CINXE.COM

<!DOCTYPE html>      <html lang='en' class='no-js'>  <head> <meta charset='utf-8'> <meta content='text/html; charset=UTF-8' http-equiv='Content-Type'> <meta content='The Journal of Clinical Investigation' name='AUTHOR'>  <meta content='width=device-width, initial-scale=1.0' name='viewport'> <link href='/rss' rel='alternate' title='JCI New Article RSS' type='application/rss+xml'> <meta name="csrf-param" content="authenticity_token" /> <meta name="csrf-token" content="Kb0KbSxmlMcQ4o4KIDiqsJdP1Q0riMy7RfkjIK0zHJiE7rewMKYtU5lsi3ckf1DsfGeWvJftEgS8iuQFjF2VNA==" /> <link rel="shortcut icon" type="image/x-icon" href="/assets/jci-favicon-378ea4dd43f03bc78136c6a261d9b28f6811fe59d12db426eae78cf0691b0008.ico" /> <title> JCI - Welcome </title> <link rel="stylesheet" media="all" href="/assets/application-4e3473ed7442aa1dc35d11f58ed4edfbd690fa57a3eb3a1daca0cd68dc7fb1e0.css" />  <style> @font-face { font-family: "klavika-bold"; src: url("///var/www/jci/jci/releases/20250410184254/vendor/common/fonts/klavika/eot/KlavikaWebBasicBold.eot") format('eot'), src: url("///var/www/jci/jci/releases/20250410184254/vendor/common/fonts/klavika/eot/KlavikaWebBasicBold.eot?#iefix") format("embedded-opentype"), url("///var/www/jci/jci/releases/20250410184254/vendor/common/fonts/klavika/woff/KlavikaWebBasicBold.woff") format("woff") } </style> <script> //Google Tag Manager Data Layer //Values must be set before GTM tags are triggered window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'siteName': 'content-jci', 'ipAddress': '8.222.208.146', 'environment': 'production', }); </script> <script src="/assets/vendor/modernizr-2f68aa04c7424c280c5bc9db8b68f7f6ff70bcd38254c5b89383eac8e89b1781.js"></script> <script type='text/javascript'> var googletag = googletag || {}; googletag.cmd = googletag.cmd || []; (function () { var gads = document.createElement('script'); gads.async = true; gads.type = 'text/javascript'; var useSSL = 'https:' == document.location.protocol; gads.src = (useSSL ? 'https:' : 'http:') + '//www.googletagservices.com/tag/js/gpt.js'; var node = document.getElementsByTagName('script')[0]; node.parentNode.insertBefore(gads, node); })(); googletag.cmd.push(function () { // NOTE: This script manages google ads, more info at doc/GoogleAds.md var mapping = googletag.sizeMapping().addSize([800, 600], [300, 250]).addSize([640, 480], [260, 217]).build(); var mapping2 = googletag.sizeMapping() .addSize([1920, 1080], [728, 90])//All desktop like resolutions are set to 728x90 .addSize([800, 600], [728, 90]) .addSize([640, 480], [728, 90]) .addSize([0, 0], [320, 50]) //Smaller than 640x480 screens .build(); googletag.defineSlot('/82117132/jci-homepage-med-rectangle-left-col-top', [[300, 250],[260, 217]], 'jci-homepage-med-rectangle-left-col-top').defineSizeMapping(mapping).addService(googletag.pubads()); googletag.defineSlot('/82117132/jci-article-interior-leaderboard-top', [[728, 90],[320, 50]], 'jci-article-interior-leaderboard-top').defineSizeMapping(mapping2).addService(googletag.pubads()); googletag.defineSlot('/82117132/jci-article-interior-leaderboard-bottom', [728, 90], 'jci-article-interior-leaderboard-bottom').addService(googletag.pubads()); googletag.defineSlot('/82117132/jci-article-interior-skyscraper-right-col', [160, 600], 'jci-article-interior-skyscraper-right-col').addService(googletag.pubads()); googletag.defineSlot('/82117132/jci-interior-skyscraper-right-col', [160, 600], 'jci-interior-skyscraper-right-col').addService(googletag.pubads()); // collapseEmptyDivs requires all slots be defined above. googletag.pubads().collapseEmptyDivs(true); googletag.enableServices(); }); </script> </head> <body class='' id='tags_controller'> <div class='off-canvas-wrap' data-offcanvas=''> <div class='inner-wrap'> <div class='fixed show-for-large-up'> <div class='row menu-align' id='logo-bar'> <div class='small-12 columns'> <div class='cross-journal-container'> Go to <a href='http://insight.jci.org'>JCI Insight</a> </div> <a href="/"><img src="/assets/common/jci-spelled-out-white-on-transparent.20160208-958617d51a205b239bcef41eae5703962aee0ae2fcc9fbda0237e635a09ac7f3.png" /></a> </div> </div> <div class='row menu-align' id='journal-bar'> <div class='small-12 columns'> <ul class='inline-list'> <li><a href="/kiosks/about">About</a></li> <li><a href="/kiosks/editorial-board">Editors</a></li> <li><a href="/kiosks/about/consulting-editors">Consulting Editors</a></li> <li><a href="/kiosks/authors">For authors</a></li> <li><a href="/kiosks/ethics">Publication