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Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is commonly used to treat degenerative lumbar spinal disorders. It facilitates a full-scale spinal decompression and interbody fusion with minimal neural retraction using the tubular retractor system. Despite the benefits of surgical efficiency and minimalism, this technique requires a long learning curve. There is currently no consensus on the learning curve characteristics and proper training methods for MI-TLIF. Thus, this systematic review aimed to discuss the cutoff point at which technical proficiency is achieved and ways to enhance the learning process.Major databases, including PubMed, Embase, and Cochrane Library, were searched for learning curve studies that have evaluated the clinical outcome and learning progress of MI-TLIF using quantitative data. The qualities of the selected studies were assessed using the Newcastle‒Ottawa scale. The plateau points in the "learning curve" were analyzed according to various outcome measures.Nine full-text articles, representing 753 cases, were included from 9743 screened studies. The most commonly used outcome measures were the operative time, followed by the complication rate. The mean cutoff point for the operative time was 31.33 ± 11.98 (range 13‒45) cases.The plateau point in the learning curve for MI-TLIF may differ according to the outcome measures used. Most studies have demonstrated the learning progress based on simple task efficiency, rather than patient outcomes. Moreover, the learning rate may be affected by the patients' and technical conditions. Therefore, great care is required in interpreting the learning curve and cutoff point for MI-TLIF proficiency.

Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

Objective: Fenestrated screw fixation with bone cement augmentation has been demonstrated to increase the pullout strength. Bone cement augmentation is performed to prevent screw failure. Although bone cement screw fixation and fenestrated screw fixation have been compared in many studies, there has been no study on the clinical effects and complication in long level percutaneous bone cement screw fixation. The study aimed to investigate the safety and efficacy of multilevel percutaneous fenestrated screw fixation with bone cement augmentation in the adult lumbar spinal deformity.Methods: We performed a retrospective study of 15 patients who underwent multilevel percutaneous fenestrated screw fixation (PFSF) with bone cement augmentation in a single spine surgeon between January 2018 and December 2020. The incidence of screw failure, body mass index (BMI), bone mineral density (BMD), past history, Visual analogue scale (VAS) score, Oswestry disability index (ODI), sagittal vertical axis (SVA), pelvic Tilt (PT), pelvic incidence (PI), sagittal slope (SS), lumbar lordosis (LL) and Cobbs angle were investigated in the patients.Results: All patients underwent percutaneous screw fixation using a bone cement additive. Mean BMD was –2.0±0.8. The mean percutaneous fenestrated screw fixation level was 6. The mean VAS score changed from 7.14 preoperatively to 4.57 postoperatively (1 month after the surgery), to 3.71 at the last follow-up. The mean ODI changed from 45.21 preoperatively to 32.5 postoperatively, to 27.0 at the last follow-up. The mean LL changed from 23.6 preoperatively to 32.96 postoperatively, to 31.67 at the last follow-up. The mean PT changed from 32.67 preoperatively to 28.11 postoperatively, to 28.70 at the last follow-up. The mean PI - LL changed from 35.20 preoperatively to 22.56 postoperatively, to 22.76 at the last follow-up. The mean Cobb’s angle decreased from 18.30 preoperatively to 6.27 postoperatively, to 5.98 at the last follow-up. The mean SVA changed from 76.65 preoperatively to 46.15 postoperatively, to 48.46 at the last follow-up. The bony fusion rate was 73.3%. There were screw loosening in 4 patients, rod fracture in 1 patient and screw fracture in 3 patients. Among the 3 patients with screw fracture, 1 patient required reoperation. Cement leakage occurred towards the anterior body of the vertebrae in 2 patients but no symptoms were observed.Conclusion: Although the current study examined a small sample with relatively short term follow up periods, our study results demonstrate that multilevel PFSF with bone cement augmentation can result in good clinical and radiological outcomes for lumbar spinal deformity. However, larger size screws or smaller through-hole screws are required to prevent screw fracture.

In this study, we aimed to develop and validate a pretreatment method for separating and analyzing the small amounts of biomarkers contained in topical cream formulations. Analyzing semisolid formulations that contain low concentrations of active ingredients is difficult. Cream formulations containing an aqueous ethanol extract of 0.1% Agrimonia pilosa is an example. Approximately 0.0013% of apigenin-7-O-glucuronide(A7OG) was contained as a biomarker in the cream. To determine the A7OG content present in the cream formulation, liquid–liquid extraction using dichlormethane was applied. In addition, the volume of the distribution liquid was measured using the peak ratios of the indicator component, A7OG, and an internal standard, baicalin. Subsequently, the A7OG content in the cream formulation was calculated. Using this time-saving method, A7OG can be simply analyzed without additional pretreatment steps, such as evaporation and reconstitution. Moreover, the validation results confirmed that this analytical method met all of the criteria. Consequently, A7OG was successfully isolated from the cream, analyzed, and quantified using the developed method.

Objective Henoch–Schonlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch–Schonlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch–Schonlein purpura. Method The medical records of children newly diagnosed as having Henoch–Schonlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. Results This study included a total of 186 patients with Henoch–Schonlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. Conclusions Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch–Schonlein purpura.

