Loading…

An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity

Introduction The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl.sub.4 ), xenobiotics, and other toxic substances through c...

Full description

Saved in:
Bibliographic Details
Published in:PLoS ONE 2023, Vol.18 (9), p.e0291125
Main Authors: Tithi, Tanzia Islam, Tahsin, Md. Rafat, Anjum, Juhaer, Zaman, Tasnuva Sharmin, Aktar, Fahima, Bahar, Nasiba Binte, Tasnim, Sabiha, Sultana, Arifa, Jahan, Ishrat, Afrin, Syeda Sadia, Akter, Tahmina, Sen, Priyanka, Koly, Fahima Jannat, Reza, Md. Selim, Chowdhury, Jakir Ahmed, Kabir, Shaila, Chowdhury, Abu Asad, Amran, Md. Shah
Format: Report
Language:English
Subjects:
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
cited_by
cites
container_end_page
container_issue 9
container_start_page e0291125
container_title PLoS ONE
container_volume 18
creator Tithi, Tanzia Islam
Tahsin, Md. Rafat
Anjum, Juhaer
Zaman, Tasnuva Sharmin
Aktar, Fahima
Bahar, Nasiba Binte
Tasnim, Sabiha
Sultana, Arifa
Jahan, Ishrat
Afrin, Syeda Sadia
Akter, Tahmina
Sen, Priyanka
Koly, Fahima Jannat
Reza, Md. Selim
Chowdhury, Jakir Ahmed
Kabir, Shaila
Chowdhury, Abu Asad
Amran, Md. Shah
description Introduction The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl.sub.4 ), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. Materials and methods Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl.sub.4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. Results and discussion Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase ([gamma]-GT) in CCl.sub.4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p
doi_str_mv 10.1371/journal.pone.0291125
format report
fullrecord <record><control><sourceid>gale</sourceid><recordid>TN_cdi_gale_infotracacademiconefile_A765430835</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A765430835</galeid><sourcerecordid>A765430835</sourcerecordid><originalsourceid>FETCH-gale_infotracacademiconefile_A7654308353</originalsourceid><addsrcrecordid>eNqVjk1Ow0AMhUcIJMrPDVj4Ag0zGZK27CLEzwHYI3c6SV1N7CgziegVODVTwYIt8sKfn5-frNSd0YWxK3N_kGlkDMUg7AtdbowpqzO1MBtbLutS2_M_fKmuYjxoXdl1XS_UV8NADDPNAsi7E0cK5AT8jGHCRMIgLaS9h70fMMkwSvIu0exhyMSJMJwcr0eeRoS8dlO_9RwfoTlNPUXiDrDLVmhlBCf9Nudm7ScwySc5SscbddFiiP72t1-r4uX5_elt2WHwH8StpBFdrp3v84PsW8p6s6qrB6vXtrL_PvgG_5Vm-Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>report</recordtype></control><display><type>report</type><title>An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity</title><source>Publicly Available Content (ProQuest)</source><source>PubMed Central</source><creator>Tithi, Tanzia Islam ; Tahsin, Md. Rafat ; Anjum, Juhaer ; Zaman, Tasnuva Sharmin ; Aktar, Fahima ; Bahar, Nasiba Binte ; Tasnim, Sabiha ; Sultana, Arifa ; Jahan, Ishrat ; Afrin, Syeda Sadia ; Akter, Tahmina ; Sen, Priyanka ; Koly, Fahima Jannat ; Reza, Md. Selim ; Chowdhury, Jakir Ahmed ; Kabir, Shaila ; Chowdhury, Abu Asad ; Amran, Md. Shah</creator><creatorcontrib>Tithi, Tanzia Islam ; Tahsin, Md. Rafat ; Anjum, Juhaer ; Zaman, Tasnuva Sharmin ; Aktar, Fahima ; Bahar, Nasiba Binte ; Tasnim, Sabiha ; Sultana, Arifa ; Jahan, Ishrat ; Afrin, Syeda Sadia ; Akter, Tahmina ; Sen, Priyanka ; Koly, Fahima Jannat ; Reza, Md. Selim ; Chowdhury, Jakir Ahmed ; Kabir, Shaila ; Chowdhury, Abu Asad ; Amran, Md. Shah</creatorcontrib><description><![CDATA[Introduction The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl.sub.4 ), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. Materials and methods Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl.sub.4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. Results and discussion Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase ([gamma]-GT) in CCl.sub.4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-[beta]1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-[alpha]). