Medicine and Health Sciences Commons^™

Identifying The Roles Of Mir-17 In Ciliogenesis And Cell Cycle, Ashwaq Alanazi, Ayan K. Barui, Ashraf M. Mohieldin, Ankan Gupta, Ramani Ramachandran, Surya M. Nauli

Pharmacy Faculty Articles and Research

Emerging evidence suggests a significant contribution of primary cilia to cell division and proliferation. MicroRNAs, especially miR-17, contribute to cell cycle regulation and proliferation. Recent investigations have highlighted the dysregulated expression of miR-17 in various malignancies, underlining its potential role in cancer. However, the correlation between primary cilia and miR-17 has yet to be fully elucidated. The present study examines the presence of miR-17 in primary cilia. The miR-17 expression is studied in selected ciliary protein knockdown cells. Using in situ hybridization (ISH), we identified the subcellular localization of miR-17 in both cilium and cell body. We confirmed the importance …

Synthesis And Characterization Of Zoledronic Acid Prodrugs: A Potential Therapeutic For Enhanced Drug Delivery And Targeted Treatment, Shweta Wani

Theses & Dissertations

Bisphosphonates, particularly zoledronic acid (ZA), are crucial in managing bone resorption and treating skeletal disorders like multiple myeloma (MM). While ZA has demonstrated significant anti-myeloma activity in-vitro, its clinical use is limited by poor systemic exposure and potential off-target effects. This thesis investigates two strategies to conjugate polyethylene glycol (PEG) and hyaluronic acid (HA) to ZA to overcome these limitations. The first strategy, targeting the tertiary alcohol group of ZA, faced significant challenges due to the difficulty in conjugation. The second strategy, focusing on the hydroxyl group of the phosphonate moiety in ZA, successfully yielded a ZA-PEG conjugate, enhancing …

The Potential Renoprotective Effects Of Ticagrelor In Rhabdomyolysis-Induced Acute Kidney Injury In Rat, Zahraa Talib Hussein, Ayad Ali Hussein

Maaen Journal for Medical Sciences

Background: Rhabdomyolysis is a potentially lethal range of symptoms results from muscle cell destruction. It is recognized by the escape of cell contents such as myoglobin, creatine kinase, and electrolyte into the bloodstream then undergo glomeruli filtering. Therefore, among the most dangerous complication of rhabdomyolysis is acute renal injury. The complex and interrelated processes underlying rhabdomyolysis that ends with acute kidney injury include obstruction and damage of tubules, inflammation, and intrarenal vasoconstriction (activation of the sympathetic, renin-angiotensin).Glycerol is frequently used to inflict this kind of harm when used as a single dose injection that given intramuscularly to an animal …

Cell-Based Medicinal Products: Progress And Perspectives, Lijian Hui, Xiang Yuan, Jingqi Wu

Bulletin of Chinese Academy of Sciences (Chinese Version)

Cell-based medicinal products are a breakthrough that has been proven to treat previously incurable diseases, making them a topic of global interest. This review delves into the current state and progress of cell therapy, highlighting the remarkable therapeutic effects of various types of cell-based medicinal products. We specifically explore the potential development of cell-based medicinal products in China, focusing on promoting clinical translation and commercialization. We propose necessary actions to achieve these goals, such as fostering cutting-edge basic research, innovative therapeutic approaches, scalable manufacturing processes, and policy changes.

