Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, 2021 University of South Florida
Drug Candidates Targeting Hsp90/Cdc37 For The Treatment Of Neurodegenerative Disease, Ryan Martin
USF Tampa Graduate Theses and Dissertations
Neurodegenerative disease refers to the death of specific populations of neurons that canresult in dementia, loss of voluntary muscle motility, and other abnormalities. Two major neurodegenerative diseases are Alzheimer’s disease (AD) and Parkinson’s disease (PD), which are linked to abnormalities in Tau and a-synuclein proteins, respectively. Currently, there is no cure for these diseases. Our group and others have shown that chaperone proteins play a critical role in the processing of Tau and a-synuclein. The inhibition of the Hsp90/Cdc37 chaperone complex is shown to affect the levels of these two proteins. Hence, we hypothesized that a drug molecule, conglobatin (Cb), …
Glutathione-S-Transferase Mu 1 (Gstm1) Gene Augmentation Attenuated Oxidative Stress Induced Changes In Retinal Pigment Epithelium Cells (Rpe), 2021 University of South Florida
Glutathione-S-Transferase Mu 1 (Gstm1) Gene Augmentation Attenuated Oxidative Stress Induced Changes In Retinal Pigment Epithelium Cells (Rpe), Riddhi Sandeep Vichare
USF Tampa Graduate Theses and Dissertations
Purpose: Loss of Retinal Pigment Epithelial (RPE) cells and photoreceptors leads to Age-related macular degeneration (AMD), one of the leading causes of blindness in the elderly worldwide. Oxidative stress-mediated damage is one of the factors that impair the survival of RPE and photoreceptors in dry-AMD. We sought to determine the role of human Glutathione S-Transferase Mu-1 (GSTM1) in protecting RPE cells from oxidative stress-induced changes.
Method: We cloned human GSTM1 cDNA with P2A tag into a lenti-plasmid vector and later made a lentivector to express GSTM1. After that, we infected human retinal pigment epithelial cells (ARPE-19), screened stable ARPE-19 cells …
New Psychoactive Substances In Taiwan: The Current Situation And Initiative For Rational Scheduling, 2021 Degree Program, College of Pharmacy, Kaohsiung Medical University, Taiwan
New Psychoactive Substances In Taiwan: The Current Situation And Initiative For Rational Scheduling, Wen-Jing Yu, Linda B. Cottler, Jih-Heng Li
Journal of Food and Drug Analysis
Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. …
A Convenient And Sensitive Colorimetric Iodide Assay Based On Directly Inducing Morphological Transformation Of Gold Nanostars, 2021 Central South University of Forestry & Technology, China
A Convenient And Sensitive Colorimetric Iodide Assay Based On Directly Inducing Morphological Transformation Of Gold Nanostars, Rongju Zhou, Xiaohui Huang, Qingxiao An, Weizhen Xu, Yi Liu, Dong Xu, Suyan Wang, Qinlu Lin, Jianglin Zhang
Journal of Food and Drug Analysis
We propose a convenient and easy colorimetric assay for highly sensitive detection of iodide by using gold nanostars (GNSs) as probes. The assay relies on that iodide directly changes the morphology of GNSs and alters their longitudinal localized surface plasmon resonance (LSPR) without surface modifications and the use of other reagents. Upon increasing iodide concentration, GNSs gradually transformed to sphere gold nanoparticles, the absorbance at longitudinal LSPR decreased, and solution color varied from greenish blue to red, as confirmed by the UV-Vis absorption spectroscopy and transmission electron microscopy. With this strategy, as low as 0.005 μM of iodide can be …
Quercetin Blocks The Aggressive Phenotype Of Triple Negative Breast Cancer By Inhibiting Igf1/Igf1r-Mediated Emt Program, 2021 Department of Biomedical Sciences, Chung Shan Medical University
Quercetin Blocks The Aggressive Phenotype Of Triple Negative Breast Cancer By Inhibiting Igf1/Igf1r-Mediated Emt Program, Wei-Jen Chen, Jie-Heng Tsai, Li-Sung Hsu, Chih-Li Lin, Hui-Mei Hong, Min-Hsiung Pan
Journal of Food and Drug Analysis