Cervical artificial discs (CADs) are a surgical option in selected patients with cervical spinal disc degeneration. Although CADs have been available for many years, concerns persist regarding long-term safety, durability, and implant-related failure. We report a case of nucleus herniation of a Mobi-C implant without trauma, which is a rare complication. Two years after implantation of a Mobi-C implant, a 47-year-old man presented with acute paraplegia without a history of trauma. On cervical magnetic resonance imaging, a T2-high signal intensity lesion was noted in the ventral aspect of the spinal cord at the T1-2 level. During emergent surgery, nucleus herniation of the Mobi-C was detected. After surgery, the patient could walk without assistance. Posterior herniation of the Mobi-C nucleus without trauma is a rare complication that should be considered in surgical planning and follow-up.

To evaluate the clinical outcomes and prognostic factors in surgically treated patients with severe brain injury (Glasgow Coma Scale [GCS] score ≤8) diagnosed with traumatic epidural hematoma (EDH).From January 2018 to June 2021, 1,122 patients with an initial GCS score ≤8 were retrospectively enrolled in the Korean Neuro-Trauma Data Bank System. Clinical data of 79 surgically treated patients with EDH were compared between the unfavorable (scores of 1-4 on the Glasgow Outcome Scale-Extended [GOSE]) and favorable (score of 5-8 on the GOSE) outcome groups.The overall mortality rate was 13.9%, and 60.8% of the patients had good outcomes at six months post-trauma. In the univariate analysis, increasing age (Despite severe brain injury, more than half of the patients with EDH had favorable outcomes after surgical treatment. Our findings suggest that prompt diagnosis and surgical treatment should be considered for such cases.

This study investigated the relationship between trauma scoring systems and outcomes in patients with severe traumatic brain injury (TBI).From January 2018 to June 2021, 1,122 patients with severe TBI were registered in the Korean Neuro-Trauma Data Bank System. Among them, 697 patients with data on trauma scoring systems were included in the study. According to the Glasgow Outcome Scale-Extended score, the patients were divided into unfavorable and favorable outcome groups. The abbreviated injury scale (AIS), injury severity score (ISS), revised trauma score (RTS), and trauma and injury severity score (TRISS) were evaluated.The AIS head score was higher in the unfavorable outcome group than in the favorable outcome group (4.39 vs. 4.06,Trauma scoring systems, including ISS, RTS, and TRISS, provide tools for quantifying posttraumatic risk and can be used to predict prognosis. Among these, TRISS is an indicator of the predicted survival rate and is considered a clinically useful tool for predicting unfavorable and favorable outcomes in patients with severe TBI.

Traumatic brain injury (TBI) is one of the most common injuries in patients with multiple trauma, and it associates with high post-traumatic mortality and morbidity. A trauma center was established to provide optimal treatment for patients with severe trauma. This study aimed to compare the treatment outcomes of patients with severe TBI between non-trauma and trauma centers based on data from the Korean Neuro-Trauma Data Bank System (KNTDBS).From January 2018 to June 2021, 1122 patients were enrolled in the KNTDBS study. Among them, 253 patients from non-traumatic centers and 253 from trauma centers were matched using propensity score analysis. We evaluated baseline characteristics, the time required from injury to hospital arrival, surgery-related factors, neuromonitoring, and outcomes.The time from injury to hospital arrival was shorter in the non-trauma centers (110.2 vs. 176.1 minutes, p=0.012). The operation time was shorter in the trauma centers (156.7 vs. 128.1 minutes, p=0.003). Neuromonitoring was performed in 9 patients (3.6%) in the non-trauma centers and 67 patients (26.5%) in the trauma centers (p0.001). Mortality rates were lower in trauma centers than in non-trauma centers (58.5% vs. 47.0%, p=0.014). The average Glasgow Coma Scale (GCS) at discharge was higher in the trauma centers (4.3 vs. 5.7, p=0.011). For the Glasgow Outcome Scale-Extended (GOSE) at discharge, the favorable outcome (GOSE 5-8) was 17.4% in the non-trauma centers and 27.3% in the trauma centers (p=0.014).This study showed lower mortality rates, higher GCS scores at discharge, and higher rates of favorable outcomes in trauma centers than in non-trauma centers. The regional trauma medical system seems to have a positive impact in treating patients with severe TBI.

Objective Previous literatures have demonstrated widely variable clinical results after transsacral epiduroscopic laser decompression (SELD) and the factors predicting outcomes are not yet established. Therefore, we analyzed the clinical outcome and associated predictive factors of SELD in patients with lumbar disc herniation. Methods Between 2015 and 2018, 82 patients who underwent single-level SELD and followed up at least 6 months were enrolled. The overall success rate (excellent or good results at final follow-up) was 58.5% according to Odom’s criteria. Based on this result, patients were divided to 2 groups: a favorable group (n = 48) and an unfavorable group (n = 34). A retrospective review of the baseline characteristics and clinical outcome were conducted to reveal the predictive factors. Results As expected, improvement of pain and patient satisfaction, was more favorable in the favorable group (p < 0.05). Moreover, the rate of additional procedure was lower in the favorable group (4.2%, 2 of 48 patients) than in the unfavorable group (35.3%, 12 of 34 patients) (p = 0.011). Among the various baseline characteristics, the only significant predictive factor for favorable outcome was the presence of a high-intensity zone (HIZ) on preoperative magnetic resonance imaging (50.0% [24 of 48 patients] in the favorable group vs. 11.8% [4 of 34 patients] in the unfavorable group; odds ratio, 15.67; p = 0.024). Conclusion Although SELD for lumbar disc herniation resulted in a less favorable clinical outcome than that reported in previous studies, in patients with a HIZ, SELD can be an effective minimally invasive surgery to relieve low back pain and/or leg pain.

