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Background: NOX2 (nicotinamide adenine dinucleotide phosphate oxidase 2), which is upregulated by a variety of neurodegenerative factors, is neuroprotective and capable of reducing detrimental aspects of pathology following ischemic and traumatic brain injury, as well as in chronic neurodegenerative disorders. The purpose of this study was to investigate NOX2 expression and the degree of functional recovery following different types of facial nerve injury and assess the effects of antioxidant intervention on nerve regeneration., Methods: A total of 40 mature (6-week-old) male Sprague-Dawley (SD) rats were used. After inducing facial injury (compression injury or cutting injury), we randomized rats into four groups: A, crushing injury only; B, crushing injury with alpha lipoic acid (ALA); C, axotomy only; and D, axotomy with ALA. Recovery from facial nerve injury was evaluated 4 and 14 days after injury by performing behavioral assessments (observational scale of vibrissae movement, modified scale of eye closing and blinking reflex) and measuring changes in NOX2 experimental/control ratio in the injured (left, experimental) facial nerve relative to that in the uninjured (right, control) facial nerve., Results: A comparison between groups according to the type of injury showed a higher NOX2 expression ratio in the axotomy group than in the crushing group ( p < 0.001). Regardless of injury type, both groups that received an injection of ALA exhibited a trend toward a higher NOX2 expression ratio, although this difference reached statistical significance only in the axotomy group ( p < 0.001). In behavioral assessments, overall behavioral test scores were significantly higher in the crushing injury group immediately after the injury compared with that in the axotomy group. Additionally, in behavioral tests conducted 4 days after the crushing injury, the group injected with ALA showed better results than the group without injection of ALA ( p = 0.031)., Conclusions: Our study showed that NOX2 expression trended higher with facial nerve injury, exhibiting a significant increase with cutting-type injury. Furthermore, intraperitoneally injection with ALA may be an efficient strategy for accelerating peripheral facial nerve recovery after a crushing injury.

To confirm that the β-phenyl-α,β-unsaturated thiocarbonyl (PUSTC) scaffold, similar to the β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold, acts as a core inhibitory structure for tyrosinase, twelve ( Z )-5-(substituted benzylidene)-4-thioxothiazolidin-2-one (( Z )-BTTZ) derivatives were designed and synthesized. Seven of the twelve derivatives showed stronger inhibitory activity than kojic acid against mushroom tyrosinase. Compound 2b (IC 50 = 0.47 ± 0.97 µM) exerted a 141-fold higher inhibitory potency than kojic acid. Kinetic studies' results confirmed that compounds 2b and 2f are competitive tyrosinase inhibitors, which was supported by high binding affinities with the active site of tyrosinase by docking simulation. Docking results using a human tyrosinase homology model indicated that 2b and 2f might potently inhibit human tyrosinase. In vitro assays of 2b and 2f were conducted using B16F10 melanoma cells. Compounds 2b and 2f significantly and concentration-dependently inhibited intracellular melanin contents, and the anti-melanogenic effects of 2b at 10 µM and 2f at 25 µM were considerably greater than the inhibitory effect of kojic acid at 25 µM. Compounds 2b and 2f similarly inhibited cellular tyrosinase activity and melanin contents, indicating that the anti-melanogenic effects of both were due to tyrosinase inhibition. A strong binding affinity with the active site of tyrosinase and potent inhibitions of mushroom tyrosinase, cellular tyrosinase activity, and melanin generation in B16F10 cells indicates the PUSTC scaffold offers an attractive platform for the development of novel tyrosinase inhibitors.

Thirteen ( Z )-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1 - 3 showed greater inhibitory activity than kojic acid (IC 50 = 18.27 ± 0.89 μM); IC 50 = 3.70 ± 0.51 μM for 1 ; IC 50 = 3.05 ± 0.95 μM for 2 ; and IC 50 = 5.00 ± 0.38 μM for 3 , and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1 - 3 could bind to the catalytic sites of tyrosinase. Compounds 1 - 3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

