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||
</a>
|
||
</span>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
|
||
</form>
|
||
|
||
|
||
<div id="article-page-header">
|
||
<div id="article-top-actions-bar" class="article-top-actions-bar">
|
||
<div class="inner-wrap">
|
||
<div class="actions-container">
|
||
<div class="return-to-search">
|
||
|
||
|
||
</div>
|
||
|
||
<div class="multiple-results-actions " role="region" aria-label="save, email, send to">
|
||
<button id="save-results-panel-trigger"
|
||
type="button"
|
||
class="save-results save-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="save-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="open">
|
||
Save
|
||
</button><button id="email-results-panel-trigger"
|
||
type="button"
|
||
class="email-results email-results-panel-trigger"
|
||
aria-expanded="false"
|
||
aria-controls="email-action-panel"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="open">
|
||
Email
|
||
</button><div class="more-actions dropdown-block"><button id="more-actions-trigger"
|
||
type="button"
|
||
class="trigger more-actions-trigger"
|
||
ref="linksrc=show_moreactions_btn"
|
||
aria-label="Send to"
|
||
aria-controls="more-actions-dropdown">Send to</button><div id="more-actions-dropdown" class="dropdown dropdown-container" hidden><div class="content"><ul class="more-actions-links"><li><a class="clipboard-panel-trigger dropdown-block-link "
|
||
href="#"
|
||
role="button"
|
||
data-ga-category="save_share"
|
||
data-ga-action="clipboard"
|
||
data-ga-label="send">
|
||
Clipboard
|
||
</a></li><li><a role="button" class="dropdown-block-link bibliography-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F37176085%2F%23open-bibliography-panel">My Bibliography</a></li><li><a role="button" class="dropdown-block-link collections-trigger-target" href="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F37176085%2F%23open-collections-panel">Collections</a></li><li><a role="button" class="citation-manager-panel-trigger dropdown-block-link citation-manager-trigger-target" href="#">Citation manager</a></li></ul></div></div></div>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region">
|
||
<button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog">
|
||
<span class="button-label">Display options</span>
|
||
</button>
|
||
|
||
<div class="dropdown" hidden>
|
||
<div class="title">
|
||
Display options
|
||
</div>
|
||
|
||
<div class="content">
|
||
|
||
<div class="format-container">
|
||
<span class="option-label">
|
||
Format
|
||
</span>
|
||
<select name="format" data-initial-value="abstract" aria-label="Display format" id="article-display-format">
|
||
<option value="abstract">Abstract</option>
|
||
|
||
<option value="pubmed">PubMed</option>
|
||
|
||
<option value="pmid">PMID</option>
|
||
|
||
</select>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
</div>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="article-panels-container" class="article-panels-container">
|
||
<div id="save-action-panel" class="save-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Save citation to file
|
||
</h2>
|
||
<form id="save-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="save-action-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="save-action-format" name="results-format" class="action-panel-selector">
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="pubmed-text">PubMed</option>
|
||
<option value="pmid">PMID</option>
|
||
<option value="abstract">Abstract (text)</option>
|
||
<option value="csv">CSV</option>
|
||
</select>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Save citations to file' panel"
|
||
ref="linksrc=close_save_panel"
|
||
aria-controls="save-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="save"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="email-action-panel"
|
||
class="email-action-panel action-panel"
|
||
aria-hidden="true"
|
||
data-recaptcha-script-url="https://www.recaptcha.net/recaptcha/enterprise.js?render=explicit&onload=onloadCaptchaCallback"
|
||
data-recaptcha-enabled="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Email citation
|
||
</h2>
|
||
<form id="email-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/send-email/"
|
||
data-by-search-action="/results-export-email-by-search-data/"
|
||
data-by-ids-action="/send-email/"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post"
|
||
method="post"
|
||
>
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<span class="action-panel-label">
|
||
Subject:
|
||
</span>
|
||
<span class="email-subject" id="email-subject" aria-label="Email subject">1 selected item: 37176085 - PubMed</span>
|
||
<input type="hidden" name="email-subject" value="1 selected item: 37176085"/>
|
||
<input type="hidden" name="email-subject-hash" value="9fb63eaccf6250e1ee9b38787a68a9d11d0900e530234ad3e25b4f67600877b3"/>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-to" class="action-panel-label required-field-asterisk">
|
||
To:
|
||
</label>
|
||
<input type="email" aria-label="Recipient Email Address" placeholder="email@example.com" id="email-to" class="email-to" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="100" required>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-from" class="action-panel-label">
|
||
From:
|
||
</label>
|
||
<input type="email" aria-label="Sender Email Address" placeholder="email@example.com" id="email-from" class="email-from" pattern="^[a-zA-Z0-9_.+-]+@[a-zA-Z0-9-]+\.[a-zA-Z0-9-.]+$" maxlength="256">
|
||
</div>
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="email-citation-format" class="action-panel-label">
|
||
Format:
|
||
</label>
|
||
<select id="email-citation-format" name="citation-format" class="action-panel-selector email-citation-format">
|
||
<option selected="selected" value="summary">Summary</option>
|
||
<option value="summary-text">Summary (text)</option>
|
||
<option value="abstract">Abstract</option>
|
||
<option value="abstract-text">Abstract (text)</option>
|
||
|
||
</select>
|
||
</div>
|
||
<div class="include-supplemental-container">
|
||
<input type="checkbox" aria-label="Include MeSH and other data" name="include-supplemental" id="email-include-supplemental" class="email-include-supplemental">
|
||
<label for="email-include-supplemental" class="email-include-supplemental-label">MeSH and other data</label>
|
||
</div>
|
||
|
||
|
||
|
||
<div class="form-field recaptcha ">
|
||
|
||
|
||
|
||
<div class="g-recaptcha" id="id-recaptcha" data-sitekey="6LfsWHMdAAAAAClKbtOpjQ2pMjgsGxvv7NdZW9uI"></div>
|
||
|
||
|
||
|
||
|
||
|
||
</div>
|
||
<div id="captcha-error-message" class="usa-input-error-message captcha-validation-message" role="alert"></div>
|
||
|
||
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="send">
|
||
Send email
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Email citations' panel"
|
||
ref="linksrc=close_email_panel"
|
||
aria-controls="email-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="email"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
<input type="hidden" name="email-search-details" value="" />
|
||
<input type="hidden" name="email-search-details-hash" value="0e42663a6c3bd85498fcb88798998fed7bfdc45d457db35281e41afe13cc0524" />
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="collections-action-panel"
|
||
class="collections-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-collections-open-panel-enabled="false"
|
||
