LC-MS/MS-based molecular networking was used to guide the targeted isolation of terpenylated coumarins from the barks of Ailanthus altissima. Five known terpenylated coumarins (1–5), along with two simple coumarins (6 and 7), were isolated from the CH 2 Cl 2 -soluble fraction. Their structures were determined using spectroscopic techniques, including 1D and 2D NMR and LC-HR-MS/MS. Notably, altissimacoumarins C (1), F (3), and H (4) demonstrated potent inhibition of LPS-induced nitric oxide production in RAW 264.7 macrophages, with IC50 values of 36.1, 27.9, and 11.2 μM, respectively. These results demonstrate the antiinflammatory properties of A. altissima, supporting its possible application in treating inflammatory disorders.

Purpose: Limited treatment options exist for patients with metastatic castration-resistant prostate cancer (mCRPC) after the failure of taxane-based chemotherapy and novel hormonal therapy. Here, we report the safety and efficacy of ifosfamide and mesna in patients with mCRPC after the failure of taxane-based chemotherapy and novel hormonal therapy (NCT06236789). Materials and Methods: Patients with histologically confirmed prostate cancer who had failed taxane-based chemotherapy and novel hormonal therapy received ifosfamide 2,500 mg/m2 and mesna 1,500 mg/m2 on days 1–3, repeated every 21 days. Safety, objective response rate, disease control rate, reduction in serum prostate-specific antigen (PSA) concentration by >50% (PSA50) or >90% (PSA90), radiographic progression-free survival (rPFS), and overall survival (OS) were analyzed. Results: A total of 47 patients with mCRPC were included in the study. The median number of lines of treatment was 5 (range, 3 to 7). All patients were previously administered docetaxel and novel hormonal therapies including abiraterone (51.1%) and/or enzalutamide (61.7%). Thirty-eight patients (80.9%) were administered cabazitaxel. The objective response and disease control rates were 21.3% and 80.9%, respectively. PSA50 and PSA90 were achieved in 31.9% and 10.6%, respectively. During a median follow-up duration of 54.3 months, rPFS and OS were 5.0 and 9.0 months, respectively. All the patients experienced treatment-related adverse events of any grades; however, no new safety signs were detected. Genomic biomarker analysis revealed that alterations in the TP53 pathway were associated with inferior rPFS and OS. Conclusion Ifosfamide and mesna showed appreciable efficacy and manageable safety profiles in heavily treated patients with mCRPC.

Purpose: Testicular torsion is a urological emergency necessitating immediate surgical intervention. However, the altered medical environment during the coronavirus disease 2019 (COVID-19) pandemic posed several challenges and the current study aimed to analyze its effects on the treatment of pediatric testicular torsion cases. Materials and Methods: We retrospectively analyzed 47 pediatric patients diagnosed with testicular torsion at Severance Children's Hospital from 2009 to 2022. Patients were categorized into pre–COVID-19 (n=38) and COVID-19 (n=8) groups. Data were collected for each patient, and the differences between the two groups were statistically analyzed. Results: The patients’ median age was from 13 years (range, 1–19 years) to 13 years (range, 1–16 years) between the pre–COVID-19 and COVID-19 period (p=0.309). The analysis revealed a significant difference between the pre–COVID-19 and COVID-19 groups in the time from symptom onset to emergency department arrival (6.4 hours [0.7–120.0] vs. 20.0 hours [1.3–288.0], p=0.031) and the time from symptom onset to surgery start (19.5 hours [4.5–124.3] vs. 28.5 hours [6.1–293.4], p=0.047). The median postoperative size of the affected testis was 9.8 mL (range, 2.0–13.9 mL) during the COVID-19 period, compared to 1.6 mL (range, 0.1–7.3 mL) in pre–COVID-19 period (p=0.012). The testicular volume ratio (affected/unaffected) was used to evaluate outcomes across patients with varying ages and testicular sizes. Conclusions The current study shows that pandemic-related delays in treatment may worsen ischemic injury in testicular torsion, emphasizing the importance of timely intervention even during global crises.

