Millions of people chew areca nut to boost work efficiency and relieve stress. Areca nut contains arecoline, which adversely affects reproductive function, although the underlying molecular mechanisms remain unclear. Herein, we evaluated arecoline-mediated reproductive toxicity using Sprague–Dawley (SD) rat models and an in vitro GC-1 cell model. Molecular docking, quantitative reverse transcription PCR (qRT-PCR), Western blot, cell-based assays, and functional rescue experiments were used to investigate the mechanisms involved. Dose-dependent spermatogenic damage was observed in male rats receiving 50, 100 and 200 mg/kg arecoline, with reduced sperm counts and quality, higher testicular MDA and lower activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). Molecular docking predicted a possible interaction between arecoline and Notch1. qRT-PCR and Western blot analyses showed that the expression of Notch1 and its ligands, Jagged-1 and Dll-1, was downregulated in testicular tissues and GC-1 cells following arecoline exposure. Notch1 expression was strongly positively correlated with seminiferous tubule diameter and seminiferous epithelium height. In vitro, arecoline induced ROS accumulation, inhibited proliferation and promoted apoptosis in GC-1 cells. Rescue experiments showed that the Notch activator valproic acid, used to enhance Notch signaling, alleviated arecoline-induced toxicity, whereas Notch inhibitor FLI-06 worsened cell injury. These findings support a role for altered Notch signaling and oxidative stress in arecoline-induced spermatogenic injury and provide insight into the molecular mechanisms of its reproductive toxicity.
Postoperative nausea and vomiting (PONV) is a common surgical complication, especially in breast and gynecologic surgery, with a high incidence despite prophylactic treatment. There is uncertainty about the effective dose and therapeutic effect of drug therapy, leading to unsatisfactory results. This study aims to investigate the effect of preoperative whey protein (WP) supplementation on postoperative recovery and PONV in gynecologic tumor patients with good nutritional status, so as to optimize postoperative rehabilitation strategies. This study was a randomized, double-blind, placebo-controlled, prospective trial involving 52 patients undergoing gynecologic tumor surgery. The experimental group received WP liquid daily for 3 days before surgery, while the R-M group received rice-milk (R-M) liquid daily. The primary endpoint was incidence of PONV and the secondary endpoints included postoperative recovery indicators such as length of hospital stay, time to first flatus and defecation, time to first ambulation, and nutritional indicators such as hemoglobin, total protein, albumin and prealbumin. Statistical analysis was performed using Python, and a P-value less than 0.05 was considered statistically significant. The results of the study showed that preoperative WP supplementation reduced the incidence of PONV within 24 h after surgery, and accelerated postoperative recovery, including shorter hospital stay and early exhaust, defecation, and ambulation time (P < 0.05). Preoperative WP supplementation reduced the incidence of PONV in the first 24 h after surgery and was associated with accelerated early postoperative recovery. This intervention may have clinical relevance in improving postoperative recovery.Clinical trial registration: Clinical trial registration number: ChiCTR2200059673; Clinical trial registration time: 06/05/2022.