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<h1>Top read articles in the last 30 days</h1> <p>This list is updated daily and reflects the last month of access data. Articles older than two years will not be shown.</p> <div class='row'> <div class='small-10 medium-7 large-5 columns'> <ul class='tabs' data-tab> <li class='tab-title small-6 text-center active'> <a href='#research'>Research</a> </li> <li class='tab-title small-6 text-center '> <a href='#review'>Review</a> </li> </ul> </div> </div> <div class='tabs-content'> <div class='content active' id='research'> <div id='research_accesses'> <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/170682">Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/170682">Catherine A. Gao, … , Benjamin D. Singer, The NU SCRIPT Study Investigators</a> <a class='hide-for-small show-more' data-reveal-id='article44160-more' href='#'> <div class='article-authors'> Catherine A. Gao, … , Benjamin D. Singer, The NU SCRIPT Study Investigators </div> </a> <span class='article-published-at'> Published April 27, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023;<a id="article_metadata" href="http://www.jci.org/133/12">133(12)</a>:e170682. <a href="https://doi.org/10.1172/JCI170682">https://doi.org/10.1172/JCI170682</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/170682">Text</a> | <a href="/articles/view/170682/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/141"><span class='label-article-type'> Clinical Research and Public Health </span> </a><a href="/tags/26"><span class='label-specialty'> Infectious disease </span> </a><a href="/tags/36"><span class='label-specialty'> Pulmonology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI170682' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44160-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/170682">Machine learning links unresolving secondary pneumonia to mortality in patients with severe pneumonia, including COVID-19</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/170682">Text</a></li> <li><a class="button tiny" href="/articles/view/170682/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND Despite guidelines promoting the prevention and aggressive treatment of ventilator-associated pneumonia (VAP), the importance of VAP as a driver of outcomes in mechanically ventilated patients, including patients with severe COVID-19, remains unclear. We aimed to determine the contribution of unsuccessful treatment of VAP to mortality for patients with severe pneumonia.METHODS We performed a single-center, prospective cohort study of 585 mechanically ventilated patients with severe pneumonia and respiratory failure, 190 of whom had COVID-19, who underwent at least 1 bronchoalveolar lavage. A panel of intensive care unit (ICU) physicians adjudicated the pneumonia episodes and endpoints on the basis of clinical and microbiological data. Given the relatively long ICU length of stay (LOS) among patients with COVID-19, we developed a machine-learning approach called CarpeDiem, which grouped similar ICU patient-days into clinical states based on electronic health record data.RESULTS CarpeDiem revealed that the long ICU LOS among patients with COVID-19 was attributable to long stays in clinical states characterized primarily by respiratory failure. While VAP was not associated with mortality overall, the mortality rate was higher for patients with 1 episode of unsuccessfully treated VAP compared with those with successfully treated VAP (76.4% versus 17.6%, P < 0.001). For all patients, including those with COVID-19, CarpeDiem demonstrated that unresolving VAP was associated with a transitions to clinical states associated with higher mortality.CONCLUSIONS Unsuccessful treatment of VAP is associated with higher mortality. The relatively long LOS for patients with COVID-19 was primarily due to prolonged respiratory failure, placing them at higher risk of VAP.FUNDING National Institute of Allergy and Infectious Diseases (NIAID), NIH grant U19AI135964; National Heart, Lung, and Blood Institute (NHLBI), NIH grants R01HL147575, R01HL149883, R01HL153122, R01HL153312, R01HL154686, R01HL158139, P01HL071643, and P01HL154998; National Heart, Lung, and Blood Institute (NHLBI), NIH training grants T32HL076139 and F32HL162377; National Institute on Aging (NIA), NIH grants K99AG068544, R21AG075423, and P01AG049665; National Library of Medicine (NLM), NIH grant R01LM013337; National Center for Advancing Translational Sciences (NCATS), NIH grant U01TR003528; Veterans Affairs grant I01CX001777; Chicago Biomedical Consortium grant; Northwestern University Dixon Translational Science Award; Simpson Querrey Lung Institute for Translational Science (SQLIFTS); Canning Thoracic Institute of Northwestern Medicine.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Catherine A. Gao, Nikolay S. Markov, Thomas Stoeger, Anna Pawlowski, Mengjia Kang, Prasanth Nannapaneni, Rogan A. Grant, Chiagozie Pickens, James M. Walter, Jacqueline M. Kruser, Luke Rasmussen, Daniel Schneider, Justin Starren, Helen K. Donnelly, Alvaro Donayre, Yuan Luo, G.R. Scott Budinger, Richard G. Wunderink, Alexander V. Misharin, Benjamin D. Singer, The NU SCRIPT Study Investigators</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 9357</p> <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/185217">Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/185217">Jun Inamo, … , Deepak A. Rao, Fan Zhang</a> <a class='hide-for-small show-more' data-reveal-id='article45855-more' href='#'> <div class='article-authors'> Jun Inamo, … , Deepak A. Rao, Fan Zhang </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e185217. <a href="https://doi.org/10.1172/JCI185217">https://doi.org/10.1172/JCI185217</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/185217">Text</a> | <a href="/articles/view/185217/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/13"><span class='label-specialty'> Autoimmunity </span> </a><a href="/tags/25"><span class='label-specialty'> Immunology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI185217' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45855-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/185217">Deep immunophenotyping reveals circulating activated lymphocytes in individuals at risk for rheumatoid arthritis</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/185217">Text</a></li> <li><a class="button tiny" href="/articles/view/185217/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Rheumatoid arthritis (RA) is a systemic autoimmune disease currently with no universally highly effective prevention strategies. Identifying pathogenic immune phenotypes in at-risk populations prior to clinical onset is crucial to establishing effective prevention strategies. Here, we applied multimodal single-cell technologies (mass cytometry and CITE-Seq) to characterize the immunophenotypes in blood from at-risk individuals (ARIs) identified through the presence of serum antibodies against citrullinated protein antigens (ACPAs) and/or first-degree relative (FDR) status, as compared with patients with established RA and people in a healthy control group. We identified significant cell expansions in ARIs compared with controls, including CCR2+CD4+ T cells, T peripheral helper (Tph) cells, type 1 T helper cells, and CXCR5+CD8+ T cells. We also found that CD15+ classical monocytes were specifically expanded in ACPA-negative FDRs, and an activated PAX5lo naive B cell population was expanded in ACPA-positive FDRs. Further, we uncovered the molecular phenotype of the CCR2+CD4+ T cells, expressing high levels of Th17- and Th22-related signature transcripts including CCR6, IL23R, KLRB1, CD96, and IL22. Our integrated study provides a promising approach to identify targets to improve prevention strategy development for RA.