Novel 3,6-Disubstituted Pyridazine Derivatives Targeting Jnk1 Pathway: Scaffold Hopping And Hybridization-Based Design, Synthesis, Molecular Modeling, In Vitro And In Vivo Anticancer Evaluation., Mai M. Shaalan, Essam Eldin A. Osman, Yasmeen M. Attia, Olfat A. Hammam, Riham F. George, Bassem H. Naguib

Pharmacy

A series of novel 3,6-disubstituted pyridazine derivatives was designed, synthesized, and biologically evaluated as preclinical anticancer candidates. Compound 9e exhibited the highest growth inhibition against most of the NCI-60 cancer cell lines. The in vivo anticancer activity of 9e was subsequently investigated at two dose levels using the Ehrlich ascites carcinoma solid tumor animal model where a reduction in the mean tumor volume allied with necrosis induction was reported, without any signs of toxicity in the treated groups. Interestingly, compound 9e was capable of downregulating c-jun N-terminal kinase-1 (JNK1) gene expression and curbing the protein levels of its phosphorylated form, …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

Cost-Utility Analysis Of Adding Daratumumab To Bortezomib Plus Dexamethasone To Treat Relapsed/Refractory Multiple Myeloma In Egypt, Menna M. Elsherbiny, Ahmed M. Kamel, Samar F. Farid

Bulletin of Faculty of Pharmacy Cairo University

Background: According to the CASTOR trial, DARA is shown to be effective as a second line for RRMM patients either as monotherapy or in combination with the gold standard regimen. The current study is the first to evaluate the cost-effectiveness of DARA based on the full results (~80-month follow-up) of the CASTOR trial. The study aimed to assess the cost-effectiveness of incorporating DARA, with bortezomib and dexamethasone, in treating patients from the perspective of a healthcare payer over a lifetime horizon.

Methods: A partition survival model (PSM) was adopted. The alternative arms chosen were daratumumab added to bortezomib plus …

Tirzepatide Protects Against Hepatic Oxidative Stress In High-Fat Induced Obesity In Male Rats, Ashraf Jameel Alathary, Zahraa Jawad Kadhim

Maaen Journal for Medical Sciences

Background

Obesity is a prevalent health issue that affects people of all ages at a high rate. Tirzepatide (TZP) is a hypoglycemic medication that acts as a dual antagonist for both the GIP-1 and GIP receptors. Previous reports have shown that TZP treatment demonstrated substantial weight reduction as well as lipid-modulating effects in obese and overweight individuals.

Objective

The aim from this study is to examine the potential protective effect of TZP on oxidative stress status and HFD induced obesity in male rats.

Methods

This research employed a total of 28 adult male Sprague-Dawley rats. Normal control group involved seven …

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …

Dmt: Mechanisms, Psychological And Physiological Effects, And Its Dual Role As A Drug Of Abuse And Potential Health Benefit, Kayla Yarbrough, Solymar Santiago Bonilla, Garrett Evins, Jean Colón, Brandon Kitchens

College of Pharmacy Student Research

N, N-Dimethyltryptamine (DMT) is a potent indolethylamine hallucinogen classified as a Schedule I substance, indicating a high potential for abuse and no accepted medical use. Despite this, DMT's unique pharmacological profile, characterized by its interaction with serotonin receptors, particularly 5-HT2A, and its ability to induce profound alterations in perception, emotion, and cognition, has spurred interest in its potential therapeutic applications. This paper explores DMT's mechanisms of action, its psychological and physiological effects, and the risks and side effects associated with its use. While DMT can cause vivid hallucinations, emotional responses ranging from euphoria to existential dread, and various physiological changes, …

The Efficacy Of Cannabis As A Substitute Addiction For Opiates, Clark Furlong

Theses and Graduate Projects

Background: Approaches to opiate addiction focus on abstinence and/or a harm reduction model that often utilizes substitute medications. Methadone and suboxone are the most prescribed drugs for opiate maintenance therapy. The long-term side effect profile and health consequences are undesirable. Research is looking for healthier alternatives.

Purpose: Opiate maintenance therapy participants have a mortality rate greater than twelve times that of the normal population, we seek to discover if cannabis can be a useful/safer alternative.

