Chemicals and Drugs Commons^™

October / November / December 2024, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the October - November - December issue of Rural Rocks from the SWOSU College of Pharmacy.

Magnetic Resonance Imaging Trackable Pathology-Triggered Polymersomes Toward Enzyme Replacement Theranostics For Gm1 Gangliosidosis, Dorian Foster

All Dissertations

This dissertation investigates the development and optimization of pathology-responsive polymersomes for simultaneous enhanced magnetic resonance imaging (MRI) and enzyme replacement therapy (ERT) in the treatment of GM1 gangliosidosis (GM1). While therapeutic strategies exist for similar, non-neuropathic lysosomal storage disorders, implementation towards GM1 faces significant challenges due to the blood-brain barrier.

Herein, we developed and characterized a range of low molecular weight hyaluronic acid-b-polylactic acid (HA-PLA) polymersomes (PSs) capable of encapsulating therapeutic enzymes in their hydrophilic core. These polymersomes exhibit pathophysiology-triggered responsiveness, degrading in the presence of acidic conditions, which is characteristic of lysosomes, and enzymes such as hexosaminidase A, which …

Impact Of Pegylated Liposomes On Cytotoxicity Of Tamoxifen And Piperine On Mcf-7 Human Breast Carcinoma Cells, Klaudi K. Vaiphei, A Prabakaran, Singh Snigdha, Satyajit Laxman Murkute, Purusottam Mohapatra, Rakesh Kumar Sahoo, Sanya Batheja, Umesh Gupta, Anu Puri, Upal Roy

Health & Biomedical Sciences Faculty Publications

Tamoxifen (TMF) is an anticancer agent used for managing estrogen receptor-positive breast cancer. It has limited therapeutic efficacy against breast cancer, which could be enhanced by the coadministration of herbal drugs like piperine (PIP). However, the hydrophobic nature of TMF and PIP restricts their therapeutic application. Therefore, the present study focuses on the impact of the anticancer activity of TMF in combination with PIP and after entrapping them into liposomes (TMF-PIP-LPs and TMF-PIP-PEG-LPs). The liposomes were prepared using the thin film hydration method. In addition, the morphology of the prepared liposomes was found spherical after SEM and TEM analyses. Further, …

Lipid-Based Niclosamide Delivery: Comparative Efficacy, Bioavailability, And Potential As A Cancer Drug, Jihoo Woo, Russel Wiggins, Shizue Mito

School of Medicine Publications

Niclosamide, an FDA-approved anti-parasitic drug, has demonstrated significant potential as a repurposed anti-cancer agent due to its ability to interfere with multiple oncogenic pathways. However, its clinical application has been hindered by poor solubility and bioavailability. Lipid-based nanocarrier systems such as liposomes, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), and lipid nanoemulsions (LNE), along with lipid prodrugs, have successfully been employed by researchers to overcome these limitations and improve niclosamide’s pharmacokinetic profile. Lipids are the core organic compounds which serve as the foundation of these advanced drug delivery methods and in turn play a critical role in enhancing niclosamide’s …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Synthesis Of Photocleavable Molecules For Neurological Applications, Nishal Madujith Egodawaththa Arachchilage Don

Theses and Dissertations

In recent biomedical research, the precise control of molecular dynamics through light activation has emerged as a powerful tool, particularly in the field of neurobiology. This approach involves the use of photocleavable cages or photoprotective groups (PPGs) that are chemically tethered to biologically active molecules such as neurotransmitters or calcium chelators. These cages remain inert until exposed to specific wavelengths of light, typically in the visible range, triggering the release of the active compound with high spatiotemporal precision.

For neurotransmitter systems, such as glutamate (Glu), which plays a critical role in synaptic transmission and memory formation, researchers have developed novel …

The Life And Discoveries Of Yellapragada Subbarow, Nikhil R, Varuni Pragya, Subramanian Ramaswamy, Shiva Prasad B N, Mahabaleshwar Mamadapur

Digital Journal of Clinical Medicine

Dr. Yellapragada Subbarow was a researcher, teacher, and a wizard of wonder drugs who constantly made efforts in the discoveries/ inventions such as vitamins, anti-vitamins, antibiotics, and many more by disentangling the mysteries of nature for the betterment of the people. He inspired the youngsters to take up the challenges and to stand up above mediocrity. The reward for his achievement was delayed. The article describes a true humanist's journey, discoveries, and his achievements that are largely unknown to date.