Purpose: To investigate whether serum levels of Dickkopf-related protein-1 (DKK1) are clinically useful in estimating cross-sectional vasculitis activity and predicting future prognosis in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Materials and Methods: This study included 76 patients with AAV. Their clinical data were retrospectively reviewed and serum DKK1 levels were measured in blood samples collected and stored at diagnosis. At diagnosis, the Birmingham vasculitis activity score (BVAS) and the five-factor score (FFS) were assessed as AAV activity indices, and the erythrocyte sedimentation rate and Creactive protein (CRP) level were recorded as acute-phase reactants. All-cause mortality and end-stage kidney disease (ESKD) were investigated as poor outcomes during follow-up. Results: Among the 76 patients with AAV (31 males, and 45 females), the median age was 63.5 years. At diagnosis, serum DKK1 levels were significantly correlated with BVAS, FFS, CRP, serum albumin, and serum creatinine levels. Using receiver operating characteristic curve analysis, the cut-off serum DKK1 level for predicting ESKD was determined to be 3925.0 pg/mL. Patients with serum DKK1 levels ≥3925.0 pg/mL at diagnosis displayed a significantly higher risk of ESKD progression (relative risk 5.357) and exhibited a significantly lower cumulative ESKD-free survival rate during follow-up than those with lower levels. Conclusion The present study is the first to demonstrate that serum DKK1 levels at diagnosis are useful in assessing vasculitis activity at diagnosis and predicting future ESKD progression in patients with AAV.

Background/Aims: This study applied the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with Behçet’s disease (BD) to investigate the proportion and clinical implications of the reclassification to the overlap syndrome of BD and AAV (OS-BD-AAV). Methods: We included 280 BD patients presenting with ANCA positivity but without medical conditions mimicking AAV at diagnosis. Demographic data, items from the 2014 revised International Criteria for BD and 2022 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for AAV, ANCA positivity, and laboratory results were recorded as clinical data at diagnosis. A total score ≥ 5 indicated microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), whereas a total score ≥ 6 indicated a diagnosis of eosinophilic GPA (EGPA). Results: The overall reclassification rate of OS-BD-AAV was 8.6%. Of the 280 patients, 16 (5.7%) and 8 (2.9%) were reclassified as having OS-BD-MPA and OS-BD-GPA, respectively; none were classified as having OS-BD-EGPA. ANCA, myeloperoxidase-ANCA (P-ANCA), proteinase 3-ANCA (C-ANCA) positivity, hearing loss, and interstitial lung disease (ILD) at diagnosis were more common in patients with OS-BD-AAV than in those without. ANCA positivity and ILD at BD diagnosis contributed to the reclassification of OS-BD-AAV. However, hearing loss was not considered a major contributor to BD due to its possibility of developing as a manifestation of BD. Conclusions To our knowledge, this is the first study to demonstrate the reclassification rate (8.6%) of patients with BD and ANCA results at diagnosis as OS-BD-AAV.

Background/Aims: This study evaluated the clinical utility of serum periostin measured at diagnosis in reflecting activity at diagnosis and predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: This study included 76 patients with AAV whose serum periostin was measured from sera collected and stored at diagnosis. The correlation of either serum periostin or the Birmingham Vasculitis Activity Score (BVAS) with other variables was evaluated. Cumulative survival rates were compared using Kaplan–Meier survival analysis. The variables at diagnosis were compared between deceased and surviving patients. Hazard ratios were obtained by Cox proportional hazard analysis. Results: The median age of the 76 patients was 64.0 years and 60.5% were female. The median BVAS and serum periostin were 5.0 and 10.9 ng/mL, respectively. Five of the 76 patients (6.6%) died. Serum periostin was independently correlated with cross-sectional BVAS, the Vasculitis Damage Index (VDI), white blood cell count, and serum albumin. Patients with serum periostin ≥ 15.9 ng/mL at diagnosis had a significantly lower cumulative survival rate than those without. In addition to high VDI, dyslipidaemia frequency, and C-reactive protein, deceased patients showed higher serum periostin than surviving patients. In multivariable Cox analysis, however, only dyslipidaemia rather than serum periostin was identified as an independent predictor of all-cause mortality. Conclusions This study is the first to demonstrate that serum periostin at diagnosis could independently reflect cross-sectional BVAS and further partially contribute to all-cause mortality prediction in patients with AAV.

