Life Sciences Commons^™

Investigation Of Riluzole’S Synaptic Protection Mechanism Through Hsf1-Bdnf Axis, Yi Zhang

Theses and Dissertations (ETD)

The FDA-approved amyotrophic lateral sclerosis (ALS) drug Riluzole has great potential in treating Alzheimer’s disease (AD) based on promising animal data as well as its known action on modulating synaptic transmission. However, its detailed mechanism of action is not fully understood. Here, we proposed work aiming to address this aspect via focus- ing on the Heat Shock Factor 1 (HSF1)-dependent mechanisms. We found that Riluzole could increase HSF1 and BDNF (Brain-Derived Neurotrophic Factor) expression both at transcriptional and translational levels. CA1 (Cornu Ammonia, the first region in the hip- pocampal circuit), is its main target. We also demonstrated a protective …

Reversal Of P-Glycoprotein And Breast Cancer Resistance Protein Mediated Multidrug Resistance In Vitro Using In Silico Identified Novel Compounds, Amila Nanayakkara

Biological Sciences Theses and Dissertations

Multidrug resistance (MDR) is a major cause of chemotherapy failure. Overexpression of ATP-binding cassette (ABC) transporters, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are two well-studied drug transporters which are associated with MDR. These two transporters also act as a major functional unit of the blood brain barrier to protect the brain from xenobiotics and toxins. Lack of clinically approved P-gp and BCRP inhibitors renders chemotherapy treatments of many MDR cancers ineffective and obstructs drug uptake into the brain.

Using computational methods, we have identified new compounds that inhibit P-gp (Brewer et al., Mol. Pharmacol. 2014). Several of …

Elucidation Of The Molecular Mechanisms Of Electrically-Induced Cardioprotection, Anne Elizabeth Roessler

Dissertations

Cardiovascular disease is the leading cause of death worldwide. A myocardial infarction (MI), commonly known as a heart attack, is a major event in cardiovascular disease characterized by reduced blood flow to the heart. The ischemia and reperfusion (I/R) injury associated with an MI results in a region of dead tissue in the heart called an infarct, the size of which influences patient prognosis. In the 1980s, it was discovered that short, non-lethal episodes of I/R, termed ischemic preconditioning (IPC), can protect the heart against a subsequent MI. Ischemic preconditioning demonstrated the phenomenon of endogenous cardioprotection. Cardioprotection has great potential …

Implementing Mass Spectrometry For The Structural And Compositional Analysis Of Proteins, Mohammad Riaz

Electronic Theses and Dissertations

Lectins are sugar-binding proteins that perform various biological functions such as cellular recognition attachments etc. Pulses the dried edible seeds of certain plants are great sources of lectins and a proteomics approach directed at lectins identification would bring substantial improvement in the lectin identification process. Lectins from nine different plant species were analyzed through SDS-PAGE and proteomics analysis. After LC-MS/MS analysis proteins were identified with protein database searches using Uniprot. Functionally uncharacterized proteins were identified with database searches were annotated with the Pfam and NCBI-CCD databases. In-vitro pharmacological screening will be carried out to assess the pharmacological effects of these …

A Mechanistic Study Of The Teratogenic Potential Of 4-O-Methylhonokiol (Mh) On Japanese Medaka (Oryzias Latipes), Santu Kumar Singha

Electronic Theses and Dissertations

An additional goal of this project was to characterize the Wnt/β-catenin signaling pathway to unravel the adverse potential of MH on the cardiovascular system (CVS). Our study suggested that MH-mediated cardiovascular injury may be caused due to upregulation of some major components of the Wnt/β-catenin pathway through expression of excessive pro-inflammatory mediators. Moreover MH decreased expression of ErbB3 and NRG-2 suggesting impaired cardiac structure. MH exposure caused a slow heartbeat blood occlusion absence of blood circulation decreased hatching efficiency and increased mortality in medaka embryos in a concentration- and time-dependent manner. MH might cause blood vessel occlusion by increasing the …

Differing Functions Of Atr Kinase In Human Epidermal Keratinocytes Exposed To Ultraviolet B Radiation, Kavya Shaj

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Ataxia-telangiectasia and Rad-3 related (ATR) is a DNA damage response protein kinase that is upregulated in various cancer cell types and has key roles in cell cycle progression, DNA repair and apoptosis. Small molecule ATR kinase inhibitors are of importance as antineoplastic agents because they sensitize cancer cells to DNA damaging chemotherapy drugs. However, only a few studies have looked at the effects of ATR kinase inhibitors on non-replicating cells, which constitute the majority of cells in the human body and have suggested an opposite, pro-apoptotic role for ATR kinase signaling in non-replicating cells in comparison to a pro-survival function …

Kinetics Of Microvesicle Particle Release In Keratinocytes, Pariksha Thapa

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Microvesicle particles (MVPs) are subcellular particles that could be involved in inter-cellular communication because they carry various bioactive substances including cytokines. Previous studies from our lab has shown that that the lipid mediator Platelet-activating Factor (1-alkyl-2-acetyl-glycerophosphocholine; PAF) and ultraviolet B radiation (UVB) enhances the release of MVP in various cell types like primary keratinocytes, epithelial cell lines, and murine skin. We hypothesized that there may be synergistic increases in MVP release after combination of treatment of keratinocytes with UVB and PAF agonist (CPAF)/phorbol ester (PMA). The combination treatment significantly increases MVP and cytokine release at 4 to 8 hours time …

Effect Of Endothelial Progenitor Cell-Derived Exosomes On High Glucose And Hypoxia/ Reoxygenation-Induced Injury Of Astrocytes, Manasi Suchit Halurkar

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In this study, we tested the protective effects of EPC-EXs (endothelial progenitor cell derived exosomes) and miR-126 EPC-EXs (microRNA-126 EPC-EXs) on the astrocytes injured by HG (high glucose) plus H/R (hypoxia/reoxygenation) model. At first, we determined the concentration and time dependent uptake of EPC-EXs by astrocytes. It was also found that the EPC-EXs were uptaken via macropinocytosis, caveolin-dependent and clathrin-mediated pathways in astrocytes. Furthermore, the astrocyte cell line was injured through the HG + H/R model. EXs, isolated by ultracentrifugation from the EPC culture supernatant were co-incubated with the injured cells. It was found that EPC-EXs and miR-126 EPC-EXs decrease …