data-collections-open-panel-url-hash="#open-collections-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to Collections
|
||
</h3>
|
||
|
||
|
||
<form id="collections-action-panel-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-add-to-collection-max-amount="1000"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
|
||
|
||
<div class="choice-group" role="radiogroup">
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_new">
|
||
<label for="collections-action-panel-new">Create a new collection</label>
|
||
</li>
|
||
<li>
|
||
<input type="radio"
|
||
id="collections-action-panel-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="collections_radio_existing">
|
||
<label for="collections-action-panel-existing">Add to an existing collection</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
|
||
<div class="controls-wrapper">
|
||
<div class="action-panel-control-wrap new-collections-controls">
|
||
<label for="collections-action-panel-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label>
|
||
<input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-panel-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="save_share"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection">
|
||
<div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div>
|
||
</div>
|
||
<div class="action-panel-control-wrap existing-collections-controls">
|
||
<label for="collections-action-panel-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label>
|
||
<select id="collections-action-panel-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="save_share"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('#collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'">
|
||
</select>
|
||
<div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="add">
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="collections"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="bibliography-action-panel"
|
||
class="bibliography-action-panel action-panel in-progress-dots-panel"
|
||
aria-hidden="true"
|
||
data-bibliography-open-panel-enabled="false"
|
||
data-bibliography-open-panel-url-hash="#open-bibliography-panel">
|
||
<div class="inner-wrap">
|
||
<h3 class="action-panel-heading">
|
||
Add to My Bibliography
|
||
</h3>
|
||
<form id="bibliography-action-panel-form"
|
||
class="bibliography-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-add-to-bibliography-max-amount="100"
|
||
data-add-to-bibliography-batch-size="10"
|
||
data-bibliography-delegates-url="/list-bibliography-delegates/"
|
||
data-add-to-bibliography-url="/add-to-bibliography/"
|
||
data-get-article-ids-by-search-url="/get-article-ids-by-search/"
|
||
data-mybib-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/mybibliography/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
|
||
|
||
<div class="action-panel-control-wrap bibliographies-controls">
|
||
<div class="choice-group">
|
||
<ul class="bibliographies-action-add radio-group-items">
|
||
<li>
|
||
<input name="bibliography" id="my-bibliography" class="my-bibliography" type="radio" checked/>
|
||
<label for="my-bibliography">My Bibliography</label>
|
||
</li>
|
||
</ul>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="bibliographies-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your delegates due to an error<br>
|
||
<a href="#">Please try again</a>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore>
|
||
Add
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Add to bibliography' panel"
|
||
ref="linksrc=close_bibliography_panel"
|
||
aria-controls="bibliography-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="mybib"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="saved-search-action-panel" class="saved-search-action-panel action-panel " aria-hidden="true"
|
||
data-saved-search-open-panel-enabled="false"
|
||
data-saved-search-open-panel-url-hash="#open-saved-search-panel">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your saved search
|
||
</h2>
|
||
|
||
<form id="saved-search-action-panel-form"
|
||
class="saved-search-action-panel-form action-panel-content action-form"
|
||
data-create-saved-search-url="/create-saved-search/"
|
||
data-try-search-terms-url="/try-search-term/"
|
||
data-saved-search-root-url="https://www.ncbi.nlm.nih.gov/myncbi/searches/">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-name" class="action-panel-label saved-search-name-label required-field-asterisk">
|
||
Name of saved search:
|
||
</label>
|
||
<input maxlength="200"
|
||
type="text"
|
||
name="saved-search-name"
|
||
id="saved-search-name"
|
||
class="saved-search-name"
|
||
value=""
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-term" class="action-panel-label required-field-asterisk">
|
||
Search terms:
|
||
</label>
|
||
<textarea name="saved-search-term" id="saved-search-term" class="saved-search-term" required></textarea>
|
||
</div>
|
||
<div class="test-search-term-wrap">
|
||
<a href="#" class="try-search-term">Test search terms</a>
|
||
</div>
|
||
<div class="choice-group action-panel-extra-margin-top">
|
||
<span class="action-panel-label" id="fieldset-label">
|
||
Would you like email updates of new search results?
|
||
</span>
|
||
<fieldset id="saved-search-alert" aria-describedby="fieldset-label">
|
||
<legend class="usa-sr-only">Saved Search Alert Radio Buttons</legend>
|
||
<ul class="radio-group-items">
|
||
<li>
|
||
<input type="radio" id="saved-search-alert-yes" class="saved-search-alert-yes" name="saved-search-alert" value="yes" checked>
|
||
<label for="saved-search-alert-yes" class="action-panel-label">Yes</label>
|
||
</li>
|
||
<li>
|
||
<input aria-label="No radio input" type="radio" id="saved-search-alert-no" class="saved-search-alert-no" name="saved-search-alert" value="no">
|
||
<label for="saved-search-alert-no" class="action-panel-label">No</label>
|
||
</li>
|
||
</ul>
|
||
</fieldset>
|
||
</div>
|
||
|
||
<div class="alert-schedule-wrap">
|
||
<div class="action-panel-control-wrap">
|
||
<label class="action-panel-label">
|
||
Email:
|
||
</label>
|
||
<span aria-label="Email address" id="saved-search-email" class="action-panel-label"><span class="action-panel-label-bold"></span> (<a class="myncbi-account-settings" href="https://www.ncbi.nlm.nih.gov/account/settings/">change</a>)</span>
|
||
</div>
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="saved-search-frequency" class="action-panel-label">
|
||
Frequency:
|
||
</label>
|
||
<select id="saved-search-frequency" class="no-border-panel-selector saved-search-frequency">
|
||
<option value="monthly">Monthly</option>
|
||
<option value="weekly">Weekly</option>
|
||
<option value="daily">Daily</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-monthly-additional">
|
||
<label for="saved-search-monthly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-monthly-on-day" class="no-border-panel-selector">
|
||
<option value="Sunday">The first Sunday</option>
|
||
<option value="Monday">The first Monday</option>
|
||
<option value="Tuesday">The first Tuesday</option>
|
||
<option value="Wednesday">The first Wednesday</option>
|
||
<option value="Thursday">The first Thursday</option>
|
||
<option value="Friday">The first Friday</option>
|
||
<option value="Saturday">The first Saturday</option>
|
||
<option value="day">The first day</option>
|
||
<option value="weekday">The first weekday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap saved-search-weekly-additional">
|
||
<label for="saved-search-weekly-on-day" class="action-panel-label">
|
||
Which day?