ethics</a></li> <li><a href="/kiosks/connect">Publication alerts by email</a></li> <li><a href="/kiosks/advertise">Advertising</a></li> <li><a href="https://the-asci.org/controllers/asci/JobBoard.php">Job board</a></li> <li><a href="/kiosks/contact">Contact</a></li> </ul> </div> </div> <div id='content-bar'> <nav class='top-bar' data-topbar=''> <section class='top-bar-section'> <ul class='left'> <li class='not-click'> <a href="/tags/141">Clinical Research and Public Health</a> </li> <li class='not-click'> <a id="topmenu_current_issue" href="/current">Current issue</a> </li> <li class='not-click'> <a href="/archive">Past issues</a> </li> <li class='has-dropdown not-click'> <a>By specialty</a> <ul class='dropdown'> <li><a href="/tags/118">COVID-19</a></li> <li><a href="/tags/15">Cardiology</a></li> <li><a href="/tags/21">Gastroenterology</a></li> <li><a href="/tags/25">Immunology</a></li> <li><a href="/tags/28">Metabolism</a></li> <li><a href="/tags/31">Nephrology</a></li> <li><a href="/tags/32">Neuroscience</a></li> <li><a href="/tags/33">Oncology</a></li> <li><a href="/tags/36">Pulmonology</a></li> <li><a href="/tags/42">Vascular biology</a></li> <li><a href="/specialties">All ...</a></li> </ul> </li> <li class='has-dropdown not-click'> <a href="/videos">Videos</a> <ul class='dropdown'> <li><a href="/videos/cgms">Conversations with Giants in Medicine</a></li> <li><a href="/videos/video_abstracts">Video Abstracts</a></li> </ul> </li> <li class='has-dropdown not-click'> <a href="/tags/reviews">Reviews</a> <ul class='dropdown'> <li> <label>Reviews</label> </li> <li><a href="/tags/reviews">View all reviews ...</a></li> <li class='divider'></li> <li> <label>Review Series</label> </li> <li><a href="/review_series/131">Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)</a></li> <li><a href="/review_series/130">Microbiome in Health and Disease (Feb 2025)</a></li> <li><a href="/review_series/127">Substance Use Disorders (Oct 2024)</a></li> <li><a href="/review_series/128">Clonal Hematopoiesis (Oct 2024)</a></li> <li><a href="/review_series/129">Sex Differences in Medicine (Sep 2024)</a></li> <li><a href="/review_series/126">Vascular Malformations (Apr 2024)</a></li> <li><a href="/review_series/125">Lung inflammatory injury and tissue repair (Jul 2023)</a></li> <li> <a href="/review_series">View all review series ...</a> </li> </ul> </li> <li class='not-click'> <a href="/tags/111">Viewpoint</a> </li> <li class='has-dropdown not-click'> <a>Collections</a> <ul class='dropdown'> <li><a href="/in-press-preview">In-Press Preview</a></li> <li><a href="/tags/141">Clinical Research and Public Health</a></li> <li><a href="/tags/127">Research Letters</a></li> <li><a href="/tags/75">Letters to the Editor</a></li> <li><a href="/tags/56">Editorials</a></li> <li><a href="/tags/44">Commentaries</a></li> <li><a href="/tags/123">Editor's notes</a></li> <li><a href="/tags/2">Reviews</a></li> <li><a href="/tags/111">Viewpoints</a></li> <li><a href="/collections/topic/jci-100th-anniversary">100th anniversary</a></li> <li><a href="/top_articles">Top read articles</a></li> </ul> </li> </ul> <ul class='right'> <li class='has-form'> <div id='search-area'> <form action="/search/results" accept-charset="UTF-8" method="get"> <input type="text" name="q" id="q" value="" placeholder="Search the JCI" /> <input type="image" src="/assets/search-black-ba9b554d6f74b1c93d6e6ab71d1c9830c18a20fc6b7e72393f136f5d875141ac.png" value="" /> </form> </div> </li> </ul> </section> </nav> </div> </div> <nav class='tab-bar hide-for-large-up fixed' id='small-navbar'> <section class='left-small'> <a class='left-off-canvas-toggle menu-icon'> <span></span> </a> </section> <section class='middle tab-bar-section'> <h1 class='title'><a href="/"><img width="40" src="/assets/common/jci-only-white-6c989e8f9744a714482158b82319d50aa8437aa4c8524c4f3dcf8450299cd4b7.png" /></a></h1> </section> </nav> <aside class='left-off-canvas-menu'> <ul class='off-canvas-list'> <li> <label>The Journal of Clinical Investigation</label> </li> <li><form action="/search/results" accept-charset="UTF-8" method="get"> <div class='row collapse' id='search-div-offcanvas'> <div class='small-8 columns'> <input name='q' placeholder='Search the JCI' type='text'> </div> <div class='small-4 columns'> <input type="image" src="/assets/common/search-white-530f3f95b9080d73eba51eaeffdf1a3922af42ccc277a2d1d987b8aa24423c96.png" id="search-icon-offcanvas" /> </div> </div> </form> </li> <li><a id="offcanvas_current_issue" href="/current">Current