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: We assessed human papillomavirus (HPV) genotype-based risk stratification and the efficacy of cytology testing for cervical cancer screening in patients with atypical squamous cells of undetermined significance (ASCUS)/low-grade squamous intraepithelial lesion (LSIL). Materials and Methods: Between 2010 and 2021, we monitored 1,273 HPV-positive women with ASCUS/LSIL every 6 months for up to 60 months. HPV infections were categorized as persistent (HPV positivity consistently observed post-enrollment), negative (HPV negativity consistently observed post-enrollment), or non-persistent (neither consistently positive nor negative). HPV genotypes were grouped into high-risk (Hr) groups 1 (types 16, 18, 31, 33, 45, 52, and 58) and 2 (types 35, 39, 51, 56, 59, 66, and 68) and a low-risk group. Hr1 was subdivided into types (a) 16 and 18; (b) 31, 33, and 45; and (c) 52 and 58. Cox regression and machine learning (ML) algorithms were used to analyze progression rates. Results: Among 1,273 participants, 17.6% with persistent HPV infections experienced disease progression versus no progression in the HPV-negative group (p < 0.001). Cox analysis revealed the highest hazard ratios (HRs) for Hr1-a (11.6, p < 0.001), followed by Hr1-b (9.26, p < 0.001) and Hr1-c (7.21, p < 0.001). HRs peaked at 12-24 months, with Hr1-a maintaining significance at 24-36 months (10.7, p=0.034). ML analysis identified the final cytology change pattern as the most significant factor, with 14-15 months the optimal time for detecting progression from the first examination. Conclusion In ASCUS/LSIL cases, follow-up strategies should be based on HPV risk types. Annual follow-up was the most effective monitoring for detecting progression/regression.

Microglial activation during aging is associated with neuroinflammation and cognitive impairment. Galectin-3 plays a crucial role in microglial activation and phagocytosis. However, the role of galectin-3 in the aged brain is not completely understood. In the present study, we investigated aging-related mechanisms and microglial galectin-3 expression in the mouse hippocampus using female 6-, 12-, and 24-month-old C57BL/6 mice. Western blot analysis revealed neurodegeneration, blood-brain barrier leakage, and increased levels of neuroinflammation-related proteins in 24-month-old mice compared to 6- and 12-month-old mice. Immunohistochemistry revealed an increase in activated microglia in the hippocampus of 24-month-old mice compared to 6- and 12-month-old mice. Furthermore, we found more galectin-3 and triggering receptor expressed on myeloid cells-2-positive microglia in 24-month-old mice compared to 6- and 12-month-old mice. Using primary mouse microglial cells, galectin -3 was also increased by lipopolysaccharide treatment. These findings suggest that galectin-3 may play an important role in microglial activation and neuroinflammation during brain aging.

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE –/–mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

Purpose: This study elucidates the mechanism of the physiological effect of cannabidiol (CBD) by assessing its impact on lipopolysaccharide (LPS)-induced inflammation in RWPE-1 cells and prostatitis-induced by 17β-estradiol and dihydrotestosterone in a rat model, focusing on its therapeutic potential for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Materials and Methods: RWPE-1 cells were stratified in vitro into three groups: (1) controls, (2) cells with LPS-induced inflammation, and (3) cells with LPS-induced inflammation and treated with CBD. Enzyme-linked immunosorbent assays and western blots were performed on cellular components and supernatants after administration of CBD. Five groups of six Sprague–Dawley male rats were assigned: (1) control, (2) CP/CPPS, (3) CP/CPPS and treated with 50 mg/kg CBD, (4) CP/CPPS and treated with 100 mg/kg CBD, and (5) CP/CPPS and treated with 150 mg/kg CBD. Prostatitis was induced through administration of 17β-estradiol and dihydrotestosterone. After four weeks of CBD treatment, a pain index was evaluated, and prostate tissue was collected for subsequent histologic examination and western blot analysis. Results: CBD demonstrated efficacy in vivo for CP/CPPS and in vitro for inflammation. It inhibited the toll-like receptor 4 (TLR4)uclear factor-kappa B (NF-κB) pathway by activating the CB2 receptor, reducing expression of interleukin-6, tumor necrosis factor-alpha, and cyclooxygenase-2 (COX2) (p<0.01). CBD exhibited analgesic effects by activating and desensitizing the TRPV1 receptor. Conclusions CBD inhibits the TLR4/NF-κB pathway by activating the CB2 receptor, desensitizes the TRPV1 receptor, and decreases the release of COX2. This results in relief of inflammation and pain in patients with CP/CPPS, indicating CBD as a potential treatment for CP/CPPS.

Background: Small cell lung cancer (SCLC) is called ‘smoker’s disease’ because it is strongly associated with smoking and most cases occur in smokers. However, it can also occur in never smokers. We investigated the clinical features of never smokers with SCLC and compared their treatment outcomes with those of smokers with SCLC. Methods: We retrospectively reviewed the clinical data of patients who had proven SCLC and had received chemotherapy at a single cancer center between July 2002 and April 2021. Results: Of 1,643 patients, 1,416 (86.2%) were enrolled in this study. A total of 162 (11.4%) and 1,254 (88.6%) patients were never smokers and smokers, respectively. There were more female never smokers than smokers (n=130; 80.2% vs. 79, 6.3%, p=0.000), and the incidence of ischemic heart disease was lower among never smokers than among smokers (4/1,416, [2.5%] vs. 83/1,416 [6.6%], p=0.036). Never smokers showed less symptoms at diagnosis than smokers (80.9% vs. 87.2%, p=0.037); however, they showed more toxicity after first-line treatment (61.7% vs. 47.8%, p=0.001). The objective response rate (ORR) was significantly higher in never smokers (74.1% vs. 59.6%, p=0.000). In the multivariate analysis, never smoking and second-line treatment were associated with a better ORR. However, progression-free survival and overall survival were not significantly different between never smokers and smokers. Conclusion In conclusion, never smokers accounted for 11.4% of patients with SCLC. They had distinguishing clinical characteristics and showed better chemotherapeutic responses than smokers.

