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Forkhead box protein O3 (FOXO3) has good inhibition ability toward fibroblast activation and extracellular matrix, especially for the treatment of idiopathic pulmonary fibrosis. How FOXO3 regulates pulmonary fibrosis remains unclear. In this study, we reported that FOXO3 had binding sequences with F-spondin 1 (SPON1) promoter, which can activate its transcription and selectively promote the expression of SPON1 circRNA (circSPON1) but not mRNA expression. We further demonstrated that circSPON1 was involved in the extracellular matrix deposition of HFL1. In the cytoplasm, circSPON1 directly interacted with TGF-β1-induced Smad3 and inhibited the activation of fibroblasts by inhibiting nuclear translocation. Moreover, circSPON1 bound to miR-942-5p and miR-520f-3p that interfered with Smad7 mRNA and promoted Smad7 expression. This study revealed the mechanism of FOXO3-regulated circSPON1 in the development of pulmonary fibrosis. Potential therapeutic targets and new insights into the diagnosis and treatment of idiopathic pulmonary fibrosis based on circRNA were also provided.
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http://dx.doi.org/10.7150/ijbs.80140 | DOI Listing |
Open Access Rheumatol
August 2025
Department of Rheumatology and Immunology, the First Affiliated Hospital, Jinan University, Guangzhou, 510632, People's Republic of China.
Objective: To evaluate the efficacy of baricitinib in combination therapy for managing refractory, rapidly progressive systemic sclerosis (SSc) with severe cardiac conduction defects and interstitial lung disease (ILD).
Methods: A 48-year-old male patient with SSc complicated by significant cardiac enlargement, third-degree atrioventricular block, heart failure, progressive ILD, and partial intestinal obstruction was included in the study. Prior treatments with mycophenolate mofetil (MMF), tacrolimus, and cyclophosphamide (CTX) had shown limited efficacy.
Front Pediatr
August 2025
Division of Pediatric Pulmonology, Department of Pediatrics, Oregon Health & Science University, Portland, OR, United States.
Background: Modulator therapy restores CFTR function and has led to health benefits for persons with cystic fibrosis (CF) (PwCF), including lower rates of pulmonary exacerbations. It is unknown if modulators affect lung function trajectories after inpatient treatment of pulmonary exacerbations (PEx).
Methods: We conducted a retrospective review of hospital encounters for PEx for subjects 6-25 years old with mild to moderate lung disease admitted to a large tertiary care center from 2014 to 2021 to capture hospitalizations of PwCF before and after starting modulators.
Front Pharmacol
August 2025
Department of Pharmacy, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Dipeptidyl peptidase 1 (DPP1) inhibitors constitute a major advance in respiratory disease therapeutics. Through selective blockade of neutrophil serine protease (NSP) activation, these agents establish novel treatment paradigms for inflammatory respiratory conditions characterized by neutrophil-driven pathology. This comprehensive review examines the development status, clinical efficacy, and safety profile of DPP1 inhibitors in neutrophil-driven diseases, particularly non-cystic fibrosis bronchiectasis (NCFBE) and chronic obstructive pulmonary disease (COPD).
View Article and Find Full Text PDFFront Med (Lausanne)
August 2025
Department of Respiratory Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China.
Traditional studies of pulmonary fibrosis (PF) have focused on alveolar epithelial cells injury and abnormal myofibroblast aggregation, but recent studies have revealed that imbalances in pulmonary capillary homeostasis also play pivotal roles in this disease. The pulmonary microvasculature, composed of aerocyte capillary (aCap) and general capillary (gCap) endothelial cells, forms the core structure of the alveolar-capillary membrane. It performs key roles in gas exchange and nutrient/metabolite transport, while modulating the trafficking of inflammatory factors and immune cells and regulating alveolar damage repair.
View Article and Find Full Text PDFImmune Netw
August 2025
Center for Metabolic and Degenerative Diseases, The Brown Foundation Institute of Molecular Medicine for Prevention of Human Diseases, UTHealth-McGovern Medical School, Houston, TX 77030, USA.
Complement anaphylatoxins C3a and C5a are potent immunomodulators whose impact extends well beyond their traditional roles in innate immunity. Acting through G protein-coupled receptors C3aR, C5aR1, and C5aR2, these peptides take part in coordinating immune cell recruitment, vascular tone, and tissue remodeling. Yet their functions are deeply context-dependent: while they play essential roles in microbial clearance and immune coordination, their overactivation contributes to immunopathology in a wide range of diseases.
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