issue</a></li> <li><a href="/archive">Past issues</a></li> <li><a href="/specialties">Specialties</a></li> <li><a href="/tags/reviews">Reviews</a></li> <li><a href="/review_series">Review series</a></li> <li> <label>Videos</label> </li> <li><a href="/videos/cgms">Conversations with Giants in Medicine</a></li> <li><a href="/videos/video_abstracts">Video Abstracts</a></li> <li> <label>Collections</label> </li> <li><a href="/in-press-preview">In-Press Preview</a></li> <li><a href="/tags/141">Clinical Research and Public Health</a></li> <li><a href="/tags/127">Research Letters</a></li> <li><a href="/tags/75">Letters to the Editor</a></li> <li><a href="/tags/56">Editorials</a></li> <li><a href="/tags/44">Commentaries</a></li> <li><a href="/tags/123">Editor's notes</a></li> <li><a href="/tags/2">Reviews</a></li> <li><a href="/tags/111">Viewpoints</a></li> <li><a href="/collections/topic/jci-100th-anniversary">100th anniversary</a></li> <li><a href="/top_articles">Top read articles</a></li> <li> <label>Journal Details</label> </li> <li><a href="/kiosks/about">About</a></li> <li><a href="/kiosks/editorial-board">Editors</a></li> <li><a href="/kiosks/about/consulting-editors">Consulting Editors</a></li> <li><a href="/kiosks/authors">For authors</a></li> <li><a href="/kiosks/ethics">Publication ethics</a></li> <li><a href="/kiosks/connect">Publication alerts by email</a></li> <li><a href="/kiosks/advertise">Advertising</a></li> <li><a href="https://the-asci.org/controllers/asci/JobBoard.php">Job board</a></li> <li><a href="/kiosks/contact">Contact</a></li> </ul> </aside> <a class='exit-off-canvas'></a>  <div class='row content-wrapper'> <div class='small-12 columns'> <div class='menu-align'> <div class='row'> <div class='large-10 medium-9 small-12 columns'> <h3>Viewpoint</h3> <div class='row'> <div class='small-10 medium-7 large-5 small-centered columns'> <ul class='tabs row' data-tab> <li class='tab-title small-6 centered active'> <a href='#articles'>145 Articles</a> </li> <li class='tab-title small-6 centered '> <a href='#posts'>0 Posts</a> </li> </ul> </div> </div> <div class='tabs-content'> <div class='content active' id='articles'> <div class='row'> <div class='small-12 columns'> <div role="navigation" aria-label="Pagination" class="pagination-centered" previous_label="<--" next_label="-->"><ul class="pagination"><li class="arrow unavailable"><a class="arrow unavailable">← Previous</a></li> <li class="current"><a class="current">1</a></li> <li><a rel="next" href="/tags/111?content=articles&page=2">2</a></li> <li><a href="/tags/111?content=articles&page=3">3</a></li> <li class="unavailable"><a>…</a></li> <li><a href="/tags/111?content=articles&page=14">14</a></li> <li><a href="/tags/111?content=articles&page=15">15</a></li> <li class="arrow"><a class="arrow" rel="next" href="/tags/111?content=articles&page=2">Next →</a></li></ul></div> </div> </div> <div class='row'> <div class='small-12 columns'> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/186418">Fat, fibrosis, and the future: navigating the maze of MASLD/MASH</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186418">Scott L. Friedman</a> <a class='hide-for-small show-more' data-reveal-id='article45919-more' href='#'> <div class='article-authors'> Scott L. Friedman </div> </a> <span class='article-published-at'> Published April 1, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/7">135(7)</a>:e186418. <a href="https://doi.org/10.1172/JCI186418">https://doi.org/10.1172/JCI186418</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186418">Text</a> | <a href="/articles/view/186418/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186418' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/186418/figure/1' ref='group' title='Concerns about the increasing worldwide prevalence, economic impact, and serious adverse sequelae of MASLD and MASH draw attention to its pathogenesis and treatment options.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/186000/186418/small/JCI186418.