Flos magnoliae (FM), the dry flower buds of Magnolia officinalis or its related species, is a traditional herbal medicine commonly used in Asia for symptomatic relief of and treating allergic rhinitis, headache, and sinusitis. Although several studies have reported the effects of FM on store-operated calcium entry (SOCE) via the ORAI1 channel, which is essential during intracellular calcium signaling cascade generation for T cell activation and mast cell degranulation, the effects of its isolated constituents on SOCE remain unidentified. Therefore, we investigated which of the five major constituents of 30% ethanoic FM (vanillic acid, tiliroside, eudesmin, magnolin, and fargesin) inhibit SOCE and their physiological effects on immune cells. The conventional whole-cell patch clamp results showed that fargesin, magnolin, and eudesmin significantly inhibited SOCE and thus human primary CD4+ T lymphocyte proliferation, as well as allergen-induced histamine release in mast cells. Among them, fargesin demonstrated the most potent inhibitory effects not only on ORAI1 (IC50 = 12.46 ± 1.300 µM) but also on T-cell proliferation (by 87.74% ± 1.835%) and mast cell degranulation (by 20.11% ± 5.366%) at 100 µM. Our findings suggest that fargesin can be a promising candidate for the development of therapeutic drugs to treat allergic diseases.

Anoctamin 6/TMEM16F (ANO6) is a dual-function protein with Ca2+-activated ion channel and Ca2+-activated phospholipid scramblase activities, requiring a high intracellular Ca2+ concentration (e.g., half-maximal effective Ca2+ concentration [EC50] of [Ca2+]i > 10 μM), and strong and sustained depolarization above 0 mV. Structural comparison with Anoctamin 1/TMEM16A (ANO1), a canonical Ca2+- activated chloride channel exhibiting higher Ca2+ sensitivity (EC50 of 1 μM) than ANO6, suggested that a homologous Ca2+-transferring site in the N-terminal domain (Nt) might be responsible for the differential Ca2+ sensitivity and kinetics of activation between ANO6 and ANO1. To elucidate the role of the putative Ca2+-transferring reservoir in the Nt (Nt-CaRes), we constructed an ANO6-1-6 chimera in which Nt-CaRes was replaced with the corresponding domain of ANO1. ANO6- 1-6 showed higher sensitivity to Ca2+ than ANO6. However, neither the speed of activation nor the voltage-dependence differed between ANO6 and ANO6-1-6. Molecular dynamics simulation revealed a reduced Ca2+ interaction with Nt- CaRes in ANO6 than ANO6-1-6. Moreover, mutations on potentially Ca2+-interacting acidic amino acids in ANO6 Nt- CaRes resulted in reduced Ca2+ sensitivity, implying direct interactions of Ca2+ with these residues. Based on these results, we cautiously suggest that the net charge of Nt- CaRes is responsible for the difference in Ca2+ sensitivity between ANO1 and ANO6.

Collecting and monitoring data in low-latency from numerous sensing devices is one of the key foundations in networked cyber-physical applications such as industrial process control, intelligent traffic control, and networked robots. As the delay in data updates can degrade the quality of networked monitoring, it is desirable to continuously maintain the optimal setting on sensing devices in terms of transmission rates and bandwidth allocation, taking into account application requirements as well as time-varying conditions of underlying network environments. In this paper, we adapt deep reinforcement learning (RL) to achieve a bandwidth allocation policy in networked monitoring. We present a transferable RL model Repot in which a policy trained in an easy-to-learn network environment can be readily adjusted in various target network environments. Specifically, we employ flow embedding and action shaping schemes in Repot that enable the systematic adaptation of a bandwidth allocation policy to the conditions of a target environment. Through experiments with the NS-3 network simulator, we show that Repot achieves stable and high monitoring performance across different network conditions, e.g., outperforming other heuristics and learning-based solutions by 14.5~20.8% in quality-of-experience (QoE) for a target network environment. We also demonstrate the sample-efficient adaptation in Repot by exploiting only 6.25% of the sample amount required for model training from scratch. We present a case study with the SUMO mobility simulator and verify the benefits of Repot in practical scenarios, showing performance gains over the others, e.g., 6.5% in urban-scale and 12.6% in suburb-scale.

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation. Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+]i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at -60 mV and ORAI1 current by 97% ± 1% at -120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.

Anaphylaxis is a severe allergic reaction that is potentially life-threatening, but post-traumatic stress symptoms (PTSS) in the caregivers of children with anaphylaxis have not been evaluated. This study aimed to investigate the psychological burden on mothers of children with recent anaphylaxis.A total of 188 children with recent anaphylaxis was recruited from 13 hospitals in Korea. Validated questionnaires, including the Korean versions of the Beck Anxiety Inventory (K-BAI), the Beck Depression Inventory (K-BDI), and the Impact of Event Scale Revised-Korean version (IES-R-K), were used to evaluate maternal anxiety, depression, and PTSS.The median ages of children and their mothers were 4 and 36 years, respectively. PTSS (IES-R-K ≥ 25) were identified in 56.9% of mothers, and 57.9% of them showed severe PTSS. The proportions of mothers who had anxiety (K-BAI ≥ 22) and depression (K-BDI ≥ 17) were 18.6% and 33.0%, respectively. Multivariable logistic regression analysis indicated that the patient's history of asthma (adjusted odds ratio [aOR], 5.46; 95% CI, 1.17-25.59) and the presence of central nervous symptoms (aOR, 3.27; 95% CI, 1.07-9.96) were associated with PTSS. Age of 2 or older (aOR, 2.87; 95% CI, 1.10-7.52) and eggs, milk, or wheat as the cause of anaphylaxis (aOR, 2.87; 95% CI, 1.10-7.52) increased the risk of severe PTSS.The rate of PTSS among mothers of children with recent anaphylaxis was high at 56.9%. Clinicians who care for pediatric anaphylaxis patients should be aware of the psychological burden on their caregivers.

