You Xujun,Li Honghan,Li Qixin,Zhang Qing,Cao Yiguo,Fu Wei,Wang Bin
Prostate cancer (PCa) is an epithelial malignancy affecting the prostate gland. Astragaloside IV combined with polypeptide extract from scorpion venom (PESV) has been reported to inhibit the growth of PCa. This study aimed to investigate the mechanisms by which this combination mitigates the progression of PCa. Bioinformatic analysis was utilized to investigate the correlation between zinc finger DHHC-type containing 1 (ZDHHC1) expression and PCa progression. The extent of pyroptosis in PCa cells was assessed by measuring cell viability, IL-1β and IL-18 secretion, LDH release, and HMGB1 content. PCa mouse models were constructed by subcutaneous injection of DU145 or PC-3 cells into nude mice, with subsequent monitoring of tumor weight and volume. ZDHHC1 expression was significantly lower in PCa patient tissues, which correlated with a poor prognosis. ZDHHC1 overexpression inhibited PC-3 and DU145 cell viability and increased IL-1β, IL-18, LDH, and HMGB1 levels in cell supernatants. Notably, the pyroptosis inhibitor LDC7559 partially reversed these effects. Co-IP assay demonstrated an interaction between ZDHHC1 and GSDMD. ZDHHC1 overexpression significantly enhanced GSDMD palmitoylation-mediated membrane translocation and pyroptosis; however, this effect was partially reversed by the palmitoylation inhibitor 2-BP. The combination of Astragaloside IV and PESV promoted GSDMD membrane translocation and pyroptosis in PCa cells, with ZDHHC1 knockdown partially reversing the effects of Astragaloside IV-PESV. Furthermore, treatment with Astragaloside IV-PESV significantly inhibited tumor tissue growth in tumor-bearing nude mouse models. Astragaloside IV-PESV enhances palmitoylation-mediated membrane translocation of GSDMD-N by upregulating ZDHHC1 expression, thereby facilitating pyroptosis in PCa cells and attenuating PCa progression.
In this study, the efficiency of five peptide-extraction methods—acetonitrile (ACN) precipitation, ultrafiltration, C18 solid-phase extraction (SPE), dispersed SPE with mesoporous carbon CMK-3, and mesoporous silica MCM-41—was quantitatively investigated. With 28 tryptic peptides as target analytes, these methods were evaluated on the basis of recovery and reproducibility by using high-performance liquid chromatography–triple-quad tandem mass spectrometry in selected-reaction-monitoring mode. Because of the distinct extraction mechanisms of the methods, their preferences for extracting peptides of different properties were revealed to be quite different, usually depending on the pI values or hydrophobicity of peptides. When target peptides were spiked in bovine serum albumin (BSA) solution, the extraction efficiency of all the methods except ACN precipitation changed significantly. The binding of BSA with target peptides and nonspecific adsorption on adsorbents were believed to be the ways through which BSA affected the extraction behavior. When spiked in plasma, the performance of all five methods deteriorated substantially, with the number of peptides having recoveries exceeding 70 % being 15 for ACN precipitation, and none for the other methods. Finally, the methods were evaluated in terms of the number of identified peptides for extraction of endogenous plasma peptides. Only ultrafiltration and CMK-3 dispersed SPE performed differently from the quantitative results with target peptides, and the wider distribution of the properties of endogenous peptides was believed to be the main reason.
Distribution of the recoveries of target peptides after treatment by the five peptide-extraction methods
The oxidative damage to vascular endothelial cells induced by smoking represents a significant pathogenic factor in the development of atherosclerosis. In the present study, we isolated ginseng oligopeptide extract (GOE), which emerges as a promising candidate for protecting human aortic endothelial cells (HAECs) from nicotine-induced oxidative stress. The underlying mechanisms were also explored. The GOE effectively reversed the decline in cell viability and protected HAECs from nicotine-induced oxidative damage by inhibiting the overproduction of intracellular reactive oxygen species (ROS) while preserving superoxide dismutase (SOD) activity. We identified five ginseng oligopeptides (GOPs) as the primary components of GOE. Furthermore, we demonstrated that GOE significantly alleviated nicotine-induced mitochondrial dysfunction in HAECs while promoting the nitric oxide (NO) release and the expression of GTP cyclohydrolase 1 (GTPCH1). Although the precise mechanism through which GOE mitigates nicotine-induced oxidative stress in HAECs remains to be fully elucidated, our findings indicate that GOP-1–5 serve as bioactive constituents of GOE and play a significant synergistic role in reducing nicotine-induced apoptosis and oxidative damages in HAECs. This is achieved through modulation of cellular antioxidant systems via maintaining balance within the Keap1/Nrf2/HO-1 signaling pathway. These findings suggest that GOE may function as a potential therapeutic agent against cigarette smoking-induced atherosclerosis.
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