Chemicals and Drugs Commons^™

Multi-Target Ligand-Guided Selection (Ligs) Against B-Cell Specific Antigens Expressed In A Single Lymphoma Cell Population, Nicole B. Williams

Dissertations, Theses, and Capstone Projects

Nucleic acid ligands called aptamers are single-stranded DNA or RNA molecules which fold into functional three-dimensional structures to facilitate their target binding with high affinity and specificity. The method used to generate aptamers is an in vitro process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). A variant of SELEX, cell-SELEX has been used to select aptamers against cell-surface proteins in their native state. We recently introduced a novel method called Ligand-Guided Selection (LIGS) to identify aptamers against cell-surface markers. Herein, we expanded LIGS method into a multiplexing platform to partition multiple aptamers against B-cell-specific antigens, CD19 and CD20, …

Comparison Of Hydrolysis Efficiency And Performance Of Four Recombinant Β- Glucuronidase Enzymes For The Detection Of Opioids In Urine Samples By Lc-Ms/Ms, Christina Fernandez

Student Theses

The United States has been experiencing a nationwide public health crisis since introducing prescription opioids in the 1990s. A central problem with opioids is their highly addictive nature causing a dose-dependent respiratory depression leading to overdoses and deaths. Drug overdose deaths have risen in the past two decades, with opioids being the dominant driver of this epidemic. Given the circumstances, accurate and efficient confirmatory analysis of opioids in urine is essential to monitoring patients’ compliance and preventing drug diversion in clinical and forensic settings. The development of recombinant β-glucuronidases allows for the hydrolysis of glucuronidated opioids using a shorter incubation …

Development Of Non-Viral Nano-Carriers For Gene Delivery And Covid-19 Vaccines, Zhongyu Li

Dissertations

Gene therapy is one of the most promising medical fields with the potential to effectively advance the treatment of difficult diseases by producing therapeutic proteins or repairing defective gene sequences. However, gene therapy presents severe challenges in delivery including renal clearance, phagocytosis, enzymatic degradation, protein absorption, and cellular internalization barriers, which have been barriers for translation into the clinic. Naked nucleic acids, with their intrinsic negative charge, electrostatically repulse the anionic cell membrane, preventing cellular uptake. Also, they are considered foreign genetic material when introduced into the body and are rapidly cleared by the reticuloendothelial system or degraded by nucleases, …

Design, Synthesis, Biological And Computational Studies Of Flavonoid Acetamide Derivatives, Daniel Kasungi Isika

Dissertations

Flavonoid compounds (FC) have extensive biological applications through potent antimicrobial, anti-inflammatory, anticancer, antidiabetic, and antioxidant properties. These applications are nevertheless limited by low bioavailability, poor aqueous solubility, enzymatic degradation, rapid metabolism, and fast body clearance. FC show unique structure-activity relationships (SARs) essential in assessing and mitigating the prevalent challenges impeding their applications. These challenges can be addressed by structural modification of the FC through functionalization of the phenolic rings, modification of the ketone group, and modification of the phenolic hydroxyl groups with bioisosteres.

The objectives of this work are to (i) design and synthesize novel flavonoid acetamide derivatives (FADs) and …

Development Of Novel Hybrid Structures For Fast Dissolution Of Hydrophobic Drugs, Mohammad Saiful Islam

Dissertations

Nanomaterials have proven to be highly effective in the design and development of biomedicine. Complementary nanostructured hybrid particles show great promise in drug delivery applications. By improving functionalization, the physicochemical properties of the particles can be enhanced resulting in a high surface area, tunable hydrophilicity and porosity. These characteristics can provide a suitable environment for drug encapsulation, biocompatibility, high drug loading, and customizable release capabilities.

The formulation of drugs with poor water solubility faces multiple challenges, such as insufficient dissolution and inconsistent therapeutic efficacy, particularly when administered orally over an extended period. To overcome these challenges, some of the beneficial …

Microrna (Mirna) Complexity In Alzheimer’S Disease (Ad), Walter J. Lukiw

School of Medicine Faculty Publications

AD is a complex, progressive, age-related neurodegenerative disorder representing the most common cause of senile dementia and neurological dysfunction in our elderly domestic population. The widely observed heterogeneity of AD is a reflection of the complexity of the AD process itself and the altered molecular-genetic mechanisms operating in the diseased human brain and CNS. One of the key players in this complex regulation of gene expression in human pathological neurobiology are microRNAs (miRNAs) that, through their actions, shape the transcriptome of brain cells that normally associate with very high rates of genetic activity, gene transcription and messenger RNA (mRNA) generation. …

Acceptability Of Fully Guided Virtual Implant Planning Software Among Dental Undergraduate Students, Shishir Ram Shetty, Colin Murray, Sausan Al Kawas, Sara Jaser, Wael Talaat, Medhini Madi, Vinayak Kamath, Nisha Manila, Raghavendra Shetty, Vidya Ajila

