Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Previous studies have shown that testosterone activates the GPRC6A-Duox1 axis, resulting in the production of H 2O 2 which leads to the apoptosis of keratinocytes and ultimately hair loss. Here, we elucidated a molecular mechanism by which the non-genomic action of testosterone regulates cellular redox status in androgenetic alopecia (AGA). Building upon this molecular understanding, we conducted a high-throughput screening assay of Nox inhibitors from a natural compounds library. This screening identified diterpenoid compounds, specifically Tanshinone I, Tanshinone IIA, Tanshinone IIB, and Cryptotanshinone, derived from Salviae Miltiorrhizae Radix. The IC50 values for Nox isozymes were found to be 2.6-12.9 μM for Tanshinone I, 1.9-7.2 μM for Tanshinone IIA, 5.2-11.9 μM for Tanshinone IIB, and 2.1-7.9 μM for Cryptotanshinone. Furthermore, 3D computational docking analysis confirmed the structural basis by which Tanshinone compounds inhibit Nox activity. These compounds were observed to substitute for NADPH at the π-π bond site between NADPH and FAD, leading to the suppression of Nox activity. Notably, Tanshinone I and Tanshinone IIA effectively inhibited Nox activity heightened by testosterone, consequently reducing the production of intracellular H2O2 and preventing cell apoptosis. In an animal study involving the application of testosterone to the back skin of 8-week-old C57BL/6J mice to inhibit hair growth, subsequent treatment with Tanshinone I or Tanshinone IIA alongside testosterone resulted in a substantial increase in hair follicle length compared to testosterone treatment alone. These findings underscore the potential efficacy of Tanshinone I and Tanshinone IIA as therapeutic agents for AGA by inhibiting Nox activity.

Background and Objectives: This study aimed to analyze the outcomes of Fontan surgery in the Republic of Korea, as there were only a few studies from Asian countries. Methods: The medical records of 1,732 patients who underwent Fontan surgery in 10 cardiac centers were reviewed. Results: Among them, 1,040 (58.8%) were men. The mean age at Fontan surgery was 4.3±4.2 years, and 395 (22.8%) patients presented with heterotaxy syndrome. According to the types of Fontan surgery, 157 patients underwent atriopulmonary (AP) type; 303, lateral tunnel (LT) type; and 1,266, extracardiac conduit (ECC) type. The overall survival rates were 91.7%, 87.1%, and 74.4% at 10, 20, and 30 years, respectively. The risk factors of early mortality were male, heterotaxy syndrome, AP-type Fontan surgery, high mean pulmonary artery pressure (mPAP) in pre-Fontan cardiac catheterization, and early Fontan surgery year. The risk factors of late mortality were heterotaxy syndrome, genetic disorder, significant atrioventricular valve regurgitation (AVVR) before Fontan surgery, high mPAP in pre-Fontan cardiac catheterization, and no fenestration. Conclusions In Asian population with a high incidence of heterotaxy syndrome, the heterotaxy syndrome was identified as the poor prognostic factors for Fontan surgery. The preoperative low mPAP and less AVVR are associated with better early and long-term outcomes of Fontan surgery.

Purpose: The aim of this study was to investigate the occurrence of dry eye syndrome (DES) in children under 18 years old before and during the COVID-19 pandemic using nationwide population-based cohort analysis. Methods: This study utilized the database provided by the Korea Disease Control and Prevention Agency and the Korean National Health Insurance Service. We used claims-based data for patients diagnosed with COVID-19 between October 8, 2020, and December 31, 2021, and those without a diagnosis of COVID-19. DES cases were defined as having at least one diagnosis of H0411 or H1621 based on the International Classification of Diseases, 10th Revision codes. The primary outcome was the evaluation of the hazard ratio for DES between the COVID-19 season and the non–COVID-19 season. Results: A total of 198,486 individuals from the COVID-19 season cohort and 211,828 individuals from the non–COVID-19 season cohort were included in the study. There were no differences in characteristics between the COVID-19 season cohort and the non–COVID-19 season cohort (all standardized mean difference, <0.1). The cumulative incidence of DES during the COVID-19 season was significantly higher than that during the non–COVID-19 season. The COVID-19 season DES incidence rate was 6,419.64 per 100,000 person-years and non–COVID-19 season DES incidence rate was 5,804.88 per 100,000 person-years. In addition, children aged 13 to 18 years, female sex, those living in metropolitan areas, and those with diabetes mellitus had a higher risk of DES. Conclusions The prevalence of diagnosed DES in children increased during the COVID-19 pandemic compared to previous years. Children aged 13 to 18 years, female sex, those living in metropolitan areas, and those with diabetes mellitus had a higher risk of DES. Further studies are needed to directly analyze the potential factors associated with the increased prevalence of DES.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.