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45919-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186418">Fat, fibrosis, and the future: navigating the maze of MASLD/MASH</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186418">Text</a></li> <li><a class="button tiny" href="/articles/view/186418/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Scott L. Friedman</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/189625">MicroRNAs: Where brilliance, perseverance, and ambition converged</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/189625">Rares Drula, George A. Calin</a> <a class='hide-for-small show-more' data-reveal-id='article45584-more' href='#'> <div class='article-authors'> Rares Drula, George A. Calin </div> </a> <span class='article-published-at'> Published December 10, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024. <a href="https://doi.org/10.1172/JCI189625">https://doi.org/10.1172/JCI189625</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/189625">Text</a> | <a href="/articles/view/189625/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI189625' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45584-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/189625">MicroRNAs: Where brilliance, perseverance, and ambition converged</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/189625">Text</a></li> <li><a class="button tiny" href="/articles/view/189625/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p> </p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Rares Drula, George A. Calin</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/186744">Hidradenitis suppurativa: key insights into treatment success and failure</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186744">Kelsey R. van Straalen, … , Vincent Piguet, Johann E. Gudjonsson</a> <a class='hide-for-small show-more' data-reveal-id='article45471-more' href='#'> <div class='article-authors'> Kelsey R. van Straalen, … , Vincent Piguet, Johann E. Gudjonsson </div> </a> <span class='article-published-at'> Published November 1, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/21">134(21)</a>:e186744. <a href="https://doi.org/10.1172/JCI186744">https://doi.org/10.1172/JCI186744</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186744">Text</a> | <a href="/articles/view/186744/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186744' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/186744/figure/1' ref='group' title='Outline of discussed current and future therapeutics within an active HS lesion. Outline of an active HS lesion with active sinus tracts demonstrating the targets of current and upcoming therapeutics. Colors used for the treatments depicted: red, promising trial results; orange, trails that failed to meet their primary endpoint or demonstrated low response; gray, no clinical trials or published data yet.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/186000/186744/small/JCI186744.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45471-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186744">Hidradenitis suppurativa: key insights into treatment success and failure</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186744">Text</a></li> <li><a class="button tiny" href="/articles/view/186744/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Kelsey R. van Straalen, Vincent Piguet, Johann E. Gudjonsson</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/186104">2024 Lasker Award Recipient Zhijian Chen elucidates how DNA stimulates immunity</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186104">Amy B. Heimberger</a> <a class='hide-for-small show-more' data-reveal-id='article45381-more' href='#'> <div class='article-authors'> Amy B. Heimberger </div> </a> <span class='article-published-at'> Published September 19, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024. <a href="https://doi.org/10.1172/JCI186104">https://doi.org/10.1172/JCI186104</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186104">Text</a> | <a href="/articles/view/186104/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186104' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/186104/figure/1' ref='group' title='cGAS/STING signaling and therapeutic targeting. (A) Activation of the cGAS/STING pathway can be triggered either through the importation of cGAMP or the presence of double-stranded DNA (dsDNA). Activated cyclic GMP-AMP synthase (cGAS) uses ATP and GTP to catalyze the formation of cGAMP that binds to STING localized on the ER membrane. STING then recruits TBK1, which activates/phosphorylates IRF3 and NF-κB, which translocates to the nucleus, thereby inducing the transcriptional activation of proinflammatory interferon responses. (B) A variety of therapeutics are being evaluated in clinical trials, such as cyclic dinucleotides or STING agonists that can trigger the activation of cGAS/STING pathway. The STING signal is terminated (denoted by the X) when activated STING in the ER-Golgi compartment binds to LC3 on the autophagy membrane, leading to the degradation of STING and the associated cytoplasmic DNA in the autolysosome. Excess intracellular cGAMP is transported out of the cell and hydrolyzed by ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) to yield AMP and GMP. ENPP1 inhibitors maintain proinflammatory cGAMP concentrations. ERGIC; endoplasmic-reticulum-Golgi intermediate compartment.