|
||
</label>
|
||
<select id="saved-search-weekly-on-day" class="no-border-panel-selector saved-search-weekly-on-day">
|
||
<option value="Sunday">Sunday</option>
|
||
<option value="Monday">Monday</option>
|
||
<option value="Tuesday">Tuesday</option>
|
||
<option value="Wednesday">Wednesday</option>
|
||
<option value="Thursday">Thursday</option>
|
||
<option value="Friday">Friday</option>
|
||
<option value="Saturday">Saturday</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-report" class="action-panel-label">
|
||
Report format:
|
||
</label>
|
||
<select id="saved-search-report" class="no-border-panel-selector saved-search-report">
|
||
<option value="DocSum">Summary</option>
|
||
<option value="DocSumText">Summary (text)</option>
|
||
<option value="Abstract">Abstract</option>
|
||
<option value="AbstractText">Abstract (text)</option>
|
||
<option value="MEDLINE">PubMed</option>
|
||
</select>
|
||
</div>
|
||
<div class="action-panel-control-wrap">
|
||
<label for="saved-search-amount" class="action-panel-label">
|
||
Send at most:
|
||
</label>
|
||
<select id="saved-search-amount" class="no-border-panel-selector saved-search-amount">
|
||
<option value="1">1 item</option>
|
||
<option value="5" selected>5 items</option>
|
||
<option value="10">10 items</option>
|
||
<option value="20">20 items</option>
|
||
<option value="50">50 items</option>
|
||
<option value="100">100 items</option>
|
||
<option value="200">200 items</option>
|
||
</select>
|
||
</div>
|
||
<div>
|
||
<input type="checkbox" id="saved-search-send-if-no-result" class="saved-search-send-if-no-result" name="saved-search-send-if-no-result">
|
||
<label for="saved-search-send-if-no-result" class="action-panel-label smaller-checkbox">
|
||
Send even when there aren't any new results
|
||
</label>
|
||
</div>
|
||
<div class="action-panel-control-wrap option-text-in-email-wrap">
|
||
<label for="saved-search-email-text" class="action-panel-label">
|
||
Optional text in email:
|
||
</label>
|
||
<textarea name="saved-search-email-text"
|
||
id="saved-search-email-text"
|
||
class="saved-search-email-text"></textarea>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Saving..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Save
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your saved search' panel"
|
||
ref="linksrc=close_saved_search_panel"
|
||
aria-controls="saved-search-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
<div id="citation-manager-action-panel" class="citation-manager-action-panel action-panel" aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Create a file for external citation management software
|
||
</h2>
|
||
<form id="citation-manager-action-panel-form"
|
||
class="action-panel-content action-form"
|
||
action="/results-export-ids/"
|
||
data-by-search-action="/results-export-search-data/"
|
||
data-by-ids-action="/results-export-ids/"
|
||
method="post"
|
||
data-by-search-method="post"
|
||
data-by-ids-method="post">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
|
||
|
||
<input name="results-format" type="hidden" value="pubmed"/>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Sending..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="save">
|
||
Create file
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Send citations to citation manager' panel"
|
||
ref="linksrc=close_citation_manager_panel"
|
||
aria-controls="citation-manager-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="citation_manager"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div id="rss-action-panel" class="rss-action-panel action-panel " aria-hidden="true">
|
||
<div class="inner-wrap">
|
||
<h2 class="action-panel-heading">
|
||
Your RSS Feed
|
||
</h2>
|
||
|
||
<form id="rss-action-panel-form"
|
||
class="rss-action-panel-form action-panel-content action-form"
|
||
data-create-rss-feed-url="/create-rss-feed-url/"
|
||
data-search-form-term-value="">
|
||
|
||
<input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h">
|
||
|
||
<div class="action-panel-control-wrap">
|
||
<label for="rss-name" class="action-panel-label required-field-asterisk">
|
||
Name of RSS Feed:
|
||
</label>
|
||
<input maxlength="200"
|
||
placeholder="Name"
|
||
type="text"
|
||
name="rss-name"
|
||
id="rss-name"
|
||
class="rss-name"
|
||
value=''
|
||
required
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/">
|
||
</div>
|
||
|
||
<div class="rss-limit-wrap">
|
||
<div class="action-panel-control-wrap action-panel-extra-margin-top">
|
||
<label for="rss-limit" class="action-panel-label">
|
||
Number of items displayed:
|
||
</label>
|
||
<select id="rss-limit" class="no-border-panel-selector rss-limit">
|
||
<option value="5">5</option>
|
||
<option value="10">10</option>
|
||
<option value="15" selected="selected">15</option>
|
||
<option value="20">20</option>
|
||
<option value="50">50</option>
|
||
<option value="100">100</option>
|
||
</select>
|
||
</div>
|
||
</div>
|
||
|
||
<div class="action-panel-actions">
|
||
<button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Creating..."