Purpose: To evaluate the relationship between distal fusion level in correction and fusion surgery for adolescent idiopathic scoliosis (AIS) and radiologic changes in the sacroiliac (SI) joint. Materials and Methods: This retrospective cohort study evaluated patients who underwent correction and fusion for AIS between 2005 and 2017 with at least 5 years of follow-up. We categorized patients into two groups: Group 1 (distal fusion above L2, 74 patients) and Group 2 (distal fusion at L3 and below, 52 patients). Radiologic parameters and SI joint changes were evaluated on plain radiographs obtained from preoperative to 5 years postoperatively. We also investigated other risk factors for SI joint change. Results: Analysis of demographic factors revealed no significant difference between the two groups. There was a significant difference in the incidence of SI joint change between Group 1 (5 patients, 6.75%) and Group 2 (18 patients, 34.61%), with Group 2 showing a faster increase in incidence according to the Kaplan-Meier method (p<0.0001). Preoperative lumbar lordosis (LL) and ΔLL had a significant relationship with SI joint changes [preoperative LL, hazard ratio (HR)=0.77, 95% confidence interval (CI)=0.64– 0.93, p=0.008; ΔLL, HR=0.79, 95% CI=0.67–0.95, p=0.01). Conclusion After AIS surgery, patients who had fusion to the lower lumbar vertebrae (L3 or L4) experienced a higher incidence and faster progression of degenerative changes in the SI joint. Low preoperative LL and inadequate correction of LL during the operation were also risk factors for SI joint degeneration.

Purpose: Smoking may have a protective role in developing ulcerative colitis (UC) but have the opposite effect on Crohn’s disease (CD). This study aimed to determine the risk of developing inflammatory bowel disease (IBD) according to smoking status and onset age of smoking. Materials and Methods: We collected data on the smoking experiences of participants aged 20–39 years who underwent biannual examinations provided by the Korean National Health Screening Program from 2009 to 2012. IBD diagnosis was identified using the National Health Insurance Service. The risk of IBD according to smoking status and onset age of smoking was analyzed after adjusting for major clinical variables. Results: During a median 10.59-year follow-up, the risk of UC in ex-smokers was significantly higher than that in non-smokers, and the earlier ex-smokers started smoking, the higher risk of UC [ex-smokers whose onset age of smoking was <20 years, adjusted hazard ratio (aHR) 1.928, 95% confidence interval (CI)=1.649–2.255; 20–24 years, aHR 1.728, 95% CI=1.541–1.939; 25–29 years, aHR 1.676, 95% CI=1.489–1.887; ≥30 years, aHR 1.226, 95% CI=1.010–1.486]. The risk of UC was significantly lower in current smokers whose onset age of smoking was 25–29 years than in non-smokers (aHR 0.825, 95% CI=0.709–0.959). The risk of CD did not differ according to smoking status and onset age of smoking. Conclusion Ex-smokers who started smoking at a young age have a high risk of UC, even after adjusting for the smoking amount.

Radiofrequency ablation (RFA) is a minimally invasive treatment modality used as an alternative to surgery in patients with benign thyroid nodules, recurrent thyroid cancers (RTCs), and primary thyroid microcarcinomas. The Korean Society of Thyroid Radiology (KSThR) initially developed recommendations for the optimal use of RFA for thyroid tumors in 2009 and revised them in 2012 and 2017. As new meaningful evidence has accumulated since 2017 and in response to a growing global interest in the use of RFA for treating malignant thyroid lesions, the task force committee members of the KSThR decided to update the guidelines on the use of RFA for the management of RTCs based on a comprehensive analysis of current literature and expert consensus.

Objective: To evaluate the safety and efficacy of coil embolization of venous segments in patients with Type IIa pelvic arteriovenous malformations (AVMs). Materials and Methods: A retrospective study was performed on 13 patients (median age, 43 years, range 20–62 years, 7 males) who underwent transvenous coil embolization for Type IIa pelvic AVM (characterized by multiple arterioles shunting to focal venous segments of a single draining vein) without the use of additional liquid embolic agents from March 2017 to February 2023. Treatment outcomes were analyzed based on clinical evaluations, post angiography findings, and follow-up CT. Results: Fourteen procedures were performed on 13 patients. Except in one patient, all treatments were completed in a single session. Transvenous access was employed in 10 procedures, whereas direct puncture was used in four sessions. The embolization procedures used an average of 55.7 ± 58.5 coils (range, 7–238) and lasted an average of 127.3 ± 39.5 minutes.The technical success rate was 92.9% (of 13/14). All patients reported symptom improvement. Follow-up CT scans showed complete occlusion of the AVM without recurrence in ten of the 13 patients. There was one minor adverse event: a small retroperitoneal hemorrhage, likely related to direct puncture, which resolved spontaneously. No other adverse events were observed. Conclusion Coil embolization of the draining vein segment, without the use of additional liquid embolic agents is a safe and effective method for managing Type IIa pelvic AVM.