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/186000/186104/small/JCI186104.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45381-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186104">2024 Lasker Award Recipient Zhijian Chen elucidates how DNA stimulates immunity</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186104">Text</a></li> <li><a class="button tiny" href="/articles/view/186104/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Amy B. Heimberger</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/186225">Joel Habener, Svetlana Mojsov, and Lotte Bjerre Knudsen awarded Lasker prize for pioneering work on GLP-1</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186225">Hossein Ardehali</a> <a class='hide-for-small show-more' data-reveal-id='article45384-more' href='#'> <div class='article-authors'> Hossein Ardehali </div> </a> <span class='article-published-at'> Published September 19, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024. <a href="https://doi.org/10.1172/JCI186225">https://doi.org/10.1172/JCI186225</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186225">Text</a> | <a href="/articles/view/186225/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186225' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/186225/figure/1' ref='group' title='Mechanism of GLP-1 production and its beneficial effects. Proglucagon is released from intestinal cells and is processed into its components, one of which is GLP-1. GLP-1 binds to its receptor in pancreas and leads to insulin secretion. GLP-1 exerts additional beneficial effects by binding to the GLP-1 receptor in other tissues or via indirectly reducing inflammation. The list of FDA-approved GLP-1RA drugs is also included in the figure.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/186000/186225/small/JCI186225.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45384-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186225">Joel Habener, Svetlana Mojsov, and Lotte Bjerre Knudsen awarded Lasker prize for pioneering work on GLP-1</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186225">Text</a></li> <li><a class="button tiny" href="/articles/view/186225/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Hossein Ardehali</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/185395">Guild-based approach for mitigating information loss and distortion issues in microbiome analysis</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/185395">Liping Zhao, … , Guojun Wu, Naisi Zhao</a> <a class='hide-for-small show-more' data-reveal-id='article45298-more' href='#'> <div class='article-authors'> Liping Zhao, … , Guojun Wu, Naisi Zhao </div> </a> <span class='article-published-at'> Published September 3, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/17">134(17)</a>:e185395. <a href="https://doi.org/10.1172/JCI185395">https://doi.org/10.1172/JCI185395</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/185395">Text</a> | <a href="/articles/view/185395/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI185395' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/185395/figure/1' ref='group' title='Guild-based analysis of microbiome datasets. A guild consists of microbes with diverse taxonomic backgrounds, but thriving or declining together, showing coabundance behavior. (i) Initial tagging and identification of individual microbial entities using ASVs or MAGs, each assigned a UUID for precise tracking. (ii) Analysis of interactions among microbial entities to identify patterns of coexistence and influence, revealing the foundational relationships within the microbiome. Clustering of microbes into guilds based on coabundance analysis, where members share ecological niches and exhibit similar abundance patterns across different conditions or samples. (iii) Emergence of complex microbial behaviors and functions from the interactions within and between guilds, highlighting the collective capabilities of the microbiome. Integration of guild activities into broader systems-level functions that affect host physiology and health, encapsulating the holistic effect of microbial interactions.