DEK-targeting aptamer DTA-64 attenuates bronchial EMT-mediated airway remodelling by suppressing TGF-beta 1/Smad, MAPK and PI3K signalling pathway in asthma
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Authors: Song, Yilan; Wang, Zhiguang; Jiang, Jingzhi; Piao, Yihua; Li, Li; Xu, Chang; Piao, Hongmei; Li, Liangchang; Yan, Guanghai
Abstract
This study is to investigate the inhibitory effects and mechanisms of DEK-targeting aptamer (DTA-64) on epithelial mesenchymaltransition (EMT)-mediated airway remodelling in mice and human bronchial epithelial cell line BEAS-2B. In the ovalbumin (OVA)-induced asthmatic mice, DTA-64 significantly reduced the infiltration of eosinophils and neutrophils in lung tissue, attenuated the airway resistance and the proliferation of goblet cells. In addition, DTA-64 reduced collagen deposition, transforming growth factor 1 (TGF-beta 1) level in BALF and IgE levels in serum, balanced Th1/Th2/Th17 ratio, and decreased mesenchymal proteins (vimentin and alpha-SMA), as well as weekend matrix metalloproteinases (MMP-2 and MMP-9) and NF-kappa B p65 activity. In the in vitro experiments, we used TGF-beta 1 to induce EMT in the human epithelial cell line BEAS-2B. DEK overexpression (ovDEK) or silencing (shDEK) up-regulated or down-regulated TGF-beta 1 expression, respectively, on the contrary, TGF-beta 1 exposure had no effect on DEK expression. Furthermore, ovDEK and TGF-beta 1 synergistically promoted EMT, whereas shDEK significantly reduced mesenchymal markers and increased epithelial markers, thus inhibiting EMT. Additionally, shDEK inhibited key proteins in TGF-beta 1-mediated signalling pathways, including Smad2/3, Smad4, p38 MAPK, ERK1/2, JNK and PI3K/AKT/mTOR. In conclusion, the effects of DTA-64 against EMT of asthmatic mice and BEAS-2B might partially be achieved through suppressing TGF-beta 1/Smad, MAPK and PI3K signalling pathways. DTA-64 may be a new therapeutic option for the management of airway remodelling in asthma patients.
Confronting the Challenges of Anatomy Education in a Competency-Based Medical Curriculum During Normal and Unprecedented Times (COVID-19 Pandemic): Pedagogical Framework Development and Implementation
JOURNAL OF MEDICAL INTERNET RESEARCH
Authors: Naidoo, Nerissa; Akhras, Aya; Banerjee, Yajnavalka
Abstract
Background: Anatomy is considered to be one of the keystones of undergraduate medical education. However, recently, there has been drastic reduction, both in gross anatomy teaching hours and its context. Additionally, a decrease in the number of trained anatomists and an increase in the costs associated with procuring human cadavers have been noted, causing a diminution of cadaveric dissections in anatomy education. Objective: To address these challenges, there is an ardent need for a pedagogical framework such that anatomy education can be disseminated through active learning principles, within a fixed time frame, using a small team of anatomists and a small number of cadaveric specimens (for live on-site sessions) as well as collaborative learning principles. The latter is particularly important when anatomy education is delivered through distance learning, as is the case currently during the COVID-19 pandemic. Methods: Here, we have blueprinted a pedagogical framework blending the instructional design models of Gagne's 9 events of instruction with Peyton's 4-step approach. The framework's applicability was validated through the delivery of anatomical concepts, using an exemplar from the structure-function course Head and Neck during the normal and COVID-19-mandated lockdown periods, employing the archetype of Frey syndrome. Preliminary evaluation of the framework was pursued using student feedback and end-of-course feedback responses. The efficiency of the framework in knowledge transfer was also appraised. Results: The blueprinted instructional plan designed to implement the pedagogical framework was successfully executed in the dissemination of anatomy education, employing a limited number of cadaveric specimens (during normal times) and a social media application (SMA)-integrated "interactome" strategy (during the COVID-19 lockdown). Students'response to the framework was positive. However, reluctance was expressed by a majority of the faculty in adopting the framework for anatomy education. To address this aspect, a strategy has been designed using Mento's 12-step change management model. The long-term benefits for any medical school to adopt the blended pedagogical framework have also been explicated by applying Bourdieu's Theory of Practice. Additionally, through the design of an SMA interactome model, the framework's applicability to the delivery of anatomy education and content during the ongoing COVID-19 pandemic was realized. Conclusions: In conclusion, the study effectively tackles some of the contemporary key challenges associated with the delivery of anatomy content in medical education during normal and unprecedented times.