Methods: Following a comprehensive literature review a 7-question online survey was designed with SurveyMonkey to gauge current Augsburg students’ perception of cannabis as an alternative …

One More Negative Regulator Of Ac6: S-Nitrosylation, Isabella Cattani-Cavalieri, Rennolds S. Ostrom

Pharmacy Faculty Articles and Research

"In this issue of the Journal, Maghsoudi and colleagues (pp. 82–96) report a series of studies that delineate the biochemical and pharmacological mechanism of this resistance (4). The study focuses on adenylyl cyclase (AC), an enzyme crucial for pulmonary vasodilation through its action of synthesizing cAMP. There are nine isoforms of AC (AC1–AC9) that are all stimulated by Gs but otherwise are distinct in their regulatory qualities, subcellular localization, and expression profiles throughout the body (5). AC6 plays a significant role in fetal and neonatal lung, especially in pulmonary artery smooth muscle cells, where …

Injectable Formulations For Localized Delivery Of Immunomodulators, Ketki Velankar

Electronic Theses and Dissertations

Dysregulation of immune homeostasis is fundamental to the development of autoimmune disorders. Fibroblastic reticular cells (FRCs) within lymph nodes play crucial roles in forming a microenvironment conducive to immune cell interactions and regulating autoreactive T cells driving autoimmune diseases. Studies have shown the potential of FRCs as a form of personalized cell therapy to correct dysregulated immune responses. Successful translational efforts, however, require the cells to be formulated as injectable suspensions while retaining their native architecture, which is essential for their regulatory functions. The main challenge resides in retaining the native reticular organization of FRCs lost in conventional monolayer cultures …

Uptake Of Extracellular Vesicles Into Brain Endothelial Cells And Development Of Motor Neuron-Derived Extracellular Vesicles For Amyotrophic Lateral Sclerosis, Jhanvi Rajan Jhaveri

Electronic Theses and Dissertations

Extracellular vehicles (EVs) are an emerging class of drug carriers and are primarily reported to be internalized into recipient cells via a combination of endocytic routes such as clathrin-mediated, caveolae-mediated and macropinocytosis pathways. In part one of this thesis, (1) we investigated potential effects of homotypic vs. heterotypic interactions by studying the cellular uptake of homologous EVs (EV donor cells and recipient cells of the same type) vs. heterologous EVs (EV donor cells and recipient cells of different types) and (2) determined the route of EV internalization into low pinocytic/hard-to-deliver cell models such as brain endothelial cells ( …

Delivery Of Mitochondria-Containing Engineered Extracellular Vesicles To The Blood-Brain Barrier For Ischemic Stroke Therapy, Kandarp Dave

Electronic Theses and Dissertations

Ischemic stroke is the second leading cause of death worldwide, and the lack of effective treatment options is an unmet clinical need for stroke survivors. Ischemic stroke-induced oxygen-glucose deprivation (OGD) in the affected brain tissue leads to mitochondrial dysfunction and adenosine triphosphate (ATP) depletion in the brain endothelial cells (BECs) lining the blood-brain barrier (BBB). ATP deprivation in the BECs dysregulates actin cytoskeleton dynamics, resulting in BBB breakdown. Restoration of blood flow (i.e., reperfusion) upon the first-line stroke treatment further leads to BBB breakdown and widens the paracellular spaces between BECs. …

Central Nervous System Antiviral Pharmacology, Sean N. Avedissian

Theses & Dissertations

Soon after viral infection, viruses like Human Immunodeficiency Virus (HIV) and SARS-CoV-2 can disseminate throughout the body and establish reservoirs in the central nervous system (CNS). The persistence of viruses in cells of these reservoirs is a major obstacle to virus eradication. This is due to the abundance of cells/receptors that these viruses utilize to gain entry into cells found at these various reservoir sites. Consequently, these same anatomical sites also may be pharmacologic sanctuaries, as evidenced by concentrations of antiretroviral drugs (ARVs) and antivirals (AVs) that are lower in reservoirs than those in peripheral blood; in some cases, these …

Synthesis And Characterization Of An Activity-Based Probe To Isolate And Quantify Adduct Formation In Ntsr1 Trt., Aadarsh Khairnar

Theses & Dissertations

Targeted radionuclide therapy (TRT) has emerged as a promising cancer treatment by offering precise delivery of radioisotopes to cancer cells via molecular targets. Recent advancements in the small molecule TRTs offer efficient targeting and rapid clearance, reducing off-target toxicity. The Neurotensin receptor 1 (NTSR1) targeted small molecule antagonist 3BP-227 when labeled with [¹⁷⁷Lu], has demonstrated effective tumor targeting but suffers from rapid washout from the target cancer cell, limiting its therapeutic potential.