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Jun Inamo, Joshua Keegan, Alec Griffith, Tusharkanti Ghosh, Alice Horisberger, Kaitlyn Howard, John F. Pulford, Ekaterina Murzin, Brandon Hancock, Salina T. Dominguez, Miranda G. Gurra, Siddarth Gurajala, Anna Helena Jonsson, Jennifer A. Seifert, Marie L. Feser, Jill M. Norris, Ye Cao, William Apruzzese, S. Louis Bridges, Vivian P. Bykerk, Susan Goodman, Laura T. Donlin, Gary S. Firestein, Joan M. Bathon, Laura B. Hughes, Andrew Filer, Costantino Pitzalis, Jennifer H. Anolik, Larry Moreland, Nir Hacohen, Joel M. Guthridge, Judith A. James, Carla M. Cuda, Harris Perlman, Michael B. Brenner, Soumya Raychaudhuri, Jeffrey A. Sparks, The Accelerating Medicines Partnership RA/SLE Network, V. Michael Holers, Kevin D. Deane, James Lederer, Deepak A. Rao, Fan Zhang</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 4920</p> <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/178722">Estimation of prevalence of autoimmune diseases in the United States using electronic health record data</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/178722">Aaron H. Abend, … , George C. Tsokos, DeLisa Fairweather</a> <a class='hide-for-small show-more' data-reveal-id='article45785-more' href='#'> <div class='article-authors'> Aaron H. Abend, … , George C. Tsokos, DeLisa Fairweather </div> </a> <span class='article-published-at'> Published December 12, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/4">135(4)</a>:e178722. <a href="https://doi.org/10.1172/JCI178722">https://doi.org/10.1172/JCI178722</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/178722">Text</a> | <a href="/articles/view/178722/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/141"><span class='label-article-type'> Clinical Research and Public Health </span> </a><a href="/tags/13"><span class='label-specialty'> Autoimmunity </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI178722' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45785-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/178722">Estimation of prevalence of autoimmune diseases in the United States using electronic health record data</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/178722">Text</a></li> <li><a class="button tiny" href="/articles/view/178722/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND Previous epidemiologic studies of autoimmune diseases in the US have included a limited number of diseases or used metaanalyses that rely on different data collection methods and analyses for each disease.METHODS To estimate the prevalence of autoimmune diseases in the US, we used electronic health record data from 6 large medical systems in the US. We developed a software program using common methodology to compute the estimated prevalence of autoimmune diseases alone and in aggregate that can be readily used by other investigators to replicate or modify the analysis over time.RESULTS Our findings indicate that over 15 million people, or 4.6% of the US population, have been diagnosed with at least 1 autoimmune disease from January 1, 2011, to June 1, 2022, and 34% of those are diagnosed with more than 1 autoimmune disease. As expected, females (63% of those with autoimmune disease) were almost twice as likely as males to be diagnosed with an autoimmune disease. We identified the top 20 autoimmune diseases based on prevalence and according to sex and age.CONCLUSION Here, we provide, for what we believe to be the first time, a large-scale prevalence estimate of autoimmune disease in the US by sex and age.FUNDING Autoimmune Registry Inc., the National Heart Lung and Blood Institute, the National Center for Advancing Translational Sciences, the Intramural Research Program of the National Institute of Environmental Health Sciences. </p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Aaron H. Abend, Ingrid He, Neil Bahroos, Stratos Christianakis, Ashley B. Crew, Leanna M. Wise, Gloria P. Lipori, Xing He, Shawn N. Murphy, Christopher D. Herrick, Jagannadha Avasarala, Mark G. Weiner, Jacob S. Zelko, Erica Matute-Arcos, Mark Abajian, Philip R.O. Payne, Albert M. Lai, Heath A. Davis, Asher A. Hoberg, Chris E. Ortman, Amit D. Gode, Bradley W. Taylor, Kristen I. Osinski, Damian N. Di Florio, Noel R. Rose, Frederick W. Miller, George C. Tsokos, DeLisa Fairweather</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 4377</p> <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/169671">Antioxidants stimulate BACH1-dependent tumor angiogenesis</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/169671">Ting Wang, … , Eckardt Treuter, Martin O. Bergo</a> <a class='hide-for-small show-more' data-reveal-id='article44438-more' href='#'> <div class='article-authors'> Ting Wang, … , Eckardt Treuter, Martin O. Bergo </div> </a> <span class='article-published-at'> Published August 31, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023;<a id="article_metadata" href="http://www.jci.org/133/20">133(20)</a>:e169671. <a href="https://doi.org/10.1172/JCI169671">https://doi.org/10.1172/JCI169671</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/169671">Text</a> | <a href="/articles/view/169671/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/12"><span class='label-specialty'> Angiogenesis </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI169671' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44438-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/169671">Antioxidants stimulate BACH1-dependent tumor angiogenesis</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/169671">Text</a></li> <li><a class="button tiny" href="/articles/view/169671/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Lung cancer progression relies on angiogenesis, which is a response to hypoxia typically coordinated by hypoxia-inducible transcription factors (HIFs), but growing evidence indicates that transcriptional programs beyond HIFs control tumor angiogenesis. Here, we show that the redox-sensitive transcription factor BTB and CNC homology 1 (BACH1) controls the transcription of a broad range of angiogenesis genes. BACH1 is stabilized by lowering ROS levels; consequently, angiogenesis gene expression in lung cancer cells, tumor organoids, and xenograft tumors increased substantially following administration of vitamins C and E and N-acetylcysteine in a BACH1-dependent fashion under normoxia. Moreover, angiogenesis gene expression increased in endogenous BACH1–overexpressing cells and decreased in BACH1-knockout cells in the absence of antioxidants. BACH1 levels also increased upon hypoxia and following administration of prolyl hydroxylase inhibitors in both HIF1A-knockout and WT cells. BACH1 was found to be a transcriptional target of HIF1α, but BACH1’s ability to stimulate angiogenesis gene expression was HIF1α independent. Antioxidants increased tumor vascularity in vivo in a BACH1-dependent fashion, and overexpressing BACH1 rendered tumors sensitive to antiangiogenesis therapy. BACH1 expression in tumor sections from patients with lung cancer correlated with angiogenesis gene and protein expression. We conclude that BACH1 is an oxygen- and redox-sensitive angiogenesis transcription factor.