Chang Gung Memorial Hospital

Areca nut is a significant risk factor for head and neck cancer (HNC), yet its molecular mechanisms, particularly miRNA-mediated regulation, remain poorly understood. This study investigates the regulatory networks underlying areca nut-induced HNC and explores therapeutic strategies through computational drug repurposing. Arecoline was used to assess its effects on invasion, migration, and cisplatin resistance in HNC cells and normal keratinocytes. Differentially expressed miRNAs and mRNAs were identified using high-throughput profiling, followed by integrative network analysis using the TCGA-HNSC dataset and multiMiR. OncoPredict was used for drug repurposing to identify therapeutic agents targeting dysregulated miRNA-mRNA networks. Arecoline exposure promoted invasion and cisplatin resistance, with more pronounced effects in normal keratinocytes, indicating a potential role in early tumorigenesis. Integrative transcriptomic analysis revealed a miRNA-mRNA regulatory network comprising 1971 oncogenes, 604 tumor suppressors, 35 oncogenic miRNA (OncomiRs), and 36 tumor suppressor miRNA (TSmiRs) regulating pathways related to cell motility and stress response. A tumor-suppressive network with miR-212-3p as a central hub and an oncogenic network modulated by miR-410 and miR-1-3p as critical hubs were identified. Drug repurposing analysis identified four potential therapeutic candidates (MK-2206, BYL-719, MG-132, and FGIN-1-27), with MK-2206 emerging as the most promising. MK-2206 effectively reversed arecoline-induced miRNA-mRNA dysregulation, mitigated malignant phenotypes, and selectively targeted HNC cells while sparing normal keratinocytes. This integrative approach elucidates areca nut-driven carcinogenesis through miRNA-mRNA interactions and highlights MK-2206 as a promising therapeutic strategy for areca nut-associated HNC.

Flexible cystoscopy is well tolerated by women. Reprocessing of cystoscopes requires sterilization or, at least, high-level disinfection (HLD). This study aims to assess the incidence of bacteriuria after flexible cystoscopy using ortho-phthalaldehyde HLD. This is a prospective study. Seventy-eight women undergoing diagnostic outpatient flexible cystoscopy were included. Exclusion criteria were microbiologically confirmed or acute urinary tract infection, significant urethral stricture, and bleeding disorders. Cystoscopes were reprocessed using ortho-phthalaldehyde. Pre-cystoscopic urine cultures were obtained via catheterization 3-5days prior. Post-cystoscopic urine cultures were obtained immediately after the procedure. No antibiotics prophylaxis. One woman (1.3%) developed post-cystoscopy bacteriuria. The overall mean age was 58.7 ± 11.2years; the mean BMI was 23.4 ± 3.3kg/m2. In the non-bacteriuric cohort, the mean age was 58.87 ± 11.3years, 40 (51.9%) were in the older age group (> 60years), 60 (77.9%) were postmenopausal, 69 (89.6%) were non-diabetic, 20 (26%) had a prior hysterectomy, 13 (16.9%) had previous pelvic reconstructive surgery, 10 (13%) had undergone anti-stress urinary incontinence surgery, and no woman had current pelvic organ prolapse. The most common indication for flexible cystoscopy was hematuria (n = 45, 58.4%). Seventy-three (94.8%) women had unremarkable cystoscopic findings. The single bacteriuric woman was 53years old, postmenopausal, non-diabetic, with a BMI of 22.3kg/m2, and an intact uterus; cystoscopy was performed for interstitial cystitis. The incidence of bacteriuria following flexible cystoscopy was 1.3%. Ortho-phthalaldehyde is effective for HLD in flexible cystoscopy, provided robust rinsing, drying, and exposure-tracking protocols are maintained.