Therapeutics Commons^™

Abcb5+ Mesenchymal Stromal Cells Therapy Protects From Hypoxia By Restoring Ca2+ Homeostasis In Vitro And In Vivo, Kaixuan Yan, Jiaxing Zheng, Mark Andreas Kluth, Lin Li, Christoph Ganss, Benito Yard, Richard Magdeburg, Markus H. Frank, Prama Pallavi, Michael Keese

Research outputs 2022 to 2026

Background:

Hypoxia in ischemic disease impairs Ca²⁺ homeostasis and may promote angiogenesis. The therapeutic efficacy of mesenchymal stromal cells (MSCs) in peripheral arterial occlusive disease is well established, yet its influence on cellular Ca²⁺ homeostasis remains to be elucidated. We addressed the influence of ATP-binding cassette subfamily B member 5 positive mesenchymal stromal cells (ABCB5⁺ MSCs) on Ca²⁺ homeostasis in hypoxic human umbilical vein endothelial cells (HUVECs) in vitro and in vivo.

Methods:

Hypoxia was induced in HUVECs by Cobalt (II) chloride (CoCl₂) or Deferoxamine (DFO). Dynamic changes in the cytosolic- and endoplasmic reticulum …

Chewed Versus Swallowed Ticagrelor In P2y12 Inhibitor-Naïve Patients Undergoing Percutaneous Coronary Intervention, Thomas F. Wilson, Muddasir Ashraf, M. Fuad Jan, Tonga Nfor, Louie Kostopoulos, Joaquin Solis, Jayant Khitha, Ahmad Khraisat, Anthony C. Defranco, Tanvir Bajwa, Suhail Q. Allaqaband

Journal of Patient-Centered Research and Reviews

Purpose: Dual antiplatelet therapy is standard for patients undergoing percutaneous coronary intervention (PCI) with stents. Traditionally, patients swallow the loading dose of a P2Y12 inhibitor before or during PCI. Time to achieve adequate platelet inhibition after swallowing the loading dose varies significantly. Chewed tablets may allow more rapid inhibition of platelet aggregation. However, data for this strategy in patients with stable ischemic heart disease or non-ST-elevation acute coronary syndrome (NSTE-ACS) are less robust.

Methods: In this single-center prospective trial, 112 P2Y12-naïve patients with stable ischemic heart disease or NSTE-ACS on aspirin therapy and who received ticagrelor after coronary angiography but …

The Effects Of A Blood–Brain Barrier Penetrating Erythropoietin In A Mouse Model Of Tauopathy, Joshua Yang, Weijun Ou, Nataraj Jagadeesan, Juste Simanauskaite, Jiahong Sun, Demi M. Castellanos, David H. Cribbs, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO), a hematopoietic neurotrophin, is a potential therapeutic for Alzheimer’s disease (AD) but has limited blood–brain barrier (BBB) permeability. EPO fused to a chimeric transferrin receptor monoclonal antibody (cTfRMAb) enters the brain via TfR-mediated transcytosis across the BBB. We previously showed that cTfRMAb-EPO is protective in a mouse model of amyloidosis, but its effects on tauopathy are not known. Given that amyloid and tau pathology are characteristics of AD, the effects of cTfRMAb-EPO were studied in a tauopathy mouse model (PS19). Six-month-old PS19 mice were injected intraperitoneally with either saline (PS19-Saline; n = 9) or cTfRMAb-EPO (PS19-cTfRMAb-EPO, 10 mg/kg; …

Moral Injury To Inform Analysis Of Post-Traumatic Stress Disorder, Amanda Julia Manea

Senior Theses

Post-traumatic stress disorder (PTSD) is a mental health condition that almost one out of ten veterans struggle with. Although the National Center for PTSD has made extensive progress in characterizing and developing new treatments for PTSD, most veterans still experience symptoms of PTSD following treatment. Novel avenues of investigation, such as developing algorithms to review electronic health record (EHR) data and better understanding moral injury, are being pursued to address the gap that still exists when it comes to treating veterans. Moral injury is the individual evaluation of exposure to a potentially morally injurious event (PMIE) and can lead to …

Amphiphilic Cell-Penetrating Peptides Containing Arginine And Hydrophobic Residues As Protein Delivery Agents, Jonathan Moreno, Khalid Zoghebi, David Salehi, Lois Kim, Sorour Khayyatnejad Shoushtari, Rakesh K. Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

The entry of proteins through the cell membrane is challenging, thus limiting their use as potential therapeutics. Seven cell-penetrating peptides, designed in our laboratory, were evaluated for the delivery of proteins. Fmoc solid-phase peptide synthesis was utilized for the synthesis of seven cyclic or hybrid cyclic–linear amphiphilic peptides composed of hydrophobic (tryptophan (W) or 3,3-diphenylalanine (Dip) and positively-charged arginine (R) residues, such as [WR]4, [WR]9, [WWRR]4, [WWRR]5, [(RW)5K](RW)5, [R5K]W7, and [DipR]5. Confocal microscopy was used to screen the peptides as a protein delivery system of model cargo proteins, green and red fluorescein proteins (GFP and RFP). Based on the confocal …

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

Sulopenem For The Treatment Of Complicated And Uncomplicated Bacterial Urinary Tract Infection (Uti), Aiyi Chen, Thanh-Liem Vu, Daniel J. Yang, Landon Olsen

Annual Research Symposium

No abstract provided.

