A diagnostic model based on five core Pueraria targets (STAT3, RIPK2, GM2A, ALOX5, and DPP4) achieved high AUCs for septic cardiomyopathy and correlated significantly with cardiac function indices.
Pueraria may mitigate septic cardiomyopathy by modulating five core programmed cell death-related targets (STAT3, RIPK2, GM2A, ALOX5, DPP4), which also serve as a highly accurate diagnostic signature.
Background: Septic cardiomyopathy (SCM) is a fatal sepsis-induced dysfunction. While Pueraria (Pue) exhibits protective effects in sepsis, its regulatory role regarding programmed cell death (PCD) in SCM remains unclear. This study aimed to identify Pue’s PCD-related targets in SCM and construct a validated diagnostic model. Methods: We analyzed 14 PCD modalities across seven GEO transcriptomic datasets. A robust machine learning framework integrating 171 algorithm combinations built a diagnostic signature. The immune landscape was profiled using single-cell RNA sequencing and enrichment analyses. Experimental validation utilized SCM patient blood samples and heart tissues from an LPS-induced murine model. Results: Nine PCD patterns were significantly altered in SCM. Intersection analysis and machine learning identified five core Pue targets: STAT3, RIPK2, GM2A, ALOX5, and DPP4. A diagnostic model constructed with these genes achieved high AUCs across all datasets. Single-cell analysis revealed cell-type-specific expression within the myocardial immune landscape. Differential expression of these five genes was validated in both human and animal samples, correlating significantly with cardiac function indices. Conclusions: Our results demonstrate that Pueraria mitigates SCM and restores cardiac function by modulating the expression of core PCD-related targets. These targets are closely associated with the localized inflammatory response, providing potential therapeutic avenues for SCM.
Liu et al. (Thu,) conducted a other in Septic cardiomyopathy. Pueraria was evaluated on Identification of PCD-related targets and construction of a diagnostic model. A diagnostic model based on five core Pueraria targets (STAT3, RIPK2, GM2A, ALOX5, and DPP4) achieved high AUCs for septic cardiomyopathy and correlated significantly with cardiac function indices.