Effects of 16.8-22.0 T high static magnetic fields on the development of zebrafish in early fertilization.

OBJECTIVES: Despite some existing studies on the safety of high static magnetic fields (SMFs), the effects of ultra-high SMFs above 20.0 T for embryonic development in early pregnancy are absent. The objective of this study is to evaluate the influence of 16.8-22.0 T SMF on the development of zebrafish embryos, which will provide important information for the future application of ultra-high field magnetic resonance imaging (MRI). METHODS: Two-hour exposure to homogenous (0 T/m) 22.0 T SMF, or 16.8 T SMFs with 123.25 T/m spatial gradient of opposite magnetic force directions was examined in the embryonic development of 200 zebrafish. Their body length, heart rate, spontaneous tail-wagging movement, hatching and survival rate, photomotor response, and visual motor response (VMR) were analyzed. RESULTS: Our results show that these ultra-high SMFs did not significantly affect the general development of zebrafish embryos, such as the body length or spontaneous tail-wagging movement. However, the hatching rate was reduced by the gradient SMFs (p < 0.05), but not the homogenous 22.0 T SMF. Moreover, although the zebrafish larva activities were differentially affected by these ultra-high SMFs (p < 0.05), the expression of several visual and neurodevelopmental genes (p < 0.05) was generally downregulated in the eyeball. CONCLUSIONS: Our findings suggest that exposure to ultra-high SMFs, especially the gradient SMFs, may have adverse effects on embryonic development, which should cause some attention to the future application of ultra-high field MRIs. CLINICAL RELEVANCE STATEMENT: As technology advances, it is conceivable that very strong magnetic fields may be adapted for use in medical imaging. Possible dangers associated with these higher Tesla fields need to be considered and evaluated prior to human use. KEY POINTS: Ultra-High static magnetic field may affect early embryonic development. High strength gradient static magnetic field exposure impacted zebrafish embryonic development. The application of very strong magnetic fields for MR technologies needs to be carefully evaluated.

Histone lactylation-ROS loop contributes to light exposure-exacerbated neutrophil recruitment in zebrafish.

Light serves as a crucial external zeitgeber for maintaining and restoring physiological homeostasis in most organisms. Disrupting of light rhythms often leads to abnormal immune function, characterized by excessive inflammatory responses. However, the underlying regulatory mechanisms behind this phenomenon remain unclear. To address this concern, we use in vivo imaging to establish inflammation models in zebrafish, allowing us to investigate the effects and underlying mechanisms of light disruption on neutrophil recruitment. Our findings reveal that under sustained light conditions (LL), neutrophil recruitment in response to caudal fin injury and otic vesicle inflammation is significantly increased. This is accompanied by elevated levels of histone (H3K18) lactylation and reactive oxygen species (ROS) content. Through ChIP-sequencing and ChIP‒qPCR analysis, we discover that H3K18 lactylation regulates the transcriptional activation of the duox gene, leading to ROS production. In turn, ROS further promote H3K18 lactylation, forming a positive feedback loop. This loop, driven by H3K18 lactylation-ROS, ultimately results in the over recruitment of neutrophils to inflammatory sites in LL conditions. Collectively, our study provides evidence of a mutual loop between histone lactylation and ROS, exacerbating neutrophil recruitment in light disorder conditions, emphasizing the significance of maintaining a proper light-dark cycle to optimize immune function.

Metformin Attenuates Neutrophil Recruitment through the H3K18 Lactylation/Reactive Oxygen Species Pathway in Zebrafish.

Beyond its well-established role in diabetes management, metformin has gained attention as a promising therapeutic for inflammation-related diseases, largely due to its antioxidant capabilities. However, the mechanistic underpinnings of this effect remain elusive. Using in vivo zebrafish models of inflammation, we explored the impact of metformin on neutrophil recruitment and the underlying mechanisms involved. Our data indicate that metformin reduces histone (H3K18) lactylation, leading to the decreased production of reactive oxygen species (ROS) and a muted neutrophil response to both caudal fin injury and otic vesicle inflammation. To investigate the precise mechanisms through which metformin modulates neutrophil migration via ROS and H3K18 lactylation, we meticulously established the correlation between metformin-induced suppression of H3K18 lactylation and ROS levels. Through supplementary experiments involving the restoration of lactate and ROS, our findings demonstrated that elevated levels of both lactate and ROS significantly promoted the inflammatory response in zebrafish. Collectively, our study illuminates previously unexplored avenues of metformin's antioxidant and anti-inflammatory actions through the downregulation of H3K18 lactylation and ROS production, highlighting the crucial role of epigenetic regulation in inflammation and pointing to metformin's potential in treating inflammation-associated conditions.