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.

Objectives: ：The authors examined the association of sleep quality and metabolic syndrome (MetS) in schizophrenic patients using actigraphy. Methods: ：A total of 101 schizophrenic patients were included in this study. Fifty-four (53.4%) patients met the criteria of MetS. Self-assessment of subjective sleep quality, daytime sleepiness, physical activities were measured using Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and International Physical Activity Questionnaire (IPAQ), respectively. Objective sleep quality and physical activity were measured by Actigraph (ActiGraph wGT3X-BT). Results: ：Total time in bed (TIB) (p=0.032), sleep latency (SL) (p=0.001), wake after sleep onset (WASO) (p<0.001) and average awakening (p=0.015) were significantly longer in patients with MetS than those of non-MetS. Results of multiple logistic regression showed that long sleep latency (OR 7.876, 95% CI 1.519, p=0.014) and low sleep efficiency (OR 9.902, 95% CI 1.111, p=0.040) were high risk factors for MetS. Conclusion ：This was the first study to find the correlations of sleep quality and MetS in schizophrenic patients by objective sleep measurements. Although long sleep latency and low sleep efficiency were associated with MetS in patients with schizophrenia, more extensive and complicated designed studies may be needed to the association of MetS and sleep problems in schizophrenic patients.

Objectives: ：The authors examined the association of sleep quality and metabolic syndrome (MetS) in schizophrenic patients using actigraphy. Methods: ：A total of 101 schizophrenic patients were included in this study. Fifty-four (53.4%) patients met the criteria of MetS. Self-assessment of subjective sleep quality, daytime sleepiness, physical activities were measured using Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS) and International Physical Activity Questionnaire (IPAQ), respectively. Objective sleep quality and physical activity were measured by Actigraph (ActiGraph wGT3X-BT). Results: ：Total time in bed (TIB) (p=0.032), sleep latency (SL) (p=0.001), wake after sleep onset (WASO) (p<0.001) and average awakening (p=0.015) were significantly longer in patients with MetS than those of non-MetS. Results of multiple logistic regression showed that long sleep latency (OR 7.876, 95% CI 1.519, p=0.014) and low sleep efficiency (OR 9.902, 95% CI 1.111, p=0.040) were high risk factors for MetS. Conclusion ：This was the first study to find the correlations of sleep quality and MetS in schizophrenic patients by objective sleep measurements. Although long sleep latency and low sleep efficiency were associated with MetS in patients with schizophrenia, more extensive and complicated designed studies may be needed to the association of MetS and sleep problems in schizophrenic patients.

Objectives: Sleep disturbance in the elderly is associated with cognitive decline. Sleep quality is known to deteriorate with age, and prospective studies seldom have examined the relationship between sleep quality and cognitive function. This study investigates the relationship between early sleep quality and cognitive function based on six-year follow-up data of community individuals older than 60 years. Methods: The participants included 622 community elderly people older than 60 years from Jinju-Si. The final analysis comprised 322 elderly people. Pittsburgh sleep quality index (PSQI) and the Korean version of Consortium to Establish a Registry for Alzheimer’s Disease (CERAD-K) were used to assess early sleep quality and cognitive function after six years. Multiple linear regression analysis was performed to investigate the association between early sleep quality and cognitive function in the elderly. Results: Early sleep quality (PSQI) was significantly associated with the results of the digit span test, clock drawing test (clox 1), and word recall test after six years. Sleep quality (PSQI) decreased significantly after six years, and lower quality of sleep (PSQI) score was associated with higher digit span test score (β = -0.167, p = 0.026) and higher clock drawing test score (β = -0.157, p = 0.031). Lower quality of sleep (PSQI) score was associated with higher word recall test (β = -0.140, p = 0.039). Conclusion The digit span test, word recall test, and clock drawing task (CLOX 1) shown to be significantly associated to sleep quality can be performed fast and easily in clinical practice. It is important to assess early cognitive function in the elderly with poor sleep quality, and further studies could suggest that these tests may be useful screening tests for early dementia in elderly with poor sleep quality.

This study was a multicenter, parallel-group, double-blind, double-dummy, randomized,noninferiority trial to evaluate the efficacy and safety of γ-linolenic acid(GLA) relative to α-lipoic acid (ALA) over a 12-week treatment period in type 2diabetes mellitus (T2DM) patients with painful diabetic peripheral neuropathy (DPN).

BACKGROUND/AIMS: Lymphocytic thyroiditis as cytology diagnosis from fine needle aspiration (FNA) is frequently detected in patients with thyroid nodules. However, the clinical outcome for upcoming hypothyroid events has been rarely clarified in euthyroid patients. METHODS: We retrospectively reviewed the data of patient who had lymphocytic thyroitidis on FNA cytology of thyroid nodule from January 2005 to December 2010 at a tertiary referral hospital. In total, 109 patients with follow-up thyroid function tests (TFT) were enrolled. Final outcomes included overt and subclinical hypothyroidism with thyroid stimulating hormone (TSH) levels ≥ 10 mIU/L. Potential parameters predicting clinical hypothyroidism were analyzed by multivariate analysis. RESULTS: Over the mean follow-up duration of 51.6 months, 14 out of 109 patients (12.8%) developed clinical hypothyroidism that required thyroid hormone replacement. The median onset time to hypothyroidism was 16 months (range, 3 to 88) and ≥ 60% of patients experienced clinical hypothyroidism within 1 year. By multivariate analysis, background thyroiditis (relative risk [RR], 9.78; p = 0.004), thyroid peroxidase antibody positivity (RR, 9.90; p = 0.003), nodule size (RR, 1.24; p < 0.001), and initial TSH (RR, 1.47; p = 0.009) were the independent risk factors for predicting hypothyroidism in euthyroid patients. CONCLUSIONS Hypothyroidism frequently occurs during the follow-up in euthyroid patients with thyroid nodules which show lymphocytic thyroiditis on FNA cytology. Close surveillance and regular TFT are needed in high-risk patients for upcoming clinical hypothyroidism.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.