Predicting Survival Of Nsclc Patients Treated With Immune Checkpoint Inhibitors: Impact And Timing Of Immune-Related Adverse Events And Prior Tyrosine Kinase Inhibitor Therapy, Michael R. Sayer, Isa Mambetsariev, Kun-Han Lu, Chi Wah Wong, Ashley Duche, Richard Beuttler, Jeremy Fricke, Rebecca Pharaon, Leonidas Arvanitis, Zahra Eftekhari, Arya Amini, Marianna Koczywas, Erminia Massarelli, Moom Rahman Roosan, Ravi Salgia

Pharmacy Faculty Articles and Research

Introduction: Immune checkpoint inhibitors (ICIs) produce a broad spectrum of immune-related adverse events (irAEs) affecting various organ systems. While ICIs are established as a therapeutic option in non-small cell lung cancer (NSCLC) treatment, most patients receiving ICI relapse. Additionally, the role of ICIs on survival in patients receiving prior targeted tyrosine kinase inhibitor (TKI) therapy has not been well-defined.

Objective: To investigate the impact of irAEs, the relative time of occurrence, and prior TKI therapy to predict clinical outcomes in NSCLC patients treated with ICIs.

Methods: A single center retrospective cohort study identified 354 adult patients with NSCLC receiving ICI …

Chimeric Antigen Receptor T-Cell Therapy And Hematopoiesis, Bryanna Reinhardt, Patrick Lee, Joshua P. Sasine

School of Medicine Faculty Publications

Chimeric Antigen Receptor (CAR) T-cell therapy is a promising treatment option for patients suffering from B-cell- and plasma cell-derived hematologic malignancies and is being adapted for the treatment of solid cancers. However, CAR T is associated with frequently severe toxicities such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), macrophage activation syndrome (MAS), and prolonged cytopenias—a reduction in the number of mature blood cells of one or more lineage. Although we understand some drivers of these toxicities, their mechanisms remain under investigation. Since the CAR T regimen is a complex, multi-step process with frequent adverse events, ways …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Second Generation Phenyloxadiazolyl Methyl Sulfones For Thiol-Specific Bioconjugations, Guillaume Dewaele-Le Roi

Dissertations, Theses, and Capstone Projects

The role of antibody-based molecular agents for diagnosis and therapy of cancer has expanded significantly over the past decades. However, most of these constructs are synthesized using traditional bioconjugation methods based on the random ligations between the molecular cargo and lysine residues within the protein. These non-specific approaches can create poorly defined conjugates with suboptimal immunoreactivity and in vivo performance while Site-specific approaches to antibody bioconjugation based on ligations between maleimides and free cysteine residues have long stood as attractive alternatives. Yet the inherent instability of the thiol-maleimide linkage has fueled the search for new, more stable thiol-reactive prosthetic groups. …

Community Risks For Sars-Cov-2 Infection Among Fully Vaccinated Us Adults By Rurality: A Retrospective Cohort Study From The National Covid Cohort Collaborative, Alfred Jerrod Anzalone, Jing Sun, Amanda J. Vinson, William H. Beasley, William B. Hillegass, Kimberly Murray, Brian M. Hendricks, Melissa Haendel, Carol Reynolds Geary, Kristina L. Bailey, Corrine K. Hanson, Lucio Miele, Ronald Horswell, Julie A. Mcmurry, J. Zachary Porterfield, Michael T. Vest, H. Timothy Bunnell, Jeremy R. Harper, Bradley S. Price

School of Medicine Faculty Publications

Background While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. Methods We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, …

Analysis Of Biologically Effective Dose For Retroactive Yttrium-90 Trans-Arterial Radioembolization Treatment Optimization, Mj Lindsey

CMC Senior Theses

Trans-arterial radioembolization (TARE) is a protracted modality of radiation therapy where radionuclides labeled with Yttrium-90 (⁹⁰Y) are inserted inside a patient's hepatic artery to treat hepatocellular carcinoma (HCC). While TARE has been shown to be a clinically effective and safe treatment, there is little understanding of the radiobiological relationship between absorbed dose and tissue response, and thus there is no dosimetric standard for treatment planning. The Biologically Effective Dose (BED) formalism, derived from the Linear-Quadratic model of radiobiology, is used to weigh the absorbed dose by the time pattern of delivery. BED is a virtual dose that can …

