Search

Cadmium (Cd) is a widely distributed environmental contaminant that is highly toxic to animals and humans. However, detailed reports on Cd-induced programmed necrosis have not been seen in chicken testicular Leydig cells. Selenium (Se) is a trace element in the human body that has cytoprotective effects in a variety of pathological damages caused by heavy metals. This study investigated the potential mechanisms of Cd-induced programmed cell necrosis and the antagonistic effect of Se on Cd toxicity. Chicken testis Leydig cells were divided into six groups, namely, control, Se (5 µmol/L Na 2 SeO 3 ), Cd (20 µmol/L CdCl 2 ), Se + Cd (5 µmol/L Na 2 SeO 3 and 20 µmol/L CdCl 2 ), 4-phenylbutyric acid (4-PBA) + Cd (10 mmol/L 4-phenylbutyric acid and 20 µmol/L CdCl 2 ), and Necrostatin-1 (Nec-1) + Cd (60 µmol/L Necrostatin-1 and 20 µmol/L CdCl 2 ). The results showed that Cd exposure decreased the activity of CAT, GSH-Px, and SOD and the concentration of GSH, and increased the concentration of MDA and the content of ROS. Relative mRNA and protein expression of GRP78, PERK, ATF6, IRE1, CHOP, and JNK increased in the Cd group, and mRNA and protein expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 significantly increased in the Cd group, while Caspase-8 mRNA and protein expression significantly decreased. The abnormal expression of endoplasmic reticulum stress-related proteins was significantly reduced by 4-PBA pretreatment; the increased expression of TNF-α, TNFR1, RIP1, RIP3, MLKL, and PARP1 caused by Cd toxicity was alleviated; and the expression of caspase-8 was upregulated. Conversely, the increased mRNA and protein expression of endoplasmic reticulum stress marker genes (GRP78, ATF6, PERK, IRE1, CHOP, JNK) caused by Cd was not affected after pretreatment with Nec-1. We also found that these Cd-induced changes were significantly attenuated in the Se + Cd group. We clarified that Cd can cause programmed necrosis of chicken testicular Leydig cells through endoplasmic reticulum stress, and Se can antagonize Cd-induced programmed necrosis of chicken testicular Leydig cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To report the surgical management, complications and prognosis of patients with penoscrotal extramammary Paget's disease (EMPD) at different clinical stages. Between 2003 and 2008, a total of 30 male patients with penoscrotal EMPD were enrolled and evaluated. All enrolled subjects received frozen biopsy-guided local wide resection and immediate reconstruction. Patients were followed every 3 months postoperatively. Among the 30 patients who accepted and underwent frozen biopsy-guided local wide resection treatment and reconstruction, two (6.7%) cases exhibited positive margins, verified by pathological examination, and underwent re-excision after surgery. The technique of primary closure or an adjacent flap was used in 10 (33.3%) cases, split-thickness skin grafts were used in 15 (50%), and an anterolateral thigh perforator flap was used in five cases (16.7%). The postoperative complications were acceptable. The mean follow-up time was 64.9±29.6 months. Of all 30 cases, 22 patients (73.3%) survived with no evidence of recurrence, four patients (13.3%) exhibited local recurrence, two patients (6.7%) exhibited both local recurrence and distant metastasis and the remaining two patients (6.7%) exhibited distant metastasis. Five patients died from metastasis or cachexia. Current surgical techniques, including primary closure, adjacent flaps, split-thickness skin flaps and anterolateral thigh perforator flaps are able to reconstruct all types of defects with acceptable complications. Some patients with negative margins went on to exhibit local recurrence, potentially due to adnexal carcinoma or internal malignancy. [ABSTRACT FROM AUTHOR]