The cancer-preventive activities of quercetin have been extensively studied in invasive breast cancer; however, the role of quercetin on triple-negative breast cancer (TNBC) with overexpression of insulin-like growth factor-1 receptor (IGF1R) has not been resolved. In this article, we demonstrated that quercetin inhibited the activation of IGF1R and its downstream kinases Akt and Erk1/2 in a dose-dependent manner in human MDA-MB-231 breast cancer cells (TNBC cell line). Related to this, quercetin markedly suppressed the metastatic phenotype and epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells by inhibiting the expression of EMT transcription factors Snail and Slug. Quercetin also increased the secretion of …
The Bioactivities Of Resveratrol And Its Naturally Occurring Derivatives On Skin, 2021 Chi Mei Medical Center, Taiwan
The Bioactivities Of Resveratrol And Its Naturally Occurring Derivatives On Skin, Ming-Hsien Lin, Chi-Feng Hung, Hsin-Ching Sung, Shih-Chun Yang, Huang-Ping Yu, Jia-You Fang
Journal of Food and Drug Analysis
Resveratrol has been extensively reported as a potential compound to treat some skin disorders, including skin cancer, photoaging, allergy, dermatitis, melanogenesis, and microbial infection. There has been an increasing interest in the discovery of cosmetic application using resveratrol as the active ingredient because of its anti-aging and skin lightening activities. The naturally occurring derivatives of resveratrol also exert a beneficial effect on the skin. There are four groups of resveratrol derivatives, including hydroxylated compounds, methoxylated compounds, glycosides, and oligomers. The major mechanism of resveratrol and its derivatives for attenuating cutaneous neoplasia, photoaging and inflammation, are related with its antioxidative activity …
Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, 2021 University of Sri Jayewardenepura, Sri Lanka
Microbiological Study In A Gneissic Cave From Sri Lanka, With Special Focus On Potential Antimicrobial Activities, Ethige Isuru P. Silva, Pathmakumara Jayasingha, Saman Senanayake, Anura Dandeniya, Dona Helani Munasinghe
International Journal of Speleology
The emergence of antibiotic resistance is a global health crisis, thus the search for novel antimicrobial compounds has become a continuous necessity. Underexplored and extreme environments, such as cave ecosystems, have been identified as a promising potential source for the discovery of novel microorganisms with novel antimicrobial compounds (AMC). This study presents the first cave microbiological investigation in Sri Lanka, with a special preference for bioprospecting of novel AMC. The cave sediment characterization demonstrated the presence of close to strong acidic conditions (pH 3.1 – 3.3) and thus indicates the possibility of isolating acidophilic microorganisms. Eight cave wall/ceiling fungal strains …
Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, 2021 Chapman University
Structural Characterization And In Vitro Antiproliferative Activity Of Non-Specific Lipid Transfer Protein 1 (Nsltp1) From Fennel (Foeniculum Vulgare) Seeds, Mekdes Megeressa
Pharmaceutical Sciences (PhD) Dissertations
Non-specific lipid transfer proteins (nsLTPs) are cationic proteins involved in intracellular lipid shuttling, in growth and reproduction, as well as in defense against pathogenic microbes. Even though the primary and spatial structures of some nsLTPs from different plants indicate their similar features, they exhibit distinct lipid-binding specificities signifying their various biological roles that dictate further structural study. The present study determined the complete amino acid sequence, in silico 3D structure modeling, and in vitro antiproliferative activity of nsLTP1 from fennel (Foeniculum vulgare) seeds.
Fennel is a member of the family Umbelliferae (Apiaceae) native to southern Europe and the …
Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, 2021 Chapman University
Amphiphilic Cell-Penetrating Peptides Containing Natural And Unnatural Amino Acids As Drug Delivery Tools And Antimicrobial Agents, David Salehi
Pharmaceutical Sciences (MS) Theses
Cell-penetrating peptides containing arginine as positively charged residues and tryptophan or diphenylalanine as hydrophobic residues were synthesized. The synthesis was accomplished through the Fmoc solid-phase peptide synthesis in the presence of HBTU and DIPEA. The side-chain protected linear peptides were cleaved from the resin and cyclized in the presence of DIC and HOAt in the solution phase overnight. MALDI-TOF mass spectrometry was used to characterize the peptides.