To enhance tumor retention and therapeutic efficacy of the NTSR1-targeted TRT, the Garrison laboratory has developed a novel approach utilizing cysteine cathepsins (CCs) and the E64 …

Pharmacokinetics And Tissue Distribution Of A Lipid-Based Extended-Release Nano-Formulation Of Mo-Oh-Nap Tropolone To Enhance Pulmonary Delivery For The Treatment Of Pulmonary Metastatic Osteosarcoma, Wafaa N. Aldhafiri

Theses & Dissertations

Osteosarcoma is the most common primary bone tumor in children and adolescents. Metastasis is prevalent in 25% of patients, at diagnosis, with the lungs being the most common metastatic site. Pulmonary metastatic osteosarcoma is a significant therapeutic challenge with a 5-year survival rate of ≤30%. Patients with pulmonary metastatic disease at diagnosis receive the same standard of care as patients with local disease, which hasn’t changed over the past 30 years. The treatment and prevention of pulmonary metastatic osteosarcoma represents a significant critical and unmet need.

MO-OH-Nap tropolone is a novel small molecule with cytotoxic activity across multiple human osteosarcoma …

Characterization Of Population Pharmacokinetics And Associated Interindividual Variability Of Drugs Used In Mass Drug Administration Against Lymphatic Filariasis, Abdullah Alshehri

Theses & Dissertations

Lymphatic filariasis (LF) is a mosquito-borne filarial infection that affects the lymphatic system. The progression of the disease is associated with severe comorbidities and social stigma among patients. The World Health Organization has categorized the disease as a public health problem, and it has been targeted by mass drug administration (MDA) campaigns over the past two decades. Several preventive chemotherapies have been used in MDA campaigns against LF, including a combination of three anti-filarial drugs (IDA therapy): albendazole (ALB), diethylcarbamazine (DEC), and ivermectin (IVM). Other antiparasitic drugs, such as moxidectin (MOX), are still under investigation for their activity against LF. …

A Third Generation Long-Acting Dimeric Dolutegravir Prodrug Nanoformulation, Bhoomika Suresh Gowda

Theses & Dissertations

Dolutegravir (DTG) is an integrase strand transfer inhibitor (INSTI) widely used as a part of first-line combination antiretroviral therapy. DTG has a high barrier to resistance However, one therapeutic challenge centers on its life-long daily use. Sub-optimal adherence to daily oral pills underscore the need for long-acting formulations. To these ends, our research activities have focused on the development and translation of ultra-long-acting ART. Monomeric ester prodrugs provided initial success in extending the apparent half-life of DTG and other INSTIs. One is the DTG prodrug formulation called NM2DTG. NM2DTG’s significantly extended the parent drug’s apparent half-life [Nature Communications, 3226 (2022)]. …

Unmc Quick Checks: An “Opt-Out” Model For Health Profession Student Appointments With Mental Health Counseling Services, Hannah K. Tandon Md, Taylor J. Kratochvil Md, Ms, Katherine L. Keiser Ms, Limhp, Nicole J. Kent Bs, Kaitlyn E. Schultis Bs, Jeffrey W. Knapp Msw, Jeffrey P. Gold

Innovations in Health Sciences Education Journal

Background: Health professions trainees experience high rates of anxiety and depression but are often reluctant to seek help. Institutional outreach during pre-clinical training may identify vulnerable students, improve resource awareness, and destigmatize psychological counseling. The University of Nebraska Medical Center (UNMC) Quick Check program is a novel opt-out program connecting health professions students to mental health counselors.