Asthma exacerbation (AE) leads to social and economic costs and long-term adverse outcomes. We aimed to predict exacerbation-prone asthma (EPA) in children.The Korean childhood Asthma Study (KAS) is a prospective nationwide pediatric asthma cohort of children aged 5-15 years followed every 6 months. Patients with AE during the 6 months prior to all three visits, with AE prior to one or two visits, and without AE prior to any visit were defined as having EPA, exacerbation-intermittent asthma (EIA), and exacerbation-resistant asthma (ERA), respectively. Risk factors and prediction models of EPA were explored.Of the 497 patients who completed three visits, 42%, 18%, and 15% had exacerbations prior to visits 1, 2, and 3 and 5%, 47%, and 48% had EPA, EIA, and ERA, respectively. Univariate and multivariable logistic regression revealed forced expiratory volume in 1 s (FEV1) z-score, forced vital capacity (FVC) z-score, white blood cell (WBC) count, and asthma control test (ACT) score as relevant EPA risk factors. The EPA prediction model comprised FVC z-score, WBC count, ACT score, sex, and parental education level (area under the receiver operating characteristic curve [AUROC] 0.841 [95% confidence interval (CI): 0.728-0.954]).With appropriate management, AE decreases over time, but persistent AEs may occur. Apart from asthma control level, baseline lung function and WBC count predicted EPA.

Objective To compare short-term treatment outcomes at hospital discharge and hospital length of stay (LOS) in patients with spontaneous intracerebral hemorrhage (sICH) before and after introduction of resident physician work time limit (WTL). Methods We retrospectively reviewed consecutive patients treated for sICH at our institution between 2016 and 2019. Then we dichotomized these patients into two groups, pre-WTL and post-WTL. We analyzed demographic elements and clinical features, and hospital length of stay (LOS). We evaluated short-term outcome using modified Rankin scale score at hospital discharge and then divided it into "good" and "poor" outcome groups. We subsequently, compared short-term treatment outcome and hospital LOS between the pre-WTL and post-WTL groups. Results Out of 779 patients, 420 patients (53.9%) were included in the pre-WTL group, and 359 (46.1%) in post-WTL. The mortality rate in sICH patients was higher in the post-WTL group (pre-WTL; 13.6% vs. post-WTL; 17.3%), but there was no statistically significant difference in short-term outcome including mortality (p=0.332) between the groups. The LOS also, was not significantly different between the two groups (pre-WTL; 19.0 days vs. post-WTL; 20.2 days) (p=0.341). The initial Glasgow Coma Scale score, personal stroke history, and mean age were the only independent outcome predicting factors for patients with sICH. Conclusions Some neurosurgeons may expect poorer outcome for sICH after implementation of the WTL of the K-MHW for resident physician however, enforcement of the WTL did not significantly influence the short-term outcome and hospital LOS for sICH in our hospital. Further well-designed multi-institutional prospective studies on the effects of WTL in sICH patient outcome, are anticipated.

Rhinorrhea in allergic rhinitis (AR) is characterized by the secretion of electrolytes in the nasal discharge. The secretion of Cl– and HCO3– is mainly regulated by cystic fibrosis transmembrane conductance regulator (CFTR) or via the calcium-activated Cl– channel anoctamin-1 (ANO1) in nasal gland serous cells. Interleukin-4 (IL-4), which is crucial in the development of allergic inflammation, increases the expression and activity of ANO1 by stimulating histamine receptors. In this study, we investigated ANO1 as a potential therapeutic target for rhinorrhea in AR using an ANO1 inhibitor derived from a natural herb. Ethanolic extracts (30%) of Spirodela polyrhiza (SPEtOH) and its five major flavonoids constituents were prepared. To elucidate whether the activity of human ANO1 (hANO1) was modulated by SPEtOH and its chemical constituents, a patch clamp experiment was performed in hANO1-HEK293T cells. Luteolin, one of the major chemical constituents in SPEtOH, significantly inhibited hANO1 activity in hANO1-HEK293T cells. Further, SPEtOH and luteolin specifically inhibited the calcium-activated chloride current, but not CFTR current in human airway epithelial Calu-3 cells. Calu-3 cells were cultured to confluency on transwell inserts in the presence of IL-4 to measure the electrolyte transport by Ussing chamber. Luteolin also significantly inhibited the ATP-induced increase in electrolyte transport, which was increased in IL-4 sensitized Calu-3 cells. Our findings indicate that SPEtOH and luteolin may be suitable candidates for the prevention and treatment of allergic rhinitis. SPEtOH- and luteolin-mediated ANO1 regulation provides a basis for the development of novel approaches for the treatment of allergic rhinitis-induced rhinorrhea.