We previously reported ( E )-β-phenyl-α,β-unsaturated carbonyl scaffold (( E )-PUSC) played an important role in showing high tyrosinase inhibitory activity and that derivatives with a 4-substituted resorcinol moiety as the β-phenyl group of the scaffold resulted in the greatest tyrosinase inhibitory activity. To examine whether the 4-substituted resorcinol moiety could impart tyrosinase inhibitory activity in the absence of the α,β-unsaturated carbonyl moiety of the ( E )-PUSC scaffold, 10 urolithin derivatives were synthesized. To obtain more candidate samples, the lactone ring in synthesized urolithins was reduced to produce nine reduced urolithins. Compounds 1c (IC 50 = 18.09 ± 0.25 μM), 1h (IC 50 = 4.14 ± 0.10 μM), and 2a (IC 50 = 15.69 ± 0.40 μM) had greater mushroom tyrosinase-inhibitory activities than kojic acid (KA) (IC 50 = 48.62 ± 3.38 μM). The SAR results suggest that the 4-substituted resorcinol motif makes an important contribution to tyrosinase inhibition. To investigate whether these compounds bind to human tyrosinase, a human tyrosinase homology model was developed. Docking simulations with mushroom and human tyrosinases showed that 1c, 1h, and 2a bind to the active site of both tyrosinases with higher binding affinities than KA. Pharmacophore analyses showed that two hydroxyl groups of the 4-substituted resorcinol entity act as hydrogen bond donors in both mushroom and human tyrosinases. Kinetic analyses indicated that these compounds were all competitive inhibitors. Compound 2a inhibited cellular tyrosinase activity and melanogenesis in α-MSH plus IBMX-stimulated B16F10 melanoma cells more strongly than KA. These results suggest that 2a is a promising candidate for the treatment of skin pigment disorders, and show the 4-substituted resorcinol entity importantly contributes to tyrosinase inhibition.

Tyrosinase is considered a key contributor to melanogenesis, and safe, potent tyrosinase inhibitors are needed for medical and cosmetic purposes to treat skin hyperpigmentation and prevent fruit and vegetable browning. According to our accumulated SAR data on tyrosinase inhibitors, the β-phenyl-α,β-unsaturated carbonyl scaffold in either E or Z configurations, can confer potent tyrosinase inhibitory activity. In this study, twelve indanedione derivatives were synthesized as chimeric compounds with a β-phenyl-α,β-unsaturated dicarbonyl scaffold. Two of these derivatives, that is, compounds 2 and 3 (85% and 96% inhibition, respectively), at 50 μM inhibited mushroom tyrosinase markedly more potently than kojic acid (49% inhibition). Docking studies predicted that compounds 2 and 3 both inhibited tyrosinase competitively, and these findings were supported by Lineweaver-Burk plots. In addition, both compounds inhibited tyrosinase activity and reduced melanin contents in B16F10 cells more than kojic acid without perceptible cytotoxicity. These results support the notion that chimeric compounds with the β-phenyl-α,β-unsaturated dicarbonyl scaffold represent promising starting points for the development of potent tyrosinase inhibitors., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The β-phenyl-α,β-unsaturated carbonyl (PUSC) scaffold confers tyrosinase inhibitory activity, and in the present study, 16 ( Z )-5-(substituted benzylidene)-3-phenyl-2-thioxooxazolidin-4-one analogues containing this scaffold were synthesized. Mushroom tyrosinase inhibitory activities were examined. Compound 1c (IC 50  = 4.70 ± 0.40 μM) and compound 1j (IC 50  = 11.18 ± 0.54 μM) inhibited tyrosinase by 4.9 and 2.1-fold, respectively, and did so more potently than kojic acid (IC 50  = 23.18 ± 0.11 μM). Kinetic analysis of tyrosinase inhibition revealed that 1c and 1j inhibited tyrosinase competitively. Results of docking simulation with mushroom tyrosinase using four docking programs suggested that 1c and 1j bind more strongly than kojic acid to the active site of tyrosinase and supported kinetic findings that both compounds are competitive inhibitors. The docking results of human tyrosinase homology model indicated that 1c and 1j can also strongly inhibit human tyrosinase. EZ-cytox assays revealed 1c and 1j were not cytotoxic to B16F10 melanoma cells. The effects of 1c and 1j on cellular tyrosinase activity and melanin production were also investigated in α-MSH- and IBMX-co-stimulated these cells. Both compounds significantly and dose-dependently reduced tyrosinase activity, and at 10 µM were more potent than kojic acid at 20 µM. Compounds 1c and 1j also inhibited melanogenesis, which suggested that the inhibitory effects of these compounds on melanin production were mainly attributable to their inhibitions of tyrosinase. These results indicate that compounds 1c and 1j with the PUSC scaffold have potential use as whitening agents for the treatment of hyperpigmentation-associated diseases., Competing Interests: 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., (© 2020 The Author(s).)

A series of ( E )-1-(furan-2-yl)prop-2-en-1-one derivatives (compounds 1 - 8 ) were synthesized and evaluated for their mushroom tyrosinase inhibitory activity. Among these series, compound 8 (2,4-dihydroxy group bearing benzylidene) showed potent tyrosinase inhibitory activity, with respective IC 50 values of 0.0433 µM and 0.28 µM for the monophenolase and diphenolase as substrates in comparison to kojic acid as standard compound 19.97 µM and 33.47 µM. Moreover, the enzyme kinetics of compound 8 were determined to be of the mixed inhibition type and inhibition constant ( K i ) values of 0.012 µM and 0.165 µM using the Lineweaver-Burk plot. Molecular docking results indicated that compound 8 can bind to the catalytic and allosteric sites 1 and 2 of tyrosinase to inhibit enzyme activity. The computational molecular dynamics analysis further revealed that compound 8 interacted with two residues in the tyrosinase active site pocket, such as ASN260 and MET280. In addition, compound 8 attenuated melanin synthesis and cellular tyrosinase activity, simulated by α-melanocyte-stimulating hormone and 1-methyl-3-isobutylxanthine. Compound 8 also decreased tyrosinase expressions in B16F10 cells. Based on in vitro and computational studies, we propose that compound 8 might be a worthy candidate for the development of an antipigmentation agent.

