The Journal of Clinical Investigation

The Journal of Clinical Investigation is a leading platform for breakthroughs in both basic and clinical biomedical research that aim to enhance medical practice.

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Endothelial dysfunction in patients with type 2 diabetes: the truth is in the blood

22 hours ago | jci.org | Sarah Costantino |Shafeeq A. Mohammed |Francesco Paneni |Aida Collado

AbstractEndothelial dysfunction remains a cornerstone of diabetic vascular complications. RBCs emerge as pivotal players in endothelial dysfunction, yet the underlying mechanisms remain elusive. In this issue of the JCI, Collado et al. show that the detrimental action of RBCs on the endothelium is mediated by extracellular vesicles (EVs).
The multiverse of CD46 and oncologic interactions

2 weeks ago | jci.org | M. Kathryn Liszewski |John Atkinson

AbstractInitially identified as a regulator of complement activation on host cells, the known roles of CD46 (membrane cofactor protein [MCP]) have expanded. We now know that this ancient molecule is expressed on almost all nucleated cells as a family of four predominant isoforms. It also is involved in human reproduction, modulation of T cell activation and immunoinflammatory effector functions, autophagy, and the newly identified intracellular complement system (complosome).
Fat, fibrosis, and the future: navigating the maze of MASLD/MASH

1 month ago | jci.org | Scott Friedman

The worldwide challenge of metabolic dysfunction–associated steatotic liver disease (MASLD) and its more advanced form, metabolic dysfunction associated steatohepatitis (MASH), has crept into our world. Previously referred to as NAFLD and NASH, respectively, these illnesses affect 30%–40% of the world’s population and are not confined to developing countries, rather affecting all regions except sub-Saharan Africa (1, 2).
Metabolic dysfunction-associated steatotic liver disease and the gut microbiome: pathogenic insights and therapeutic innovations

1 month ago | jci.org | Bernd Schnabl |Christopher J. Damman |Rotonya M. Carr

AbstractMetabolic dysfunction–associated steatotic liver disease (MASLD) is a major cause of liver disease worldwide, and our understanding of its pathogenesis continues to evolve. MASLD progresses from steatosis to steatohepatitis, fibrosis, and cirrhosis, and this Review explores how the gut microbiome and their metabolites contribute to MASLD pathogenesis.
Ending one conversation, starting another

1 month ago | jci.org | Ushma S. Neill

With this entry, the Conversations with Giants in Medicine series comes to a close. The JCI is heading in a new direction with its video content, and I too will be heading in a different career direction that makes it hard to continue the series with the same care. As is often noted, “All good things must come to an end.” To watch a supercut of the last question I asked each subject, “What other vocation could have kept you as motivated?” see the JCI website at https://www.jci.org/videos/cgms.
Spermidine restricts neonatal inflammation via metabolic shaping of polymorphonuclear myeloid-derived suppressor cells

1 month ago | jci.org | Jiale Chen |Lin Zhu |Zhaohai Cui |Yuxin Zhang

AbstractNewborns exhibit a heightened vulnerability to inflammatory disorders due to their underdeveloped immune system, yet the underlying mechanisms remain poorly understood. Here we report that plasma spermidine is correlated with the maturity of human newborns and reduced risk of inflammation. Administration of spermidine led to the remission of neonatal inflammation in mice.
Post-transfusion activation of coagulation pathways during severe COVID-19 correlates with COVID-19 convalescent plasma antibody profiles

1 month ago | jci.org | Svenja Weiss |Hung-Mo Lin |Eric Acosta |Natalia L. Komarova |Ping Chen |Dominik Wodarz | +10 more

AbstractEarly antibody therapy can prevent severe SARS-CoV-2 infection (COVID-19). However, the effectiveness of COVID-19 convalescent plasma (CCP) therapy in treating severe COVID-19 remains inconclusive. To test a hypothesis that some CCP units are associated with a coagulopathy hazard in severe disease that offsets its benefits, we tracked 304 CCP units administered to 414 hospitalized COVID-19 patients to assess their association with the onset of unfavorable post-transfusion D-dimer trends.
Macrophages: key conductors behind perivascular inflammation and vascular remodeling in hypoxia-induced pulmonary hypertension

1 month ago | jci.org | Edda Spiekerkoetter |Rahul Kumar |Qadar Pasha |Brian Graham

AbstractPulmonary hypertension (PH) encompasses a heterogenous group of disorders with the common feature of increased pulmonary arterial pressures. Patients with PH associated with lung disease and/or hypoxia undergo immune-mediated vascular remodeling that includes thickening of the muscular layer surrounding arteries and arterioles. In this issue of the JCI, Kumar and colleagues examined the role of interstitial macrophages in a model of high-altitude PH.
Transcriptomic profiling after B-cell depletion reveals central and peripheral immune cell changes in multiple sclerosis

2 months ago | jci.org | Jessica Wei |Jeonghyeon Moon |Yoshiaki Yasumizu |Le Fu Zhang

ResearchAutoimmunityImmunologyOpen Access | 10.1172/JCI182790 J Clin Invest. https://doi.org/10.1172/JCI182790. Copyright © 2025, Wei et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
The saponin monophosphoryl lipid A nanoparticle adjuvant induces dose-dependent HIV vaccine responses in non-human primates

2 months ago | jci.org | Parham Ramezani-Rad |Ester Marina-Zárate |Laura Maiorino |Amber Myers

ResearchAIDS/HIVImmunologyOpen Access | 10.1172/JCI185292 J Clin Invest. https://doi.org/10.1172/JCI185292. Copyright © 2025, Ramezani-Rad et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.