Biology subjects

Choi, Y. D.

Publications and source records attributed to Choi, Y. D..

3 recordsLinked to original sources

bioRxiv2026

APOE4 genotype and old age interact to impact cerebrovascular function, brain volume, and neuroinflammation in mice

Old age and the apolipoprotein E {varepsilon}4 (APOE4) genotype are two of the greatest risk factors for late-onset Alzheimers disease (LOAD). However, the interaction between these is poorly understood, as most preclinical studies use young mice. Therefore, we assessed the interaction between APOE genotype and age across a comprehensive set of cerebrovascular and related outcomes. We performed in vivo imaging, ex vivo cerebral artery studies, behavioral tests, and molecular analyses in male and female homozygous APOE3 and APOE4 mice at [~]6 months (young) and [~]24 months (old). APOE4 interacted with old age to lead to deficits in brain volume and greater microglia content. Old APOE4 mice also exhibited greater cerebral artery vasoconstriction to endothelin-1 (ET-1) than old APOE3 mice, a response concomitant with age-and genotype-related differences in the expression of ET-1 receptors and endothelin-converting enzyme. While we found several interactions between age and APOE genotype, only age impacted cognitive function, cerebral artery endothelial function, and arterial stiffness. In summary, we found that brain volume, neuroinflammation, and ET-1-related outcomes were influenced by the interaction of APOE genotype and age, while other outcomes were affected only by age. As such, an altered ET-1 response and greater neuroinflammation may contribute to the increased risk for LOAD in APOE4 carriers.

neuroscience↗

bioRxiv2025

The Impact of Age and Sex on Cerebral and Large Artery Stiffness and the Response to Pulse Pressure

Vascular aging is characterized by a tandem increase in pulse pressure and large elastic artery stiffness. Greater stiffness of the large arteries leads to elevated pulse pressure transmitted into the cerebral circulation, causing dysfunction. However, little is known in females about age-related stiffening of the arteries and the impacts of high pulse pressure on the cerebral vasculature. To examine the effects of sex and age on the cerebral artery response to pulse pressure, we studied cerebral arteries collected from young and old female and male C57BL/6 mice. Isolated cerebral arteries were exposed ex vivo to static pressure, low pulse pressure, and high pulse pressure. Exposure to high pulse pressure impaired endothelium-dependent dilation in cerebral arteries from young female and male mice, with impairments also occurring in young female cerebral arteries after exposure to low pulse pressure. In contrast, exposure to low or high pulse pressure did not impact cerebral artery endothelium-dependent dilation for old male or female mice. During exposure to high pulse pressure, young females had higher cerebral artery compliance compared with young males and old females. Old mice also had higher cerebral artery passive stiffness and aortic pulse wave velocity compared with young mice. We also found age and sex differences in arterial wall thickness, collagen and elastin content, and matrix metalloproteinase 9 expression. Taken together, young female mice have more compliant cerebral arteries, which are more susceptible to endothelial dysfunction caused by pulse pressure.

physiology↗

bioRxiv2020

Prostate Epithelial Genes Define Docetaxel-Sensitive Prostate Cancer Molecular Subtype

BACKGROUND & OBJECTIVESAnalysis of the transcriptomic landscape of prostate adenocarcinoma shows multidimensional gene expression variability. Understanding cancer transcriptome complexity can provide biological insight and therapeutic guidance. To avoid potential confounding factors, such as stromal contamination and stress-related material degradation, we utilized a set of genes expressed by prostate epithelial cells from single-cell transcriptome data of the human prostate gland. MATERIALS & METHODSAnalyzing publicly available bulk and single-cell RNA sequencing data, we defined 1,629 genes expressed by prostate epithelial cells. Consensus clustering and CIBERSORT deconvolution were used for class discovery and proportion estimate analysis. The Cancer Genome Atlas Prostate Adenocarcinoma (TCGA-PRAD) dataset served as a training set. The resulting clusters were analyzed in association with clinical, pathologic, and genomic characteristics and impact on survival. RESULTSTCGA-PRAD tumors were separated into four subtypes: A (30.0%), B (26.0%), C (14.7%), D (4.2%), and mixed (25.0%). Subtype A was characterized by low frequency of ETS-family fusions and high expression of KLK3, which encodes prostate-specific antigen (PSA). Subtype B showed the highest expression of ACP3, encoding PAP (prostatic acid phosphatase). Subtypes C and D were commonly associated with advanced T/N stages, high Gleason grades, and p53 or PIK3CA mutations. In silico drug-sensitivity screening suggested that subtype B is likely sensitive to docetaxel and paclitaxel. Serum PSA/PAP ratio was predictive of a radiographic response to docetaxel in metastatic castration-resistant prostate cancer patients. CONCLUSIONWe propose four prostate adenocarcinoma subtypes with distinct transcriptomic, genomic, and pathologic characteristics. PSA/PAP ratio in advanced cancer may aid in determining which patients would benefit from maximized androgen receptor inhibition or early use of antimicrotubule agents. Molecular subtypes and biomarkers must be validated in a prospective cohort study.

cancer biology↗