Biology subjects

Neil, D.

Publications and source records attributed to Neil, D..

2 recordsLinked to original sources

bioRxiv2025

Mitochondrial Responses to Conventional and Ultra-high Dose Rate (FLASH) Radiation

PurposeUltra-high dose rate (>40 Gy/s, FLASH) radiation therapy (RT) provides equivalent tumor control while reducing normal tissue toxicity relative to conventional dose rate (CONV) RT. However, the mechanisms underlying the observed FLASH effect are unknown. We hypothesized that the preservation of mitochondrial integrity in nontumorigenic cells by FLASH RT could be a key factor in reducing normal tissue toxicity and improving overall treatment outcomes. MethodsWe examined mitochondrial health and function after CONV and FLASH in vitro, ex vivo, and in vivo through assays of metabolic flux, mitochondrial membrane potential, mitochondrial reactive oxygen species (ROS), mitochondrial DNA damage and copy number, mitochondrial morphology, and tumor growth and survival. ResultsIn in vitro assays, murine pancreatic cancer (PDAC) cells showed evidence of equal mitochondrial damage in response to CONV and FLASH, but nontumorigenic pancreatic cells were spared by FLASH. These results were recapitulated ex vivo, and mice treated with FLASH showed higher response rates and longer survival time than mice treated with CONV in an in vivo tumor model. ConclusionsCollectively, these results suggest that FLASH spares mitochondrial function in nontumorigenic cells, but not in PDAC cells, relative to CONV. The preservation of mitochondrial integrity in nontumorigenic cells may be a key mechanism underlying the reduced normal tissue toxicity observed with FLASH RT.

cancer biology↗

bioRxiv2025

Utilizing combined spatial transcriptomics to elucidate localized immune responses within human coronary arteries throughout the progression of atherosclerosis

Atherosclerosis is a complex inflammatory disease characterized by the accumulation of lipids and immune cells in the arterial wall, leading to the narrowing and stiffening of blood vessels. The involvement of both innate and adaptive immunity in the pathogenesis of human atherosclerosis is increasingly recognised. However, the spatial organization and specific roles of immune cells during the various stages of disease progression remain poorly understood, underscoring the necessity for additional research to elucidate their functions throughout the disease course. A better understanding of the immune responses contribution to atherosclerosis progression could unveil novel therapeutic targets to mitigate plaque development and rupture, ultimately reducing the burden of cardiovascular events. In this study, we utilised NanoString GeoMx(R) and CosMx technologies to analyse serial sections of human coronary arteries from patients with varying degrees of atherosclerotic lesion severity. Our work consists of a series of investigations, and integrated findings from both the GeoMx(R) and CosMx datasets, including pathway analyses, cell typing, and neighbourhood analysis. This workflow underscores the power of combining these spatial transcriptomics platforms to elucidate biological processes at the single-cell level, hence unbiasedly providing molecules and pathways of relevance to aid in the understanding of disease pathogenesis and assessing the opportunity of novel therapies.

immunology↗