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Biology subjects

Budyak, E. I.

Publications and source records attributed to Budyak, E. I..

2 recordsLinked to original sources

TREM2 Alteration Increases AD Biomarkers and is Associated with Key Genes with 5xFAD Mice Model Analysis on MODEL-AD Database

Alzheimer Disease is a multifactorial disorder characterized by cognitive decline and memory loss. A key gene associated with AD is the TREM2 gene which has been identified as a risk factor for AD. Studies show that TREM2 functions in microglia regulation that controls the amount of AB proteins by the mechanisms of clearance and degradation. However, the exact mechanism of how the TREM2 variations like TREM2 KO and TREM2 R47H contribute to the progression of Alzheimer is still debated. Moreover, research into the levels of gene expression and measurements of biomarkers that contribute to progression of AD is very limited. In this paper, we conduct a comprehensive analysis of the biomarker concentration and gene regulatory behavior in TREM2 KO and TREM2 R47H mutated mice models from the MODEL AD database in order to gain understanding of how these variations contribute to the formation of biomarkers and contribute to AD progression. Our research indicates a correlation between the mutated mice model and the different biomarker concentrations in the brain like insoluble AB40 and 42 proteins, soluble AB40 and 42 proteins, and NFL, which shows that TREM2 gene may be associated with multiple biomarkers. Moreover, we identified some key genes that were associated with the downregulation of the TREM2 gene with the TREM2 KO mice model gene analysis. Finally, we took the confocal images of the TREM2 KO mice model to analyze the effect that the lack of TREM2 extracellular receptor has on the neuritic dystrophy in the brain. Overall, we analyzed the biomarker concentration, gene regulatory activity, and the neuritic effects of the TREM2 KO and TREM2 R47H mutated variants of the TREM2 gene.

neuroscience↗

Measurement of Oxidative Stress in Huh-7 Cell Line to Determine the Effectiveness of PNPLA3 Targeted Gene Therapy for Mitigation of Lipid and Alcohol Induced Oxidative Stress in the Liver

NAFLD is a condition of increased buildup of fat in the liver, causing lipotoxicity that can manifest to cirrhosis, steatosis and fibrosis, which can cause significant and eventually irreversible damage to the liver. A key gene associated is the PNPLA3 I148M variant, which has been shown to display lipogenesis functionality. However, the role of PNPLA3 in increased ROS formation is debated. Moreover, there are no studies determining correlation between the variant and alcohol-induced oxidative stress. This project determines the following mechanistic functions of the PNPLA I148M variant to test for the efficiency of PNPLA3 gene therapy for patients with fatty liver disease and alcohol liver disease. There is a strong correlation between lipid induced oxidative stress and PNPLA3 148M variant. DCFDA shows increased concentration of H2O2 for PNPLA3 148M overexpressed cell lines for both ethanol and FFA treatment groups. Moreover, there is a statistical correlation between PNPLA3 148M overexpressed cell lines and increased mitochondrial oxidative stress by MitoSOX cellular ROS analysis methods. This study confirmed the significant decrease in oxidative stress levels for 148I variant overexpressed cell lines and proved the efficiency of PNPLA3 targeted gene therapy to NAFLD patients and suggested the potential use of the therapeutic method to patients with ALD. To ensure gene therapeutic effectiveness for patients with NAFLD and alcoholic liver diseases, further experiments may be needed to verify molecular pathways of ROS formation by PNPLA3 with qPCR analysis.

biochemistry↗