Chemicals and Drugs Commons^™

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Brain Delivery Of Erythropoietin Results In A Significant Reduction Of Brain Aβ And Spatial Memory Deficits In The App Knock-In Mouse Model, Rudy Tieu Chang, Devaraj V. Chandrashekar, Grace-Ann Chuli Roules, Emi Iwasaki, Nataraj Jagadeesan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Background

Although novel treatments for Alzheimer’s disease (AD) have begun to show modest therapeutic effects, agents that target hallmark AD pathology and offer neuroprotection are desired. Erythropoietin (EPO) is a glycoprotein hormone with neuroprotective effects but is faced with challenges including limited brain uptake and increased hematopoietic side effects with long-term dosing. Therefore, EPO has been modified and bound to a chimeric transferrin receptor monoclonal antibody (cTfRMAb); the latter shuttles EPO past the blood-brain barrier (BBB) into brain parenchyma and reduces its plasma exposure and potential for side effects. Our study sought to characterize the safety and pharmacokinetics (PK) of …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …

Nutritional, Phytochemical, And Antimicrobial Properties Of Carica Papaya Leaves: Implications For Health Benefits And Food Applications, Rajni Choudhary, Ravinder Kaushik, Ansab Akhtar, Suvendu Manna, Jyoti Sharma, Aarti Bains

School of Medicine Faculty Publications

BACKGROUND: Papaya leaves (PLs) are known for their therapeutic benefits and traditional use in treating inflammation, infections, and various health conditions. Rich in bioactive compounds, PLs are studied for their potential applications in functional foods. This study analyzed their nutritional, phytochemical, structural, thermal, and antimicrobial properties to evaluate their role as a health-promoting ingredient. METHODS: Phytochemicals were quantified spectrophotometrically and identified via GC-MS. Antioxidant activity was assessed using DPPH and FRAP assays. Mineral content was determined using ICP-OES. Structural and thermal properties were evaluated using FTIR, XRD, and calorimetry, and antimicrobial activity was tested via the agar well diffusion method. …

Retreatability Of Endosequence® Bcs™ Hiflow Utilizing Both Chloroform And An Aqueous Solution, Dijana Elmejdoubi, Thomas E. Lallier, Masyn Cameron, Albert F. Mcmullen Iii

School of Dentistry Faculty Publications

Purpose: When RCT fails, retreatment of the case usually requires removal of the previous root canal fill (RCF). The aim of our research was to evaluate the retreatability of a root canal initially filled with gutta percha and EndoSequence® BCS™ HiFlow utilizing chloroform followed by 18% HCl, 18% HCl alone, chloroform alone or saline solution. Methods: 40 extracted single canal teeth were decoronated and obturated utilizing a single cone gutta percha technique and Endosequence BCS, stored one week in an incubator, and then we attempted to remove the previous RCF. Teeth were divided in 4 different groups (n=10). Canals were …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

In Vivo Evaluation Of Novel Nanoparticles And Repurposed Pharmaceuticals To Combat Antimicrobial Resistance, Sarah E. Evans

Theses, Dissertations and Capstones

In a 2019 report by the Centers for Disease Control and Prevention (CDC), infections resistant to antibiotic treatment amount to about three million infections and 48,000 deaths. Antimicrobial resistance is an escalating global threat as existing antibiotics lose efficacy over time. The project described is focused on partnering with pharmaceutical researchers and producers to test new nanoparticle-based or repurposed compounds. The central hypothesis of this thesis is that pharmaceutical formulations such as nanoparticles may provide a cost-effective means of combating the emerging antimicrobial resistance. The nanoparticle compounds allowed for a wide range of customization for the pharmaceutical design, since the …

Exploring Microrna Pathways And Metformin's Anti-Inflammatory Potential In Osteoarthritis, Quang D La, Benjamin Tangkamolsuk, David F Lo

Rowan-Virtua School of Osteopathic Medicine Departmental Research

No abstract provided.

