METHODS: Sixty-one patients with mTBI (Glasgow Coma Scale score 13-15) were recruited prospectively, categorized according to baseline computed tomography findings, and subjected to neuropsychological assessment at initial admission (n = 61) as well as at a 6-month follow-up (n = 30). The paired t test, Cohen's d effect size calculation, and repeated-measures analysis of variance were used to establish the differences between the 2 groups in terms of neuropsychological performance.
RESULTS: A trend toward poorer neuropsychological performance among the patients with complicated mTBI was observed during admission; however, performance in this group improved over time. In contrast, the uncomplicated mTBI group showed slower recovery, especially in tasks of memory, visuospatial processing, and executive functions, at follow-up.
CONCLUSIONS: Our findings suggest that despite the broad umbrella designation of mTBI, the current classification schemes of injury severity for mild neurotrauma should be revisited. They also raise questions about the clinical relevance of both traumatic focal lesions and the absence of visible traumatic lesions on brain imaging studies in patients with milder forms of head trauma.
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.