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Browsing by Author "Borkowski, Kamil"
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Item Blood Levels of Endocannabinoids, Oxylipins, and Metabolites Are Altered in Hemodialysis Patients(MDPI, 2022-08-29) Watkins, Bruce A.; Friedman, Allon N.; Kim, Jeffrey; Borkowski, Kamil; Kaiser, Shaun; Fiehn, Oliver; Newman, John W.; Medicine, School of MedicineHemodialysis patients (HDPs) have higher blood pressure, higher levels of inflammation, a higher risk of cardiovascular disease, and unusually low plasma n-3 polyunsaturated fatty acid (PUFA) levels compared to healthy subjects. The objective of our investigation was to examine the levels of endocannabinoids (eCBs) and oxylipins (OxLs) in female HDPs compared to healthy matched female controls, with the underlying hypothesis that differences in specific PUFA levels in hemodialysis patients would result in changes in eCBs and OxLs. Plasma phospholipid fatty acids were analyzed by gas chromatography. Plasma was extracted and analyzed using ultra-performance liquid chromatography followed by electrospray ionization and tandem MS for eCBs and OxLs. The global untargeted metabolite profiling of plasma was performed by GCTOF MS. Compared to the controls, HDPs showed lower levels of plasma EPA and the associated OxL metabolites 5- and 12-HEPE, 14,15-DiHETE, as well as DHA derived 19(20)-EpDPE. Meanwhile, no changes in arachidonylethanolamide or 2-arachidonylglycerol in the open circulation were detected. Higher levels of multiple N-acylethanolamides, monoacylglycerols, biomarkers of progressive kidney disease, the nitric oxide metabolism-linked citrulline, and the uremic toxins kynurenine and creatine were observed in HDP. These metabolic differences in cCBs and OxLs help explain the severe inflammatory and cardiovascular disease manifested by HDPs, and they should be explored in future studies.Item Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner(Wiley, 2024) Chen, Tianlu; Wang, Lu; Xie, Guoxiang; Kristal, Bruce S.; Zheng, Xiaojiao; Sun, Tao; Arnold, Matthias; Louie, Gregory; Li, Mengci; Wu, Lirong; Mahmoudiandehkordi, Siamak; Sniatynski, Matthew J.; Borkowski, Kamil; Guo, Qihao; Kuang, Junliang; Wang, Jieyi; Nho, Kwangsik; Ren, Zhenxing; Kueider-Paisley, Alexandra; Blach, Colette; Kaddurah-Daouk, Rima; Jia, Wei; Alzheimer’s Disease Neuroimaging Initiative (ADNI); Alzheimer Disease Metabolomics Consortium (ADMC); Radiology and Imaging Sciences, School of MedicineSex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs and 58 BA features in 4 219 samples collected from 1 180 participants from the Alzheimer's Disease Neuroimaging Initiative. The findings revealed that these BA features exhibited significant correlations with clinical stages, encompassing cognitively normal (CN), early and late mild cognitive impairment, and AD, as well as cognitive performance. Importantly, these associations are more pronounced in men than women. Among participants with progressive disease stages (n = 660), BAs underwent early changes in men, occurring before AD. By incorporating BA features into diagnostic and predictive models, positive enhancements are achieved for all models. The area under the receiver operating characteristic curve improved from 0.78 to 0.91 for men and from 0.76 to 0.83 for women for the differentiation of CN and AD. Additionally, the key findings are validated in a subset of participants (n = 578) with cerebrospinal fluid amyloid-beta and tau levels. These findings underscore the role of BAs in AD progression, offering potential improvements in the accuracy of AD prediction.