Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication,
2024
Seattle Pacific University
Repurposing Clinically Relevant Metabolic Inhibitor Drugs, Difluoromethylornithine (Dfmo) And Orlistat, For Gammaherpesvirus Replication, Lay Paw
Honors Projects
Viruses, including herpesviruses, contribute up to 15% of all human cancers. Murine gammaherpesvirus-68 (MHV-68), a pathogen commonly found in mice, is studied due to its shared homology with several human herpesviruses. Studies done in the Delgado lab via metabolomics analysis show MHV-68 infected cells increase host cell metabolism. Clinically relevant metabolic inhibitor drugs, ɑ-Difluoromethylornithine (DFMO) and Orlistat, respectively block polyamine and lipid production demonstrated a reduction in MHV-68 viral production. Repurposing clinically relevant drugs through the exploration of a different target shows great promise in reducing oncogenic viral titer.
Fluorescence-Based Techniques For The Identification Of Small Biomolecules,
2024
Seton Hall University
Fluorescence-Based Techniques For The Identification Of Small Biomolecules, Charnette Frederic
Seton Hall University Dissertations and Theses (ETDs)
Understanding fluorescence-based methods for detecting small biomolecules is a crucial area of focus in research investigations. Our studies focused on the challenge in two parts: Non-intrinsic fluorescence and intrinsic fluorescence. For studies on Non-intrinsic fluorescence, Rifampicin (Rif), an antibiotic harnessed for treating diverse bacterial infections, including tuberculosis (TB), serves as a focal point. Leveraging the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) process, aptamers emerged from the nonspecific 40-mer Deoxyribonucleic Acid (DNA) library to interact with its target, Rif. During each SELEX cycle, the recovered nucleotides underwent amplification via Polymerase Chain Reaction (PCR) until the most selective aptamers were …
A Model Of Oocyte Population Dynamics For Fish Oogenesis,
2024
INRAE (Institut national de recherche pour l’agriculture, l’alimentation et l’environnement)
A Model Of Oocyte Population Dynamics For Fish Oogenesis, Louis Fostier, Frédérique Clément, Romain Yvinec, Violette Thermes
Biology and Medicine Through Mathematics Conference
No abstract provided.
Effects Of Drug Delivery On Ppi-Responsive Esophageal Eosinophilia,
2024
Children's Mercy Kansas City
Effects Of Drug Delivery On Ppi-Responsive Esophageal Eosinophilia, Alex Biller, Rachel Chevalier, Amornluck Krasaelap, Janelle R. Noel-Macdonnell
Research Days
Determine if formulation of proton pump inhibitory (pill/capsule vs liquid) affects eosinophilic infiltration of esophagus in patients with PPI-Responsive Esophageal Eosinophilia.
Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells,
2024
Thomas Jefferson University
Selective And Brain-Penetrant Acss2 Inhibitors Target Breast Cancer Brain Metastatic Cells, Emily Esquea, Lorela Ciraku, Riley Young, Jessica Merzy, Alexandra Talarico, Nusaiba Ahmed, Mangalam Karuppiah, Anna Ramesh, Adam Chatoff, Claudia Crispim, Adel Rashad, Simon Cocklin, Nathaniel Snyder, Joris Beld, Nicole Simone, Mauricio Reginato, Alexej Dick
Kimmel Cancer Center Faculty Papers
Breast cancer brain metastasis (BCBM) typically results in an end-stage diagnosis and is hindered by a lack of brain-penetrant drugs. Tumors in the brain rely on the conversion of acetate to acetyl-CoA by the enzyme acetyl-CoA synthetase 2 (ACSS2), a key regulator of fatty acid synthesis and protein acetylation. Here, we used a computational pipeline to identify novel brain-penetrant ACSS2 inhibitors combining pharmacophore-based shape screen methodology with absorption, distribution, metabolism, and excretion (ADME) property predictions. We identified compounds AD-5584 and AD-8007 that were validated for specific binding affinity to ACSS2. Treatment of BCBM cells with AD-5584 and AD-8007 leads to …
Antiseizure Properties Of Fenamate Nsaids Determined In Mature Human Stem-Cell Derived Neuroglial Circuits.,
2024
University of the Pacific
Antiseizure Properties Of Fenamate Nsaids Determined In Mature Human Stem-Cell Derived Neuroglial Circuits., Hamed Salmanzadeh, Robert F. Halliwell
School of Pharmacy Faculty Articles
Repeated and uncontrolled seizures in epilepsy result in brain cell loss and neural inflammation. Current anticonvulsants primarily target ion channels and receptors implicated in seizure activity. Identification of neurotherapeutics that can inhibit epileptiform activity and reduce inflammation in the brain may offer significant benefits in the long-term management of epilepsy. Fenamates are unique because they are both non-steroidal anti-inflammatory drugs (NSAIDs) and highly subunit selective modulators of GABAA receptors. In the current study we have investigated the hypothesis that fenamates have antiseizure properties using mature human stem cell-derived neuro-glia cell cultures, maintained in long-term culture, and previously shown to …
