Screening Therapeutic Core Genes in Sepsis Using Network Pharmacology and Single-Cell RNA Sequencing

Area of Science:

• Immunology
• Genomics
• Pharmacology

Background:

• Sepsis is a critical condition with high mortality due to systemic inflammation and organ dysfunction.
• Honeysuckle shows potential in mitigating sepsis-related damage, but its molecular mechanisms are not fully understood.

Purpose of the Study:

• To investigate the molecular mechanisms of honeysuckle's therapeutic effects in sepsis using a multi-omics approach.
• To identify key genes and cellular targets involved in sepsis pathogenesis and potential honeysuckle intervention.

Main Methods:

• RNA sequencing of sepsis patients and healthy controls to identify differentially expressed genes.
• Network pharmacology to predict honeysuckle's active compounds and targets.
• Meta-analysis of gene expression in sepsis survivors versus non-survivors.
• Single-cell RNA sequencing to determine the cellular localization of target genes.

Main Results:

• Identified 1328 differentially expressed genes in sepsis.
• Network analysis linked 15 genes to 12 honeysuckle components.
• DPP4, CD40LG, BCL2, and TP53 were identified as core therapeutic targets, with distinct expression patterns in survivors and non-survivors.
• Single-cell analysis revealed primary expression of these targets in T cells and immune cells.

Conclusions:

• DPP4, CD40LG, BCL2, and TP53 are key regulatory targets in sepsis, primarily expressed in immune cells.
• These findings offer insights into sepsis mechanisms and potential honeysuckle-based therapies.
• Further experimental validation is required to confirm honeysuckle compound interactions with identified targets.