Objective: The purpose of this study was to evaluate student perceptions and utilization of mental health resources after participation in the UNMC Quick Check program.

Methods: For this limited pilot study, second-year pharmacy students were assigned to UNMC Quick Check appointments with UNMC …

Advancement In In-Silico Drug Discovery From Virtual Screening Molecular Dockings To De-Novo Drug Design Transformer-Based Generative Ai And Reinforcement Learning, Dony Ang

Computational and Data Sciences (PhD) Dissertations

The field of drug discovery has seen remarkable advancements over the past few decades, transitioning from traditional experimental methods to highly sophisticated computational approaches. One of the pivotal techniques in this evolution is virtual screening, which utilizes molecular docking to predict the interaction between small molecules and target proteins. This method has significantly accelerated the initial stages of drug discovery by enabling the high-throughput screening of large chemical libraries. By simulating the binding affinity and stability of potential drug candidates, virtual screening has become a cornerstone in identifying promising compounds for further development.

A notable application of virtual screening was …

Development Of A Novel Drug Delivery Platform To Treat Hiv-Associated Neurocognitive Disorder, Lina Zhou

Alternative Theses and Dissertations (AETDs)

Despite the significant reduction in HIV prevalence and improvement in life expectancy achieved through the availability of widespread antiretroviral therapy (ART), there remains no definitive cure for HIV. Further, HIV infects the brain as early as eight days after initial peripheral infection leading to neuroHIV and subsequently neuronal damage and cognitive impairment. HIV can enter the brain through several mechanisms, including the migration of infected immune cells (Trojan Horse Mechanism), direct infection of endothelial cells, and cytokine-mediated disruption of the blood-brain barrier (BBB). Consequently, HIV-associated neurocognitive disorder (HAND) remains a significant challenge in the ART era, with an estimated prevalence …

Enhancing The Anticancer Effects Of Apiaceae Spice Phytochemicals., Jared Lee Scott

Electronic Theses and Dissertations

Breast cancer (BC) is a leading contributor to the death of women and is the most common type of cancer. Many chemotherapy drugs are developed from plants, and some plant extracts can exhibit significant anticancer activities while also having less toxic side effects. The Apiaceae plant family consists of several species that are used as culinarily spices which have demonstrated antioxidant, chemopreventive, and anticancer activities. The encapsulation of anticancer phytochemicals into naturally produced membrane-bound nanoparticles known as exosomes could improve their systemic distribution and efficacy. Exosomes are involved in cell-to-cell communication through the delivery of proteins, nucleic acids, and small …

Access To Medicines For Parkinson's Disease In Kenya: A Qualitative Exploration, Natasha Fothergill-Misbah, Juzar Hooker, Judith Kwasa, Richard Walker

Internal Medicine, East Africa

Background: The accessibility of Parkinson’s disease medicines is limited across sub-Saharan Africa,which can have negative health, social and financial consequences for people with Parkinson’s disease andtheir families. However, there is a stark gap in the literature regarding the impact of poor access to medicineson individuals.

Objectives: The study objective was to understand the accessibility of Parkinson’s disease medicines in Kenyafrom the perspective of people with Parkinson’s disease, their caregivers and neurologists.MethodsMethods: In-depth qualitative interviews were conducted with 55 people with Parkinson’s disease, 23 caregiversand 8 neurologists to understand their experience regarding challenges with accessing Parkinson’s diseasemedicines and the health, social …

Diesel Exhaust Particles Alter Mitochondrial Bioenergetics And Camp Producing Capacity In Human Bronchial Epithelial Cells, Isabella Cattani-Cavalieri, Marina Trombetta-Lima, Hong Yan, Ana L. Manzano-Covarrubias, Hoeke A. Baarsma, Asmaa Oun, Melissa Mol Van Der Veen, Emily Oosterhout, Amalia M. Dolga, Rennolds S. Ostrom, Samuel Santos Valenca, Martina Schmidt

Pharmacy Faculty Articles and Research

Introduction: Air pollution from diesel combustion is linked in part to the generation of diesel exhaust particles (DEP). DEP exposure induces various processes, including inflammation and oxidative stress, which ultimately contribute to a decline in lung function. Cyclic AMP (cAMP) signaling is critical for lung homeostasis. The impact of DEP on cAMP signaling is largely unknown.