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="save">
|
||
Create RSS
|
||
</button>
|
||
<button class="action-panel-cancel"
|
||
aria-label="Close 'Your RSS' panel"
|
||
ref="linksrc=close_rss_panel"
|
||
aria-controls="rss-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="save_share"
|
||
data-ga-action="alert"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button>
|
||
</div>
|
||
|
||
<div class="action-panel-control-wrap rss-link-copy-wrap">
|
||
<label for="rss-link" class="usa-sr-only">RSS Link</label>
|
||
<input placeholder="Your RSS Feed Link" type="text" name="rss-link" id="rss-link" class="rss-link" title="RSS Link">
|
||
<button
|
||
type="button"
|
||
disabled
|
||
class="rss-link-copy-button disabled"
|
||
data-ga-category="save_share"
|
||
data-ga-action="rss"
|
||
data-ga-label="copy">
|
||
Copy
|
||
</button>
|
||
</div>
|
||
</form>
|
||
</div>
|
||
</div>
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="article-page" id="article-page" data-article-pmid="37176085">
|
||
<aside class="page-sidebar">
|
||
<div class="inner-wrap">
|
||
|
||
<div class="full-text-links">
|
||
<div class="full-view">
|
||
<h3 class="title">
|
||
Full text links
|
||
</h3>
|
||
<div class="full-text-links-list">
|
||
<a class="link-item
|
||
|
||
dialog-focus"
|
||
href="https://www.mdpi.com/resolver?pii=ijms24098379"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=False&PrId=6383&itool=Abstract-def&log$=linkouticon&uid=37176085&db=pubmed&nlmid=101092791"
|
||
title="See full text options at MDPI"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="MDPI"
|
||
data-ga-label="37176085"
|
||
><img src="https://cdn.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--res.mdpi.com-data-pubmed-linkout.png" alt="MDPI full text link"><span class="text">
|
||
|
||
MDPI
|
||
|
||
</span></a><a class="link-item
|
||
pmc
|
||
"
|
||
href="https://pmc.ncbi.nlm.nih.gov/articles/pmid/37176085/"
|
||
target="_blank"
|
||
rel="noopener"
|
||
|
||
ref="linksrc=fulltextorjournal_fulltext&is_pmc=True&PrId=3494&itool=Abstract-def&log$=linkouticon&uid=37176085&db=pubmed&nlmid=101092791"
|
||
title="Free full text at PubMed Central"
|
||
|
||
data-ga-category="full_text"
|
||
data-ga-action="PMC"
|
||
data-ga-label="37176085"
|
||
><span class="text">
|
||
|
||
Free PMC article
|
||
|
||
</span></a>
|
||
</div>
|
||
|
||
</div>
|
||
|
||
<div class="short-view">
|
||
<a href="#" class="full-text-links-button full-text-links-dialog-trigger">
|
||
Full text links
|
||
</a>
|
||
</div>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
<div class="actions-buttons sidebar"><h3 class="title">Actions</h3><div class="inner-wrap"><button class="citation-button citation-dialog-trigger"
|
||
aria-label="Open dialog with citation text in different styles"
|
||
data-ga-category="save_share"
|
||
data-ga-action="cite"
|
||
data-ga-label="open"
|
||
data-all-citations-url="/37176085/citations/"
|
||
data-citation-style="nlm"
|
||
data-pubmed-format-link="/37176085/export/"><span class="button-label">Cite</span></button><link type="text/css" href="ncbi-overlay-block/src/overlay-block.css"><div class="collections-button-container" data-article-id="37176085" data-article-db="pubmed"><button class="collections-button collections-dialog-trigger"
|
||
aria-label="Save article in MyNCBI collections."
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_button"
|
||
data-collections-open-dialog-enabled="false"
|
||
data-collections-open-dialog-url="https://account.ncbi.nlm.nih.gov/?back_url=https%3A%2F%2Fpubmed.ncbi.nlm.nih.gov%2F37176085%2F%23open-collections-dialog"
|
||
data-in-collections="false"><span class="button-label">Collections</span></button><div class="overlay" role="dialog"><div id="collections-action-dialog"
|
||
class="dialog collections-dialog"
|
||
aria-hidden="true"><div class="title">Add to Collections</div><div class="collections-action-panel action-panel"><form id="collections-action-dialog-form"
|
||
class="collections-action-panel-form action-panel-content action-form action-panel-smaller-selectors"
|
||
data-existing-collections-url="/list-existing-collections/"
|
||
data-add-to-existing-collection-url="/add-to-existing-collection/"
|
||
data-create-and-add-to-new-collection-url="/create-and-add-to-new-collection/"
|
||
data-myncbi-max-collection-name-length="100"
|
||
data-collections-root-url="https://www.ncbi.nlm.nih.gov/myncbi/collections/"><input type="hidden" name="csrfmiddlewaretoken" value="QRKVyhRhyckhvd8Q3pQHJLNO4eJ4V6vX7Eu0b7kD8N7LpEeGGItJdTjsCirgOH3h"><div class="choice-group" role="radiogroup"><ul class="radio-group-items"><li><input type="radio"
|
||
id="collections-action-dialog-new"
|
||
class="collections-new"
|
||
name="collections"
|
||
value="new"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_new"><label for="collections-action-dialog-new">Create a new collection</label></li><li><input type="radio"
|
||
id="collections-action-dialog-existing"
|
||
class="collections-existing"
|
||
name="collections"
|
||
value="existing"
|
||
checked="true"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="collections_radio_existing"><label for="collections-action-dialog-existing">Add to an existing collection</label></li></ul></div><div class="controls-wrapper"><div class="action-panel-control-wrap new-collections-controls"><label for="collections-action-dialog-add-to-new" class="action-panel-label required-field-asterisk">
|
||
Name your collection:
|
||
</label><input
|
||
type="text"
|
||
name="add-to-new-collection"
|
||
id="collections-action-dialog-add-to-new"
|
||
class="collections-action-add-to-new"
|
||
pattern="[^"&=<>\/]*" title="The following characters are not allowed in the Name field: "&=<>/"
|
||
maxlength="100"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="create_collection"
|
||
data-ga-label="non_favorties_collection"><div class="collections-new-name-too-long usa-input-error-message selection-validation-message">
|
||
Name must be less than 100 characters
|
||
</div></div><div class="action-panel-control-wrap existing-collections-controls"><label for="collections-action-dialog-add-to-existing" class="action-panel-label">
|
||
Choose a collection:
|
||
</label><select id="collections-action-dialog-add-to-existing"
|
||
class="action-panel-selector collections-action-add-to-existing"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="select_collection"
|
||
data-ga-label="($('.collections-action-add-to-existing').val() === 'Favorites') ? 'Favorites' : 'non_favorites_collection'"></select><div class="collections-retry-load-on-error usa-input-error-message selection-validation-message">
|
||
Unable to load your collection due to an error<br><a href="#">Please try again</a></div></div></div><div class="action-panel-actions"><button class="action-panel-submit"
|
||
type="submit"
|
||
data-loading-label="Adding..."