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

An Assessment Of The Impact Of Fentanyl On Post-Mortem Interval From A Decomposition And Biochemical Perspective, Kaylene Mcdonald

Senior Honors Theses

In the realm of body decomposition, bodies undergo a plethora of different metabolic and chemical changes. The human body follows a very consistent pattern and predictable time frame, with the exclusion of extenuating circumstances. The presence of fentanyl at the time of death provides the possibility of changes in decomposition rates, potentially skewing the time of death estimations. This research analyzes the varying decompositional stages of a body and their subsequent close relations with activity in the environment around it, specifically investigating the impacts of fentanyl on those surroundings and postmortem interval estimation determinations. This research found evidence that fentanyl …

Akt Kinases As Therapeutic Targets, Dalal Hassan, Craig Menges, Joseph Testa, Alfonso Bellacosa

Student Papers, Posters & Projects

AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While …

Role Of Myeloid Cell-Specific Adenylyl Cyclase Type 7 In Lipopolysaccharide- And Alcohol-Induced Immune Responses, Yawen Hu, Sonika Patial, Yogesh Saini, Masami Yoshimura

School of Graduate Studies Faculty Publications

Clinical and experimental evidence indicates that alcohol use causes various abnormalities in the immune system and compromises immune functions. However, the mechanistic understanding of ethanol’s effects on the immune system remains limited. Cyclic AMP (cAMP) regulates multiple processes, including immune responses. Earlier research indicated that type 7 adenylyl cyclase (AC7) regulates the immune system and is highly responsive to ethanol. Therefore, we hypothesized that AC7 is a central player in regulating the effects of alcohol on innate immune responses. To test this hypothesis, we utilized a myeloid lineage-specific AC7 KO mouse model and compared the effects of acute and chronic …

Functions Of Tam Receptors And Ligands Protein S And Gas6 In Atherosclerosis And Cardiovascular Disease, Teagan Prouse, Samarpan Majumder, Rinku Majumder

School of Medicine Faculty Publications

Atherosclerosis and cardiovascular disease are associated with high morbidity and mortality in industrialized nations. The Tyro3, Axl, and Mer (TAM) family of receptor tyrosine kinases is involved in the amplification or resolution of atherosclerosis pathology and other cardiovascular pathology. The ligands of these receptors, Protein S (PS) and growth arrest specific protein 6 (Gas6), are essential for TAM receptor functions in the amplification and resolution of atherosclerosis. The Axl-Gas6 interaction has various effects on cardiovascular disease. Mer and PS dampen inflammation, thereby protecting against atherosclerosis progression. Tyro3, the least studied TAM receptor in cardiovascular disease, appears to protect against fibrosis …

Association Between Various Types Of Corticosteroids And Mortality For Severe Community-Acquired Pneumonia In Adults: A Systematic Review And Network Meta-Analysis, Peng Wang, Jun Wan, Qiaoyu You, Yuxin Zheng, Wenhao Xu, Jialing He, Liyuan Peng, Cuyubamba Dominguez Jorge Luis, Yuning Feng, Ping Xu, Xinrong Li, Weelic Chong, Yang Hai, Lu Jia, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

OBJECTIVE: This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.

DATA SOURCES: This study conducted …

Cabotegravir Maintains Protective Efficacy In The Setting Of Bacterial Stis: A Secondary Analysis Of Hptn 083, Meredith E. Clement, Brett Hanscom, Daniel Haines, Jose A. Bazan, Nuntisa Chotirosniramit, Ryan Kofron, Sharon Mannheimer, Kenneth H. Mayer, Mayara Secco Torres Silva, Lydia Soto-Torres, Alex R. Rinehart, James F. Rooney, A Jennings, K Gomez-Feliciano, Marybeth Mccauley, Beatriz Grinsztejn, Raphael J. Landovitz, Et Al.

School of Medicine Faculty Publications

BACKGROUND: Sexually transmitted infections (STIs) have been shown to facilitate HIV transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea and chlamydia) were present. METHODS: STI events per 100 person-years (PY) were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors …

Cocaine-Induced Dna-Dependent Protein Kinase Relieves Rnap Ii Pausing By Promoting Trim28 Phosphorylation And Rnap Ii Hyperphosphorylation To Enhance Hiv Transcription, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Meenata Khumallambam, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Drug abuse continues to pose a significant challenge in HIV control efforts. In our investigation, we discovered that cocaine not only upregulates the expression of the DNA-dependent protein kinase (DNA-PK) but also augments DNA-PK activation by enhancing its phosphorylation at S2056. Moreover, DNA-PK phosphorylation triggers the higher localization of the DNA-PK into the nucleus. The finding that cocaine increases the nuclear localization of the DNA-PK provides further support to our observation of enhanced DNA-PK recruitment at the HIV long terminal repeat (LTR) following cocaine exposure. By activating and facilitating the nuclear localization of the DNA-PK, cocaine effectively orchestrates multiple stages …

Low Concentrations Of Hexavalent Chromium In Drinking Water Induce Alzheimer’S Disease Neuropathology: Using A Toxic Aging Coin Approach To Assess Hexavalent Chromium Neurotoxicity, Liam Buchanan, Samuel Vielee, Spencer Roof, Haiyan Lu, Jamie L Young, Idoia Meaza Isusi, Aggie Williams, Joseph Kouokam, Sandra Wise, Luping Guo, Jun Cai, John Wise, John P. Wise Jr.