School of Dentistry Faculty Publications

Background: Fully guided implant surgery as a technique is gaining popularity. It has been observed that use of surgical guides improves precision and predictability for dental implant placement. However, like any other newer technology, the acceptance of fully guided dental implant technology among users is based upon its perceived usability. This study aimed at evaluating the perception about using Virtual Implant Planning Software (VIPS) among undergraduate dental students at the university of Sharjah. Methods: Ninety-Six dental surgery students from the University of Sharjah were included in the study. One week after the Virtual Implant Planning Software (Planmeca Romexis version 6.2 …

Ethical Issues And Standards Of Responsible Research Conduct And Monitoring In An Adventist Institution Of Higher Learning - The Babcock Experience, Kayode O. Ogunwenmo, Godswill N. Anyasor, Grace O. Tayo

Adventist Human-Subject Researchers Association

Ethical issues and standards of responsible research conduct involving human participants are important considerations in any institution of higher learning and in particular Adventist institutions. Research conduct and ethics are reviewed and approved before they begin by the Babcock University Health Research Ethics Committee (BUHREC)

Driving Under The Influence Of Cannabis: Impact Of Combining Toxicology Testing With Field Sobriety Tests, Robert L. Fitzgerald, Anya Umlauf, Jacqueline A. Hubbard, Melissa A. Hoffman, Philip M. Sobolesky, Shannon E. Ellis, David J. Grelotti, Raymond T. Suhandynata, Marilyn A. Huestis, Igor Grant, Thomas D. Marcotte

Institute of Emerging Health Professions Faculty Papers

BACKGROUND: Cannabis is increasingly used both medically and recreationally. With widespread use, there is growing concern about how to identify cannabis-impaired drivers.

METHODS: A placebo-controlled randomized double-blinded protocol was conducted to study the effects of cannabis on driving performance. One hundred ninety-one participants were randomized to smoke ad libitum a cannabis cigarette containing placebo or delta-9-tetrahydrocannabinol (THC) (5.9% or 13.4%). Blood, oral fluid (OF), and breath samples were collected along with longitudinal driving performance on a simulator (standard deviation of lateral position [SDLP] and car following [coherence]) over a 5-hour period. Law enforcement officers performed field sobriety tests (FSTs) to …

The Role Of Alpha-2 Agonists For Attention Deficit Hyperactivity Disorder In Children: A Review, Elisa E. Neuchat, Brooke E. Bocklud, Kali Kingsley, William T. Barham, Patrick M. Luther, Shahab Ahmadzadeh, Sahar Shekoohi, Elyse M. Cornett, Alan D. Kaye

School of Medicine Faculty Publications

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack …

Design, Synthesis, And Antiproliferative Activity Of Benzopyran-4-One-Isoxazole Hybrid Compounds, Shilpi Gupta, Shang Eun Park, Saghar Mozaffari, Bishoy El-Aarag, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

The biological significance of benzopyran-4-ones as cytotoxic agents against multi-drug resistant cancer cell lines and isoxazoles as anti-inflammatory agents in cellular assays prompted us to design and synthesize their hybrid compounds and explore their antiproliferative activity against a panel of six cancer cell lines and two normal cell lines. Compounds 5a–d displayed significant antiproliferative activities against all the cancer cell lines tested, and IC₅₀ values were in the range of 5.2–22.2 μM against MDA-MB-231 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. The IC₅₀ values of 5a–d …

Photoisomerizable Membrane Active Peptides, Cristina Ventura

Seton Hall University Dissertations and Theses (ETDs)

Membrane active peptides (MAPs) bind and partition into the cell membrane thus causing permeabilization. Many α-helical membrane active peptides contain central proline residues that distinguish the hydrophobic and hydrophilic faces of the helix. The proline induces a bend that produces a helix-hinge-helix motif. Mutation of these proline residues has a significant effect on the activity of the MAP. Azobenzene is a photoisomerizable molecule that switches from its trans to cis isomer upon excitation with ultraviolet (UV) light and from its cis to trans isomer upon excitation with visible light (VL). In this work it is hypothesized that the hinge function …

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …

Novel Allosteric Effectors Targeting Human Transcription Factor Tead, Mayar Terek Ibrahim, Gennady M. Verkhivker, Jyoti Misra, Peng Tao

Mathematics, Physics, and Computer Science Faculty Articles and Research

The Hippo pathway is an evolutionary conserved signaling network involved in several cellular regulatory processes. Dephosphorylation and overexpression of Yes-associated proteins (YAPs) in the Hippo-off state are common in several types of solid tumors. YAP overexpression results in its nuclear translocation and interaction with transcriptional enhanced associate domain 1-4 (TEAD1-4) transcription factors. Covalent and non-covalent inhibitors have been developed to target several interaction sites between TEAD and YAP. The most targeted and effective site for these developed inhibitors is the palmitate-binding pocket in the TEAD1-4 proteins. Screening of a DNA-encoded library against the TEAD central pocket was performed experimentally to …