Gardenia jasminoides (GJ) is a widely used herbal medicine with antiinflammatory properties, but its effects on the ORAI1 channel, which is important in generating intracellular calcium signaling for T cell activation, remain unknown. In this study, we investigated whether 70% ethanolic GJ extract (GJEtOH) and its subsequent fractions inhibit ORAI1 and determined which constituents contributed to this effect. Whole-cell patch clamp analysis revealed that GJEtOH (64.7% ± 3.83% inhibition at 0.1 mg/ml) and all its fractions showed inhibitory effects on the ORAI1 channel. Among the GJ fractions, the hexane fraction (GJHEX, 66.8% ± 9.95% at 0.1 mg/ml) had the most potent inhibitory effects in hORAI1-hSTIM1 co-transfected HEK293T cells. Chemical constituent analysis revealed that the strong ORAI1 inhibitory effect of GJHEX was due to linoleic acid, and in other fractions, we found that genipin inhibited ORAI1. Genipin significantly inhibited IORAI1 and interleukin-2 production in CD3/ CD28-stimulated Jurkat T lymphocytes by 35.9% ± 3.02% and 54.7% ± 1.32% at 30 μM, respectively. Furthermore, the same genipin concentration inhibited the proliferation of human primary CD4+ T lymphocytes stimulated with CD3/CD28 antibodies by 54.9% ± 8.22%, as evaluated by carboxyfluorescein succinimidyl ester assay. Our findings suggest that genipin may be one of the active components of GJ responsible for T cell suppression, which is partially mediated by activation of the ORAI1 channel. This study helps us understand the mechanisms of GJ in the treatment of inflammatory diseases.

Objective We aimed to identify the relation between perioperative cerebrospinal fluid (CSF) drain through lumbar drainage (LD) and development of postoperative (POP) remote intracerebral hemorrhage (rICH) in craniotomy to treat ruptured intracranial aneurysms. Methods We retrospectively reviewed consecutive patients who underwent craniotomy for ruptured cerebral aneurysms at the authors’ institution between 1998 and 2004. We subsequently compared the incidence and characteristics of POP rICH between the patients who had a perioperative LD and those who did not. All statistical analyses were conducted using the software package SPSS 19.0 (SPSS Inc., Chicago, IL, USA). A p value of

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children.Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children.Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma.Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed.Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

Objective : Deep learning is a machine learning approach based on artificial neural network training, and object detection algorithm using deep learning is used as the most powerful tool in image analysis. We analyzed and evaluated the diagnostic performance of a deep learning algorithm to identify skull fractures in plain radiographic images and investigated its clinical applicability.Methods : A total of 2026 plain radiographic images of the skull (fracture, 991; normal, 1035) were obtained from 741 patients. The RetinaNet architecture was used as a deep learning model. Precision, recall, and average precision were measured to evaluate the deep learning algorithm’s diagnostic performance.Results : In ResNet-152, the average precision for intersection over union (IOU) 0.1, 0.3, and 0.5, were 0.7240, 0.6698, and 0.3687, respectively. When the intersection over union (IOU) and confidence threshold were 0.1, the precision was 0.7292, and the recall was 0.7650. When the IOU threshold was 0.1, and the confidence threshold was 0.6, the true and false rates were 82.9% and 17.1%, respectively. There were significant differences in the true/false and false-positive/false-negative ratios between the anteriorposterior, towne, and both lateral views (p=0.032 and p=0.003). Objects detected in false positives had vascular grooves and suture lines. In false negatives, the detection performance of the diastatic fractures, fractures crossing the suture line, and fractures around the vascular grooves and orbit was poor.Conclusion : The object detection algorithm applied with deep learning is expected to be a valuable tool in diagnosing skull fractures.

Huntington's disease (HD) is an inherited neurodegenerative disorder with adult-onset clinical symptoms, but the mechanism by which aging drives the onset of neurodegeneration in patients with HD remains unclear. In this study we examined striatal medium spiny neurons (MSNs) directly reprogrammed from fibroblasts of patients with HD to model the age-dependent onset of pathology. We found that pronounced neuronal death occurred selectively in reprogrammed MSNs from symptomatic patients with HD (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and control MSNs from age-matched healthy individuals. We observed age-associated alterations in chromatin accessibility between HD-MSNs and pre-HD-MSNs and identified miR-29b-3p, whose age-associated upregulation promotes HD-MSN degeneration by impairing autophagic function through human-specific targeting of the STAT3 3' untranslated region. Reducing miR-29b-3p or chemically promoting autophagy increased the resilience of HD-MSNs against neurodegeneration. Our results demonstrate miRNA upregulation with aging in HD as a detrimental process driving MSN degeneration and potential approaches for enhancing autophagy and resilience of HD-MSNs.

KELCH-ECH-associated protein 1 (KEAP1) is an adaptor protein of Cullin 3 (CUL3) E3 ubiquitin ligase that targets a redox sensitive transcription factor, NF-E2-related factor 2 (NRF2). BRCA1-associated protein 1 (BAP1) is a tumor suppressor and deubiquitinase whose mutations increase the risk of several types of familial cancers. In the present study, we have identified that BAP1 deubiquitinates KEAP1 by binding to the BTB domain. Lentiviral transduction of BAP1 decreased the expression of NRF2 target genes, suppressed the migration and invasion, and sensitized cisplatin-induced apoptosis in human lung adenocarcinoma (LUAD) A549 cells. Examination of the lung tissues in KrasG12D/+ mice demonstrated that the level of Bap1 and Keap1 mRNAs progressively decreases during lung tumor progression, and it is correlated with NRF2 activation and the inhibition of oxidative stress. Supporting this observation, lentiviral transduction of BAP1 decreased the growth of A549 xenografts in athymic nude mice. Transcriptome analysis of human lung tissues showed that the levels of Bap1 mRNA are significantly higher in normal samples than LUAD samples. Moreover, the expression of Bap1 mRNA is associated with a better survival of LUAD patients. Together, our study demonstrates that KEAP1 deubiquitination by BAP1 is novel tumor suppressive mechanism of LUAD.