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Ting Wang, Yongqiang Dong, Zhiqiang Huang, Guoqing Zhang, Ying Zhao, Haidong Yao, Jianjiang Hu, Elin Tüksammel, Huan Cai, Ning Liang, Xiufeng Xu, Xijie Yang, Sarah Schmidt, Xi Qiao, Susanne Schlisio, Staffan Strömblad, Hong Qian, Changtao Jiang, Eckardt Treuter, Martin O. Bergo</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 4308</p> <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/183745">Activating antiviral immune responses potentiates immune checkpoint inhibition in glioblastoma models</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/183745">Deepa Seetharam, … , Defne Bayik, Ashish H. Shah</a> <a class='hide-for-small show-more' data-reveal-id='article45851-more' href='#'> <div class='article-authors'> Deepa Seetharam, … , Defne Bayik, Ashish H. Shah </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e183745. <a href="https://doi.org/10.1172/JCI183745">https://doi.org/10.1172/JCI183745</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/183745">Text</a> | <a href="/articles/view/183745/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/33"><span class='label-specialty'> Oncology </span> </a><a href="/tags/43"><span class='label-specialty'> Virology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI183745' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45851-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/183745">Activating antiviral immune responses potentiates immune checkpoint inhibition in glioblastoma models</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/183745">Text</a></li> <li><a class="button tiny" href="/articles/view/183745/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Viral mimicry refers to the activation of innate antiviral immune responses due to the induction of endogenous retroelements (REs). Viral mimicry augments antitumor immune responses and sensitizes solid tumors to immunotherapy. Here, we found that targeting what we believe to be a novel, master epigenetic regulator, Zinc Finger Protein 638 (ZNF638), induces viral mimicry in glioblastoma (GBM) preclinical models and potentiates immune checkpoint inhibition (ICI). ZNF638 recruits the HUSH complex, which precipitates repressive H3K9me3 marks on endogenous REs. In GBM, ZNF638 is associated with marked locoregional immunosuppressive transcriptional signatures, reduced endogenous RE expression, and poor immune cell infiltration. Targeting ZNF638 decreased H3K9 trimethylation, increased REs, and activated intracellular dsRNA signaling cascades. Furthermore, ZNF638 knockdown upregulated antiviral immune programs and significantly increased PD-L1 immune checkpoint expression in diverse GBM models. Importantly, targeting ZNF638 sensitized mice to ICI in syngeneic murine orthotopic models through innate IFN signaling. This response was recapitulated in recurrent GBM (rGBM) samples with radiographic responses to checkpoint inhibition with widely increased expression of dsRNA, PD-L1, and perivascular CD8 cell infiltration, suggesting that dsRNA signaling may mediate response to immunotherapy. Finally, low ZNF638 expression was a biomarker of clinical response to ICI and improved survival in patients with rGBM and patients with melanoma. Our findings suggest that ZNF638 could serve as a target to potentiate immunotherapy in gliomas.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Deepa Seetharam, Jay Chandar, Christian K. Ramsoomair, Jelisah F. Desgraves, Alexandra Alvarado Medina, Anna Jane Hudson, Ava Amidei, Jesus R. Castro, Vaidya Govindarajan, Sarah Wang, Yong Zhang, Adam M. Sonabend, Mynor J. Mendez Valdez, Dragan Maric, Vasundara Govindarajan, Sarah R. Rivas, Victor M. Lu, Ritika Tiwari, Nima Sharifi, Emmanuel Thomas, Marcus Alexander, Catherine DeMarino, Kory Johnson, Macarena I. De La Fuente, Ruham Alshiekh Nasany, Teresa Maria Rosaria Noviello, Michael E. Ivan, Ricardo J. Komotar, Antonio Iavarone, Avindra Nath, John Heiss, Michele Ceccarelli, Katherine B. Chiappinelli, Maria E. Figueroa, Defne Bayik, Ashish H. Shah</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 4298</p> <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/181671">Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/181671">Tingting Qin, … , Maureen A. Sartor, Sara I. Pai</a> <a class='hide-for-small show-more' data-reveal-id='article45871-more' href='#'> <div class='article-authors'> Tingting Qin, … , Maureen A. Sartor, Sara I. Pai </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e181671. <a href="https://doi.org/10.1172/JCI181671">https://doi.org/10.1172/JCI181671</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/181671">Text</a> | <a href="/articles/view/181671/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/141"><span class='label-article-type'> Clinical Research and Public Health </span> </a><a href="/tags/25"><span class='label-specialty'> Immunology </span> </a><a href="/tags/33"><span class='label-specialty'> Oncology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI181671' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45871-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/181671">Epigenetic therapy sensitizes anti–PD-1 refractory head and neck cancers to immunotherapy rechallenge</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/181671">Text</a></li> <li><a class="button tiny" href="/articles/view/181671/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND Immune checkpoint blockade (ICB) is an effective treatment in a subset of patients diagnosed with head and neck squamous cell carcinoma (HNSCC); however, the majority of patients are refractory.METHODS In a nonrandomized, open-label Phase 1b clinical trial, participants with recurrent and/or metastatic (R/M) HNSCC were treated with low-dose 5-azacytidine (5-aza) daily for either 5 or 10 days in combination with durvalumab and tremelimumab after progression on ICB. The primary objective was to assess the biologically effective dose of 5-aza as determined by molecular changes in paired baseline and on-treatment tumor biopsies; the secondary objective was safety.RESULTS Thirty-eight percent (3 of 8) of participants with evaluable paired tissue samples had a greater-than 2-fold increase from baseline in IFN-γ signature and CD274 (programmed cell death protein 1 ligand, PD-L1) expression within the tumor microenvironment (TME), which was associated with increased CD8+ T cell infiltration and decreased infiltration of CD4+ T regulatory cells. The mean neutrophil-to-lymphocyte ratio (NLR) decreased by greater than 50%, from 14.2 (SD 22.6) to 6.9 (SD 5.2). Median overall survival (OS) was 16.3 months (95% CI 1.9, NA), 2-year OS rate was 24.7% (95% CI: 4.5%, 53.2%), and 58% (7 of 12) of treated participants demonstrated prolonged OS of greater than 12 months.CONCLUSION Our findings suggest that low-dose 5-aza can reprogram systemic host immune responses and the local TME to increase IFN-γ and PD-L1 expression. The increased expression of these established biomarkers correlated with prolonged OS upon ICB rechallenge.TRIAL REGISTRATION ClinicalTrials.gov NCT03019003.FUNDING NIH/NCI P01 CA240239.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Tingting Qin, Austin K. Mattox, Jean S. Campbell, Jong Chul Park, Kee-Young Shin, Shiting Li, Peter M. Sadow, William C. Faquin, Goran Micevic, Andrew J. Daniels, Robert Haddad, Christopher S. Garris, Mikael J. Pittet, Thorsten R. Mempel, Anne ONeill, Maureen A. Sartor, Sara I. Pai</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 3363</p> <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/185340">Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/185340">Yu-Sheng Yeh, … , Irfan J. Lodhi, Babak Razani</a> <a class='hide-for-small show-more' data-reveal-id='article45866-more' href='#'> <div class='article-authors'> Yu-Sheng Yeh, … , Irfan J. Lodhi, Babak Razani </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e185340. <a href="https://doi.org/10.1172/JCI185340">https://doi.org/10.1172/JCI185340</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/185340">Text</a> | <a href="/articles/view/185340/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/20"><span class='label-specialty'> Endocrinology </span> </a><a href="/tags/28"><span class='label-specialty'> Metabolism </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI185340' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45866-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/185340">Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/185340">Text</a></li> <li><a class="button tiny" href="/articles/view/185340/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. Furthermore, adipocyte LIPA deficiency impaired thermogenesis and oxygen consumption and rendered mice susceptible to diet-induced obesity. Importantly, lysosomal lipolysis was independent of adipose triglyceride lipase, the rate-limiting enzyme of cytosolic lipolysis. Our data suggest a significant role for LIPA and lysosomal lipolysis in adipocyte lipid metabolism beyond classical cytosolic lipolysis.