How Sleep Disturbances Affect Those With Borderline Personality Disorder And The Implications For Treatment, Molly L. Schmanke

Regis University Student Publications (comprehensive collection)

This thesis argues that there is limited research on Borderline Personality Disorder’s comorbidity with sleep disorders, and by pointing out the gaps in knowledge this will encourage researchers and doctors to consider this topic as important in the health care field. Sleep disorders can be anything from reduced total sleep time, fragmented sleep, and changes in sleep architecture, and all of these can cause and be caused by disruption of the circadian clock. There are various ways in which circadian clock disruption can cause diseases, cancer, and mental disorders through genes, sleep, and the environment. Borderline Personality Disorder comorbid with …

An Acute Respiratory Distress Syndrome Drug Development Collaboration Stimulated By The Virginia Drug Discovery Consortium, John S. Lazo, Ruben M.L. Colunga-Biancatelli, Pavel A. Solopov, John D. Catravas

Bioelectrics Publications

The genesis of most older medicinal agents has generally been empirical. During the past one and a half centuries, at least in the Western countries, discovering and developing drugs has been primarily the domain of pharmaceutical companies largely built upon concepts emerging from organic chemistry. Public sector funding for the discovery of new therapeutics has more recently stimulated local, national, and international groups to band together and focus on new human disease targets and novel treatment approaches. This Perspective describes one contemporary example of a newly formed collaboration that was simulated by a regional drug discovery consortium. University of Virginia, …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE_J: Science Undergraduate Research Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

The Impact Of Covid-19 On The Treatment Of Opioid Use Disorder In Carceral Facilities: A Cross-Sectional Study, Elizabeth C. Saunders, Milan F. Satcher, Laura B. Monico, Ryan D. Mcdonald, Sandra A. Springer, David Farabee, Jan Gryczynski, Amesika Nyaku, Elizabeth Needham Waddell, Multiple Additional Authors

OHSU-PSU School of Public Health Faculty Publications and Presentations

While the COVID-19 pandemic disrupted healthcare delivery everywhere, persons with carceral system involvement and opioid use disorder (OUD) were disproportionately impacted and vulnerable to severe COVID-associated illness. Carceral settings and community treatment programs (CTPs) rapidly developed protocols to sustain healthcare delivery while reducing risk of COVID-19 transmission. This survey study assessed changes to OUD treatment, telemedicine use, and re-entry support services among carceral and CTPs participating in the National Institute on Drug Abuse (NIDA)-funded study, Long-Acting Buprenorphine vs. Naltrexone Opioid Treatments in Criminal Justice System-Involved Adults (EXIT-CJS) study. In December 2020, carceral sites (n = 6; median pre-COVID 2020 …

High Anxiety In Pediatric Oncology Patients? What About Art Therapy?, Rebekah Love

Symposium of Student Scholars

Anxiety and depression are becoming more prevalent in the pediatric population today. In addition to the general pediatric population experiencing an increased risk of mental illness, children with an oncology related diagnosis have an even heightened risk. Most pediatric oncology patients reported fear or worry daily, which is cited to be most severe when they had an appointment or went to the hospital for a fever. It is imperative we discover interventions to lessen the anxiety and depression pediatric oncology patients experience daily. A literature review revealed conclusive interventions have not been determined. The purpose of this research is to …

Designing And Synthesizing A Warhead-Fragment Inhibitory Ligand For Ivyp1 Through Fragment-Based Drug Discovery, Samuel Moore

Symposium of Student Scholars

Fragment-based drug discovery (FBDD) is a powerful tool for developing anticancer and antimicrobial agents. Within this, magnetic resonance spectroscopy (NMR) provides a comprehensive qualitative and quantitative approach to screening and validating weak and robust binders with targeted proteins, making NMR among the most attractive strategies in FBDD. Inhibitor of vertebrate lysozyme (Ivyp1) of P. aeruginosa serves as an excellent target because of its active cellular location and implications in clinical prognosis for cystic fibrosis and immunocompromised patients. This study uses current NMR and biophysical techniques to develop a covalent, fragment-linked warhead inhibitor for Ivyp1 through synthetic methods, warhead linking, and …

Indwelling Pleural Catheterization Maximizes Functionality And Quality Of Life In Management Of Recurrent Malignant Pleural Effusions, Avinash Ramkissoon

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using:

Davies HE, Mishra EK, Kahan BC, et al. Effect of an indwelling pleural catheter vs chest tube and talc pleurodesis for relieving dyspnea in patients with malignant pleural effusion: The TIME2 randomized controlled trial. J Am Med Assoc. 2012;307(22):2383-2389. https://doi.org/10.1001/jama.2012.5535

for the management of recurrent malignant pleural effusions in a patient with metastatic renal cell carcinoma.