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Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and often fatal disorder. Two U.S. Food and Drug Administration-approved antifibrotic drugs, nintedanib and pirfenidone, slow the rate of decline in lung function, but responses are variable and side effects are common. Objectives: Using an in silico data-driven approach, we identified a robust connection between the transcriptomic perturbations in IPF disease and those induced by saracatinib, a selective Src kinase inhibitor originally developed for oncological indications. Based on these observations, we hypothesized that saracatinib would be effective at attenuating pulmonary fibrosis. Methods: We investigated the antifibrotic efficacy of saracatinib relative to nintedanib and pirfenidone in three preclinical models: 1 ) in vitro in normal human lung fibroblasts; 2 ) in vivo in bleomycin and recombinant Ad-TGF-β (adenovirus transforming growth factor-β) murine models of pulmonary fibrosis; and 3 ) ex vivo in mice and human precision-cut lung slices from these two murine models as well as patients with IPF and healthy donors. Measurements and Main Results: In each model, the effectiveness of saracatinib in blocking fibrogenic responses was equal or superior to nintedanib and pirfenidone. Transcriptomic analyses of TGF-β-stimulated normal human lung fibroblasts identified specific gene sets associated with fibrosis, including epithelial-mesenchymal transition, TGF-β, and WNT signaling that was uniquely altered by saracatinib. Transcriptomic analysis of whole-lung extracts from the two animal models of pulmonary fibrosis revealed that saracatinib reverted many fibrogenic pathways, including epithelial-mesenchymal transition, immune responses, and extracellular matrix organization. Amelioration of fibrosis and inflammatory cascades in human precision-cut lung slices confirmed the potential therapeutic efficacy of saracatinib in human lung fibrosis. Conclusions: These studies identify novel Src-dependent fibrogenic pathways and support the study of the therapeutic effectiveness of saracatinib in IPF treatment.

Indigenous Peoples are underrepresented in many of the Health and Human Services Educational Programs (HHSEP, e.g.: Nursing, Social Work). As various studies have reported the benefits of diversifying HHSEP, the barriers and facilitators of increasing the number of Indigenous Peoples in these professions must be identified. The purpose of this exploratory study is to identify and understand the barriers and facilitators Indigenous Peoples face when entering, learning or working in HHSEP. A narrative approach was used in the facilitation of culturally safe sharing circles with Indigenous students and staff to collect perspectives based on their individual experiences in HHSEP. Inductive thematic analysis was used to identify emerging themes in participant experiences and the impact of those experiences on participation in learning and working at the university in these educational programs. Results from this exploratory study identified current academic structures and ideologies rooted in colonialism, that act as barriers for engagement and inclusion of Indigenous students, staff, and clinical and academic faculty. These findings shaped the main themes of this study including negotiation of identity in different spaces, negotiating colonial structures in HHSEP, and negotiating changes and transitions in HHSEP. We anticipate these preliminary results will act as a catalyst for uncovering further changes to be made regarding attitudes, procedures, and practices present in an academic environment that limit the inclusion of Indigenous Peoples in HHSEP., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)