Study on the mechanism of action of the active ingredient of Calculus Bovis in the treatment of sepsis by integrating single-cell sequencing and machine learning
Year: 2025
Type: article
Abstract: BACKGROUND: Sepsis, a complex inflammatory condition with high mortality rates, lacks effective treatments. This study explores the therapeutic mechanisms of Calculus Bovis in sepsis using network pharmacology and RNA sequencing. METHODS: Sepsis data from the China National GeneBank Database were analyzed for differentially expressed genes (FC ≥ 2, FDR < 0.05). Active components of Calculus Bovis were identified via the HERB and BATMAN-TCM databases, with target interactions assessed through protein-protein interaction (PPI) networks. GO and KEGG analyses identified pathway enrichments (P ≤ .01). Survival analysis using the GSE65682 database evaluated prognosis-related genes (P < .05). Four machine learning models (XGBoost, SVM, Decision Tree, KNN) were constructed to assess diagnostic potential, with AUC values evaluating accuracy. Immunofluorescence and single-cell RNA sequencing localized key genes, while molecular docking and molecular dynamics simulations (MD) assessed binding affinities and stability of Calculus Bovis compounds with target proteins. RESULTS: We identified 593 targets for Calculus Bovis and 4329 sepsis-related genes, with 149 overlapping. Key genes ADAM17, CASP1, CD81, and MGMT were linked to improved prognosis (P < .05) and involved in inflammatory responses and pyroptosis (P ≤ .01). The XGBoost model achieved high diagnostic accuracy (AUC: training = 1.000, test = 0.964). Molecular docking showed strong binding (energy < -6.0 kcal/mol), and MD indicated stable interactions, particularly with ADAM17 and CD81. CONCLUSION: This study highlights the potential of Calculus Bovis in sepsis treatment, identifying key genes as therapeutic targets.
Source: Medicine
Authors: Hao Wang, Yingchun Hu, Li Hu
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,950
Funder: Southwest Medical University
OpenAlex ID: W4409696642