Background: Rhinoplasty surgeons are aware that the nasal profile differs according to body position, namely, the erect position in the consultation room vs the supine position on the operating table. It is not clear whether this difference is caused by an optical illusion or skin laxity due to positional change., Objectives: To evaluate anthropometric measurements of the nose with different body positions and determine whether the supine position affects the nasal profile., Methods: In this retrospective study, 103 patients who underwent primary rhinoplasty were enrolled. Preoperatively, all patients underwent lateral cephalography in the erect position, and facial computed tomography (CT), in the supine position. We measured four nasal anthropometric parameters (the nasofrontal, nasolabial, and nasomental angles, and Simon's ratio) on lateral cephalograms and facial CT images, and compared these parameters between the two body positions., Results: The nasofrontal angle was greater on facial CT than on cephalograms (P < 0.01). This difference was not related to age, sex, or body mass index (P > 0.05 each). We found no significant difference (P > 0.05) between the two positions in the nasolabial angle, nasomental angle, or Simon's ratio., Conclusions: The supine position does affect the nasal profile, especially in the radix area. Surgeons need to consider this difference in patients undergoing rhinoplasty., Level of Evidence: 2., (© 2017 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com)

Background and Objectives: This study examined whether the prognosis of sudden deafness was dependent on the time of onset and evaluated the factors affecting prognosis during each period., Subjects and Methods: Patients who developed sudden hearing loss from January 2005 to December 2015 were evaluated retrospectively. Meteorological data were obtained from the official website of the Korea Meteorological Administration. Factors prognostic of hearing recovery rate were analyzed., Results: The hearing recovery rate of the 318 patients who developed sudden deafness did not differ significantly by month. Mean temperature and daily temperature range at onset of sudden deafness were not associated with recovery rate., Conclusions: The recovery rate in patients with sudden deafness did not differ markedly by season., Competing Interests: Conflicts of interest: The authors have no financial conflicts of interest.

Objective: To determine the effect of a postoperative proton pump inhibitor (PPI) on voice outcomes after phonomicrosurgery in patients with vocal fold polyp., Study Design: This is a prospective, randomized controlled study., Settings: This study was carried out in a tertiary care referral medical centre., Participants: A total of 48 patients underwent phonomicrosurgery for vocal fold polyps. After surgery, patients were randomized to the PPI group (lansoprazole 15 mg twice daily for 2 months) and the non-PPI group., Main Outcome Measures: Voice handicap index (VHI) and perceptual and acoustic voice analysis were evaluated at baseline and 2 months after surgery., Results: Among 48 enrolled patients, a total of 42 patients [non-PPI group (n = 23), PPI group (n = 19)] completed the study. The VHI, perceptual and most acoustic parameters significantly improved in both groups after surgery. However, there was no significant difference in the per cent of change in those parameters., Conclusion: Postoperative PPI treatment did not significantly influence voice outcomes after phonomicrosurgery in patients with vocal fold polyp., (© 2015 John Wiley & Sons Ltd.)

Conclusion: Compared with normal-weight individuals, obese young adults exhibited a significantly higher taste threshold for salty taste. Smoking also affected taste functions in this population., Objective: The aim of this study was to investigate the differences in taste detection thresholds between normal-weight and obese young adults., Methods: Taste threshold was measured using electrogustometry (EGM) and chemically with sucrose, NaCl, citric acid, and quinine hydrochloride in 41 volunteers in their twenties, 23 with body mass index (BMI) <23 kg/m(2) (normal-weight group) and 18 with BMI >25 kg/m(2) (obese group)., Results: BMI was significantly higher in the obese than in the normal-weight group (p < 0.05). The obese group exhibited significantly higher EGM thresholds than the normal-weight group on the right (p < 0.05) and left (p < 0.05) posterior tongue. In chemical taste tests, the obese group had higher thresholds for sweet, salty, sour, and bitter tastes than the normal-weight group, although the difference in threshold was significant only for salty taste (p < 0.05). Smoking had an impact on taste threshold, with smokers having higher thresholds than non-smokers, with significantly higher EGM thresholds on the right anterior and posterior and the left anterior tongue (p < 0.05 each).