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/185000/185395/small/JCI185395.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45298-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/185395">Guild-based approach for mitigating information loss and distortion issues in microbiome analysis</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/185395">Text</a></li> <li><a class="button tiny" href="/articles/view/185395/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Liping Zhao, Guojun Wu, Naisi Zhao</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/182652">The cancer-associated secretory phenotype: a new frontier in targeted therapeutics</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/182652">Xiaochao Tan, … , Shike Wang, Jonathan M. Kurie</a> <a class='hide-for-small show-more' data-reveal-id='article45315-more' href='#'> <div class='article-authors'> Xiaochao Tan, … , Shike Wang, Jonathan M. Kurie </div> </a> <span class='article-published-at'> Published September 3, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/17">134(17)</a>:e182652. <a href="https://doi.org/10.1172/JCI182652">https://doi.org/10.1172/JCI182652</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/182652">Text</a> | <a href="/articles/view/182652/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI182652' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/182652/figure/1' ref='group' title='Blockade of secretory vesicle biogenesis provides a therapeutic strategy for targeting cancer. (A) Phosphatidylinositol-4-phosphate (PI4P) is the Golgi membrane insertion site for Golgi phosphoprotein 3 (GOLPH3), a pivotal regulator of Golgi membrane dynamics and vesicle biogenesis. Golgi PI4P is generated by two Golgi-localized phosphatidylinositol 4-kinases (PI4Ks): PI4KIIIβ and PI4KIIα. PI4K antagonists block PI4P synthesis and impair secretion. (B) Golgi scaffold GOLIM4 recruits effectors of vesicle biogenesis (GOLPH3) and cargo sorting (ATP2C1) to activate secretion. GOLIM4 is degraded by manganese (Mn), resulting in diminished secretion. (C) P53 loss increased the expression levels of the Golgi scaffold GRASP55. GOLGIN45 is a client of GRASP55 and generates a protein complex that promotes vesicle biogenesis. GRASPIN disrupts the interaction between GRASP55 and GOLGIN45. (D) The Golgi scaffold PAQR11 is induced upon the loss of P53. PAQR11 promotes the secretion of PLAU, which functions in an autocrine manner by binding to the PLAU receptor (PLAUR). Activated PLAUR, in turn, promotes the expression of PAQR11. PLAUR inhibitor (PLAURi) prevents the binding of secreted PLAU to PLAUR, effectively terminating an autocrine signaling pathway that drives secretion.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/182000/182652/small/JCI182652.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45315-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/182652">The cancer-associated secretory phenotype: a new frontier in targeted therapeutics</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/182652">Text</a></li> <li><a class="button tiny" href="/articles/view/182652/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/178003">Status check: next-generation sequencing for infectious-disease diagnostics</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/178003">Kyle G. Rodino, Patricia J. Simner</a> <a class='hide-for-small show-more' data-reveal-id='article44784-more' href='#'> <div class='article-authors'> Kyle G. Rodino, Patricia J. Simner </div> </a> <span class='article-published-at'> Published February 15, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/4">134(4)</a>:e178003. <a href="https://doi.org/10.1172/JCI178003">https://doi.org/10.1172/JCI178003</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/178003">Text</a> | <a href="/articles/view/178003/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI178003' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/178003/figure/1' ref='group' title='NGS applications can be used in the diagnosis of infectious diseases. (A) Microbes grown from patient samples provide microbial DNA for WGS in which millions of fragments are read in parallel and assembled to reconstruct the microbial genome. WGS is especially useful for the identification of pathogens associated with hospital outbreaks and detection of AMR genes. (B) tNGS directly amplifies