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Yu-Sheng Yeh, Trent D. Evans, Mari Iwase, Se-Jin Jeong, Xiangyu Zhang, Ziyang Liu, Arick Park, Ali Ghasemian, Borna Dianati, Ali Javaheri, Dagmar Kratky, Satoko Kawarasaki, Tsuyoshi Goto, Hanrui Zhang, Partha Dutta, Francisco J. Schopfer, Adam C. Straub, Jaehyung Cho, Irfan J. Lodhi, Babak Razani</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 3072</p> <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/186889">Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186889">Maude A. Liegeois, … , Tillie-Louise Hackett, John V. Fahy</a> <a class='hide-for-small show-more' data-reveal-id='article45862-more' href='#'> <div class='article-authors'> Maude A. Liegeois, … , Tillie-Louise Hackett, John V. Fahy </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e186889. <a href="https://doi.org/10.1172/JCI186889">https://doi.org/10.1172/JCI186889</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186889">Text</a> | <a href="/articles/view/186889/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/141"><span class='label-article-type'> Clinical Research and Public Health </span> </a><a href="/tags/25"><span class='label-specialty'> Immunology </span> </a><a href="/tags/36"><span class='label-specialty'> Pulmonology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186889' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45862-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186889">Cellular and molecular features of asthma mucus plugs provide clues about their formation and persistence</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186889">Text</a></li> <li><a class="button tiny" href="/articles/view/186889/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>BACKGROUND Mucus plugs form in acute asthma and persist in chronic disease. Although eosinophils are implicated in mechanisms of mucus pathology, many mechanistic details about mucus plug formation and persistence in asthma are unknown.METHODS Using histology and spatial, single-cell proteomics, we characterized mucus-plugged airways from nontransplantable donor lungs of 14 patients with asthma (9 with fatal asthma and 5 with nonfatal asthma) and individuals acting as controls (10 with chronic obstructive pulmonary disease and 14 free of lung disease). Additionally, we used an airway epithelial cell–eosinophil (AEC-eosinophil) coculture model to explore how AEC mucus affects eosinophil degranulation.RESULTS Asthma mucus plugs were tethered to airways showing infiltration with innate lymphoid type 2 cells and hyperplasia of smooth muscle cells and MUC5AC-expressing goblet cells. Asthma mucus plugs were infiltrated with immune cells that were mostly dual positive for eosinophil peroxidase (EPX) and neutrophil elastase, suggesting that neutrophils internalize EPX from degranulating eosinophils. Indeed, eosinophils exposed to mucus from IL-13–activated AECs underwent CD11b- and glycan-dependent cytolytic degranulation. Dual-positive granulocytes varied in frequency in mucus plugs. Whereas paucigranulocytic plugs were MUC5AC rich, granulocytic plugs had a mix of MUC5AC, MUC5B, and extracellular DNA traps. Paucigranulocytic plugs occurred more frequently in (acute) fatal asthma and granulocytic plugs predominated in (chronic) nonfatal asthma.CONCLUSION Together, our data suggest that mucin-rich mucus plugs in fatal asthma form because of acute goblet cell degranulation in remodeled airways and that granulocytic mucus plugs in chronic asthma persist because of a sustaining niche characterized by epithelial cell–mucin-granulocyte cross-talk.FUNDING NIH grants HL080414, HL107202, and AI077439.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Maude A. Liegeois, Aileen Hsieh, May Al-Fouadi, Annabelle R. Charbit, Chen Xi Yang, Tillie-Louise Hackett, John V. Fahy</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2730</p> <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/179137">Estrogen receptor-α ablation reverses muscle fibrosis and inguinal hernias</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/179137">Tanvi Potluri, … , Hong Zhao, Serdar E. Bulun</a> <a class='hide-for-small show-more' data-reveal-id='article45857-more' href='#'> <div class='article-authors'> Tanvi Potluri, … , Hong Zhao, Serdar E. Bulun </div> </a> <span class='article-published-at'> Published February 4, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e179137. <a href="https://doi.org/10.1172/JCI179137">https://doi.org/10.1172/JCI179137</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/179137">Text</a> | <a href="/articles/view/179137/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/16"><span class='label-specialty'> Cell biology </span> </a><a href="/tags/30"><span class='label-specialty'> Muscle biology </span> </a><a href="/tags/37"><span class='label-specialty'> Reproductive biology </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI179137' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45857-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/179137">Estrogen receptor-α ablation reverses muscle fibrosis and inguinal hernias</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/179137">Text</a></li> <li><a class="button tiny" href="/articles/view/179137/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Fibrosis of the lower abdominal muscle (LAM) contributes to muscle weakening and inguinal hernia formation, an ailment that affects a noteworthy 50% of men by age 75 and necessitates surgical correction as the singular therapy. Despite its prevalence, the mechanisms driving LAM fibrosis and hernia development remain poorly understood. Using a humanized mouse model that replicates the elevated skeletal muscle tissue estrogen concentrations seen in aging men, we identified estrogen receptor-α (ESR1) as a key driver of LAM fibroblast proliferation, extracellular matrix deposition, and hernia formation. Fibroblast-specific ESR1 ablation effectively prevented muscle fibrosis and herniation, while pharmacological ESR1 inhibition with fulvestrant reversed hernias and restored normal muscle architecture. Multiomics analyses of in vitro LAM fibroblasts from humanized mice unveiled an estrogen/ESR1-mediated activation of a distinct profibrotic cistrome and gene expression signature, concordant with observations in inguinal hernia tissues in human males. Our findings hold significant promise for prospective medical interventions targeting fibrotic conditions and present non-surgical avenues for addressing inguinal hernias.