|
||
data-pinger-ignore
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="add">
|
||
Add
|
||
</button><button class="action-panel-cancel"
|
||
aria-label="Close 'Add to Collections' panel"
|
||
ref="linksrc=close_collections_panel"
|
||
aria-controls="collections-action-panel"
|
||
aria-expanded="false"
|
||
data-ga-category="collections_button"
|
||
data-ga-action="click"
|
||
data-ga-label="cancel">
|
||
Cancel
|
||
</button></div></form></div></div></div></div><button class="more-actions-button more-actions-dialog-trigger"
|
||
title="Open dialog with more actions to take"
|
||
ref="linksrc=more_actions_btn"></button><div class="display-options" data-format-key="format"
|
||
data-default-format-value="abstract"
|
||
data-current-format-value="abstract" role="region"><button
|
||
class="trigger usa-button"
|
||
title="Change format"
|
||
data-ga-category="display_options"
|
||
data-ga-action="display_options_dialog"><span class="button-label">Display options</span></button><div class="dropdown" hidden><div class="title">
|
||
Display options
|
||
</div><div class="content"><div class="format-container"><span class="option-label">
|
||
Format
|
||
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</a></li></ul></div></div></div><span class="period">. </span><span class="cit">2023 May 6;24(9):8379.</span>
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Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction
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Vitamin C Regulates the Profibrotic Activity of Fibroblasts in In Vitro Replica Settings of Myocardial Infarction
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><sup class="key">6</sup> Institute of Applied Medical Engineering, Helmholtz Institute, Medical Faculty, RWTH Aachen University, 52074 Aachen, Germany.</li>
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<li data-affiliation-id="short-view-affiliation-7"
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><sup class="key">7</sup> National Heart Center Singapore, 5 Hospital Dr., Singapore 169609, Singapore.</li>
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Extracellular collagen remodeling is one of the central mechanisms responsible for the structural and compositional coherence of myocardium in patients undergoing myocardial infarction (MI). Activated primary cardiac fibroblasts following myocardial infarction are extensively investigated to establish anti-fibrotic therapies to improve left ventricular remodeling. To systematically assess vitamin C functions as a potential modulator involved in collagen fibrillogenesis in an in vitro model mimicking heart tissue healing after MI. Mouse primary cardiac fibroblasts were isolated from wild-type C57BL/6 mice and cultured under normal and profibrotic (hypoxic + transforming growth factor beta 1) conditions on freshly prepared coatings mimicking extracellular matrix (ECM) remodeling during healing after an MI. At 10 μg/mL, vitamin C reprogramed the respiratory mitochondrial metabolism, which is effectively associated with a more increased accumulation of intracellular reactive oxygen species (iROS) than the number of those generated by mitochondrial reactive oxygen species (mROS). The mRNA/protein expression of subtypes I, III collagen, and fibroblasts differentiations markers were upregulated over time, particularly in the presence of vitamin C. The collagen substrate potentiated the modulator role of vitamin C in reinforcing the structure of types I and III collagen synthesis by reducing collagen V expression in a timely manner, which is important in the initiation of fibrillogenesis. Altogether, our study evidenced the synergistic function of vitamin C at an optimum dose on maintaining the equilibrium functionality of radical scavenger and gene transcription, which are important in the initial phases after healing after an MI, while modulating the synthesis of de novo collagen fibrils, which is important in the final stage of tissue healing.
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antioxidant capacity; collagen modulator; fibroblast; gene transcription regulator; vitamin C.
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Conflict of interest statement
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<p xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:p1="http://pubmed.gov/pub-one">The authors declare that the manuscript was prepared in the absence of any conflict of interest.</p>
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<div class="figure-caption-contents"><p> Odd and even effects of… </p></div>
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<div class="figure-caption-contents"><p> Odd and even effects of low and high vitamin C concentrations stimulate or… </p></div>
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Figure 1
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<div class="figure-caption-contents">Odd and even effects of low and high vitamin C concentrations stimulate or disrupt the bioenergetic status in primary cardiac fibroblasts. A concentration of 10 μg/mL of vitamin C selectively increases the respiration profile of mitochondria, whereas at higher concentrations, the nonmitochondrial respiration is significantly reduced in normoxia (<b>A</b>) and in hypoxic conditions (<b>B</b>). Data are normalized to total protein. Error bars indicate standard error of the mean; n = 3 independent experiments per condition.</div>
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<div class="figure-caption-contents"><p> Fibronectin potentiates the radical scavenging… </p></div>
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<div class="figure-caption-contents"><p> Fibronectin potentiates the radical scavenging role of vitamin C under normal settings. iROS… </p></div>
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<div class="figure-caption-contents">Fibronectin potentiates the radical scavenging role of vitamin C under normal settings. iROS formation is shortly upregulated on fibronectin-containing coatings (<b>A</b>). Vitamin C significantly potentiates the formation of iROS at the late incubation time, independent of coating composition (<b>B</b>). Similarly, mROS formation is shortly upregulated, independent of coating composition (<b>C</b>). Vitamin C scavenges timely mROS only on fibronectin coating, but not in primary cardiac fibroblasts cultured on collagen-containing coatings (<b>D</b>). Both iROS and mROS were detected via DHE–mitoSOX–DAPI co-staining of primary cardiac fibroblasts (10,000 cells/well). Error bars indicate standard error of the mean; * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen); mROS (mitochondrial reactive oxygen species); iROS (intracellular reactive oxygen species).</div>
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<div class="figure-caption-contents"><p> Profibrotic conditions potentiate the radical… </p></div>
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<div class="figure-caption-contents"><p> Profibrotic conditions potentiate the radical scavenging functionality of vitamin C. iROS formation is… </p></div>
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<div class="figure-caption-contents">Profibrotic conditions potentiate the radical scavenging functionality of vitamin C. iROS formation is upregulated in a timely manner (<b>A</b>). Vitamin C downregulates iROS formation at the late incubation time (<b>B</b>). Similarly, mROS follows a decay trend in time (<b>C</b>), and it vanishes even more in the presence of vitamin C (<b>D</b>). Likewise, iROS and mROS were detected via DHE–mitoSOX–DAPI co-staining of primary cardiac fibroblasts (10,000 cells/well). Error bars indicate standard error of the mean; * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen); mROS (mitochondrial reactive oxygen species); iROS (intracellular reactive oxygen species).</div>
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<div class="figure-caption-contents"><p> Synthesis of fibrillar collagen depends moderately on substrate composition and is not associated… </p></div>
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<strong class="figure-label">
|
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Figure 4
|
||
</strong>
|
||
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|
||
<div class="figure-caption-contents">Synthesis of fibrillar collagen depends moderately on substrate composition and is not associated with primary cardiac fibroblasts’ activity. In normal settings, SM22 expression levels are significantly upregulated in control group and decrease systematically with the incubation time on different substrates (<b>A</b>). Col1a1 mRNA expression was upregulated at the early stage of incubation and decreased later only on collagen-based coatings (<b>B</b>). Type I procollagen expression remained constant on fibronectin coatings (<b>C</b>), whereas at the protein level, independent of coatings’ composition, type I collagen expression increases at 72 h (<b>D</b>). Fibronectin-based coatings significantly potentiate both col3a1 mRNA (<b>E</b>) and type III collagen expressions (<b>F</b>). Col5a1 mRNA expression is upregulated at 24 h on fibronectin–collagen mix (<b>G</b>) whereas collagen coatings promote the upregulation of type V collagen at the later incubation stage (<b>H</b>). Schematic overview of results over time. The solid line towards mature collagen fibers formation serves as a guide to the reader (<b>I</b>). Error bars indicate standard error of the mean; ns stands for not significant <i>p</i>-value, * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen).</div>
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src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb3/10179686/5d5f683265a5/ijms-24-08379-g005.gif"
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|