The cytotoxicity of the synthesized peptides was determined in CCRF-CEM (human, lymphoblast peripheral blood), and HEK-293 (human, embryonic epithelial kidney healthy) cells using the MTS assay. A concentration of 10 µM was found …
Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, 2021 Virginia Commonwealth University
Nebulizer-Based Systems To Improve Pharmaceutical Aerosol Delivery To The Lungs, Benjamin M. Spence
Theses and Dissertations
Combining vibrating mesh nebulizers with additional new technologies leads to substantial improvements in pharmaceutical aerosol delivery to the lungs across therapeutic administration methods. In this dissertation, streamlined components, aerosol administration synchronization, and/or Excipient Enhanced Growth (EEG) technologies were utilized to develop and test several novel devices and aerosol delivery systems. The first focus of this work was to improve the poor delivery efficiency, e.g., 3.6% of nominal dose (Dugernier et al. 2017), of aerosolized medication administration to adult human subjects concurrent with high flow nasal cannula (HFNC) therapy, a form of continuous-flow non-invasive ventilation (NIV). The developed Low-Volume Mixer-Heater (LVMH) …
Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, 2021 TU Dublin
Structure Based Prediction Of A Novel Gpr120 Antagonist Based On Pharmacophore Screening And Molecular Dynamics Simulations, Ajay Pal Mr, James Curtin, Gemma K. Kinsella
Articles
The G-protein coupled receptor, GPR120, has ubiquitous expression and multifaceted roles in modulating metabolic and anti-inflammatory processes. Recent implications of its role in cancer progression have presented GPR120 as an attractive oncogenic drug target. GPR120 gene knockdown in breast cancer studies revealed a role of GPR120-induced chemoresistance in epirubicin and cisplatin-induced DNA damage in tumour cells. Higher expression and activation levels of GPR120 is also reported to promote tumour angiogenesis and cell migration in colorectal cancer. Some agonists targeting GPR120 have been reported, such as TUG891 and Compound39, but to date development of small-molecule inhibitors of GPR120 is limited. …
Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, 2021 Penn State Dickinson Law
Achieving Better Care In Pennsylvania By Allowing Pharmacists To Practice Pharmacy, Travis Murray
Dickinson Law Review (2017-Present)
Traditionally, state legislatures implemented Prescription Drug Monitoring Programs (“PDMPs”) to assist prescribers, pharmacists, and law enforcement in identifying patients likely to misuse, abuse, or divert controlled substances. PDMP databases contain a catalog of a patient’s recent controlled substances that pharmacies have filled, including the date, location, the quantity of medication filled, and the prescribing health care provider. Prescribers in Pennsylvania have a duty to query the PDMP before prescribing controlled substances in most clinical settings. Pharmacists have a similar duty in Pennsylvania to dispense safe and effective medication therapy to patients and to screen patients for potential signs of misuse, …
Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, 2021 Virginia Commonwealth University
Pharmacophoric Evaluation Of 5-Ht2a And 5-Ht2b Serotonin Recpeptors, Prithvi Hemanth
Theses and Dissertations
Serotonin (5-HT) receptors represent a class of receptors involved in a variety of physiological processes including regulation of mood, perception, cognition, appetite, and heart function, and thus serve as drug targets of several drugs such as antipsychotic agents, hallucinogenic drugs, and appetite suppressant drugs. Due to the structural similarity of certain 5-HT receptor subtypes, particularly 5-HT2 receptors (5-HT2A, 5-HT2B receptors) determination and refinement of pharmacophore models of these receptor subtypes can greatly improve the therapeutic efficacy of drugs that target them.
The goals of this study were to define and/or refine existing pharmacophore models for 5-HT …
Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), 2021 Virginia Commonwealth University
Dendrimer-Based Antibiotics For The Treatment Of Bacterial Biofilm In Cystic Fibrosis (Cf), Younan Ma
Theses and Dissertations
Pseudomonas aeruginosa (PA) is the predominant pathogen in chronic lung infections of cystic fibrosis (CF) patients. The most important mechanism of adaptation of PA to host defense and antibiotic treatment is the formation of biofilms within the mucus layer covering the lung bronchi. The effectiveness of antibiotics such as aminoglycosides is significantly attenuated by their limited penetration through thick mucus and embedded biofilm matrix in patients’ lung. Inhaled tobramycin (Tobra), which is the most commonly used antibiotics in the treatment of PA infections for CF patients, is usually found to be in very high concentration in patients’ lung, and yet …
Science-Based Regulation Of Pharmacological Substances In Competition Horses, 2021 University of Kentucky
Science-Based Regulation Of Pharmacological Substances In Competition Horses, Jacob Machin
