Therapeutic potential of Da Cheng Qi Decoction and its ingredients in regulating ferroptosis via the NOX2-GPX4 signaling pathway to alleviate and predict severe acute pancreatitis
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View abstract on PubMed
Summary
This summary is machine-generated.Da Cheng Qi Decoction (DCQD) protects against severe acute pancreatitis (SAP) by inhibiting ferroptosis via the NOX2/GPX4 pathway. A novel predictive signature and nomogram derived from this study aid in acute pancreatitis (AP) risk assessment and personalized treatment.
Area Of Science
- Biomedical Research
- Molecular Biology
- Pharmacology
Background
- Severe acute pancreatitis (SAP) is a critical condition with significant morbidity and mortality.
- Ferroptosis, a regulated form of cell death, plays a crucial role in the pathogenesis of acute pancreatitis (AP).
- Traditional Chinese Medicine, like Da Cheng Qi Decoction (DCQD), shows potential therapeutic benefits, but its mechanisms in SAP require elucidation.
Purpose Of The Study
- To investigate the protective effects of DCQD against ferroptosis in pancreatic acinar cells in SAP.
- To identify key genes and pathways involved in DCQD's action on ferroptosis in SAP.
- To develop a predictive signature and nomogram for AP risk assessment and prognosis.
Main Methods
- Microarray analysis of gene expression in healthy controls and AP patients.
- Establishment of SAP models and utilization of NOX2-deficient cells to study ferroptosis.
- Assessment of DCQD and ferroptosis inhibitor (Fer-1) effects on gene expression, oxidative stress, and inflammation.
- Application of machine learning algorithms to identify differentially expressed genes (DEGs) sensitive to DCQD, SAP, and ferroptosis (DSNFGs).
- Development and validation of a predictive nomogram using DSNFGs and single-cell RNA sequencing (scRNA-seq).
Main Results
- Microarray revealed NOX2 upregulation and GPX4 downregulation in AP, correlating with severity.
- DCQD treatment ameliorated SAP-induced pancreatic acinar cell damage and ferroptosis, enhancing GPX4 expression and reducing inflammation.
- NOX2 knockout mitigated ferroptosis, highlighting its role in SAP.
- DCQD and Fer-1 modulated ferroptosis-related genes, reduced reactive oxygen species (ROS) and HMGB1, and suppressed inflammation.
- Eight DCQD components were identified with ferroptosis-modulating capacity.
- A predictive signature of 48 DSNFGs was identified, with five genes showing significant predictive value.
- A LASSO regression-based nomogram demonstrated high accuracy in predicting AP risk.
- scRNA-seq and CellChat analysis revealed pancreatic cell heterogeneity and communication networks during pancreatitis recovery.
Conclusions
- DCQD and its key ingredients protect against SAP by inhibiting ferroptosis through the NOX2/GPX4 pathway.
- The developed DCQD-SAP-ferroptosis-related signature and nomogram serve as novel tools for AP risk assessment and prognosis.
- This research provides a basis for personalized therapeutic strategies in SAP management.
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