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<p> Figure 5 </p>
|
||
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|
||
|
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|
||
<div class="figure-caption-contents"><p> Profibrotic settings stimulate col5a1 collagen… </p></div>
|
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<strong class="figure-label">
|
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<p> Figure 5 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Profibrotic settings stimulate col5a1 collagen gene transcription. Profibrotic settings stimulated SM22 expression over… </p></div>
|
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|
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|
||
</div>
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<figcaption id="figure-caption-4" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
|
||
Figure 5
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Profibrotic settings stimulate col5a1 collagen gene transcription. Profibrotic settings stimulated SM22 expression over time mostly on fibronectin coatings (<b>A</b>). The mix of fibronectin–collagen coatings barely influenced the expression of col1a1 mRNA in time, but it decreased on fibronectin and collagen coatings in a timely manner (<b>B</b>). The expression level of type I procollagen barely varied over time, but it decreased more then that of the control group (<b>C</b>). Type I collagen increased in a timely manner only on collagen-containing coatings (<b>D</b>). Col3a1 mRNA expression was suppressed in activated primary cardiac fibroblasts on each substrate (<b>E</b>), whereas fibronectin and non-collagen-based coatings potentiated the expression type III collagen at the later time point (<b>F</b>). Strikingly, col5a1 mRNA expression increased about 4-fold more than that of control group on each coating (<b>G</b>), whereas on collagen-based coatings, type V collagen protein expression stayed elevated (<b>H</b>). Schematic overview of results over time. The solid line towards mature collagen fibers formation serves as a guide to the reader (<b>I</b>). Error bars indicate standard error of the mean; * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen).</div>
|
||
|
||
|
||
|
||
|
||
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|
||
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||
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||
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||
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||
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|
||
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|
||
data-figure-id="ijms-24-08379-f006">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-5"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb3/10179686/98d869d5a238/ijms-24-08379-g006.gif"
|
||
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|
||
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|
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<strong class="figure-label">
|
||
<p> Figure 6 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Vitamin C potentiates type III… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
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<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
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||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 6 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Vitamin C potentiates type III collagen turnover at the later time point under… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
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<figcaption id="figure-caption-5" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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<strong class="figure-label">
|
||
Figure 6
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Vitamin C potentiates type III collagen turnover at the later time point under normal settings. SM22 expression levels is significantly upregulated in control group and decreases after incubation on different substrates (<b>A</b>). Col1a1 mRNA expression is enhanced, mostly on fibronectin–collagen mix and collagen coatings (<b>B</b>). Type I procollagen expression downregulates at the later time point, independent of coating composition (<b>C</b>). Type I collagen expression increases over time, peaking on fibronectin–collagen mix (<b>D</b>). The expression levels of col3a1 mRNA are constant over time, independent of coating composition (<b>E</b>), whereas the amount of type III collagen significantly increases over time (<b>F</b>). Col5a1 mRNA expression displays constant levels over time, independent of coating composition (<b>G</b>). Protein conversion levels of type V collagen reaches maximum values at the later time point on collagen coatings (<b>H</b>). Schematic overview of results, in time. The solid line towards mature collagen fibers formation serves as a guide to the reader (<b>I</b>). Error bars indicate standard error of the mean; ns stands for not significant <i>p</i>-value, * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen).</div>
|
||
|
||
|
||
|
||
|
||
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||
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||
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||
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||
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||
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|
||
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|
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|
||
data-image-alt="Figure 7"
|
||
data-pmc-id="PMC10179686"
|
||
data-figure-id="ijms-24-08379-f007">
|
||
<img class="figure-thumb" itemprop="thumbnail"
|
||
id="article-image-6"
|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb3/10179686/b45d2b58e1ca/ijms-24-08379-g007.gif"
|
||
alt="Figure 7" />
|
||
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|
||
|
||
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|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 7 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Collagen synthesis is modulated in… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
</div>
|
||
|
||
<div class="figure-caption-medium figure-caption-text" aria-hidden="true">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 7 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Collagen synthesis is modulated in a timely manner by vitamin C. Under profibrotic… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-6" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
Figure 7
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Collagen synthesis is modulated in a timely manner by vitamin C. Under profibrotic settings, vitamin C downregulates SM22 expression in primary cardiac fibroblasts cultured on collagen-based coatings (<b>A</b>). Col1a1 mRNA expression decreases in time on collagen coatings, but is significantly upregulated at the later time point on the fibronectin–collagen mix coating (<b>B</b>). Type I procollagen expression remains elevated in time on fibronectin coatings and exhibits the lowest expression value on collagen coatings (<b>C</b>), which is associated with the increased levels of type I collagen, mostly on fibronectin coatings (<b>D</b>). Vitamin C significantly increases the expression levels of col3a1 mRNA over time (<b>E</b>), which is associated with the elevated expression of type III collagen on fibronectin–collagen mix (<b>F</b>). Vitamin C significantly increases the col5a1 mRNA expression over time, exhibiting a maximum value on fibronectin coatings (<b>G</b>). This finding is associated with the increased levels of type V collagen expression on fibronectin coatings, but not on collagen substrates (<b>H</b>). Schematic overview of results over time. The solid line towards mature collagen fibers formation serves as a guide to the reader (<b>I</b>). Error bars indicate standard error of the mean; * <i>p</i> ≤ 0.05; ** <i>p</i> ≤ 0.01; *** <i>p</i> ≤ 0.001; **** <i>p</i> ≤ 0.0001. n = 3 experiments per condition. Fbn (Fibronectin); Coll (Collagen).</div>
|
||
|
||
|
||
|
||
|
||
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|
||
|
||
|
||
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||
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||
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||
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|
||
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|
||
data-figure-id="ijms-24-08379-f008">
|
||
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|
||
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|
||
src="https://cdn.ncbi.nlm.nih.gov/pmc/blobs/abb3/10179686/fef442615fff/ijms-24-08379-g008.gif"
|
||
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|
||
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||
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|
||
|
||
|
||
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||
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||
|
||
<strong class="figure-label">
|
||
<p> Figure 8 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Overview of the workflow, including… </p></div>
|
||
|
||
|
||
|
||
|
||
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|
||
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|
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|
||
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||
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||
|
||
|
||
|
||
|
||
<strong class="figure-label">
|
||
<p> Figure 8 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> Overview of the workflow, including the inclusion criteria and methodologies. </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-7" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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||