Delivering Crispr To The Hiv-1 Reservoirs,
2024
Thomas Jefferson University
Delivering Crispr To The Hiv-1 Reservoirs, Theodore Gurrola, Samuel Effah, Ilker Sariyer, Will Dampier, Michael Nonnemacher, Brian Wigdahl
Kimmel Cancer Center Faculty Papers
Human immunodeficiency virus type 1 (HIV-1) infection is well known as one of the most complex and difficult viral infections to cure. The difficulty in developing curative strategies arises in large part from the development of latent viral reservoirs (LVRs) within anatomical and cellular compartments of a host. The clustered regularly interspaced short palindromic repeats/ CRISPR-associated protein 9 (CRISPR/Cas9) system shows remarkable potential for the inactivation and/or elimination of integrated proviral DNA within host cells, however, delivery of the CRISPR/Cas9 system to infected cells is still a challenge. In this review, the main factors impacting delivery, the challenges for delivery …
Psilocybin Utilization In Alcohol Use Disorder,
2024
Ohio Northern
Psilocybin Utilization In Alcohol Use Disorder, Hannah Hall, Sarah Turske, Hannah Blake, Abigail Carter, Connor Dains, Haylee Whyde, Brianna Lu, Joshua Honaker, Lindsey Peters
Pharmacy and Wellness Review
Alcohol use disorder (AUD) is a medical condition that arises from the inability to control alcohol consumption regardless of negative consequences. Over 10% of the US population met the diagnostic criteria for having AUD in 2022.1 Each individual presents with symptoms of AUD differently and may therefore need more personalized treatment. Research has shown that using a combination of currently available pharmacological and non-pharmacological treatment options provides the best results for patients with AUD. However, there still remains a pressing need for the development of newer treatment options. Psilocybin, a naturally occurring psychedelic compound, is currently under investigation due to …
Understanding The Relationship Between How The Availability Of Vaping Devices And Student Use Are Related: A Quantitative Study,
2024
Arkansas Tech University
Understanding The Relationship Between How The Availability Of Vaping Devices And Student Use Are Related: A Quantitative Study, Felicia L. Owen
ATU Theses and Dissertations 2021 - Present
The number of teens in Arkansas who are vaping continues to increase despite state and national laws and regulations. The availability of vaping devices to teens continues to occur; but limited research is available that explores if the availability is accessible through peers, families, or community members, or is self-sought. It is crucial to gain a better understanding of why vaping continues to increase among high school students in Arkansas. The purpose of this study is to understand the relationship between how the availability of vaping devices and student use are related. The analysis of exposure and student use varies …
Benzo[A]Pyrene-Induced Multigenerational Gene Expression And Dna Methylation Changes Are Influenced By Paternal Epigenome,
2024
University of Mississippi
Benzo[A]Pyrene-Induced Multigenerational Gene Expression And Dna Methylation Changes Are Influenced By Paternal Epigenome, Caroline Sturgis
Honors Theses
The objectives of this study were to determine the sex-dependent contributions to developmental and behavioral effects of preconceptional exposure to benzo[a]pyrene (BaP). BaP is implicated in numerous adverse outcomes in offspring of exposed parents, but the molecular mechanisms for the developmental and multigenerational effects associated with BaP exposures have yet to be fully elucidated. To assess the role of the aryl hydrocarbon receptor (Ahr), a waterborne exposure of the offspring of ahr heterozygous (ahr+/-) parents was conducted. At 120 hpf, BaP treated fish moved significantly less in the dark phase regardless of genotype. At 3 wpf, there …
Fe(Iii) And Mn(Ii) Binding De Novo Designed Peptides And Their Oxidation With H2o2,
2024
University of Mississippi Main Campus
Fe(Iii) And Mn(Ii) Binding De Novo Designed Peptides And Their Oxidation With H2o2, Hannah Randall, Russ Upton
Honors Theses
