-Blackwell Journals; MEDLINE |
subjects | 1-Phosphatidylinositol 3-kinase AKT protein Alanine Alanine transaminase Anti-Inflammatory Agents - pharmacology antioxidant activity Antioxidants Antioxidants - pharmacology anti‐inflammatory activity Apoptosis Aspartate aminotransferase Catalase chemical toxins Chemicals Cytokines Fatty liver Fibrosis Flavones Flavonoids Glutathione Glutathione - metabolism Hepatitis Hepatocellular carcinoma Humans Inflammation Injury prevention Interleukin 6 Liver Liver cancer Liver diseases Liver Diseases - drug therapy Nitric oxide Oxidative Stress Pharmacology Phosphatidylinositol 3-Kinases - metabolism Resveratrol Resveratrol - pharmacology Steatosis Subgroups Superoxide dismutase TOR protein Transaminases Wines |
title | Hepatoprotective and therapeutic effects of resveratrol: A focus on anti‐inflammatory and antioxidative activities |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T18%3A36%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Hepatoprotective%20and%20therapeutic%20effects%20of%20resveratrol:%20A%20focus%20on%20anti%E2%80%90inflammatory%20and%20antioxidative%20activities&rft.jtitle=Fundamental%20&%20clinical%20pharmacology&rft.au=Chupradit,%20Supat&rft.date=2022-06&rft.volume=36&rft.issue=3&rft.spage=468&rft.epage=485&rft.pages=468-485&rft.issn=0767-3981&rft.eissn=1472-8206&rft_id=info:doi/10.1111/fcp.12746&rft_dat=%3Cproquest_cross%3E2662359074%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2662359074&rft_id=info:pmid/34935193&rfr_iscdi=true |