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||
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||
|
||
<strong class="figure-label">
|
||
Figure 8
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents">Overview of the workflow, including the inclusion criteria and methodologies.</div>
|
||
|
||
|
||
|
||
|
||
</figcaption>
|
||
|
||
|
||
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|
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|
||
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|
||
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|
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|
||
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|
||
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|
||
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|
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|
||
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||
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||
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||
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||
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<strong class="figure-label">
|
||
<p> Figure 9 </p>
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> The synergistic and complementary functionalities… </p></div>
|
||
|
||
|
||
|
||
|
||
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|
||
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|
||
|
||
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|
||
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||
|
||
|
||
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||
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||
|
||
<strong class="figure-label">
|
||
<p> Figure 9 </p>
|
||
</strong>
|
||
|
||
|
||
|
||
<div class="figure-caption-contents"><p> The synergistic and complementary functionalities of vitamin C in in vitro MI replica… </p></div>
|
||
|
||
|
||
|
||
|
||
</div>
|
||
|
||
<figcaption id="figure-caption-8" class="figure-caption-full figure-caption-text" itemtype="http://schema.org/ImageObject" itemprop="description">
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||
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|
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<strong class="figure-label">
|
||
Figure 9
|
||
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|
||
|
||
|
||
|
||
<div class="figure-caption-contents">The synergistic and complementary functionalities of vitamin C in in vitro MI replica on fibrillar collagen formation becomes evident at the later incubation time point. In normal conditions, primary cardiac fibroblasts regulate naturally the internal ROS formation to low levels, which are relevant for optimal functionality of cells. The radical scavenger role of vitamin C is highly potentiated over time at the level of the oxidative protection of primary cardiac fibroblasts activation under normal conditions. The synergistic activity of vitamin C and coating composition is clearly visible through the massive upregulation of col5a1 mRNA and downregulation of ROS under profibrotic vs. normal settings. The increase expression of col5a1 mRNA translates into structurally stable type I and III collagen fibers, which is a process that is mainly potentiated by (i) fibronectin–collagen mixture coating in normal settings and (ii) fibronectin and collagen coatings, respectively, in profibrotic conditions. Altogether, optimum supplementation doses of cell media with vitamin C are required to prove its radical scavenging activity and gene and protein stabilizer/modulator role for the synthesis of structurally and compositionally stable collagen fibrils.</div>
|
||
|
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|
||
|
||
|
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Virani S.S., Alonso A., Benjamin E.J., Bittencourt M.S., Callaway C.W., Carson A.P., Chamberlain A.M., Chang A.R., Cheng S., Delling F.N., et al. Heart Disease and Stroke Statistics-2020 Update: A Report From the American Heart Association. Circulation. 2020;141:e139–e596. doi: 10.1161/CIR.0000000000000757.
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Rusu M., Hilse K., Schuh A., Martin L., Slabu I., Stoppe C., Liehn E.A. Biomechanical assessment of remote and postinfarction scar remodeling following myocardial infarction. Sci. Rep. 2019;9:16744. doi: 10.1038/s41598-019-53351-7.
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Zhang W., Liang J., Han P. Cardiac cell type-specific responses to injury and contributions to heart regeneration. Cell Regen. 2021;10:4. doi: 10.1186/s13619-020-00065-1.
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Liu Z., Liu L., Cheng J., Zhang H. Risk Prediction Model Based on Biomarkers of Remodeling in Patients with Acute Anterior ST-Segment Elevation Myocardial Infarction. Med. Sci. Monit. Int. Med. J. Exp. Clin. Res. 2021;27:e927404. doi: 10.12659/MSM.927404.
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Mice, Inbred C57BL"[MeSH]"
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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|
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Mice, Inbred C57BL"[MeSH]"
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link major"
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aria-label="Toggle dropdown menu for keyword Myocardial Infarction* / metabolism"
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aria-expanded="false"
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data-pinger-ignore>
|
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Myocardial Infarction* / metabolism
|
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</button><div id="keyword-actions-mesh-terms-major-7"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Myocardial Infarction* / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Myocardial+Infarction%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Myocardial+Infarction%2Fmetabolism%22%5BMAJR%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Myocardial Infarction/metabolism"[MAJR]"
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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data-pinger-ignore>
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Myocardium / metabolism
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</button><div id="keyword-actions-mesh-terms-8"
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hidden
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aria-label="Dropdown menu for keyword Myocardium / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Myocardium%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Myocardium%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Myocardium/metabolism"[MeSH]"
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data-ga-category="search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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data-pinger-ignore>
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Reactive Oxygen Species / metabolism
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</button><div id="keyword-actions-mesh-terms-9"
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hidden
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aria-label="Dropdown menu for keyword Reactive Oxygen Species / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Reactive+Oxygen+Species%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Reactive+Oxygen+Species%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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Ventricular Remodeling / physiology
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
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aria-label="Dropdown menu for keyword Ventricular Remodeling / physiology"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Ventricular+Remodeling%2Fphysiology%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Ventricular+Remodeling%2Fphysiology%22%5BMeSH%5D&sort=date&sort_order=desc"
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Search in PubMed
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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data-search-term=""Ventricular Remodeling/physiology"[MeSH]"
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data-ga-category="search"
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Add to Search
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Vitamins / metabolism"
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tabindex="0"
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data-pinger-ignore>
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Vitamins / metabolism
|
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</button><div id="keyword-actions-mesh-terms-11"
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Vitamins / metabolism"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
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href="/?term=%22Vitamins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Vitamins%2Fmetabolism%22%5BMeSH%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&mesh="Vitamins/metabolism"[MeSH]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=Vitamins"
|
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data-ga-category="search_mesh"
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data-ga-action="mesh_term_link"
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Search in MeSH
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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role="button"
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data-search-term=""Vitamins/metabolism"[MeSH]"