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Tanvi Potluri, Tianming You, Ping Yin, John Coon V, Jonah J. Stulberg, Yang Dai, David J. Escobar, Richard L. Lieber, Hong Zhao, Serdar E. Bulun</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2714</p> <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/172595">RNase L represses hair follicle regeneration through altered innate immune signaling</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/172595">Charles S. Kirby, … , Robert H. Silverman, Luis A. Garza</a> <a class='hide-for-small show-more' data-reveal-id='article45879-more' href='#'> <div class='article-authors'> Charles S. Kirby, … , Robert H. Silverman, Luis A. Garza </div> </a> <span class='article-published-at'> Published February 4, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e172595. <a href="https://doi.org/10.1172/JCI172595">https://doi.org/10.1172/JCI172595</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/172595">Text</a> | <a href="/articles/view/172595/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/51"><span class='label-article-type'> Research Article </span> </a><a href="/tags/18"><span class='label-specialty'> Dermatology </span> </a><a href="/tags/27"><span class='label-specialty'> Inflammation </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI172595' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45879-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/172595">RNase L represses hair follicle regeneration through altered innate immune signaling</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/172595">Text</a></li> <li><a class="button tiny" href="/articles/view/172595/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Mammalian injury responses are predominantly characterized by fibrosis and scarring rather than functional regeneration. This limited regenerative capacity in mammals could reflect a loss of proregeneration programs or active suppression by genes functioning akin to tumor suppressors. To uncover programs governing regeneration in mammals, we screened transcripts in human participants following laser rejuvenation treatment and compared them with mice with enhanced wound-induced hair neogenesis (WIHN), a rare example of mammalian organogenesis. We found that Rnasel–/– mice exhibit an increased regenerative capacity, with elevated WIHN through enhanced IL-36α. Consistent with RNase L’s known role to stimulate caspase-1, we found that pharmacologic inhibition of caspases promoted regeneration in an IL-36–dependent manner in multiple epithelial tissues. We identified a negative feedback loop, where RNase L–activated caspase-1 restrains the proregenerative dsRNA-TLR3 signaling cascade through the cleavage of toll-like adaptor protein TRIF. Through integrated single-cell RNA-seq and spatial transcriptomic profiling, we confirmed OAS & IL-36 genes to be highly expressed at the site of wounding and elevated in Rnasel–/– mouse wounds. This work suggests that RNase L functions as a regeneration repressor gene, in a functional trade off that tempers immune hyperactivation during viral infection at the cost of inhibiting regeneration.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Charles S. Kirby, Nasif Islam, Eric Wier, Martin P. Alphonse, Evan Sweren, Gaofeng Wang, Haiyun Liu, Dongwon Kim, Ang Li, Sam S. Lee, Andrew M. Overmiller, Yingchao Xue, Sashank Reddy, Nathan K. Archer, Lloyd S. Miller, Jianshi Yu, Weiliang Huang, Jace W. Jones, Sooah Kim, Maureen A. Kane, Robert H. Silverman, Luis A. Garza</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2635</p> </div> <p class='load-more'> <a data-url="/top_articles/load_more?type=research" class="small button radius" href="#">Show more results</a> <img src="/assets/load_more-93e7795de3f8255a217ec4db19b59e809b92bcb89ee47f2231e37013d1ff5471.gif" /> </p> </div> <div class='content ' id='review'> <div id='review_accesses'> <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/187996">Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/187996">Minyoung Kevin Kim, … , Paul L. Bollyky, Jessica C. Sacher</a> <a class='hide-for-small show-more' data-reveal-id='article45820-more' href='#'> <div class='article-authors'> Minyoung Kevin Kim, … , Paul L. Bollyky, Jessica C. Sacher </div> </a> <span class='article-published-at'> Published March 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/5">135(5)</a>:e187996. <a href="https://doi.org/10.1172/JCI187996">https://doi.org/10.1172/JCI187996</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/187996">Text</a> | <a href="/articles/view/187996/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI187996' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45820-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/187996">Bacteriophage therapy for multidrug-resistant infections: current technologies and therapeutic approaches</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/187996">Text</a></li> <li><a class="button tiny" href="/articles/view/187996/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Bacteriophage (phage) therapy has emerged as a promising solution to combat the growing crisis of multidrug-resistant (MDR) infections. There are several international centers actively engaged in implementation of phage therapy, and recent case series have reported encouraging success rates in patients receiving personalized, compassionate phage therapy for difficult-to-treat infections. Nonetheless, substantial hurdles remain in the way of more widespread adoption and more consistent success. This Review offers a comprehensive overview of current phage therapy technologies and therapeutic approaches. We first delineate the common steps in phage therapy development, from phage bank establishment to clinical administration, and examine the spectrum of therapeutic approaches, from personalized to fixed phage cocktails. Using the framework of a conventional drug development pipeline, we then identify critical knowledge gaps in areas such as cocktail design, formulation, pharmacology, and clinical trial design. We conclude that, while phage therapy holds promise, a structured drug development pipeline and sustained government support are crucial for widespread adoption of phage therapy for MDR infections.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Minyoung Kevin Kim, Gina A. Suh, Grace D. Cullen, Saumel Perez Rodriguez, Tejas Dharmaraj, Tony Hong Wei Chang, Zhiwei Li, Qingquan Chen, Sabrina I. Green, Rob Lavigne, Jean-Paul Pirnay, Paul L. Bollyky, Jessica C. Sacher</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 4102</p> <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/188358">Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/188358">Megan L. Baker, Lloyd G. Cantley</a> <a class='hide-for-small show-more' data-reveal-id='article45860-more' href='#'> <div class='article-authors'> Megan L. Baker, Lloyd G. Cantley </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e188358. <a href="https://doi.org/10.1172/JCI188358">https://doi.org/10.1172/JCI188358</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/188358">Text</a> | <a href="/articles/view/188358/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI188358' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45860-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/188358">Adding insult to injury: the spectrum of tubulointerstitial responses in acute kidney injury</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/188358">Text</a></li> <li><a class="button tiny" href="/articles/view/188358/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Acute kidney injury (AKI) encompasses pathophysiology ranging from glomerular hypofiltration to tubular cell injury and outflow obstruction. This Review will focus on the tubulointerstitial processes that underlie most cases of AKI. Tubular epithelial cell (TEC) injury can occur via distinct insults, including ischemia, nephrotoxins, sepsis, and primary immune-mediated processes. Following these initial insults, tubular cells can activate survival and repair responses or they can develop mitochondrial dysfunction and metabolic reprogramming, cell-cycle arrest, and programmed cell death. Developing evidence suggests that the fate of individual tubular cells to survive and proliferate or undergo cell death or senescence is frequently determined by a biphasic immune response with initial proinflammatory macrophage, neutrophil, and lymphocyte infiltration exacerbating injury and activating programmed cell death, while alternatively activated macrophages and specific lymphocyte subsets subsequently modulate inflammation and promote repair. Functional recovery requires that this reparative phase supports proteolytic degradation of tubular casts, proliferation of surviving TECs, and restoration of TEC differentiation. Incomplete resolution or persistence of inflammation can lead to failed tubular repair, fibrosis, and chronic kidney disease. Despite extensive research in animal models, translating preclinical findings to therapies remains challenging, emphasizing the need for integrated multiomic approaches to advance AKI understanding and treatment.