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.]]></description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0291125</identifier><language>eng</language><publisher>Public Library of Science</publisher><subject>Care and treatment ; Diagnosis ; Health aspects ; Liver diseases ; Properties ; Spinach</subject><ispartof>PLoS ONE, 2023, Vol.18 (9), p.e0291125</ispartof><rights>COPYRIGHT 2023 Public Library of Science</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>776,780,4476,27902</link.rule.ids></links><search><creatorcontrib>Tithi, Tanzia Islam</creatorcontrib><creatorcontrib>Tahsin, Md. Rafat</creatorcontrib><creatorcontrib>Anjum, Juhaer</creatorcontrib><creatorcontrib>Zaman, Tasnuva Sharmin</creatorcontrib><creatorcontrib>Aktar, Fahima</creatorcontrib><creatorcontrib>Bahar, Nasiba Binte</creatorcontrib><creatorcontrib>Tasnim, Sabiha</creatorcontrib><creatorcontrib>Sultana, Arifa</creatorcontrib><creatorcontrib>Jahan, Ishrat</creatorcontrib><creatorcontrib>Afrin, Syeda Sadia</creatorcontrib><creatorcontrib>Akter, Tahmina</creatorcontrib><creatorcontrib>Sen, Priyanka</creatorcontrib><creatorcontrib>Koly, Fahima Jannat</creatorcontrib><creatorcontrib>Reza, Md. Selim</creatorcontrib><creatorcontrib>Chowdhury, Jakir Ahmed</creatorcontrib><creatorcontrib>Kabir, Shaila</creatorcontrib><creatorcontrib>Chowdhury, Abu Asad</creatorcontrib><creatorcontrib>Amran, Md. Shah</creatorcontrib><title>An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity</title><title>PLoS ONE</title><description><![CDATA[Introduction The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl.sub.4 ), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. Materials and methods Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl.sub.4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. Results and discussion Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase ([gamma]-GT) in CCl.sub.4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-[beta]1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-[alpha]). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.]]></description><subject>Care and treatment</subject><subject>Diagnosis</subject><subject>Health aspects</subject><subject>Liver diseases</subject><subject>Properties</subject><subject>Spinach</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>report</rsrctype><creationdate>2023</creationdate><recordtype>report</recordtype><sourceid/><recordid>eNqVjk1Ow0AMhUcIJMrPDVj4Ag0zGZK27CLEzwHYI3c6SV1N7CgziegVODVTwYIt8sKfn5-frNSd0YWxK3N_kGlkDMUg7AtdbowpqzO1MBtbLutS2_M_fKmuYjxoXdl1XS_UV8NADDPNAsi7E0cK5AT8jGHCRMIgLaS9h70fMMkwSvIu0exhyMSJMJwcr0eeRoS8dlO_9RwfoTlNPUXiDrDLVmhlBCf9Nudm7ScwySc5SscbddFiiP72t1-r4uX5_elt2WHwH8StpBFdrp3v84PsW8p6s6qrB6vXtrL_PvgG_5Vm-Q</recordid><startdate>20230915</startdate><enddate>20230915</enddate><creator>Tithi, Tanzia Islam</creator><creator>Tahsin, Md. Rafat</creator><creator>Anjum, Juhaer</creator><creator>Zaman, Tasnuva Sharmin</creator><creator>Aktar, Fahima</creator><creator>Bahar, Nasiba Binte</creator><creator>Tasnim, Sabiha</creator><creator>Sultana, Arifa</creator><creator>Jahan, Ishrat</creator><creator>Afrin, Syeda Sadia</creator><creator>Akter, Tahmina</creator><creator>Sen, Priyanka</creator><creator>Koly, Fahima Jannat</creator><creator>Reza, Md. Selim</creator><creator>Chowdhury, Jakir Ahmed</creator><creator>Kabir, Shaila</creator><creator>Chowdhury, Abu