Inappropriate adolescent health behavior can be influenced by the negative impact of physical and mental health promotion. Obesity influences subjective improper weight perception. This study aimed to verify Korean normal-weight adolescents’ subjective experience of weight control, mental health, physical activity, and subjective status based on their body mass index (BMI). As a result, efforts to control weight appeared less in normal-weight boys. Thin girls were less likely to carry out 60 min of physical activity 7 or 5 days per a week. Obese boys were less likely to carry out vigorous physical activity 3 days per a week. Normal- weight girls were less likely to practice muscular strength training 3 days per a week. Thin boys and thing girls were less likely to practice regular physical activity, and less likely to practice at the rate stipulated in the sedentary behavior guideline. In conclusion, boys and girls with inappropriate weight perception reported feeling stressed and depressed, and reported subjective sleep fulfillment, perceived subjective happiness, and perceived subjective health.

Purpose: This study was conducted to investigate the usefulness of a polyester urethane dural substitute (Neuro-Patch®, B. Braun, Boulogne, France) as an anti-adhesion agent in subsequent cranioplasty by analyzing the use of Neuro-Patch® during decompressive craniectomy in traumatic brain injury patients. Methods: We retrospectively analyzed patients with traumatic brain injury who underwent decompressive craniectomy followed by cranioplasty from January 2015 to December 2018. Patients were analyzed according to whether they received treatment with Neuro-Patch® or not (Neuro-Patch® group, n=71; control group, n=55). Patients’ baseline characteristics were analyzed to identify factors that could affect cranioplasty results, including age, sex, hypertension, diabetes mellitus, use of antiplatelet agents or anticoagulant medication, the interval between craniectomy and cranioplasty, and the type of bone used in cranioplasty. The cranioplasty results were analyzed according to the following factors: operation time, blood loss, postoperative hospitalization period, surgical site infection, and revision surgery due to extra-axial hematoma. Results: No significant difference was found between the two groups regarding patients’ baseline characteristics. For the cranioplasty procedures, the operation time (155 vs. 190 minutes, p=0.003), intraoperative blood loss (350 vs. 450 mL, p=0.012), and number of surgical site infections (4 vs. 11 cases, p=0.024) were significantly lower in the Neuro-Patch® group than in the control group. Conclusions: The use of Neuro-Patch® was associated with a shorter operation time, less blood loss, and a lower number of surgical site infections in subsequent cranioplasties. These results may provide a rationale for prospective studies investigating the efficacy of Neuro-Patch®.

The C1-C2 angle has been shown to correlate with subaxial alignment under various conditions. The aim of this study was to evaluate the correlation between the C1-C2 fixation angle and subaxial sagittal alignment as well as the impact of the sagittal vertical axis (SVA) on functional outcomes in traumatic atlantoaxial (A-A) instabilities. The data of 36 patients who underwent posterior C1-C2 fixation for traumatic A-A instability between December 2005 and September 2015 were retrospectively reviewed. Radiographic parameters, including the C1-C2 angle, occipitocervical angle, C2-C7 angle, and C2-C7 SVA, were measured before surgery and at 1-year follow-up. Clinical outcomes were measured using the visual analogue scale (VAS) and Neck Disability Index (NDI). The preoperative and postoperative relationships between parameters were analyzed. In preoperative and postoperative radiographs, the C1-C2 angle correlated with the C2-C7 angle (r = −0.347, p = 0.038, and r = −0.339, p = 0.043, respectively) and the C2-C7 SVA (r = 0.648, p The postoperative C2-C7 SVA was affected by the preoperative C2-C7 SVA and the postoperative C1-C2 angle and showed significant positive correlation with postoperative NDI. The C1-C2 fixation angle and the preoperative C2-C7 SVA should be carefully considered to avoid postoperative sagittal imbalance.

Background:The objective of this study was to illustrate a novel technique for lifting of the aging upper lip with nasal tip plasty in Asians. With this procedure, a shortening of the philtrum, an increase of the vermilion, and a natural and nicer mouth can be obtained, with increase of the tip of t

