Video abstracts
In this video collection, authors of findings published in JCI Insight present personally guided tours of their results. The journal accepts video submissions from authors of recently accepted manuscripts. Instructions can be found on the Video Abstracts Guidelines page.
The immune system is critical for detecting and eradicating aberrant, tumorigenic cells, and failure of the immunosurveillance system to target these nascent, emerging tumors leads to cancer development. In this episode, Robert Binder and colleagues determined that compared to WT animals, mice lacking the receptor CD91 on antigen-presenting cells are more susceptible to chemical-induced tumor formation as the result of underdeveloped early effector immune responses that in turn enable emergence of neo-antigen-expressing tumors. Moreover, in patients with lung squamous cell carcinomas and skin cutaneous melanomas, CD91 polymorphisms that affect ligand binding associated with poorer immune response. These results indicate that CD91 has potential to predict cancer risk and progression.
Precise control of airway mucin secretion is essential for maintaining proper lung function. In this episode, Burton Dickey, Ana Jaramillo, and colleagues evaluate the role of different isoforms of the scaffolding protein Munc18 in the airway. Munc18a was required for baseline mucin secretion, Munc18b was linked to mucin secretion in response to stimuli, and Munc18c did not contribute to airway mucin secretion. Moreover, Munc18b-deficinet mice showed a reduction of pathogenic phenotypes in multiple models of airway disease, including allergic asthma, cystic fibrosis, and emphysema. These results highlight differences in exocytic machinery at baseline and in response to stimuli that have potential as therapeutic targets.
Heterogeneity of cells of the same type within a given tissue is well documented. However, as imaging individual cells in the same tissue over time is a challenge, little is known about the relevance of this variation for health and in disease. In this episode, Johnny Tam and colleagues use adaptive optics fluorescence microscopy to longitudinally evaluate mosaicism of retinal pigment epithelial (RPE) cells directly in the human eye. Patterns of cell mosaicism in the RPE were stable over time in healthy subjects; however, patterns were not stable over time in a subject with Bietti crystalline dystrophy. These results demonstrate that within the eye patterns of heterogeneity have long-term stability but these patterns can be disrupted in disease.
The release of protein disulfide isomerase (PDI) from cells during disease or in response to injury can exacerbate pathological processes, including thromboembolism, and, as such, is currently being explored as a therapeutic target. In this episode, Jeffrey Zwicker and colleagues report on the results of a multicenter phase 2 trial of the PDI-targeting flavonoid isoquercetin in cancer patients at high risk of thrombosis. Isoquercetin inhibited PDI activity in plasma and decreased platelet-dependent thrombin generation in a dose-dependent manner. Moreover, patients that received a higher dose had reduced levels of coagulation markers in circulation, supporting further evaluation of isoquercetin in patients at risk of thrombosis.
Intrauterine infection with the oral anaerobe Fusobacterium nucleatum during pregnancy has been linked to adverse fetal outcomes. In this episode, Yiping Han and colleagues characterize the etiology of F. nucleatum-induced placental inflammation in pregnant mice. Moreover, animals given omega-3 fatty acids prior to infection had reduced placental inflammation, decreased bacterial burden, and improved fetal outcomes. Together, these result support further exploration of omega-3 fatty acid supplementation improving adverse pregnancy outcomes.