Asad</creator><creator>Amran, Md. Shah</creator><general>Public Library of Science</general><scope/></search><sort><creationdate>20230915</creationdate><title>An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity</title><author>Tithi, Tanzia Islam ; Tahsin, Md. Rafat ; Anjum, Juhaer ; Zaman, Tasnuva Sharmin ; Aktar, Fahima ; Bahar, Nasiba Binte ; Tasnim, Sabiha ; Sultana, Arifa ; Jahan, Ishrat ; Afrin, Syeda Sadia ; Akter, Tahmina ; Sen, Priyanka ; Koly, Fahima Jannat ; Reza, Md. Selim ; Chowdhury, Jakir Ahmed ; Kabir, Shaila ; Chowdhury, Abu Asad ; Amran, Md. Shah</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-gale_infotracacademiconefile_A7654308353</frbrgroupid><rsrctype>reports</rsrctype><prefilter>reports</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Care and treatment</topic><topic>Diagnosis</topic><topic>Health aspects</topic><topic>Liver diseases</topic><topic>Properties</topic><topic>Spinach</topic><toplevel>online_resources</toplevel><creatorcontrib>Tithi, Tanzia Islam</creatorcontrib><creatorcontrib>Tahsin, Md. Rafat</creatorcontrib><creatorcontrib>Anjum, Juhaer</creatorcontrib><creatorcontrib>Zaman, Tasnuva Sharmin</creatorcontrib><creatorcontrib>Aktar, Fahima</creatorcontrib><creatorcontrib>Bahar, Nasiba Binte</creatorcontrib><creatorcontrib>Tasnim, Sabiha</creatorcontrib><creatorcontrib>Sultana, Arifa</creatorcontrib><creatorcontrib>Jahan, Ishrat</creatorcontrib><creatorcontrib>Afrin, Syeda Sadia</creatorcontrib><creatorcontrib>Akter, Tahmina</creatorcontrib><creatorcontrib>Sen, Priyanka</creatorcontrib><creatorcontrib>Koly, Fahima Jannat</creatorcontrib><creatorcontrib>Reza, Md. Selim</creatorcontrib><creatorcontrib>Chowdhury, Jakir Ahmed</creatorcontrib><creatorcontrib>Kabir, Shaila</creatorcontrib><creatorcontrib>Chowdhury, Abu Asad</creatorcontrib><creatorcontrib>Amran, Md. Shah</creatorcontrib></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tithi, Tanzia Islam</au><au>Tahsin, Md. Rafat</au><au>Anjum, Juhaer</au><au>Zaman, Tasnuva Sharmin</au><au>Aktar, Fahima</au><au>Bahar, Nasiba Binte</au><au>Tasnim, Sabiha</au><au>Sultana, Arifa</au><au>Jahan, Ishrat</au><au>Afrin, Syeda Sadia</au><au>Akter, Tahmina</au><au>Sen, Priyanka</au><au>Koly, Fahima Jannat</au><au>Reza, Md. Selim</au><au>Chowdhury, Jakir Ahmed</au><au>Kabir, Shaila</au><au>Chowdhury, Abu Asad</au><au>Amran, Md. Shah</au><format>book</format><genre>unknown</genre><ristype>RPRT</ristype><atitle>An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity</atitle><jtitle>PLoS ONE</jtitle><date>2023-09-15</date><risdate>2023</risdate><volume>18</volume><issue>9</issue><spage>e0291125</spage><pages>e0291125-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract><![CDATA[Introduction The liver, the most important metabolic organ of the body, performs a wide variety of vital functions. Hepatic cell injury occurs by the activation of reactive oxygen species (ROS) that are generated by carbon tetrachloride (CCl.sub.4 ), xenobiotics, and other toxic substances through cytochrome P450-dependent steps resulting from the covalent bond formation with lipoproteins and nucleic acids. Observing the urgent state of hepatotoxic patients worldwide, different medicinal plants and their properties can be explored to combat such free radical damage to the liver. In vivo and in silico studies were designed and conducted to evaluate the antioxidant and hepatoprotective properties of Gynura procumbens in rats. Materials and methods Gynura procumbens leaves were collected and extracted using 70% ethanol. The required chemicals CCl.sub.4, standard drug (silymarin), and blood serum analysis kits were stocked. The in vivo