Improved Synthesis And Anticancer Activity Of A Potent Neuronal Nitric Oxide Synthase Inhibitor, Dhananjayan Vasu, Cory T. Reidl, Eric Wang, Sun Yang, Richard B. Silverman

Pharmacy Faculty Articles and Research

An improved synthesis of 4-methyl-7-(3-((methylamino)methyl)phenethyl)quinolin-2-amine (1) is reported. A scalable, rapid, and efficient methodology was developed to access this compound with an overall yield of 35%, which is 5.9-fold higher than the previous report. The key differences in the improved synthesis are a high yielding quinoline synthesis by a Knorr reaction, a copper-mediated Sonogashira coupling to the internal alkyne in excellent yield, and a crucial deprotection of the N-acetyl and N-Boc groups achieved under acidic conditions in a single step rather than a poor yielding quinoline N-oxide strategy, basic deprotection conditions, and low yielding copper-free conditions that …

Diffusion Of Ionic Liquid-Modified Polymer Nanoparticles Through Nasal Mucus, Mary Vanlandingham

Honors Theses

Mucosal barriers are a natural defense system for preventing the entry of foreign objects into the body; however, they pose as obstacles for effective drug delivery. Coated polymer nanoparticles have been proven to possess improved rates of diffusion across mucus compared to their uncoated, or bare, counterparts. When choline-based ionic liquids (ILs) are introduced to an aqueous system, their dissociation leads to an increase in solution conductivity which ultimately reduces the viscosity of mucus without significantly affecting its structure. Additionally, ILs are highly tunable, so they work well in a range of pHs and conductivities, making ILs an ideal choice …

Botulinum Toxin For Abductor Type Spasmodic Dysphonia: A Systematic Review, Keyona Sutton

Honors Theses

A systematic review was conducted to show that BTX (Botulinum Toxin) is the most effective treatment for Abductor Spasmodic Dysphonia (ABSD). There were a total of 117 records screened for inclusion in this review. After the initial screening, there were seven successive rounds of screening for eligibility. This process produced a total of three eligible records that met the following conditions: patients presented with spastic abduction, electromyography BTX type A injection into the posterior cricoarytenoid muscle, and measurement of results with acoustic dimensions. After surveying all eligible studies, it was concluded that BTX is an effective treatment for ABSD. Every …

Dextromethorphan/Quinidine For The Pseudobulbar Affect In Neurological Disorders And Injuries: Systematic Review And Meta-Analysis, Magnolia Livingston

Honors Theses

AVP-923, commonly known as Nuedexta or Zenvia, is a drug that has recently been suggested as a potential treatment for Pseudobulbar Affect in patients affected by different neurological disorders and injuries. Studies have been done to examine the effectiveness of AVP-923 on PBA, but the results of these studies don’t seem to be comparable. The goal of this meta-analysis is to assess the efficacy and safety of AVP-923. 781 individuals from six trials were included in the analysis. The analysis's findings revealed that AVP-923 considerably lowered the Center for Neurological Study Lability Scale (CNS-LS) scores and the frequency and severity …

Eco-Interoception: What Plants, Fungi And Protista Have Taught My Body, Sara Riley Dotterer

Art Theses and Dissertations

To me, ecology is the relational, full-body awareness that I am made up of and deeply connected to everything around me; and for better or worse, this is reciprocal. I form ecotones, an ecological transitional zone between two ecosystems, with the world around me. I use this ecotonal lens to blur binaries and dissolve boundaries between me and the world “outside my body.” During my Masters of Fine Arts at Southern Methodist University, I have continuously explored and represented the lives of various more-than-human species outside of my body, including plants, fungi and protista through an ecotonal lens. Although these …

Balancing Functional Tradeoffs Between Protein Stability And Ace2 Binding In The Sars-Cov-2 Omicron Ba.2, Ba.2.75 And Xbb Lineages: Dynamics-Based Network Models Reveal Epistatic Effects Modulating Compensatory Dynamic And Energetic Changes, Gennady M. Verkhivker, Mohammed Alshahrani, Grace Gupta

Mathematics, Physics, and Computer Science Faculty Articles and Research

Evolutionary and functional studies suggested that the emergence of the Omicron variants can be determined by multiple fitness trade-offs including the immune escape, binding affinity for ACE2, conformational plasticity, protein stability and allosteric modulation. In this study, we systematically characterize conformational dynamics, structural stability and binding affinities of the SARS-CoV-2 Spike Omicron complexes with the host receptor ACE2 for BA.2, BA.2.75, XBB.1 and XBB.1.5 variants. We combined multiscale molecular simulations and dynamic analysis of allosteric interactions together with the ensemble-based mutational scanning of the protein residues and network modeling of epistatic interactions. This multifaceted computational study characterized molecular mechanisms and …