Purpose: In this study, we investigated the effect of bisphenol-A (BPA) and its major analogs, bisphenol-F (BPF), and bisphenol-S (BPS), on spermatogonial stem cells (SSCs) populations using in vitro SSC culture and in vivo transplantation models. Materials and Methods: SSCs enriched from 6- to 8-day-old C57BL/6-eGFP+ male mice testes were treated with varying concentrations of bisphenols for 7 days to examine bisphenol-derived cytotoxicity and changes in SSC characteristics. We utilized flow cytometry, immunocytochemistry, real-time quantitative reverse transcription-PCR, and western blot analysis. The functional alteration of SSCs was further investigated by examining donor SSC-derived spermatogenesis evaluation through in vivo transplantation and subsequent testis analysis. Results: BPF exhibited a similar inhibitory effect on SSCs as BPA, demonstrating a significant decrease in SSC survival, inhibition of proliferation, and induction of apoptosis. On the other hand, while BPS was comparatively weaker than BPA and BPF, it still showed significant SSC cytotoxicity. Importantly, SSCs exposed to BPA, BPF, and BPS exhibited a significant reduction in donor SSC-derived germ cell colonies per total number of cultured cells, indicating that, like BPA, BPF, and BPS can induce a comparable reduction in functional SSCs in the recipient animals. However, the progress of spermatogenesis, as evidenced by histochemistry and the expressions of PCNA and SSC specific markers, collectively indicates that BPA, BPF, and BPS may not adversely affect the spermatogenesis. Conclusions Our findings indicate that the major BPA substitutes, BPF and BPS, have significant cytotoxic effects on SSCs, similar to BPA. These effects may lead to a reduction in the functional self-renewal stem cell population and potential impacts on male fertility.

Background/Aims: This study applied the 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) criteria for antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) to patients with Behçet’s disease (BD) to investigate the proportion and clinical implications of the reclassification to the overlap syndrome of BD and AAV (OS-BD-AAV). Methods: We included 280 BD patients presenting with ANCA positivity but without medical conditions mimicking AAV at diagnosis. Demographic data, items from the 2014 revised International Criteria for BD and 2022 American College of Rheumatology and European Alliance of Associations for Rheumatology criteria for AAV, ANCA positivity, and laboratory results were recorded as clinical data at diagnosis. A total score ≥ 5 indicated microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA), whereas a total score ≥ 6 indicated a diagnosis of eosinophilic GPA (EGPA). Results: The overall reclassification rate of OS-BD-AAV was 8.6%. Of the 280 patients, 16 (5.7%) and 8 (2.9%) were reclassified as having OS-BD-MPA and OS-BD-GPA, respectively; none were classified as having OS-BD-EGPA. ANCA, myeloperoxidase-ANCA (P-ANCA), proteinase 3-ANCA (C-ANCA) positivity, hearing loss, and interstitial lung disease (ILD) at diagnosis were more common in patients with OS-BD-AAV than in those without. ANCA positivity and ILD at BD diagnosis contributed to the reclassification of OS-BD-AAV. However, hearing loss was not considered a major contributor to BD due to its possibility of developing as a manifestation of BD. Conclusions To our knowledge, this is the first study to demonstrate the reclassification rate (8.6%) of patients with BD and ANCA results at diagnosis as OS-BD-AAV.

Background/Aims: This study evaluated the clinical utility of serum periostin measured at diagnosis in reflecting activity at diagnosis and predicting all-cause mortality during follow-up in patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: This study included 76 patients with AAV whose serum periostin was measured from sera collected and stored at diagnosis. The correlation of either serum periostin or the Birmingham Vasculitis Activity Score (BVAS) with other variables was evaluated. Cumulative survival rates were compared using Kaplan–Meier survival analysis. The variables at diagnosis were compared between deceased and surviving patients. Hazard ratios were obtained by Cox proportional hazard analysis. Results: The median age of the 76 patients was 64.0 years and 60.5% were female. The median BVAS and serum periostin were 5.0 and 10.9 ng/mL, respectively. Five of the 76 patients (6.6%) died. Serum periostin was independently correlated with cross-sectional BVAS, the Vasculitis Damage Index (VDI), white blood cell count, and serum albumin. Patients with serum periostin ≥ 15.9 ng/mL at diagnosis had a significantly lower cumulative survival rate than those without. In addition to high VDI, dyslipidaemia frequency, and C-reactive protein, deceased patients showed higher serum periostin than surviving patients. In multivariable Cox analysis, however, only dyslipidaemia rather than serum periostin was identified as an independent predictor of all-cause mortality. Conclusions This study is the first to demonstrate that serum periostin at diagnosis could independently reflect cross-sectional BVAS and further partially contribute to all-cause mortality prediction in patients with AAV.