tests were performed in 140 healthy Wister albino rats of either sex under well-controlled parameters divided into 14 groups, strictly maintaining Institutional Animal Ethics Committee (IEAC) protocols. For the histopathology study, 10% buffered neutral formalin was used for organ preservation. Later the specimens were studied under a fluorescence microscope. In silico molecular docking and absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies were performed, and the results were analyzed statistically. Results and discussion Gynura procumbens partially negate the deleterious effect of carbon tetrachloride on normal weight gain in rats. The elevated level of serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP), creatinine, LDH, total cholesterol (TC), low-density lipoprotein (LDL), triglycerides (TG), malondialdehyde (MDA), deoxyribonucleic acid (DNA) fragmentation ranges, gamma-glutamyl transferase ([gamma]-GT) in CCl.sub.4 treated groups were decreased by both standard drug silymarin and G. procumbens leaf extract. We have found significant & highly significant changes statistically for different doses, here p<0.05 & p<0.01, respectively. On the other hand, G. procumbens and silymarin displayed Statistically significant (p<0.05) and high significant(p<0.01) increased levels of HDL, CAT SOD (here p<0.05 & p<0.01 for different doses) when the treatment groups were compared with the disease control group. Because the therapeutic activity imparted by plants and drugs accelerates the movement of the disturbed pathophysiological state toward the healthy state. In the molecular docking analysis, G. procumbens phytoconstituents performed poorly against transforming growth factor-beta 1 (TGF-[beta]1) compared to the control drug silymarin. In contrast, 26 phytoconstituents scored better than the control bezafibrate against peroxisome proliferator-activated receptor alpha (PPAR-[alpha]). The top scoring compounds for both macromolecules were observed to form stable complexes in the molecular dynamics simulations. Flavonoids and phenolic compounds performed better than other constituents in providing hepatoprotective activity. It can, thus, be inferred that the extract of G. procumbens showed good hepatoprotective properties in rats.]]></abstract><pub>Public Library of Science</pub><doi>10.1371/journal.pone.0291125</doi></addata></record>
fulltext fulltext
identifier ISSN: 1932-6203
ispartof PLoS ONE, 2023, Vol.18 (9), p.e0291125
issn 1932-6203
1932-6203
language eng
recordid cdi_gale_infotracacademiconefile_A765430835
source Publicly Available Content (ProQuest); PubMed Central
subjects Care and treatment
Diagnosis
Health aspects
Liver diseases
Properties
Spinach
title An in vivo and in silico evaluation of the hepatoprotective potential of Gynura procumbens: A promising agent for combating hepatotoxicity
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-24T02%3A11%3A30IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale&rft_val_fmt=info:ofi/fmt:kev:mtx:book&rft.genre=unknown&rft.atitle=An%20in%20vivo%20and%20in%20silico%20evaluation%20of%20the%20hepatoprotective%20potential%20of%20Gynura%20procumbens:%20A%20promising%20agent%20for%20combating%20hepatotoxicity&rft.jtitle=PLoS%20ONE&rft.au=Tithi,%20Tanzia%20Islam&rft.date=2023-09-15&rft.volume=18&rft.issue=9&rft.spage=e0291125&rft.pages=e0291125-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0291125&rft_dat=%3Cgale%3EA765430835%3C/gale%3E%3Cgrp_id%3Ecdi_FETCH-gale_infotracacademiconefile_A7654308353%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_id=info:pmid/&rft_galeid=A765430835&rfr_iscdi=true