METHODS: Computational Fluid Dynamics (CFD) approach is used to simulate the airflow in a neonate, an infant and an adult in sedentary breathing conditions. The healthy CT scans are segmented using MIMICS 21.0 (Materialise, Ann arbor, MI). The patient-specific 3D airway models are analyzed for low Reynolds number flow using ANSYS FLUENT 2020 R2. The applicability of the Grid Convergence Index (GCI) for polyhedral mesh adopted in this work is also verified.
RESULTS: This study shows that the inferior meatus of neonates accounted for only 15% of the total airflow. This was in contrast to the infants and adults who experienced 49 and 31% of airflow at the inferior meatus region. Superior meatus experienced 25% of total flow which is more than normal for the neonate. The highest velocity of 1.8, 2.6 and 3.7 m/s was observed at the nasal valve region for neonates, infants and adults, respectively. The anterior portion of the nasal cavity experienced maximum wall shear stress with average values of 0.48, 0.25 and 0.58 Pa for the neonates, infants and adults.
CONCLUSIONS: The neonates have an underdeveloped nasal cavity which significantly affects their airway distribution. The absence of inferior meatus in the neonates has limited the flow through the inferior regions and resulted in uneven flow distribution.
METHODS: In silico target prediction was first employed to predict the probability of the bromophenols interacting with key protein targets based on a model trained on known bioactivity data and chemical similarity considerations. Next, we tested the functional effect of natural bromophenols from Symphyocladia latiuscula on the CCK2 receptor followed by a molecular docking simulation to predict interactions between a compound and the binding site of the target protein.
RESULTS: Results of cell-based functional G-protein coupled receptor (GPCR) assays demonstrate that bromophenols 2,3,6-tribromo-4,5-dihydroxybenzyl alcohol (1), 2,3,6-tribromo-4,5-dihydroxybenzyl methyl ether (2), and bis-(2,3,6-tribromo-4,5-dihydroxybenzyl) ether (3) are full CCK2 antagonists. Molecular docking simulation of 1‒3 with CCK2 demonstrated strong binding by means of interaction with prime interacting residues: Arg356, Asn353, Val349, His376, Phe227, and Pro210. Simulation results predicted good binding scores and interactions with prime residues, such as the reference antagonist YM022.
CONCLUSIONS: The results of this study suggest bromophenols 1-3 are CCK2R antagonists that could be novel therapeutic agents for CCK2R-related diseases, especially anxiety and depression.