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Megan L. Baker, Lloyd G. Cantley</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2815</p> <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/188127">Nonvesicular cholesterol transport in physiology</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/188127">Alessandra Ferrari, Peter Tontonoz</a> <a class='hide-for-small show-more' data-reveal-id='article45864-more' href='#'> <div class='article-authors'> Alessandra Ferrari, Peter Tontonoz </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e188127. <a href="https://doi.org/10.1172/JCI188127">https://doi.org/10.1172/JCI188127</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/188127">Text</a> | <a href="/articles/view/188127/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI188127' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45864-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/188127">Nonvesicular cholesterol transport in physiology</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/188127">Text</a></li> <li><a class="button tiny" href="/articles/view/188127/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>In mammalian cells cholesterol can be synthesized endogenously or obtained exogenously through lipoprotein uptake. Plasma membrane (PM) is the primary intracellular destination for both sources of cholesterol, and maintaining appropriate membrane cholesterol levels is critical for cellular viability. The endoplasmic reticulum (ER) acts as a cellular cholesterol sensor, regulating synthesis in response to cellular needs and determining the metabolic fates of cholesterol. Upon reaching the ER, cholesterol can be esterified to facilitate its incorporation into lipoproteins and lipid droplets or converted into other molecules such as bile acids and oxysterols. In recent years, it has become clear that the intracellular redistribution of lipids, including cholesterol, is critical for the regulation of various biological processes. This Review highlights physiology and mechanisms of nonvesicular (protein-mediated) intracellular cholesterol trafficking, with a focus on the role of Aster proteins in PM to ER cholesterol transport.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Alessandra Ferrari, Peter Tontonoz</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2388</p> <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/172837">Extracranial arteriovenous malformations: towards etiology-based therapeutic management</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/172837">Julien Coulie, … , Miikka Vikkula, Laurence M. Boon</a> <a class='hide-for-small show-more' data-reveal-id='article45839-more' href='#'> <div class='article-authors'> Julien Coulie, … , Miikka Vikkula, Laurence M. Boon </div> </a> <span class='article-published-at'> Published March 17, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/6">135(6)</a>:e172837. <a href="https://doi.org/10.1172/JCI172837">https://doi.org/10.1172/JCI172837</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/172837">Text</a> | <a href="/articles/view/172837/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI172837' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45839-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/172837">Extracranial arteriovenous malformations: towards etiology-based therapeutic management</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/172837">Text</a></li> <li><a class="button tiny" href="/articles/view/172837/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Anomalies during angiogenesis can initiate the formation of arteriovenous malformations (AVMs), characterized by aberrant connections between arteries and veins and fast lesional blood flow. These anomalies can manifest anywhere in the body, including the brain, and they typically appear at birth and evolve alongside growth of the individual. Depending on their location and size, AVMs can induce progressive deformation, chronic pain, functional impairment, and ulceration and pose life-threatening risks such as hemorrhage and organ dysfunction. The primary treatment modalities entail surgical intervention or embolization followed by surgery. However, these approaches are often challenging and seldom offer definitive resolution. In addition, inadequately performed surgery may trigger angiogenic rebound, fostering AVM recurrence. Advancements in comprehending the molecular pathways underlying AVMs have sparked interest in repurposing targeted therapies initially devised for cancer treatment. The first results are promising, giving new hope to the patients affected with these often devastating and debilitating lesions, the management of which presents major clinical challenges.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Julien Coulie, Emmanuel Seront, Miikka Vikkula, Laurence M. Boon</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2181</p> <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/185102">Implications of gene × environment interactions in post-traumatic stress disorder risk and treatment</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/185102">Carina Seah, … , Laura M. Huckins, Kristen J. Brennand</a> <a class='hide-for-small show-more' data-reveal-id='article45815-more' href='#'> <div class='article-authors'> Carina Seah, … , Laura M. Huckins, Kristen J. Brennand </div> </a> <span class='article-published-at'> Published March 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/5">135(5)</a>:e185102. <a href="https://doi.org/10.1172/JCI185102">https://doi.org/10.1172/JCI185102</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/185102">Text</a> | <a href="/articles/view/185102/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI185102' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45815-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/185102">Implications of gene × environment interactions in post-traumatic stress disorder risk and treatment</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/185102">Text</a></li> <li><a class="button tiny" href="/articles/view/185102/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Exposure to traumatic stress is common in the general population. Variation in the brain’s molecular encoding of stress potentially contributes to the heterogeneous clinical outcomes in response to traumatic experiences. For instance, only a minority of those exposed to trauma will develop post-traumatic stress disorder (PTSD). Risk for PTSD is at least partially heritable, with a growing number of genetic factors identified through GWAS. A major limitation of genetic studies is that they capture only the genetic component of risk, whereas PTSD by definition requires an environmental traumatic exposure. Furthermore, the extent, timing, and type of trauma affects susceptibility. Here, we discuss the molecular mechanisms of PTSD risk together with gene × environment interactions, with a focus on how either might inform genetic screening for individuals at high risk for disease, reveal biological mechanisms that might one day yield novel therapeutics, and impact best clinical practices even today. To close, we discuss the interaction of trauma with sex, gender, and race, with a focus on the implications for treatment. Altogether, we suggest that predicting, preventing, and treating PTSD will require integrating both genotypic and environmental information.