Exploring Cost-Effective And Asymmetric Alternatives To 9-Bbn, Annaliese Franklin

ASPIRE 2025

Catechol borane, pinacol borane, and 9-borabicyclo[3.3.1]nonane, 9-BBN, are versatile cyclic borane (CB) hydroboration agents.1,2 The borinates/boronates obtained from their reactions with alkenes and alkynes are good candidates for various Suzuki-Miyaura coupling reactions–a very important reaction that has been used in the synthesis of multiple drugs. However, CBs do have a few drawbacks, such as the high cost of 9-BBN, and are relatively unreactive compared to their dialkylborane analogs. Furthermore, none of these boranes provides the chiral environment required for asymmetric induction by themselves.3,4 A quick survey of natural products revealed many terpene dienes such as limonene, ɑ-phellandrene, and valencene that …

Vonoprazan Vs. Lansoprazole In The Healing & Maintenance Phase Of Erosive Esophagitis, Sushil Rayamajhi, Syed Hasham Ali, Hareesha Bharadwaj, Ali Tariq

North Florida Division GME Research Day 2025

No abstract provided.

Efficacy Of Collagenase Injection In Dupuytren’S Contracture, Janson Witcher

The PA Department Journal of Medical Science

Introduction: Dupuytren's contracture is a debilitating hand condition characterized by progressive contracture of the palmar fascia. The use of collagenase clostridium histolyticum injections has emerged as a minimally invasive alternative to surgical interventions, with varying degrees of efficacy and safety compared to traditional methods like limited fasciectomy and percutaneous needle fasciotomy.

Methods: A comprehensive literature review was conducted using PubMed to assess the efficacy and safety of collagenase injections for treating Dupuytren's contracture. The search focused on peer-reviewed randomized controlled trials, systematic reviews, and meta-analyses published in the last five years. Five relevant studies were selected based on the robustness …

Defend The Season: A Quality Approach To Influenza Vaccination, Robert Reinhart, Michaela Mckissack

Central & West Texas and San Antonio GME Research Day 2025

No abstract provided.

Severe Hypokalemic Paralysis Following Rituximab Infusion In A Patient With Type I Rta, Ayham Alsaab, Yousuf Sherwani, Emily Devine, Sarah Faheem, Vikas Gullapalli, Mohan Sengodan

North Texas Research Forum 2025

Rituximab is a CD-20 monoclonal antibody used in the treatment of _. Rituximab is a steroid-sparing agent that can be used to control a variety of diseases. (find sources but I found several possible uses). As with any therapy, there are side effects. One potential side effect of Rituximab that has only been described a few times in the literature is hypokalemia. One such report is a case report from 2020 that describes symptomatic hypokalemia in an 18-year-old female with steroid-dependent nephrotic syndrome after her 6th rituximab infusion, with K dropping from 4.0 prior to infusion to 2.3 at the …

Cannabis Induced 2nd Degree Av Block, Shivani Gandhi, Vineeth Lekkala, Muhammad Suleman, Anvitha Manduva

North Texas Research Forum 2025

Cannabis use, both medical and non-medical, has seen a marked increase following the growing trend of legalization. While the immediate effects of cannabis on mental and physiological states are well-documented, its potential impact on the cardiovascular system remains an area of growing concern. Cannabis-induced arrhythmias, particularly atrioventricular (AV) block, are rare but potentially life-threatening events that can present in young, otherwise healthy individuals (Heckle et al., 2018). This case highlights the importance of recognizing cannabis as a potential contributing factor in the development of AV block.

Painfully Obvious: Expanding Inpatient Buprenorphine For Opioid Use Disorder, Aline Levy-Sitnoveter, Mark Delic, Jonathan Aires Pinheiro, Eleana Estrella, Sankalp Goberdhan, Lauren Hundley, Richard Henriquez, Shamol Williams

North Florida Division GME Research Day 2025

No abstract provided.

Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White

Department of Biomedical and Translational Sciences Faculty Publications

Myosins produce force and movement in cells through interactions with F-actin¹. Generation of movement is thought to arise through actin-catalysed conversion of myosin from an ATP-generated primed (pre-powerstroke) state to a post-powerstroke state, accompanied by myosin lever swing²,³. However, the initial, primed actomyosin state has never been observed, and the mechanism by which actin catalyses myosin ATPase activity is unclear. Here, to address these issues, we performed time-resolved cryogenic electron microscopy (cryo-EM)⁴ of a myosin-5 mutant having slow hydrolysis product release⁵,⁶. Primed actomyosin was predominantly captured 10 ms after …

A Scoping Review Of Population Diversity In The Common Genomic Aberrations Of Clear Cell Renal Cell Carcinoma, Sean S. Kumar, Ninad Khandekar, Komal Dani, Saina R. Bhatt, Vinay Duddalwar, Anishka D' Souza