Metalloenzymes perform a wide variety of reactions that are instrumental to the basic functions of life. Learning more about those enzymes–their structure, folding, active sites, and co-factors–can help to not only better understand the finer details of the chemical world, but also help provide answers and possible solutions to questions pertaining to alternative energy. Particulate Methane Monooxygenase (pMMO) is a metalloenzyme that oxidizes methane into methanol in the biological processes of some methanogenic bacteria, a valuable part of their process to obtain energy. One of its active sites, CuB, has a relatively unknown function. Heptad repeats of model enzymes have …
Emotion Regulation Strategies And Perceived Emotional Intelligence: The Effect Of Age.,
2024
Aristotle University of Thessaloniki
Emotion Regulation Strategies And Perceived Emotional Intelligence: The Effect Of Age., Iwanna Sepiadou
Adultspan Journal
The aim of this study was to investigate the relationship between perceived emotional intelligence and the reported use of cognitive reappraisal and expressive suppression. We also investigated the possible effects of age on the aforementioned variables. The total sample consisted of 379 people (158 men, 220 women, 1 unreported). Across participants, 273 were young (20-39 years old) and 106 were middle-aged (40-65 years old). We found statistically significant positive correlations between the dimensions of perceived emotional intelligence and the reported use of cognitive reappraisal and negative primarily correlations between the dimensions of perceived emotional intelligence and the reported use of …
Zinc-Containing Over-The-Counter Product Causing Sideroblastic Anemia And Neutropenia,
2024
Our Lady of the Lake Regional Hospital, Baton Rouge, LA
Zinc-Containing Over-The-Counter Product Causing Sideroblastic Anemia And Neutropenia, Marshall Patrick Stagg, Jennifer Miatech, Baseera Majid, Ravali Polala
School of Medicine Faculty Publications
Sideroblastic anemia is characterized by anemia, granulocytopenia, and bone marrow findings of vacuolated precursors and ringed sideroblasts. Zinc-induced copper deficiency can present as sideroblastic anemia and neutropenia. We report the case of a previously healthy 74-year-old female who presented with newly discovered sideroblastic anemia as a result of an over-the-counter oral vitamin and mineral supplement. Serum analysis revealed increased zinc levels, decreased copper levels, and a decrease in ceruloplasmin. Bone marrow evaluation revealed ringed sideroblasts and cytoplasmic vacuolization in myeloid precursors. She demonstrated improvement in her hematologic profile with discontinuation of the over-the-counter product and administration of oral copper supplementation. …
Investigation And Synthesis Of 2-Deoxy-Pyr(Mp),
2024
University of South Alabama
Investigation And Synthesis Of 2-Deoxy-Pyr(Mp), Juanita Monteiro-Pai
Poster Presentations
Cellular energy metabolism is complex, and NAD, or nicotinamide adenine dinucleotide, plays a huge role as an organic redox cofactor, driving metabolic reactions. The abundance of pathways dependent on NAD has led to an increase in the studies of NAD and its precursors. As a result, NR, or nicotinamide riboside, is now a popular nutraceutical taken to increase levels of NAD in the body. NR is a precursor to NAD inside cells. Metabolites with the same molecular formula as NR are found in urine and blood. Yet, NR is usually associated with these species in extracellular regions although NR is …
Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders,
2024
University of Nebraska Medical Center
Translational Pathways For Ultra Long-Acting Medicines For Chronic Disease: From Hiv To Substance Use Disorders, Suyash Sanjay Deodhar
Theses & Dissertations
Human immunodeficiency virus (HIV) and opioid use disorder (OUD) are among the top global public health challenges, with a significant overlap in the number of cases and higher mortality risks compared to the general population. Treatment and recreational opioid use lead to addictive disorders. Both conditions require repeated dosing of therapy where adherence to a strict lifelong regimen remains a major challenge. Notably, people living with HIV/AIDS (PLWHA) and struggling with opioid use disorders (OUD) show suboptimal adherence to antiretroviral drugs (ARVs). Also, the risk of transmitting HIV and other blood-borne infections through the sharing of needles and other injection …
Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations,
2024
University of Nebraska Medical Center
Development Of Long-Acting Antiviral And Antimicrobial Prodrug Nanoformulations, Srijanee Das
Theses & Dissertations