Methods: We exposed human bronchial epithelial (BEAS-2B) cells to DEP for 24–72 h and evaluated mitochondrial bioenergetics, markers of oxidative stress and inflammation and the components of cAMP signaling. Mitochondrial bioenergetics was measured at 72 h to capture the potential and accumulative effects of …

Impact Of A Pharmacist-Led Hcv Treatment Program At A Federally Qualified Health Center, Jerika T. Lam, Sharon Xavioer

Pharmacy Faculty Articles and Research

Pharmacists are key players who can help to eliminate the hepatitis C virus (HCV) epidemic in the United States. This pilot retrospective study evaluated the impact of a pharmacist-led HCV treatment program in a federally qualified health center (FQHC) primary care clinic setting. The primary outcome was to assess sustained virologic response (SVR) rates 12 weeks after patients were initiated and completed their oral direct acting antiviral (DAA) treatment regimens. Methods: This pilot retrospective study included historical analyses of patients who received DAA treatment in the pharmacist-led HCV treatment program in a FQHC clinic between 1 January 2019 and 31 …

Comments Re: Draft Nih Intramural Research Program Policy: Promoting Equity Through Access Planning, Fred Ledley M.D., Edward Zhou Pharmd., Paula Chaves Da Silva Ph.D.

CISI Publication

We commend the NIH initiative to require that licensees of technologies that enable discovery or development of FDA-approved products arising from the NIH intramural program to include an Access Plan to promote “product affordability, availability, acceptability, and sustainability” and recognition that such protections are essential to ensuring a “return on taxpayers' investment in biomedical research.” Recognizing the complexity of anticipating appropriate terms for products that are in pre-clinical or early clinical development at the time of licensing, we also support the proposal that the Access Plan be submitted in late-stage clinical development, though we argue that …

Formative Research About Shared Decision Making In The Treatment Of Opioid Use Disorder In Pregnant Women, Ruth Jeminiwa, Phd, Fadel Dadabaev, Pharmd, Heeyoung Kim, Pharmd, Caroline Popielaski, Pharmd, Sohyeon Park, Pharmd, Meghan Gannon, Phd Msph, Diane Abatemarco, Phd, Msw, Ronald Myers, Phd, Dsw

College of Pharmacy Posters

Background

• Shared Decision Making (SDM) is an evidence-based practice that involves a discussion between a health care professional and patient to reach a mutual agreed upon treatment plan.(1)
• A recent nationally-representative study indicates that only 39% of physicians use SDM for 50% or fewer Pregnant Women with Opioid Use Disorders (PWOUD).(2)
• Little is known about factors that affect SDM among PWOUD. This research project aimed to address this knowledge gap.

Transitions Of Care Practice Models: Innovations Across Different Health Settings, Laressa Bethishou, Noah Fang

Pharmacy Faculty Articles and Research

"Being discharged from a hospital may be a joyous occasion for a patient with a long length of stay, but this process may also be riddled with medication issues. With a deluge of new medications, unclear instructions, and new costs that may be unaffordable, many patients face challenges that are all too common. Additionally, the medication list may be fraught with discrepancies of missing or inaccurate home medications, duplicate therapies of new medications prescribed, or drug-drug interactions of old and new medications.

Pharmacists and pharmacy personnel who support patients during transitions of care (TOC) are very familiar with the consequences …