This study examined adult health related factors of the Korea National Health and Nutrition Examination Survey in 2017. Metabolic syndrome prevalence and perceived stress with physical activity and sedentary time were analyzed. Subjects are 4,459 over 40 year adults. The data were analyzed odds ratio (OR) and confidence interval by logistic regression analysis. First, male, moderate intensity occupational physical activity (OPA) and high intensity leisure time physical activity (LTPA) (OR, 1.337) between metabolic syndrome prevalence tended to increase. Vigorous intensity OPA (OR, 0.847), transport physical activity (TPA) (OR, 0.968), and moderate intensity LTPA (OR, 0.927) between metabolic syndrome prevalence tends to decrease. Female, vigorous intensity OPA (OR, 1.238) between metabolic syndrome prevalence tended to increase. Moderate intensity OPA (OR, 0.878), TPA (OR, 0.875), vigorous intensity LTPA (OR, 0.691), and moderate intensity LTPA (OR, 0.479) between metabolic syndrome prevalence tended to decrease. Male, vigorous intensity OPA (OR, 1.584), moderate intensity OPA (OR, 1.752), and vigorous intensity LTPA (OR, 1.316) between perceived stress tended to increase. TPA (OR, 0.753) and moderate intensity LTPA (OR, 0.983) between perceived stress tended to decrease. Female, moderate intensity OPA (OR, 2.331) between perceived stress tended to increase. Vigorous intensity OPA (OR, 0.732), TPA (OR, 0.836), vigorous intensity LTPA (OR, 0.990), and moderate intensity LTPA (OR, 0.837) between perceived stress tended to decrease.

Microscopic anterior cervical foraminotomy (MACF) is a surgical technique for unilateral cervical radiculopathy that preserves segmental motion and avoids adjacent segmental degeneration, but little is known of its long-term outcomes.A retrospective minimum 10-year follow-up study was conducted on patients treated by 1 surgeon. Clinical outcomes were assessed using a visual analog scale of neck and arm pain, Neck Disability Index, and Odom criteria. Surgical outcomes were assessed using additional procedure rates. Radiologic outcomes were estimated by measuring disc heights, segmental angles, and range of motion at the surgical level and adjacent segments, and so on.Of the 94 patients who underwent MACF between January 2000 and December 2004 by 1 surgeon, 69 were enrolled in this study. Median follow-up period was 11.9 years (range, 10.0-14.5 years). Visual analog scales for neck or arm pain and Neck Disability Index improved significantly during follow-up period (P0.001). Also, according to the Odom criteria, an excellent or good outcome was achieved in 62 patients (89.9%) at final follow-up. An additional procedure was performed in 10 patients (14.5%) for symptom recurrence during the follow-up period. The only risk factor found to be related to the need for an additional procedure was a small preoperative range of motion at the surgical level (P = 0.018). Although mean disc height at the surgical level decreased significantly (from 6.23 ± 1.10 to 5.17 ± 1.12 mm; P = 0.004), adjacent discs were not significantly affected.Although some radiologic results have shortcomings, the results of this study suggest that MACF has favorable long-term outcomes.

Intracellular calcium signaling is crucial for type 2 helper T cell and mast cell activation, which is essential for allergic inflammation. It is initiated by antigen-mediated receptor stimulation that triggers store-operated calcium entry (SOCE) via ORAI1 calcium channel. Flos Magnoliae (FM) is widely used to treat allergic diseases such as allergic rhinitis and asthma. Although many studies have reported that FM regulates intracellular calcium signaling, research on the exact type of calcium channel modulated by FM is scarce. Therefore, we hypothesized that the anti-allergic effects of FM might result from ORAI1 inhibition in T cells. We investigated whether a 70% ethanolic extract of FM (FM[Formula: see text] and its constituents inhibit ORAI1 channel activity and subsequent T cell activation. We performed conventional whole-cell patch clamp studies in hSTIM1 and hORAI1-overexpressing HEK293T cells (HEK[Formula: see text]. Intracellular calcium concentration was determined using Fura-2 dye and cytokine production measurement in Jurkat T lymphocytes. FMEtOH(0.03 mg/mL) and its fractions, especially hexane fraction (FMHex, 0.01 mg/mL), significantly inhibited SOCE and IL-2 cytokine production in Jurkat T lymphocytes. GC/MS analysis showed linoleic acid (LA) as the major component of FMHex. FMHexat 0.01 mg/mL (equivalent to 10 [Formula: see text]M LA) inhibited not only SOCE but also IL-2 production, as well as CD3/CD28 receptor co-stimulation induced calcium signaling in Jurkat T lymphocytes. FMEtOHand LA suppressed CD4[Formula: see text] T lymphocyte activation, at least in part, by inhibiting [Formula: see text]. Thus, [Formula: see text] inhibition may be a potential strategy to inhibit immune responses in inflammation.

Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive.Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively.Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR.Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 μM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 μM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR.Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002–2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P

Background As one of the main components of mangosteen (Garcinia mangostana), a tropical fruit, α-mangostin has been reported to have numerous pharmacological benefits such as anti-cancer, anti-inflammatory, and anti-allergic effects through various mechanisms of action. The effects of α-mangostin on intracellular signaling proteins is well studied, but the effects of α-mangostin on ion channels and its physiological effects in immune cells are unknown. Generation of intracellular calcium signaling is a fundamental step for T cell receptor stimulation. This signaling is mediated not only by the ORAI1 calcium channel, but also by potassium ion channels, which provide the electrical driving forces for generating sufficient calcium ion influx. This study investigated whether α-mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (Kv1.3 and KCa3.1), which are normally expressed in human T cells. Methods This study analyzed the inhibitory effect of α-mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells. Results α-mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC50 value was 1.27 ± 1.144 µM. Kv1.3 was suppressed by 41.38 ± 6.191% at 3 µM, and KCa3.1 was suppressed by 51.16 ± 5.385% at 3 µM. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and α-mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of α-mangostin, the main component of mangosteen, through the regulation of calcium signals.