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Carina Seah, Anne Elizabeth Sidamon-Eristoff, Laura M. Huckins, Kristen J. Brennand</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 2113</p> <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/172883">Stress and substance use disorders: risk, relapse, and treatment outcomes</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/172883">Rajita Sinha</a> <a class='hide-for-small show-more' data-reveal-id='article45285-more' href='#'> <div class='article-authors'> Rajita Sinha </div> </a> <span class='article-published-at'> Published August 15, 2024 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2024;<a id="article_metadata" href="http://www.jci.org/134/16">134(16)</a>:e172883. <a href="https://doi.org/10.1172/JCI172883">https://doi.org/10.1172/JCI172883</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/172883">Text</a> | <a href="/articles/view/172883/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/58"><span class='label-article-type'> Review Series </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI172883' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45285-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/172883">Stress and substance use disorders: risk, relapse, and treatment outcomes</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/172883">Text</a></li> <li><a class="button tiny" href="/articles/view/172883/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Stress has long been associated with substance misuse and substance use disorders (SUDs). The past two decades have seen a surge in research aimed at understanding the underlying mechanisms driving this association. This Review introduces a multilevel “adaptive stress response” framework, encompassing a stress baseline, acute reaction, and recovery with return-to-homeostasis phase that occurs at varying response times and across domains of analysis. It also discusses evidence showing the disruption of this adaptive stress response in the context of chronic and repeated stressors, trauma, adverse social and drug-related environments, as well as with acute and chronic drug misuse and with drug withdrawal and abstinence sequelae. Subjective, cognitive, peripheral, and neurobiological disruptions in the adaptive stress response phases and their link to inflexible, maladaptive coping; increased craving; relapse risk; and maintenance of drug intake are also presented. Finally, the prevention and treatment implications of targeting this “stress pathophysiology of addiction” are discussed, along with specific aspects that may be targeted in intervention development to rescue stress-related alterations in drug motivation and to improve SUD treatment outcomes.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Rajita Sinha</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 1535</p> <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/186702">Basic science and translational implications of current knowledge on neuroendocrine tumors</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/186702">Lynnette Fernandez-Cuesta, … , Thomas Walter, Matthieu Foll</a> <a class='hide-for-small show-more' data-reveal-id='article45822-more' href='#'> <div class='article-authors'> Lynnette Fernandez-Cuesta, … , Thomas Walter, Matthieu Foll </div> </a> <span class='article-published-at'> Published March 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/5">135(5)</a>:e186702. <a href="https://doi.org/10.1172/JCI186702">https://doi.org/10.1172/JCI186702</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/186702">Text</a> | <a href="/articles/view/186702/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI186702' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45822-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/186702">Basic science and translational implications of current knowledge on neuroendocrine tumors</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/186702">Text</a></li> <li><a class="button tiny" href="/articles/view/186702/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Neuroendocrine tumors (NETs) are a diverse group of malignancies that can occur in various organs, with a notable prevalence in the lungs and gastrointestinal tract, which are the focus of this Review. Although NETs are rare in individual organs, their incidence has increased over recent decades, highlighting the urgent need for current classification systems to evolve by incorporating recent advances in the understanding of NET biology. Several omics studies have revealed molecular subtypes, which, when integrated into existing classification frameworks, may provide more clinically relevant insights for patients with NETs. This Review examines recent progress in elucidating the biology of NETs, with a particular emphasis on the tumor microenvironment and cells of origin. The existence of different cells of origin, which may contribute to distinct molecular groups, along with profiles of immune infiltration — despite being generally low — could explain the emergence of more aggressive cases and the potential for metastatic progression. Given the molecular heterogeneity of NETs and the diversity of their microenvironments and different cells of origin, there is an urgent need to develop morphomolecular classification systems. Such systems would make it possible to better characterize tumor progression, identify new therapeutic targets, and, ultimately, guide the development of personalized therapies.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Lynnette Fernandez-Cuesta, Nicolas Alcala, Emilie Mathian, Jules Derks, Chrissie Thirlwell, Talya Dayton, Ilaria Marinoni, Aurel Perren, Thomas Walter, Matthieu Foll</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 1498</p> <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/184321">The gut microbiome and cancer response to immune checkpoint inhibitors</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/184321">Francesca S. Gazzaniga, Dennis L. Kasper</a> <a class='hide-for-small show-more' data-reveal-id='article45726-more' href='#'> <div class='article-authors'> Francesca S. Gazzaniga, Dennis L. Kasper </div> </a> <span class='article-published-at'> Published February 3, 2025 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2025;<a id="article_metadata" href="http://www.jci.org/135/3">135(3)</a>:e184321. <a href="https://doi.org/10.1172/JCI184321">https://doi.org/10.1172/JCI184321</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/184321">Text</a> | <a href="/articles/view/184321/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/58"><span class='label-article-type'> Review Series </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI184321' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article45726-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/184321">The gut microbiome and cancer response to immune checkpoint inhibitors</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/184321">Text</a></li> <li><a class="button