Development of targeted therapies for pulmonary diseases is limited by the availability of preclinical testing methods with the ability to predict regional aerosol delivery. Leveraging 3D printing to generate patient-specific lung models, we outline the design of a high-throughput, in vitro experimental setup for quantifying lobular pulmonary deposition. This system is made with a combination of commercially available and 3D printed components and allows the flow rate through each lobe of the lung to be independently controlled. Delivery of fluorescent aerosols to each lobe is measured using fluorescence microscopy. This protocol has the potential to promote the growth of personalized medicine for respiratory diseases through its ability to model a wide range of patient demographics and disease states. Both the geometry of the 3D printed lung model and the air flow profile setting can be easily modulated to reflect clinical data for patients with varying age, race, and gender. Clinically relevant drug delivery devices, such as the endotracheal tube shown here, can be incorporated into the testing setup to more accurately predict a device's capacity to target therapeutic delivery to a diseased region of the lung. The versatility of this experimental setup allows it to be customized to reflect a multitude of inhalation conditions, enhancing the rigor of preclinical therapeutic testing.
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http://dx.doi.org/10.3791/61706 | DOI Listing |
Eur J Med Chem
January 2025
Laboratory of Gastrointestinal Cancer and Liver Disease, Department of Gastroenterology and Hepatology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. Electronic address:
Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound A16 showed potent kinase activity comparable to that of AZD4547.
View Article and Find Full Text PDFEquine Vet J
January 2025
Setor de Patologia Veterinária, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
Background: In horses, systemic calcinosis is a rare syndrome characterised by muscle lesion associated with the mineralisation of large muscle groups or other organs, in the absence of an alternative cause for the calcification, such as toxic, enzootic or metabolic. Molecular and histopathological aspects of the disease are still poorly elucidated.
Objectives: To describe the epidemiological, pathological and molecular aspects of systemic calcinosis in a convenience sample of six horses submitted to necropsy in the Southern and Midwestern regions of Brazil.
Am J Respir Cell Mol Biol
January 2025
Duke Medicine, Medicine, Durham, North Carolina, United States.
Becoming more frequent due to climate change, ozone (O) exposures can cause lung injury. Alveolar type 2 (AT2) cells and hyaluronan (HA), a matrix component, are critical to repairing lung injury and restoring homeostasis. Here, we define the impact of HA on AT2 cells following acute O exposure.
View Article and Find Full Text PDFCureus
December 2024
Pathology, Tokyo Metropolitan Tama Medical Center, Fuchu, JPN.
Pulmonary amyloidosis is diagnosed by identifying amyloid deposits using Congo red stain (CR) and birefringence under polarized light. However, collagen fibers can also produce similar staining results, complicating diagnosis. We report a case of a 55-year-old male patient with lung opacities, initially suspected to have amyloidosis based on CR positivity and green birefringence.
View Article and Find Full Text PDFMult Scler
January 2025
Department of Neurology, National Hospital Organization, Fukuoka Higashi Medical Center, Koga, Japan.
An 80-year-old man with aquaporin-4-antibody-positive neuromyelitis optica spectrum disorder presented with a 2-week history of cough and hiccups, followed by progressive bilateral lower limb weakness, a bandlike burning sensation in the upper body, and urinary retention. Magnetic resonance imaging showed area postrema and thoracic central medullary lesions. Thorax computed tomography showed bilateral upper lung lobe consolidations.
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