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It remains unknown that the degree of bias in computational fluid dynamics results without considering coronary cyclic bending. This study aims to investigate the influence of different rates of coronary cyclic bending on coronary hemodynamics. To model coronary bending, a multi-ring-controlled fluid-structural interaction model was designed. A coronary artery was simulated with various cyclic bending rates (0.5, 0.75 and 1 s, corresponding to heart rates of 120, 80 and 60 bpm) and compared against a stable model. The simulated results show that the hemodynamic parameters of vortex Q-criterion, temporal wall shear stress (WSS), time-averaged WSS (TaWSS) and oscillatory shear index (OSI) were sensitive to the changes in cyclic rate. A higher heart rate resulted in higher magnitude and larger variance in the hemodynamic parameters. Whereas, the values and distributions of flow velocity and relative residence time (RRT) did not show significant differences between different bending periods. This study suggests that a stable coronary model is not sufficient to represent the hemodynamics in a bending coronary artery. Different heart rate conditions were found to have significant impact on the hemodynamic parameters. Thus, cyclic bending should be considered to mimic the realistic hemodynamics in future patient-specific coronary hemodynamics studies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetic nephropathy (DN) is resulted from activations of polyol pathway and oxidative stress by abnormal metabolism of glucose, and no specific medication is available. We designed a novel class of benzoxazolone derivatives, and a number of individuals were found to have significant antioxidant activity and inhibition of aldose reductase of the key enzyme in the polyol pathway. The outstanding compound (E)-2-(7-(4-hydroxy-3-methoxystyryl)-2-oxobenzo[d]oxazol-3(2H)-yl)acetic acid was identified to reduce urinary proteins in diabetic mice suggesting an alleviation in the diabetic nephropathy, and this was confirmed by kidney hematoxylin-eosin staining. Further investigations showed blood glucose normalization, declined in the polyol pathway and lipid peroxides, and raised glutathione and superoxide dismutase activity. Thus, we suggest a therapeutic function of the compound for DN which could be attributed to the combination of hypoglycemic, aldose reductase inhibition and antioxidant., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Dihydrobenzoxazinone based design and synthesis produced two series of compounds as aldose reductase (ALR2) inhibitor candidates. In particular, phenolic residues were embodied into the compounds for the combination of strengthening the inhibitory acitvity and antioxidant ability to retard the progression of diabetic complications. Most of the derivatives with styryl side chains exhibited excellent activities on selective ALR2 inhibition with IC 50 values ranging from 0.082 to 0.308 μM, and {8-[2-(4-hydroxy-phenyl)-vinyl]-2-oxo-2,3-dihydro-benzo[1,4]oxazin-4-yl}-acetic acid (3a) was the most potent. More significantly, most of dihydrobenzoxazinone compounds revealed not only good inhibitory effect on ALR2, but also showed powerful antioxidant activity. Notably, phenolic compound 3a was even comparable to the well-known antioxidant Trolox, confirming that the C8 p-hydroxystyryl substitution was key structure of lowering oxidative stress. Therefore, these results provided an achievement of multifunctional ALR2 inhibitors possessing capacities for both ALR2 inhibition and as antioxidants., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A series of quinoxalinone scaffold-based acyl sulfonamides were designed as aldose reductase inhibitors and evaluated for aldose reductase (ALR2)/aldehyde reductase (ALR1) inhibition and antioxidation. Compounds 9b-g containing styryl side chains at C3-side exhibited good ALR2 inhibitory activity and selectivity. Of them, 9g demonstrated the most potent inhibitory activity with an IC 50 value of 0.100 μM, and also exhibited excellent antioxidant activity, even comparable to the typical antioxidant Trolox. Compounds 9 had higher lipid-water partition coefficients relative to the carboxylic acid compounds 8, indicating that they may have better lipophilicity and membrane permeability. Structure-activity relationship (SAR) studies found that acyl trifluoromethanesulfonamide group at N1 and the C3-dihydroxystyryl side chain were the key structure for improving the aldose reductase inhibitory activity and antioxidant activity., (Copyright © 2019 Elsevier Ltd. All rights reserved.)