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The significant mechanism and treatments of cell death in heatstroke

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Abstract

With global warming, extreme environmental heat is becoming a social issue of concern, which can cause adverse health results including heatstroke (HS). Severe heat stress is characterized by cell death of direct heat damage, excessive inflammatory responses, and coagulation disorders that can lead to multiple organ dysfunction (MODS) and even death. However, the significant pathophysiological mechanism and treatment of HS are still not fully clear. Various modes of cell death, including apoptosis, pyroptosis, ferroptosis, necroptosis and PANoptosis are involved in MODS induced by heatstroke. In this review, we summarized molecular mechanism, key transcriptional regulation as for HSF1, NRF2, NF-κB and PARP-1, and potential therapies of cell death resulting in CNS, liver, intestine, reproductive system and kidney injury induced by heat stress. Understanding the mechanism of cell death provides new targets to protect multi-organ function in HS.

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Funding

This work was supported by grants from the Medical Science and Technology Projects in Guangdong [A2023269] and Science and Technology Projects in Guangzhou [2024A03J0640].

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Author notes

  1. Zixin Wang and Jie Zhu contributed equally to this work.

Authors and Affiliations

  1. Department of Metabolic Surgery, **shazhou Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510010, China

    Zixin Wang & Liang** Wu

  2. Department of Pediatric, General Hospital of Southern Theater Command of PLA, Guangzhou, 510010, China

    Jie Zhu

  3. Department of Medicine Intensive Care Unit, General Hospital of Southern Theater Command of PLA, Guangzhou, 510010, China

    Dingshun Zhang & Zhifeng Liu

  4. Department of Thoracic Surgery, Foshan Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China

    **ke Lv

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  1. Zixin Wang
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  2. Jie Zhu
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  3. Dingshun Zhang
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  4. **ke Lv
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  5. Liang** Wu
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  6. Zhifeng Liu
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Contributions

Zixin Wang and Jie Zhu wrote the main manuscript text. Dingshun Zhang prepared Figs. 1, 2 and 3. **ke Lv prepared Tables 1 and 2. Zhifeng Liu and Liang** Wu identified the topic of this review. All authors reviewed the manuscript.

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Correspondence to Liang** Wu or Zhifeng Liu.

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Wang, Z., Zhu, J., Zhang, D. et al. The significant mechanism and treatments of cell death in heatstroke. Apoptosis (2024). https://doi.org/10.1007/s10495-024-01979-w

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