tiny" href="/articles/view/184321/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Immune checkpoint inhibitors (ICIs) are widely used for cancer immunotherapy, yet only a fraction of patients respond. Remarkably, gut bacteria impact the efficacy of ICIs in fighting tumors outside of the gut. Certain strains of commensal gut bacteria promote antitumor responses to ICIs in a variety of preclinical mouse tumor models. Patients with cancer who respond to ICIs have a different microbiome compared with that of patients who don’t respond. Fecal microbiota transplants (FMTs) from patients into mice phenocopy the patient tumor responses: FMTs from responders promote response to ICIs, whereas FMTs from nonresponders do not promote a response. In patients, FMTs from patients who have had a complete response to ICIs can overcome resistance in patients who progress on treatment. However, the responses to FMTs are variable. Though emerging studies indicate that gut bacteria can promote antitumor immunity in the absence of ICIs, this Review will focus on studies that demonstrate relationships between the gut microbiome and response to ICIs. We will explore studies investigating which bacteria promote response to ICIs in preclinical models, which bacteria are associated with response in patients with cancer receiving ICIs, the mechanisms by which gut bacteria promote antitumor immunity, and how microbiome-based therapies can be translated to the clinic.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Francesca S. Gazzaniga, Dennis L. Kasper</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 1492</p> <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/176345">Alcohol-associated liver disease</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/176345">Bryan Mackowiak, … , Luca Maccioni, Bin Gao</a> <a class='hide-for-small show-more' data-reveal-id='article44745-more' href='#'> <div class='article-authors'> Bryan Mackowiak, … , Luca Maccioni, Bin Gao </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>:e176345. <a href="https://doi.org/10.1172/JCI176345">https://doi.org/10.1172/JCI176345</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/176345">Text</a> | <a href="/articles/view/176345/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/2"><span class='label-article-type'> Review </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI176345' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44745-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/176345">Alcohol-associated liver disease</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/176345">Text</a></li> <li><a class="button tiny" href="/articles/view/176345/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Alcohol-associated liver disease (ALD) is a major cause of chronic liver disease worldwide, and comprises a spectrum of several different disorders, including simple steatosis, steatohepatitis, cirrhosis, and superimposed hepatocellular carcinoma. Although tremendous progress has been made in the field of ALD over the last 20 years, the pathogenesis of ALD remains obscure, and there are currently no FDA-approved drugs for the treatment of ALD. In this Review, we discuss new insights into the pathogenesis and therapeutic targets of ALD, utilizing the study of multiomics and other cutting-edge approaches. The potential translation of these studies into clinical practice and therapy is deliberated. We also discuss preclinical models of ALD, interplay of ALD and metabolic dysfunction, alcohol-associated liver cancer, the heterogeneity of ALD, and some potential translational research prospects for ALD.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Bryan Mackowiak, Yaojie Fu, Luca Maccioni, Bin Gao</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 1293</p> <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/170500">Recent advances in lung organoid development and applications in disease modeling</a></h5> </div> </div> <div class='row'> <div class='small-12 columns article-metadata'> <a class="show-for-small" href="/articles/view/170500">Ana I. Vazquez-Armendariz, Purushothama Rao Tata</a> <a class='hide-for-small show-more' data-reveal-id='article44534-more' href='#'> <div class='article-authors'> Ana I. Vazquez-Armendariz, Purushothama Rao Tata </div> </a> <span class='article-published-at'> Published November 15, 2023 </span> <br/>Citation Information: <i>J Clin Invest.</i> 2023;<a id="article_metadata" href="http://www.jci.org/133/22">133(22)</a>:e170500. <a href="https://doi.org/10.1172/JCI170500">https://doi.org/10.1172/JCI170500</a>. <div class='row'> <div class='small-12 columns article-links'> View: <a href="/articles/view/170500">Text</a> | <a href="/articles/view/170500/pdf">PDF</a> </div> </div> <div class='row'> <div class='small-12 columns'> <a href="/tags/58"><span class='label-article-type'> Review Series </span> </a><span class='altmetric-embed' data-badge-popover='bottom' data-badge-type='2' data-doi='10.1172/JCI170500' data-hide-no-mentions='true'></span> </div> </div> </div> </div> </div> </div> <div class='reveal-modal xlarge' data-reveal='' id='article44534-more'> <div class='row'> <div class='small-12 columns'> <h4><a href="/articles/view/170500">Recent advances in lung organoid development and applications in disease modeling</a></h4> </div> <div class='small-12 columns'> <ul class='button-group'> <li><a class="button tiny" href="/articles/view/170500">Text</a></li> <li><a class="button tiny" href="/articles/view/170500/pdf">PDF</a></li> </ul> </div> <div class='small-12 columns'> <h5>Abstract</h5> </div> <div class='small-12 columns'> <p>Over the last decade, several organoid models have evolved to acquire increasing cellular, structural, and functional complexity. Advanced lung organoid platforms derived from various sources, including adult, fetal, and induced pluripotent stem cells, have now been generated, which more closely mimic the cellular architecture found within the airways and alveoli. In this regard, the establishment of novel protocols with optimized stem cell isolation and culture conditions has given rise to an array of models able to study key cellular and molecular players involved in lung injury and repair. In addition, introduction of other nonepithelial cellular components, such as immune, mesenchymal, and endothelial cells, and employment of novel precision gene editing tools have further broadened the range of applications for these systems by providing a microenvironment and/or phenotype closer to the desired in vivo scenario. Thus, these developments in organoid technology have enhanced our ability to model various aspects of lung biology, including pathogenesis of diseases such as chronic obstructive pulmonary disease, pulmonary fibrosis, cystic fibrosis, and infectious disease and host-microbe interactions, in ways that are often difficult to undertake using only in vivo models. In this Review, we summarize the latest developments in lung organoid technology and their applicability for disease modeling and outline their strengths, drawbacks, and potential avenues for future development.</p> </div> <div class='small-12 columns'> <h5>Authors</h5> </div> <div class='small-12 columns'> <p>Ana I. Vazquez-Armendariz, Purushothama Rao Tata</p> </div> </div> <a class='close-reveal-modal'>×</a> </div> <p>Total views: 1261</p> </div> <p class='load-more'> <a data-url="/top_articles/load_more?type=review" class="small button radius" href="#">Show more results</a> <img src="/assets/load_more-93e7795de3f8255a217ec4db19b59e809b92bcb89ee47f2231e37013d1ff5471.gif" /> </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> <script> $(".tabs").on('toggled', function() {$(document).foundation('equalizer', 'reflow');}); </script>  </body> </html>