Department of Medicine Faculty Publications

Introduction: Previous literature has shown that clear cell renal cell carcinoma (ccRCC) is becoming a more prevalent diagnosis and that the incidence and mortality differ both regionally and racially. While the molecular profiles for ccRCC are studied regionally through biopsy and sequencing techniques, the genomic landscape and ccRCC diversity data are not well studied. We conducted a review of the known genomic data on 6 of the most clinically relevant DNA biomarkers in ccRCC: von Hippel-Lindau (vHL), Polybromo-1 (PBRM1), Breast Cancer Gene 1-Associated Protein 1 (BAP1), Histone-Lysine N-Methyltransferase Domain-Containing 2 (SETD2), Mammalian Target of Rapamycin (mTOR), and Lysine-Specific Demethylase 5C …

Never Admit Or Release Without Considering A Naloxone Script (Narcan), Farid Mughni, Mustafa Ibrahim, Dante Janolo, Samuel Ramos, Emma Rivas, Olga Karasik

North Florida Division GME Research Day 2025

No abstract provided.

Anti-Pd-1 Monoclonal Antibody Induced Diabetic Ketoacidosis In Melanoma, Boney Lapsiwala, Jacqueline Bekhit, Indira Tata, Vibhuti Veeranna

North Texas Research Forum 2025

Background: Immune checkpoint inhibitors (ICIs), including pembrolizumab, are increasingly used in cancer therapy, particularly for melanoma. While effective, these agents are associated with various immune-related adverse events (IRAEs), including endocrine disorders like diabetic ketoacidosis (DKA). This report aims to contribute to the understanding of pembrolizumab-induced DKA, especially in patients with pre-existing prediabetes. Case Presentation: A 78-year-old male with a history of melanoma, prediabetes, and other comorbidities developed DKA after 1.5 years of pembrolizumab treatment. He presented with symptoms of weakness, thirst, dry mouth, and diarrhea, alongside severe hyperglycemia and metabolic acidosis. Diagnostic workup confirmed DKA, and his clinical improvement followed …

Atn Masquerading Rapidly Progressive Glomerulonephritis: Atypical Presentation Of P-Anca Associated Vasculitis With Rpgn, Nimmy Joy, Anabel Al Abdallah, Andrea Francis, Saurabh Pande

Central & West Texas and San Antonio GME Research Day 2025

No abstract provided.

An Electrochemical Sensor For Tenofovir Monitoring, Abdellatif Ait Lahcen, Gymama Slaughter

Center for Bioelectronics Publications

Effective monitoring of tenofovir (TFV) adherence is critical for ensuring the success of antiretroviral therapies in preventing and managing HIV, as nonadherence can lead to treatment failure and the development of drug-resistant strains. In this study, a highly sensitive and selective novel biomimetic sensor for TFV determination is developed utilizing laser-scribed graphene (LSG) modified with gold spiky nanostructures (AuNSp) and molecularly imprinted polymer (MIP). The MIP layer is engineered with precise control to maximize molecular specificity for TFV. Electrochemical characterization demonstrates excellent performance, including the broadest linear detection range (10 nM to 200 μM) reported to date with a sensitivity …

Optimizing Opioid Selection For Vaso-Occlusive Crisis: Identifying The Best Option To Reduce Hospital Length Of Stay, Benjamin H. Bridges, Laura Strom, Eric Belcher, Winston Daniels, Ansley Connelly, Joshua Ferrell

South Atlantic Division GME Research Day 2025

No abstract provided.

Atorvastatin Alters Neuronal Morphology Data Set, Carolyn L. Pytte

Publications and Research

Statins are highly effective and widely prescribed cholesterol lowering drugs. However, statins cross the blood-brain barrier and decrease neural cholesterol in animal models, raising concern that long-term statin use may impact cholesterol-dependent structures and functions in the brain. Cholesterol is a fundamental component of cell membranes and experimentally decreasing membrane cholesterol has been shown to alter cell morphology in vitro. In addition, brain regions that undergo adult neurogenesis rely on local brain cholesterol for the manufacture of new neuronal membranes. Thus neurogenesis may be particularly vulnerable to long-term statin use. Here we asked whether oral statin treatment impacts neurogenesis …

