Project description:Intervertebral disc degeneration is highly prevalent in the elderly population and is a leading cause of chronic back pain and disability. Studies have linked degenration with increased disc cell senescence. Likewise, senolytics such as Dasatinib + Quercetin combination may provide a novel approach to mitigate age-dependnt disc degeneration. We used microarrays to explore the transcriptomics of differentially expressed genes between aged disc compartments: AF vs NP at 23M, AF: D+Q vs Veh and NP: D+Q vs Veh.
Project description:The flavonol compound quercetin is considered to be an anti-aging agent due to its cytoprotective actions as an antioxidant. The RNA sequencing analysis of oocytes after in vitro maturation from aged mice identified many genes altered by quercetin treatment and suggested that such treatment has a pronounced impact on genetic programs associated with mitochondrial dysfunction.
Project description:Senolytics are a class of drugs that selectively remove senescent cells. Dasatinib and quercetin have been discovered, and their combination has shown various anti-ageing effects. The SAMP10 mouse strain is a model of brain ageing. Here, we investigated the effect of combination on frailty characteristics in SAMP10. By comparing SAMP10 with SAMR1 mice as normal ageing controls, we investigated some frailty characteristics. Frailty was assessed at 18-38 weeks of age with a clinical frailty index. Motor and cognitive function of these mice were evaluated using behavioral experiments. SAMP10 mice were divided into vehicle and combination, and these functions and histological changes in the brain hippocampus were investigated. Finally, the in vitro effects of combination on oxidative stress-induced senescent muscle and neuronal cells were investigated. As a result, we found that frailty index was higher in SAMP10 than SAMR1. Motor and cognitive function were worse in SAMP10 than SAMR1. Furthermore, combination therapy improved frailty, motor and cognitive function, and the senescent phenotype of the hippocampus compared with vehicle in SAMP10. In summary, SAMP10 showed more marked frailty characteristics than SAMR1, and dasatinib and quercetin attenuated them in SAMP10. From our results, senolytic therapy might contribute protective effects against frailty.
Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis. RNA from three dasatinib-resistant (MiaPaCa2, Panc1, SU8686) and three dasatinib-sensitive (Panc0504, Panc0403, Panc1005) pancreatic cancer cell lines were extracted. Biological triplicates were employed for each cell line. Complementary DNA microarray analysis was performed using Illumina Human HT-12 v4 BeadChip (Illumina, San Diego, CA) at the National University of Singapore Core Facility following the manufacturer’s instructions.
Project description:Gene profiles from three dasatinib-resistant and three dasatinib-sensitive pancreatic cancer cell lines were compared by microarray analysis.
Project description:HLA-DQ molecules can be formed as both cis and trans variants. So far, the progress for predicting HLA-DQ antigen presentation has been limited. In addition, the contribution of trans-only variants in shaping the HLA-DQ immunopeptidome remains largely unresolved. Here, we address these issues by integrating state-of-the-art immunoinformatics data mining models with large volumes of high-quality HLA-DQ specific immunopeptidomics data. The analysis demonstrated a highly improved predictive power and molecular coverage for models trained with these novel HLA-DQ data and a limited to no contribution for trans-only HLA-DQ variants to the overall HLA-DQ immunopeptidome.