Alisol B 23‑acetate (AB23A) is a natural triterpenoid isolated from Alismatis rhizoma, which exhibits a number of pharmacological activities. In the present study, AB23A‑induced anticancer efficacy was examined in AGS gastric cancer cells. Cell viability assay, cell cycle analysis, caspase activity assay, western blotting and reactive oxygen species (ROS) assay were used to investigate the anticancer effects of AB23A on AGS cells. AB23A reduced the viability of AGS cells, increased the sub‑G1 cell fraction and depolarized the mitochondrial membrane. Notably, AB23A‑induced cell death was associated with downregulation of the B‑cell lymphoma 2 and survivin proteins, and upregulation of the Bax protein. In addition, AB23A increased caspase‑3 and ‑9 activities, and regulated the activation of mitogen‑activated protein kinases (MAPK). Moreover, AB23A increased the production of reactive oxygen species. These results suggested that AB23A may induce apoptosis through cell cycle arrest and the mitochondrial pathway, accompanied by the caspase and MAPK signaling cascades. In conclusion, AB23A may have potential as a novel anticancer drug for the treatment of gastric cancer.

To compare lateral (direct [DLIF] or oblique [OLIF]) and posterior (posterior [PLIF] or transforaminal [TLIF]) lumbar interbody fusion results in patients with the same indication of discogenic low back pain.We enrolled 46 patients who underwent single-level DLIF/OLIF or PLIF/TLIF with at least 1 year of follow-up. Patients were divided into two groups: a lateral group (n=24) who underwent DLIF/OLIF and a posterior group (n=22) who underwent PLIF/TLIF. Clinical, surgical, and radiological outcomes were retrospectively evaluated.Baseline factors, including demographic data, preoperative symptoms, and preoperative radiological findings, were not significantly different between the two groups. In addition, the clinical and radiological outcomes at 1-year post-surgery did not differ between the two groups. However, the DLIF/OLIF procedure conferred significant advantages as follows: favorable postoperative low back pain and patient satisfaction at 1-week and 1-month post-surgery; shorter operation time (mean 173.33 ± 11.54 versus 208.64 ± 17.48 min, p0.001); less blood loss during surgery (mean 127.50 ± 41.36 versus 372.73 ± 123.21 mL, p0.001); and greater restoration of calibrated disc height at 1-year post-surgery (mean 5.80 ± 1.44 versus 0.50 ± 1.22, p=0.008). There was no statistically significant difference in the incidence of complications between the two groups. However, complications tended to be more frequent in the lateral group; 7 (29.2%) patients in the lateral group and 3 patients (13.6%) in the posterior group.Our findings suggest that the lateral group achieved better perioperative outcomes and disc height restoration than the posterior group, although there was no significant difference in the 1-year clinical outcomes.

MicroRNAs (miRNAs), miR-9/9*, and miR-124 (miR-9/9*-124) display fate-reprogramming activities when ectopically expressed in human fibroblasts by erasing the fibroblast identity and evoking a pan-neuronal state. In contrast to induced pluripotent stem cell-derived neurons, miRNA-induced neurons (miNs) retain the biological age of the starting fibroblasts through direct fate conversion and thus provide a human neuron-based platform to study cellular properties inherent in aged neurons and model adult-onset neurodegenerative disorders using patient-derived cells. Furthermore, expression of neuronal subtype-specific transcription factors in conjunction with miR-9/9*-124 guides the miNs to distinct neuronal fates, a feature critical for modeling disorders that affect specific neuronal subtypes. Here, we describe the miR-9/9*-124-based neuronal reprogramming protocols for the generation of several disease-relevant neuronal subtypes: striatal medium spiny neurons, cortical neurons, and spinal cord motor neurons.

MicroRNAs (miRNAs), miR-9/9

Skin photoaging occurs due to chronic exposure to solar ultraviolet radiation (UV), the main factor contributing to extrinsic skin aging. Clinical signs of photoaging include the formation of deep, coarse skin wrinkles and hyperpigmentation. Although melanogenesis and skin wrinkling occur in different skin cells and have different underlying mechanisms, their initiation involves intracellular calcium signaling via calcium ion channels. The ORAI1 channel initiates melanogenesis in melanocytes, and the TRPV1 channel initiates MMP-1 production in keratinocytes in response to UV stimulation. We aimed to develop a drug that may simultaneously inhibit ORAI1 and TRPV1 activity to help prevent photoaging. We synthesized nootkatol, a chemical derivative of valencene. TRPV1 and ORAI1 activities were measured using the whole-cell patch-clamp technique. Intracellular calcium concentration [Ca2+]i was measured using calcium-sensitive fluorescent dye (Fura-2 AM). UV-induced melanin formation and MMP-1 production were quantified in B16F10 melanoma cells and HaCaT cells, respectively. Our results indicate that nootkatol (90 μM) reduced TRPV1 current by 94% ± 2% at –60 mV and ORAI1 current by 97% ± 1% at –120 mV. Intracellular calcium signaling was significantly inhibited by nootkatol in response to ORAI1 activation in human primary melanocytes (51.6% ± 0.98% at 100 μM). Additionally, UV-induced melanin synthesis was reduced by 76.38% ± 5.90% in B16F10 melanoma cells, and UV-induced MMP-1 production was reduced by 59.33% ± 1.49% in HaCaT cells. In conclusion, nootkatol inhibits both TRPV1 and ORAI1 to prevent photoaging, and targeting ion channels may be a promising strategy for preventing photoaging.