Over the past decade, the global burden of infectious diseases has increased substantively, underscoring the need for more effective treatment strategies. However, the discovery and development of new drugs with desirable safety, pharmacokinetics, and efficacy is a time consuming and costly process with great uncertainty around success rate. As an alternative to new drug development, prodrugs and novel drug delivery systems have increasingly been explored. Both serve to overcome the drug development challenges. Such drug formulations that permit extended dosing intervals of potent native drugs serve multiple purposes by promoting patient adherence to in improving treatment outcomes. This is especially …
Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice.,
2024
University of Nebraska Medical Center
Pharmacodynamic Effects Of Zsj-0228 On Complement Protein Deposition In The Kidneys Of Focal Segmental Glomerulosclerosis-Afflicted Mice., Braeden Pinkerton
Theses & Dissertations
Chronic inflammation, when left untreated, may result in significant morbidity and in severe cases, mortality. While glucocorticoids (GCs) are still being extensively used clinically as a class of very potent anti-inflammatory agents, they are also notorious for diverse adverse side effects. To mitigate these side effects, we have developed a polyethylene glycol (PEG)-based prodrug (ZSJ-0228) of dexamethasone (Dex). When tested on rodent models of Lupus Nephritis and Focal Segmental Glomerulosclerosis (FSGS), ZSJ-0228 was found to provide potent and sustained therapeutic efficacy without any detectable typical GC-associated side effects. Given ZSJ-0228’s transient renal exposure after systemic administration, it is yet to …
Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond,
2024
University of Nebraska Medical Center
Therapeutic Effects Of Bet Protein Inhibition In B-Cell Malignancies And Beyond, Audrey L. Smith
Theses & Dissertations
Chronic lymphocytic leukemia (CLL) develops through a combination of intrinsic genetic defects, constitutively active survival/proliferation signaling pathways, and complex microenvironment interactions. Redundant tumor microenvironment (TME) immuno-suppressive mechanisms and epigenetic maintenance of terminal T-cell dysfunction also greatly hinder anti-tumor T-cell responses in CLL. Small-molecule agents targeting the B-cell receptor (BCR) pathway and anti-apoptotic proteins alone or in combination with chemo-immunotherapy have revolutionized the management of CLL, yet there is still a significant need for novel therapeutic strategies to yield durable tumor elimination. Bromodomain and extra-terminal domain (BET) proteins are epigenetic readers that bind to acetyl-lysine residues on histones to regulate gene …
Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies,
2024
University of Nebraska Medical Center
Novel Spirocyclic Dimer (Spid3) Displays Potent Preclinical Effects In Hematological Malignancies, Alexandria Eiken
Theses & Dissertations
Chronic lymphocytic leukemia (CLL) is a heterogeneous disease characterized by the accumulation of mature CD5+ B-cells in the peripheral blood, bone marrow, and secondary lymphoid tissues (e.g., spleen and lymph nodes).Despite the efficacy of front-line therapies, CLL is still an incurable disease, highlighting the need for development of novel therapeutics and further study of resistance mechanisms. Within the lymph node CLL tumor microenvironment (TME), there is an upregulation of gene signatures associated with B-cell receptor (BCR) and downstream nuclear factor kappa B (NF-κB) signaling compared to CLL cells found within the blood or bone marrow niches. Additionally, BCR signaling …
Bioactive Glass Bead Characterization: Further Applications In Passive Drug Delivery,
2024
Ursinus College
Bioactive Glass Bead Characterization: Further Applications In Passive Drug Delivery, Marie O. Sykes
Physics and Astronomy Honors Papers
Bioactive glass beads were discovered for their bone repair properties in 1969. This properties, along with their bactericidalness, high ability to be engineered, bioactiveness and their versatile structures, mark them as excellent candidates for explorations in other biomedical applications in addition to bone repair. One alternative application includes passive drug delivery, especially when the biomaterial is in a porous, microsphere structure. In this work, we first explore various samples of bioactive glass compositions and structures in order to target the best bead for the application of drug delivery. The targeted beads are then thoroughly characterized using optical microscopy, Scanning Electron …