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data-ga-category="search"
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data-ga-action="add_to_search"
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href="#">
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Add to Search
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</a></li></ul></div></div></div></li></ul>
|
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</div>
|
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|
||
|
||
|
||
|
||
|
||
<div id="substances" class="substances keywords-section">
|
||
<h2 class="title">
|
||
Substances
|
||
</h2>
|
||
|
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<ul class="keywords-list"><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
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aria-label="Toggle dropdown menu for keyword Ascorbic Acid"
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tabindex="0"
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aria-expanded="false"
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data-pinger-ignore>
|
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Ascorbic Acid
|
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</button><div id="keyword-actions-substances-0"
|
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class="keyword-actions-dropdown dropdown dropdown-container"
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hidden
|
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aria-label="Dropdown menu for keyword Ascorbic Acid"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
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href="/?term=%22Ascorbic+Acid%22%5Bnm%5D&sort=date&sort_order=desc"
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data-href="/?term=%22Ascorbic+Acid%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Ascorbic Acid"[nm]"
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Search in PubMed
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Ascorbic+Acid%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Ascorbic Acid">
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Search in MeSH
|
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</a></li><li><a class="add-to-search-link dropdown-block-link"
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ref="linksrc=add_to_search_link"
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role="button"
|
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data-search-term=""Ascorbic Acid"[nm]"
|
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data-ga-category="search"
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data-ga-action="add_to_search"
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data-ga-label=""Ascorbic Acid"[nm]"
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href="#">
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Add to Search
|
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</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Reactive Oxygen Species"
|
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tabindex="0"
|
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aria-controls="keyword-actions-substances-1"
|
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aria-expanded="false"
|
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data-pinger-ignore>
|
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Reactive Oxygen Species
|
||
</button><div id="keyword-actions-substances-1"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
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hidden
|
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aria-label="Dropdown menu for keyword Reactive Oxygen Species"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Reactive+Oxygen+Species%22%5Bnm%5D&sort=date&sort_order=desc"
|
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data-href="/?term=%22Reactive+Oxygen+Species%22%5Bnm%5D&sort=date&sort_order=desc"
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Reactive Oxygen Species"[nm]"
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data-ga-category="search"
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data-ga-action="substance"
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data-ga-label="Reactive Oxygen Species">
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Reactive+Oxygen+Species%22"
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data-ga-category="search_mesh"
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data-ga-action="substance_link"
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data-ga-label="Reactive Oxygen Species">
|
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Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
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role="button"
|
||
data-search-term=""Reactive Oxygen Species"[nm]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Reactive Oxygen Species"[nm]"
|
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href="#">
|
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Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Collagen"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-2"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Collagen
|
||
</button><div id="keyword-actions-substances-2"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Collagen"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Collagen%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Collagen%22%5Bnm%5D&sort=date&sort_order=desc"
|
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ref="linksrc=search_in_pubmed_keyword_link&keyword="Collagen"[nm]"
|
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data-ga-category="search"
|
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data-ga-action="substance"
|
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data-ga-label="Collagen">
|
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Search in PubMed
|
||
</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
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ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Collagen%22"
|
||
data-ga-category="search_mesh"
|
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data-ga-action="substance_link"
|
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data-ga-label="Collagen">
|
||
Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Collagen"[nm]"
|
||
data-ga-category="search"
|
||
data-ga-action="add_to_search"
|
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data-ga-label=""Collagen"[nm]"
|
||
href="#">
|
||
Add to Search
|
||
</a></li></ul></div></div></div></li><li><div class="keyword-actions dropdown-block"><button class="keyword-actions-trigger trigger keyword-link"
|
||
aria-label="Toggle dropdown menu for keyword Vitamins"
|
||
tabindex="0"
|
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aria-controls="keyword-actions-substances-3"
|
||
aria-expanded="false"
|
||
data-pinger-ignore>
|
||
Vitamins
|
||
</button><div id="keyword-actions-substances-3"
|
||
class="keyword-actions-dropdown dropdown dropdown-container"
|
||
hidden
|
||
aria-label="Dropdown menu for keyword Vitamins"><div class="title">Actions</div><div class="content"><ul class="keyword-actions-links"><li><a class="search-in-pubmed-link dropdown-block-link"
|
||
href="/?term=%22Vitamins%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
data-href="/?term=%22Vitamins%22%5Bnm%5D&sort=date&sort_order=desc"
|
||
ref="linksrc=search_in_pubmed_keyword_link&keyword="Vitamins"[nm]"
|
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data-ga-category="search"
|
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data-ga-action="substance"
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data-ga-label="Vitamins">
|
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Search in PubMed
|
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</a></li><li><a class="search-in-mesh-link dropdown-block-link"
|
||
ref="linksrc=search_in_mesh_link"
|
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href="https://www.ncbi.nlm.nih.gov/mesh?term=%22Vitamins%22"
|
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data-ga-category="search_mesh"
|
||
data-ga-action="substance_link"
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data-ga-label="Vitamins">
|
||
Search in MeSH
|
||
</a></li><li><a class="add-to-search-link dropdown-block-link"
|
||
ref="linksrc=add_to_search_link"
|
||
role="button"
|
||
data-search-term=""Vitamins"[nm]"
|
||
data-ga-category="search"
|
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data-ga-action="add_to_search"
|
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data-ga-label=""Vitamins"[nm]"
|
||
href="#">
|
||
Add to Search
|
||
</a></li></ul></div></div></div></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
|
||
<div id="related-links" class="related-links">
|
||
<h2 class="title">
|
||
Related information
|
||
</h2>
|
||
|
||
<ul class="related-links-list"><li><a title="Related information in MedGen" href="https://www.ncbi.nlm.nih.gov/medgen?linkname=pubmed_medgen&from_uid=37176085"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=37176085&ordinalpos=1&linkpos=1">
|
||
MedGen
|
||
</a></li><li><a title="Related PubChem Compound via MeSH" href="https://www.ncbi.nlm.nih.gov/pccompound?linkname=pubmed_pccompound_mesh&from_uid=37176085"
|
||
ref="log$=recordlinks&logdbfrom=pubmed&ncbi_uid=37176085&ordinalpos=1&linkpos=2">
|
||
PubChem Compound (MeSH Keyword)
|
||
</a></li></ul>
|
||
</div>
|
||
|
||
|
||
|
||
|
||
|
||
<div id="grants" class="grants">
|
||
<h2 class="title">
|
||
Grants and funding
|
||
</h2>
|
||
<div class="grants-list"><ul id="grants-head-list"><li class="grant-item"><a
|
||
title="All articles for grant No 120661/University of Southern Denmark"
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