Theses and Dissertations--Toxicology and Cancer Biology
Current testing methodologies within equine forensic toxicology focus on arbitrary thresholds and zero-tolerance policy. Modern analytical chemistry’s limits of detection are low enough that oftentimes femtogram-per-milliliter amounts of a substance can readily be identified in both blood and urine of a horse. For most pharmacologically relevant compounds, these concentrations have no relevance to pharmacological effect. It is therefore crucial that testing methodologies to determine appropriate thresholds and cut-offs be developed that are driven by biological activity rather than arbitrary limits of detection. This dissertation looks to address this by suggesting a system of calculated Effective Plasma Concentrations by which a …
Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, 2021 Wayne State University
Protein Phosphatase 2a In Metformin’S Action In Primary Human Skeletal Muscle Cells, Aktham H. Mestareehi
Wayne State University Dissertations
Diabetes is a group of metabolic diseases characterized by hyperglycemia caused by defects in insulin secretion, insulin action, or both. Diabetes is associated with damage, dysfunction, and failure of various organs, such as the eyes, heart, kid-neys, and brain. Diabetes is mainly classified into type 1 (T1DM) and type 2 diabetes (T2D). Diabetes affects more than 34 million people in the USA (about 1 in 10) and more than 90% of diabetic patients have type 2 diabetes (T2D). Insulin resistance is a main characteristic feature of type 2 diabetes. Skeletal muscle insulin resistance is con-sidered to be the primary defect …
Valorization Of Xylan In Agroforestry Waste Streams, 2021 West Virginia University
Valorization Of Xylan In Agroforestry Waste Streams, Harrison Appiah
Graduate Theses, Dissertations, and Problem Reports
Valorization of Xylan in Agroforestry Waste Streams.
Harrison Appiah
Microwave-assisted deep eutectic solvent and gamma-valerolactone metallic chloride catalyzed conversion of xylan to furfural were investigated using a 2x3 factorial experimental design at two levels of percent microwave power, reaction time, and catalyst concentration. The levels of each factor studied were (20%, 60% microwave power, 2, 4 minutes, and 10, 20mg) respectively. The effect of three metallic chloride catalysts (LiCl, FeCl3.6H20, CuCl2) on the conversion of xylan to furfural was also investigated. The gamma-valerolactone-ferric chloride sent system exhibited the highest mean yield of furfural (56.50%). The next highest furfural yield of …
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, 2021 West Virginia University Health Sciences Center
Bypassing The Blood-Brain Barrier: A Physical And Pharmacological Approach For The Treatment Of Metastatic Brain Tumors, Samuel A. Sprowls
Graduate Theses, Dissertations, and Problem Reports
This dissertation (a) provided an in depth literature review of methods to disrupt the BBB/BTB and improve therapeutic distribution to brain tumors, (b) evaluated the use of azacitidine as a single agent therapy for the treatment of brain metastasis of breast cancer and a potential molecular mechanism by which brain tropic cells are sensitized to hypomethylating agents, (c) determined the impact cannabidiol has on P-glycoprotein mediated efflux at the blood-brain barrier and its potential for use as a single agent treatment for metastatic brain tumors, (d) developed a preclinical radiation therapy protocol for use in small animals and in vitro …
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., 2021 Colby College
Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant
Honors Theses
Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …
Lemongrass (Cymbopogon Citratus) Ethanolic Extract Exhibited Activities That Inhibit -Glucosidase Enzymes And Postprandial Blood Glucose Elevation, 2020 Department of Food Technology, Faculty of Life Sciences and Technology, Swiss German University, Tangerang 15143, Indonesia
Lemongrass (Cymbopogon Citratus) Ethanolic Extract Exhibited Activities That Inhibit -Glucosidase Enzymes And Postprandial Blood Glucose Elevation, Maria Dewi Puspitasari Tirtaningtyas Gunawan Puteri, Felicia Melissa Tjiptadi, Phebe Hendra, Filiana Santoso, Zalinar Udin, Nina Artanti, Florence Ignatia Florence Ignatia
Makara Journal of Science
Lemongrass is a common ingredient in Indonesian traditional herbal medicine that potently inhibits carbohydrate hydrolysis. In this study, the in vitro α-glucosidase inhibitory (AGI) activity of lemongrass was compared with its in vivo activity to retard postprandial blood glucose elevation, and the bioactive compounds responsible for these activities were observed. Both water and ethanolic extracts of lemongrass (WLG and ELG, respectively) were tested in vitro for its inhibition of the sucrose and maltose hydrolyzing activities of rat intestinal glucosidase. ELG was observed to exert higher inhibitory activities (Sucrase IC50 = 8.74 mg/mL; Maltase IC50 = 18.93 mg/mL) than …