The Cardinal Edge

Introduction: We are currently facing an aging crisis, as 20% of the U.S. population will be geriatric (65+) by 2030. This growing geriatric population will result in increasing prevalence of age-related diseases, coinciding with increasingly prevalent environmental pollution. Environmental pollution is a ubiquitous health threat that affects people at all ages and contributes to aging pathology. However, geriatric individuals are likely more susceptible to the negative health effects from environmental pollution. The distinct effects of environmental pollutants across age groups are currently understudied. We use a Toxic Aging Coin approach to investigate: 1) how age impacts toxicity (heads), …

Takeout Or Delivery? Reoperation Rates In Lower Extremity Long Bone Osteomyelitis Treated With Debridement And Local Antibiotic Delivery Systems, Nolan M. Reinhart, Jackson P. Tate, Jacob S. Budin, Julianna E. Winter, Olivia C. Lee, William F. Sherman

School of Medicine Faculty Publications

BACKGROUND: Early diagnosis and treatment of osteomyelitis is essential to prevent potential complications including sepsis, extensive bone resection, amputation, and death. Despite current treatment strategies for management of osteomyelitis, recurrence rates reported in the literature are upwards of 25 %. Current evidence comparing the efficacy of differing surgical treatments of osteomyelitis is inconclusive. The purpose of this study is to compare rates of re-debridement and amputation in patients who receive either debridement alone or debridement with placement of local antibiotic delivery systems as initial treatment for lower extremity long bone osteomyelitis. METHODS: A retrospective cohort study was performed to investigate …

Maternal Substance Use And Neonatal Intensive Care Unit (Nicu) Admission Among Medicaid Beneficiaries: A State-Wide Audit, Vidhani Goel, Ana L. Reyes, Bertille Assoumou, Dodds P. Simangan, Farooq Abdulla, Megumi Akiyama, Deborah A. Kuhls, Kavita Batra

Undergraduate Research Symposium Podium Presentations

Introduction: Mounting evidence suggested a strong association between maternal substance abuse and poor neonatal outcomes. This study aims to investigate an association between maternal substance abuse and NICU admissions and transitions in the LOC among newborns who were Medicaid beneficiaries.

Methods: A hybrid linkage approach was utilized to link two datasets (Birth Registry and Nevada Medicaid Claims) spanning 2015-2021 with nearly 85% linkage efficiency. The infant records were analyzed using univariate and bivariate statistical methods with significance level set at 5%.

Results: A total of 84,181 infant records were identified, of which 70,817 (84.1%) admitted to a single LOC during …

Unravelling The Erythropoietin Heterodimeric Complex: In Silico Analysis Of Complex Assembly And Binding Interface, Atiya Habib, Urooj Qureshi, Mohammad Nur-E-Alam, Aftab Ahmed, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Erythropoietin (Epo), a glycosylated protein categorized as a member of the cytokine family, is responsible for the modulation of erythrogenesis. Besides this, the nonhaematopoietic effects of Epo are associated with tissue-protective activity via an antiapoptotic pathway. This function of Epo is linked with its heterodimeric form, i.e. EpoR/βcR belonging to the cytokine family as well. Both receptors are dissected into three domains: extracellular (also known as ligand-binding domain), transmembrane and cytoplasmic domain. The transmembrane and cytoplasmic domains are assumed to play a paramount role in dimerization and tissue protection. However, the tertiary structure of cytoplasmic domains of both …

Acute Stress Activates Basolateral Amygdala Neurons Expressing Corticotropin-Releasing Hormone Receptor Type 1 (Crhr1): Topographical Distribution And Projection-Specific Activation In Male And Female Rats, Robert J. Aukema, Gavin N. Petrie, Samantha L. Baglot, Nicholas W. Gilpin, Matthew N. Hill

School of Medicine Faculty Publications

Although the basolateral amygdala (BLA) and corticotropin releasing hormone receptor type I (CRHR1) signaling are both central to the stress response, the spatial and circuit-specific distribution of CRHR1 have not been identified in the BLA at a high resolution. We used transgenic male and female CRHR1-Cre-tdTomato rats to topographically map the distribution of BLA neurons and identify whether they are activated by acute stress. Additionally, we used the BLA circuits projecting to the central amygdala (CeA) and nucleus accumbens (NAc) as a model to test circuit-specific expression of CRHR1 in the BLA. We established several key findings. First, CRHR1 had …