genes from a clinical specimen prior to sequencing. This technique often focuses on genes that are shared among all members of a microbial kingdom, such as the 16S rRNA gene for bacteria. The sequencing of amplified products allows for detection and identification of the composition of the targeted microorganisms in the specimen. Expanded applications can assess thousands of genes in parallel, covering pathogens and AMR targets. (C) mNGS involves sequencing all nucleic acids contained within a sample (e.g. CSF), including those derived from the host, microbes, and even contaminating nucleic acid. mNGS shows promise in detecting rare pathogens in which diagnostics are unavailable, unsuspected pathogens based on the patients’ symptoms with conditions that affect routine testing results, and in situations with insidious organisms.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/178000/178003/small/JCI178003.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44784-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/178003">Status check: next-generation sequencing for infectious-disease diagnostics</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/178003">Text</a></li> <li><a class="button tiny" href="/articles/view/178003/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Next-generation sequencing (NGS) applications for the diagnostics of infectious diseases has demonstrated great potential with three distinct approaches: whole-genome sequencing (WGS), targeted NGS (tNGS), and metagenomic NGS (mNGS, also known as clinical metagenomics). These approaches provide several advantages over traditional microbiologic methods, though challenges still exist.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Kyle G. Rodino, Patricia J. Simner</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 medium-9 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/176736">Molecular and cellular mechanisms underlying the failure of mitochondrial metabolism drugs in cancer clinical trials</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/176736">Karthik Vasan, Navdeep S. Chandel</a> <a class='hide-for-small show-more' data-reveal-id='article44746-more' href='#'> <div class='article-authors'> Karthik Vasan, Navdeep S. Chandel </div> </a> <span class='article-published-at'> Published February 1, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/3">134(3)</a>:e176736. <a href="https://doi.org/10.1172/JCI176736">https://doi.org/10.1172/JCI176736</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/176736">Text</a> | <a href="/articles/view/176736/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI176736' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> <div class='medium-3 hide-for-small columns'> <a href='https://www.jci.org/articles/view/176736/figure/1' ref='group' title='Drugs that target the mitochondrial electron transport chain in cancer cells have antineoplastic properties. Mitochondrial electron transport chain (ETC) is necessary to sustain metabolites required for cancer cell growth. Metformin’s primary anticancer mechanism involves the inhibition of mitochondrial ETC complex I. The drug’s safety and efficacy are associated with organic cation transporters (OCTs), which have varying presence across regular tissues and cancers. Metformin relies on OCTs for cell entry, and variability in OCT expression levels along with the ability of cancer cells to metabolically adjust to the tumor microenvironment might account for inconsistent results in clinical trials. New drugs on the horizon targeting the ETC include the antimalaria drug atovaquone, an inhibitor of mitochondrial complex III, and ONC201, an activator of mitochondrial protease caseinolytic protease P (CLPP) that degrades ETC proteins. The molecular determinants that would make these drugs effective and their specific therapeutic window need to be addressed.'