Burns & Trauma最新文献

Fibrosis is a pathological process marked by excessive extracellular matrix deposition, ultimately resulting in irreversible tissue damage. This aberrant process manifests across multiple organs, including the skin, lung, cardiovascular system, liver, kidneys, and eyes. However, the underlying mechanisms driving tissue fibrosis remain incompletely elucidated, and effective therapeutics are still lacking. In recent years, increasing attention has turned toward the contribution of mechanical signals to fibrotic progression. Within this context, the Piezo family of mechanosensitive ion channels, recently identified as key mediators of mechanotransduction, has emerged as a compelling focus of investigation in diverse pathological settings. This review summarizes current evidence on the central role of Piezo1 in orchestrating fibrotic responses across various tissues. Moreover, we examine the application of Piezo1 modulators in experimental models and their potential to modulate fibrosis, thereby informing the development of novel antifibrotic interventions. By integrating mechanobiological insights into the study of fibrosis, this work highlights promising translational avenues for advancing therapeutic strategies and improving clinical outcomes in fibrotic disease.

Background: The high mortality rate of severe heat stroke is mainly related to multiple organ dysfunction syndrome (MODS), and respiratory failure caused by acute lung injury (ALI) is a significant factor in the development of MODS during the course of severe heat stroke. Previous research has demonstrated that severe heat stroke-induced acute lung injury (sHS-ALI) is associated with an increase in reactive oxygen species (ROS) in vascular endothelial cells (VECs), but the specific initiating factors and intermediate mechanisms involved are unclear.

Methods: In this study, the mRNA profiles of mouse lung tissues were analysed using high-throughput sequencing. Genome-wide knockout was performed using CRISPR-Cas9 technology to identify a cohort of differentially expressed genes that promote human umbilical vein endothelial cells survival after heat stress. The expression of key proteins [fibroblast growth factor 23 (FGF23), phosphorylated fibroblast growth factor receptor-1 (p-FGFR-1), FGFR-1, phosphorylated phospholipase C-γ2 (p-PLC-γ2), PLC-γ2, p-p47^phox, p67^phox, p22^phox, p40^phox, and nicotinamide adenine dinucleotide phosphate oxidase isoform 2 (NOX2)] involved in the FGF23/FGFR-1 mechanism was examined using western blotting and immunohistochemistry.

Results: In this study, we first screened sHS-ALI target genes by cross-comparison in vivo and in vitro and found that FGF23 is the upstream promoter of sHS-ALI. Subsequent investigations involving the interference or inhibition of FGF23 expression revealed that FGF23 induced FGFR-1 Y766 phosphorylation during heat stress-induced VECs damage. In addition, FGF23 participated in NOX2 activation and ROS accumulation and was involved in the process of sHS-ALI. These findings indicated that the FGFR-1 Y766 site mutation strongly suppressed the production of p-PLC-γ2 and heat stress-induced NOX2-ROS activation in VECs. More importantly, mutation of the FGFR-1 Y766 phosphorylation site had no effect on FGF23 expression, and it was impossible to significantly induce the expression of p-PLC-γ2. Moreover, NOX2-ROS activation was inhibited, even in the presence of heat stress, the recombinant FGF23 protein, or combined stimulation.

Conclusions: This study confirmed that FGF23/FGFR1 signalling, as an upstream priming factor, mediated NOX2-ROS activation in VECs after heat stress, thus participating in the sHS-ALI process. FGFR-1 Y766 phosphorylation is essential for FGF23/FGFR-1 signalling activation in VECs, which is involved in sHS-ALI. These findings further clarify the mechanism underlying sHS-ALI and contribute to reducing the mortality and morbidity of severe heat stroke.

Wound injuries, including severe burns, diabetic foot ulcers, and chronic skin defects, remain a significant clinical burden due to their complexity, susceptibility to infection, and impaired healing, particularly in elderly individuals and patients with diabetes or vascular diseases. In these conditions, the wound healing process is disrupted by excessive oxidative stress, persistent inflammation, and microbial infection, ultimately leading to impaired tissue regeneration. These challenges highlight the urgent need for advanced wound care strategies capable of actively modulating the wound microenvironment to facilitate effective and timely healing. Among various hydrogel systems, injectable horseradish peroxidase (HRP)-catalyzed hydrogels have gained attention due to their biocompatibility, ease of application, tunable properties, ability to fill irregular wound geometries, versatility in material selection, and mild crosslinking conditions. These features make them promising candidates for multifunctional wound dressings in both acute and chronic wound management. This review provides a comprehensive overview of recent advancements in the development of injectable HRP-catalyzed hydrogels for wound treatment. We highlight key design strategies that confer multifunctional therapeutic capabilities, including hemostatic function, antibacterial activity, and reactive oxygen species-releasing and scavenging properties. Particular emphasis is placed on the incorporation of gasotransmitter-releasing components to regulate the wound microenvironment effectively. Furthermore, we discuss emerging strategies aimed at transforming these hydrogels into smart wound dressings with advanced functionalities, such as oxygen-releasing ability, electrical conductivity, and microbiome-modulating features. Finally, we emphasize the importance of developing scalable, safe, and personalized hydrogel systems capable of addressing the complex pathophysiology of chronic wounds and improving patient-specific wound care outcomes.