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Background <p>Ferroptosis, an iron-dependent regulated cell death, plays a critical role in the pathophysiology of sepsis. This study aimed to identify core targets and therapeutic agents related to ferroptosis in sepsis.</p> Methods <p>Differential analysis of peripheral blood RNA-sequencing data from 19 patients with sepsis and 10 healthy controls was performed. Ferroptosis-related hub genes were identified via a PPI network and validated by Mendelian randomization, protein cohort studies, and survival/meta-analyses. Single-cell sequencing localized core genes, and in vitro/in vivo experiments explored targeted drugs.</p> Results <p>High TFRC expression correlated with poor sepsis prognosis. TFRC was predominantly expressed in monocytes and B cells, with more monocytes in non-survivors. γ‑Tocotrienol (γ‑T3) treatment was associated with reduced TFRC expression, lower ROS and IL‑1β levels, and improved survival in septic zebrafish and mice.</p> Conclusion <p>TFRC is a potential therapeutic target for ferroptosis in sepsis. γ‑T3 alleviates LPS-induced TFRC upregulation and improves survival in septic mice, suggesting its potential as a therapeutic agent.</p> <p><i>Study Registration</i>: ChiCTR1900021261 (Chinese Clinical Trial Registry), registered February 4, 2019. Type of study: retrospective observational study using archived biological samples.</p>

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Ferroptosis-related TFRC: a potential therapeutic target in sepsis and regulatory effect of γ-Tocotrienol

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月8日

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  • Yandong Yao,
  • Gege Ke,
  • Yuanxin Wu,
  • Haili Li,
  • Yingchun Hu,
  • Muhu Chen

摘要

Background

Ferroptosis, an iron-dependent regulated cell death, plays a critical role in the pathophysiology of sepsis. This study aimed to identify core targets and therapeutic agents related to ferroptosis in sepsis.

Methods

Differential analysis of peripheral blood RNA-sequencing data from 19 patients with sepsis and 10 healthy controls was performed. Ferroptosis-related hub genes were identified via a PPI network and validated by Mendelian randomization, protein cohort studies, and survival/meta-analyses. Single-cell sequencing localized core genes, and in vitro/in vivo experiments explored targeted drugs.

Results

High TFRC expression correlated with poor sepsis prognosis. TFRC was predominantly expressed in monocytes and B cells, with more monocytes in non-survivors. γ‑Tocotrienol (γ‑T3) treatment was associated with reduced TFRC expression, lower ROS and IL‑1β levels, and improved survival in septic zebrafish and mice.

Conclusion

TFRC is a potential therapeutic target for ferroptosis in sepsis. γ‑T3 alleviates LPS-induced TFRC upregulation and improves survival in septic mice, suggesting its potential as a therapeutic agent.

Study Registration: ChiCTR1900021261 (Chinese Clinical Trial Registry), registered February 4, 2019. Type of study: retrospective observational study using archived biological samples.