Author's Take
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 Author's Take Guidelines page.
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.
Human papilloma virus (HPV) is an etiological agent of oropharyngeal squamous cell carcinoma (OPSCC). Patients with HPV+ OPSCC have high long-term survival rates: however, current radiation protocols are aggressive and can result in life-long morbidities, including difficulty swallowing, chronic dry-mouth, and altered speech. In this episode, Curtis Pickering and colleagues evaluated gene expression profiles, tumor presentation, and clinical response in a cohort of patients with HPV+ OPSCC and identified a signature associated with poor treatment response. This signature has potential to inform treatment of patients with HPV+ OPSCC, thereby reducing radiation for those with low-risk disease.
Polymyxin B (PMB) is a potent antibiotic that is used for treating life-threatening Gram-negative infections; however, PMB is considered a last line of defense due to dose-limiting nephrotoxicity. Analogs of PMB are being developed with the goal of retaining antibiotic activity while reducing drug toxicity, which is challenging to determine in preclinical animal models. In this episode, Edward Kelly and colleagues use a microphysiological system to model the human kidney proximal tubule to evaluate the toxicity of PMB and two structural polymyxin analogs. The results of this study indicate that organ on chip systems have high potential for drug toxicity screening and for elucidating mechanisms of toxicity.