> <img src='//dm5migu4zj3pb.cloudfront.net/manuscripts/176000/176736/small/JCI176736.f1.gif'> </a> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44746-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/176736">Molecular and cellular mechanisms underlying the failure of mitochondrial metabolism drugs in cancer clinical trials</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/176736">Text</a></li> <li><a class="button tiny" href="/articles/view/176736/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Karthik Vasan, Navdeep S. Chandel</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <hr> <div class='row'> <div class='small-12 columns'> <div class='row'> <div class='small-12 columns'> <h5 class='article-title' style='display: inline-block;'><a href="/articles/view/178332">Keeping translational research grounded in human biology</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/178332">Saptarsi M. Haldar</a> <a class='hide-for-small show-more' data-reveal-id='article44665-more' href='#'> <div class='article-authors'> Saptarsi M. Haldar </div> </a> <span class='article-published-at'> Published January 16, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/2">134(2)</a>:e178332. <a href="https://doi.org/10.1172/JCI178332">https://doi.org/10.1172/JCI178332</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/178332">Text</a> | <a href="/articles/view/178332/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI178332' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44665-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/178332">Keeping translational research grounded in human biology</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/178332">Text</a></li> <li><a class="button tiny" href="/articles/view/178332/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p></p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Saptarsi M. Haldar</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> </div> </div> <div class='row'> <div class='small-12 columns'> <div role="navigation" aria-label="Pagination" class="pagination-centered" previous_label="<--" next_label="-->"><ul class="pagination"><li class="arrow unavailable"><a class="arrow unavailable">← Previous</a></li> <li class="current"><a class="current">1</a></li> <li><a rel="next" href="/tags/111?content=articles&page=2">2</a></li> <li><a href="/tags/111?content=articles&page=3">3</a></li> <li class="unavailable"><a>…</a></li> <li><a href="/tags/111?content=articles&page=14">14</a></li> <li><a href="/tags/111?content=articles&page=15">15</a></li> <li class="arrow"><a class="arrow" rel="next" href="/tags/111?content=articles&page=2">Next →</a></li></ul></div> </div> </div> </div> <div class='content ' id='posts'> <p>No posts were found with this tag.</p> </div> </div> </div> <div class='large-2 medium-3 hide-for-small columns' style='padding: 12px 9px 12px 9px;'> <div style='width:100%; text-align: center;'> <div id='jci-interior-skyscraper-right-col'> <span class='secondary label'>Advertisement</span> <script> try { googletag.cmd.push(function () { googletag.display('jci-interior-skyscraper-right-col'); }); } catch(e){} </script> </div> </div> </div> </div> </div> </div> </div> </div> <div id='footer'> <div class='row panel-padding'> <div class='small-6 columns'> <div id='social-links'> <a onclick="trackOutboundLink('/twitter?ref=footer');" href="/twitter"><img title="Twitter" src="/assets/social/twitter-round-blue-78025a92064e3594e44e4ccf5446aefeafba696cd3c8e4a7be1850c7c9f62aba.png" /></a> <a onclick="trackOutboundLink('/facebook?ref=footer');" href="/facebook"><img title="Facebook" src="/assets/social/facebook-round-blue-2787910d46dcbdbee4bd34030fee044e5a77cfda2221af9191d437b2f5fadeb1.png" /></a> <a href="/rss"><img title="RSS" src="/assets/social/rss-round-color-6f5fa8e93dc066ee4923a36ba6a7cb97d53c5b77de78a2c7b2a721adc603f342.png" /></a> </div> <br> Copyright © 2025 <a href="http://www.the-asci.org">American Society for Clinical Investigation</a> <br> ISSN: 0021-9738 (print), 1558-8238 (online) </div> <div class='small-6 columns'> <div class='row'> <div class='small-12 columns'> <h4 class='notices-signup'>Sign up for email alerts</h4> <form action='https://notices.jci.org/subscribers/new' method='get'> <input name='utm_source' type='hidden' value='jci'> <input name='utm_medium' type='hidden' value='web'> <input name='utm_campaign' type='hidden' value='email_signup'> <input name='utm_content' type='hidden' value='footer'> <div class='row'> <div class='small-12 medium-9 columns'> <input name='email_address' placeholder='Your email address' required type='text'> </div> <div class='small-12 medium-3 columns'> <input class='button tiny orange' type='submit' value='Sign up'> </div> </div> </form> </div> </div> </div> </div> </div> </div> <script src="/assets/application-27f18b5fe3b7302e5b3e3c6d7cf9bb3f54759fad32679209f5aef429b89f3aef.js"></script>  <script src="//s7.addthis.com/js/300/addthis_widget.js#pubid=ra-4d8389db4b0bb592" async="async"></script> <script src="//d1bxh8uas1mnw7.cloudfront.net/assets/embed.js" async="async"></script>  </body> </html>