Dasom Kong1,4, Ki Hoon Park2,4, Da-Hyun Kim1 , Nam Gyo Kim1 , Seung-Eun Lee1 , Nari Shin1 , Myung Geun Kook1 ,
Young Bong Kim3✉ and Kyung-Sun Kang 1✉
© The Author(s) 2023
A correlation between COVID-19 and Alzheimer’s disease (AD) has been proposed recently. Although the number of case reports on neuroinflammation in COVID-19 patients has increased, studies of SARS-CoV-2 neurotrophic pathology using brain organoids have
restricted recapitulation of those phenotypes due to insufficiency of immune cells and absence of vasculature. Cerebral pericytes and endothelial cells, the major components of blood-brain barrier, express viral entry receptors for SARS-CoV-2 and response to
systemic inflammation including direct cell death. To overcome the limitations, we developed cortical-blood vessel assembloids by fusing cortical organoid with blood vessel organoid to provide vasculature to brain organoids a nd obtained the characteristics of increased expression of microglia and astrocytes in brain organoids. Furthermore, we observed AD pathologies, including β-amyloid plaques, which were affected by the inflammatory response from SARS-CoV-2 infection. These findings provide an advanced platform to investigate human neurotrophic diseases, including COVID-19, and suggest that neuroinflammation caused by viral infection facilitates AD pathology.
Cell Death Discovery (2023) 9:32 ; https://doi.org/10.1038/s41420-022-01288-8
Xiaolong A. Zhou1 | Michael B. Burns2 | Ziyou Ren1 | Elise Stagaman2 | Stefan J. Green3 | Lok Yiu Ashley Wu3 |
Lynna Yang1 | Stephanie Rangel1 | Lydia Rabbaa1 | Amy S. Paller1
1Department of Dermatology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois, USA | 2Department of Biology, Loyola University
Chicago, Chicago, Illinois, USA | 3Genomics and Microbiome Core Facility, Rush University Medical Center, Chicago, Illinois, USA
Correspondence: Amy S. Paller (该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。)
Received: 6 February 2025 | Revised: 6 June 2025 | Accepted: 3 August 2025
Funding: This work was supported by Applied Pharma Research.
Keywords: acid-oxidising solution | epidermolysis bullosa | hypochlorous acid | microbiome | Staphylococcus aureus | wounds
ABSTRACT
Epidermolysis bullosa (EB) is a group of rare genetic skin disorders characterised by skin fragility and chronic, painful wounds that are highly susceptible to bacterial infection, particularly by Staphylococcus aureus (SA). This study evaluated the efficacy of an acid-oxidising solution containing hypochlorous acid (HOCl) in reducing SA colonisation, promoting wound healing, and restoring a healthier microbiome in EB wounds. In a 12-week open-label pilot study, 15EB patients applied the HOCl-based spray (APR-TD011) daily to chronic wounds for 8weeks, with full-length 16S rRNA sequencing of wound swabs performed before, during, and after treatment. At baseline, 87% of patients were culture-positive for SA, and sequencing revealed that SA had the highest relative abundance (34%), followed by Acinetobacter guillouiae and Pseudomonas poae. SA relative abundance decreased precipitously by Weeks 4 (to 11%) and 8 (primary endpoint; to 10%, p<0.01), and this effect persisted at 4weeks post-treatment (Week 12; to 9.7%), including for methicillin-resistant SA. Concurrently, bacterial diversity increased, and wound sizes diminished in correlation with reduced SA levels (r=0.64). Younger patients exhibited greater SA reduction trends. The treatment was well-tolerated, with minimal adverse effects and high patient satisfaction. This study underscores the role of microbial dysbiosis in EB wounds and highlights HOCl-based solutions as a promising therapy to mitigate pathogenic burden and enhance wound healing.
长期从事影像诊断和介入放射学诊疗工作,擅长肿瘤和血管病的介入治疗。
佛山市禅城区中心医院慢性伤口造口专科主任。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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