It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be…
It has been well established that mitochondria play a critical role in the pathology of Friedreich's Ataxia. This disease is believed to be caused by a deficiency of frataxin, which research suggests is responsible for iron sulfur cluster assembly. This incomplete assembly of iron sulfur clusters is believed to be linked with dysfunctional complexes in the mitochondrial respiratory chain, increased oxidative stress, and potential cell death. Increased understanding of the pathophysiology of this disease has enabled the development of various therapeutic strategies aimed at restoring mitochondrial respiration. This thesis contains an analysis of the biological activity of several classes of antioxidants against oxidative stress induced by diethyl maleate in Friedreich's Ataxia lymphocytes and CEM leukemia cells. Analogues of vitamin E α-tocopherol have been shown to protect cells under oxidative stress. However, these same analogues show various levels of inhibition towards the electron transport chain complex I. Bicyclic pyridinols containing a ten carbon substituent provided favorable cytoprotection. N-hydroxy-4-pyridone compounds were observed to provide little protection. Similarly, analogues of CoQ10 in the form of pyridinol and pyrimidinol compounds also preserved cell viability at low concentrations.
Asphalt is a widely used mixture in the paving and roofing industries and its sales are expected to increase by 57% in the next eight years alone (Mandaokar, 2024). However, it is known to have highly toxic constituents such as benzo[a]pyrene (BaP) and catechol, (National Institute, 1977, Hazard Review,…
Asphalt is a widely used mixture in the paving and roofing industries and its sales are expected to increase by 57% in the next eight years alone (Mandaokar, 2024). However, it is known to have highly toxic constituents such as benzo[a]pyrene (BaP) and catechol, (National Institute, 1977, Hazard Review, 2000, Neghab et al., 2015, and Rozewski et al., 2023). Lemon juice, which is an inexpensive and easily accessible natural substance that is shown to have health benefits such as increasing insulin sensitivity, aiding with weight loss, and preventing heart disease (Tejpal et al., 2020), may counteract the effects of asphalt. The question of what the biological effects of asphalt, lemon juice, and the combination of the two on adipocytes was tested via computational analysis and experiments. It was predicted that catechol and lemon juice components will show biological effects in adipocytes that could be opposing, additive, or synergistic. A computational analysis involving the docking of fourteen components of asphalt and thirty-five components of lemon juice constituents to a targetome of 7,529 proteins (Ovanessians et al., 2024) suggests that asphalt and lemon juice components have many possible protein targets. Experiments were carried out with 3T3L1 mouse adipocytes to study five different lemon extracts (crude, hexane organic and aqueous, and ether organic and aqueous), and two components of asphalt (catechol and BaP): 1) Thiazolyl Blue Tetrazolium Bromide (MTT) cell viability and toxicity assay, 2) reactive oxygen species fluorescence assay, 3) Nile red staining assay, 4) red oil o staining assay, and a 5) lipidomics analysis on the hexane and ether organic extracts of lemon juice. This study has shown that asphalt components BaP and catechol and lemon juice components combined have the following biological effects on adipocytes: 1) Of the 5 lemon extracts tested, the organic layer of the hexane extract solubilized in DMSO (LE4) decreases differentiation the most. 2) Nile red staining is inhibited by 0.1 mg/mL of LE4, 1 µM BaP, and 20 µM catechol at a similar level. 3) Cell morphology differs between LE4, BaP, and catechol. Future work will include an insulin sensitivity assay to confirm the indicative inhibitory relationship found between lemon juice and asphalt. Expanding upon the lipidomic results of the lemon juices, as well as maximizing the potential of dockings by connecting results with the experiments, may also prove to be useful in future studies.
Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal protrusion, dyspareunia, and difficulties with waste excretion. Risk factors are…
Pelvic organ prolapse (POP) is a condition involving the weakening of the pelvic floor, with a prevalence of up to 50% of women experiencing the condition to some degree. Individuals with the condition are susceptible to multiple symptoms include vaginal protrusion, dyspareunia, and difficulties with waste excretion. Risk factors are common and numerous for POP, and the economic burden of the condition poses a significant cost to nations worldwide. For many years, the primary solution to POP was the usage of transvaginal meshes, often composed of polypropylene, but rising reports of harmful side effects have led to their recall. Due to this, the space is open for novel solutions, and treatments based in regenerative medicine are on the rise. One such potential treatment is the usage of functionalized polyvinyl alcohol scaffolds to support the regeneration and strengthening of the pelvic floor. To validate the usage of this scaffold, this study focuses on the biocompatibility of the scaffolds, with specific focus on the maintenance of cell viability and proliferation on the scaffold. Through usage of metabolic assays and fluorescence microscopy, scaffolds composed of functional polyvinyl alcohol with cellulose have shown promise in supporting the cell types necessary for reconstructing the pelvic floor.
