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.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

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.

Purpose: Feeding intolerance (FI) is a prevalent clinically sequential condition in preterm infants. To clarify its relationship with the gut microbiota, we compared microbial diversity and taxonomic composition at 2 and 4 weeks of age in infants born before 32 weeks of gestation. Methods: Between August 2021 and December 2022, we prospectively enrolled infants who delivered before 32 weeks of gestation and were admitted to the neonatal intensive care unit at CHA Bundang Medical Center. Forty-four preterm infants were grouped based on the presence (n=16) or absence (n=28) of FI. Fecal samples were obtained at 2 and 4 weeks after birth and analyzed using 16S rRNA gene sequencing to determine microbial profiles. Results: Microbial α-diversity and β-diversity did not differ significantly between groups at either time point. At the genus level, Staphylococcus was significantly more abundant in the FI group than in the feeding tolerance group at 2 weeks postnatal age (P=0.016). Linear discriminant analysis effect size revealed that Staphylococcus, Pseudomonas, and Escherichia were markedly enriched in the FI group at all time points. Conclusion Early colonization by potentially pathogenic genera, particularly Staphylococcus, may precede the development of FI in preterm infants. These findings highlight the potential microbial composition associated with FI and may provide preliminary insights for future microbiome-targeted research in neonatal care.

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: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

The LEPR (leptin receptor) genotype is associated with obesity. Gut microbiome composition differs between obese and nonobese adults. However, the impact of LEPR genotype on gut microbiome composition in humans has not yet been studied. In this study, the association between LEPR single nucleotide polymorphism (rs1173100, rs1137101, and rs790419) and the gut microbiome composition in 65 non-obese Korean adults was investigated. Leptin, triglyceride, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol levels were also measured in all participants. Mean ± SD (standard deviation) of age, body mass index, and leptin hormone levels of participants was 35.2 ± 8.1 years, 21.4 ± 1.8 kg/m 2 , and 7989.1 ± 6687.4 pg/mL, respectively. Gut microbiome analysis was performed at the phylum level by 16S rRNA sequencing. Among the 11 phyla detected, only one showed significantly different relative abundances between LEPR genotypes. The relative abundance of Candidatus Saccharibacteria was higher in the G/A genotype group than in the G/G genotype group for the rs1137101 single nucleotide polymorphism (p=0.0322). Participant characteristics, including body mass index, leptin levels, and other lipid levels, were similar between the rs1137101 G/G and G/A genotypes. In addition, the relative abundances of Fusobacteria and Tenericutes showed significant positive relationship with plasma leptin concentrations (p=0.0036 and p=0.0000, respectively). In conclusion, LEPR genotype and gut microbiome may be associated even in normal-weight Korean adults. However, further studies with a greater number of obese adults are needed to confirm whether LEPR genotype is related to gut microbiome composition.