Characterizing And Targeting The Non-Catalytic Functions Of Phosphatase Of Regenerating Liver 3 (Prl-3) In Oncogenesis And Cancer Progression, Jeffery T. Jolly

Theses and Dissertations--Molecular and Cellular Biochemistry

Phosphatase of Regenerating Liver 3 (PRL-3) is frequently upregulated in various cancers and is associated with poor patient prognosis. Although traditionally studied for its phosphatase activity, PRL-3 also interacts with the CNNM family of magnesium transporters through its catalytic site, and these two functions are mutually exclusive at any given time. Most previous studies relied on a commonly used PRL-3 mutation that disrupts both phosphatase activity and CNNM binding, making it challenging to determine which function drives its oncogenic effects. To address this gap in the field, I utilized a panel of PRL-3 mutants that selectively disrupt either phosphatase activity …

Baseline Disease Characteristics By Surgery History Among Patients With Chronic Rhinosinusitis With Nasal Polyps (Crswnp) In The Global Aroma Registry, Shigeharu Fujieda, Jayant M. Pinto, David W. Jang, Joseph K. Han, James Mims, Eugenio De Corso, Martin Wagenmann, Changming Xia, Thomas Plucinak, Mark Corbett, Scott Nash, Amr Radwan

Department of Otolaryngology (ENT) Faculty Publications

Purpose

The global Assessing long-teRm Outcomes in dupiluMAb (AROMA) registry study aims to characterize the long-term, real-world use of dupilumab in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). This paper reports interim analysis of the baseline characteristics for the first 303 patients enrolled in AROMA.

Methods and materials

AROMA is currently ongoing in adult patients with CRSwNP who initiated dupilumab for up to 36 months. This interim analysis describes baseline demographics; systemic/oral corticosteroid (SCS/OCS) and antibiotic use; disease burden; healthcare resource utilization; and medical history. All outcomes are summarized descriptively.

Results

As of February 2023, AROMA had enrolled 303 …

Combination Of Hsp90 Inhibitors And Hsp70 Inducers Prevent Hydrochloric Acid-Induced Pulmonary Fibrosis In Rabbits, Ruben M. L. Colunga Biancatelli, Pavel A. Solopov, Tierney Day, Dan E. Austin Jr., Len E. Murray, John D. Catravas

Bioelectrics Publications

Combined therapies with Heat Shock Protein 90 (HSP90) inhibitors and Heat Shock Protein 70 (HSP70) inducers are gaining significant interest in cancer and cardiovascular research. Here, we tested the hypothesis that HSP90 inhibitors and HSP70 inducers, together, can block the development of pulmonary fibrosis. We exposed New Zealand White Rabbits to hydrochloric acid (HCl, 0.1 N, 1.5 mL/kg), one of the top five chemicals most commonly involved in accidental exposures and inhalation injuries worldwide, and treated animals with either the orally available HSP90 inhibitor TAS-116 (1.7 mg/kg 5x/week) or TAS-116 combined with the HSP70 inducer, geranylgeranyl acetone (GGA, 50 mg/kg, …

Synthesis, Characterization, And Biological Activity Of Ni(Ii) And Co(Iii) Thiosemicarbazone Complexes As Potential Anticancer Agents, Jack Martin

Pitzer Senior Theses

The mechanics by which Reactive Oxygen Species work is an area of great interest given ROS’s wide range of biological applications. From cell signaling and mitochondrial regulation to pathogenesis and tumor cell death, varying concentrations of ROS in a system can lead to a whole host of positive and negative effects. In a similar vein, thiosemicarbazones are known to be equally useful for their myriad of antibacterial, antifungal, antiviral, and antitumoral effects. They have been at the core of the pharmaceutical world or the better part of the last century. The purpose of this work is to synthesize, characterize and …

Has The Elimination Of Mandatory Buprenorphine X-Waiver Increased Presciptions Of This Medication Upon Discharge From The Hospital?, Kendall Moore, Robyn Meadows, Robyn Hoelle, Matthew Calestino

North Florida Division GME Research Day 2025

No abstract provided.

Adverse Bleeding Events In Patients Taking Verapamil With Apixaban Or Rivaroxaban, Heena Patel, Franklin Hernandez, Kathleen Mattingly, Seth Sukriti, Chandan Mitra

North Florida Division GME Research Day 2025

No abstract provided.