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Naphthalimide derivatives have multiple biological activities, including antitumour and anti-inflammatory activities. We previously synthesized several naphthalimide derivatives; of them, compound 5 was found to exert the strongest inhibitory effect on human DNA topoisomerase II activity. However, the effects of naphthalimide derivatives on platelet activation have not yet been investigated. Therefore, the mechanism underlying the antiplatelet activity of compound 5 was determined in this study. The data revealed that compound 5 (5-10 μM) inhibited collagen- and convulxin- but not thrombin- or U46619-mediated platelet aggregation, suggesting that compound 5 is more sensitive to the inhibition of glycoprotein VI (GPVI) signalling. Indeed, compound 5 could inhibit the phosphorylation of signalling molecules downstream of GPVI, followed by the inhibition of calcium mobilization, granule release and GPIIb/IIIa activation. Moreover, compound 5 prevented pulmonary embolism and prolonged the occlusion time, but tended to prolong the bleeding time, indicating that it can prevent thrombus formation but may increase bleeding risk. This study is the first to demonstrate that the naphthalimide derivative compound 5 exerts antiplatelet and antithrombotic effects. Future studies should modify compound 5 to synthesize more potent and efficient antiplatelet agents while minimizing bleeding risk, which may offer a therapeutic potential for cardiovascular diseases., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Objectives/hypothesis: Benign paroxysmal positional vertigo (BPPV) is the most common vestibular disorder with an incidence between 10.7 and 17.3 per 100,000 persons per year. The mechanism for BPPV has been postulated to involve displaced otoconia resulting in canalithiasis. Although particulate matter has been observed in the endolymph of affected patients undergoing posterior canal occlusion surgery, an otoconial origin for the disease is still questioned., Study Design: In this study, particulate matter was extracted from the posterior semicircular canal of two patients and examined with scanning electron microscopy., Methods: The samples were obtained from two patients intraoperatively during posterior semicircular canal occlusion. The particles were fixed, stored in ethanol, and chemically dehydrated. The samples were sputter coated and viewed under a scanning electron microscope. Digital images were obtained., Results: Intact and degenerating otoconia with and without linking filaments were found attached to amorphous particulate matter. Many otoconia appeared to be partially embedded in a gel matrix, presumably that which encases and anchors the otoconia within the otolith membrane, whereas others stood alone with no attached filaments and matrix. The otoconia measured roughly 2 to 8 μm in length and displayed a uniform outer shape with a cylindrical bulbous body and a 3 + 3 rhombohedral plane at each end., Conclusions: These findings suggest that the source of the particulate matter in the semicircular canals of patients with BPPV is broken off fragments of the utricular otolithic membrane with attached and detached otoconia., Level of Evidence: NA Laryngoscope, 127:709-714, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Major depression is an important comorbidity in Alzheimer's disease, which is definitely associated with the apolipoprotein E (apo E) polymorphism. The aim of this study was to explore the role of the different apo E polymorphisms in major depressive disorder (MDD) in a Taiwanese population., Method: We examined apo E genotypes in 273 Taiwanese patients with MDD and 429 healthy community controls, and compared their polymorphism distribution., Results: The allelic frequency of apo epsilon2 was significantly lower in patients with MDD than in the controls, whereas no significant difference in apo epsilon4 allelic frequency between these two groups was found., Conclusion: The apo epsilon4 allele was not associated with MDD in this study. However, the finding of a lower frequency of the apo epsilon2 allele in MDD could lead to the conclusion that the apo epsilon2 allele likely provides a protective effect against MDD in the Taiwanese population.