Chemicals and Drugs Commons^™

Alphafold2 Modeling And Molecular Dynamics Simulations Of The Conformational Ensembles For The Sars-Cov-2 Spike Omicron Jn.1, Kp.2 And Kp.3 Variants: Mutational Profiling Of Binding Energetics Reveals Epistatic Drivers Of The Ace2 Affinity And Escape Hotspots Of Antibody Resistance, Nishank Raisinghani, Mohammed Alshahrani, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized the molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that protect and restore …

Breathe Easy: The Potential Of Vitamins As Adjunct Therapy In Asthma Management, Elena Dike, Alex Zuo

Research Colloquium

Asthma, a prevalent respiratory disease, imposes a heavy burden on patients and healthcare systems. This research poster reviews recent findings on the potential of Vitamins A, C and E as adjunct therapies in asthma management. Comprehensive searches in PubMed, the NIH and Google Scholar identify multiple relevant publications and articles. Key results indicate that Vitamin A reduces Th2/Th17 levels and ROS, protecting the airway epithelium; Vitamin C decreases inflammatory cells and increases cGMP levels, reducing airway hyper-reactivity; and Vitamin E reduces eosinophils, basophils and neutrophils while also reducing ROS. These findings suggest that increasing intake of these vitamins, under medical …

Targeting Ribosome Biogenesis Is A Novel Approach For The Management Of Pancreatic Cancer, Mudassier Ahmad, Haider Ahsan, Carlos Perez, Muhammad Bangash, Andrew Massey, Emmanuel Anning, Manish Tripathi, Dae Kim, Subhash C. Chauhan, Bilal Bin Hafeez

Research Colloquium

Pancreatic ductal adenocarcinoma is the third leading cause of cancer-related deaths in the United States with limited therapeutic options available. Gemcitabine, a deoxycytidine nucleoside analog is currently considered the most effective therapy for PanCa. However, it shows only a marginal survival benefit of six months. Aberrant ribosome biogenesis occurs in most tumor types. We observed that PanCa cells are addicted to ribosome biogenesis, which supports their highly aggressive metastatic phenotypes. Thus, strategically targeting ribosome biogenesis process could be one of the ideal strategies for the prevention and treatment of PanCa. In this study, we elucidated the molecular mechanisms of POLR1A …

Mouse Monocytes Express Cd127 By Immune Cells, Not Lps, Reza Yazdani, Mozhde Askari, Amir Moghadam-Ahmadi, Gholamreza Azizi, Bogoljub Ciric, Alexandra Boehm, Guang-Xian Zhang, Mohamad Rostami

Department of Neurology Faculty Papers

The essential role of interleukin 7 (IL-7) signaling via its receptor (IL-7Rα; CD127) in T cell development and function has been well documented. However, CD127 expression and function in myeloid cells, including monocytes, are less clear, especially in mice. In the present study we report an inducible CD127 expression in mouse monocytes/macrophages. This induction is dependent on the presence of other immune cells, highlighting that regulation of CD127 expression on monocytes differs in mice and humans. We demonstrate that CD127 is functional, as IL-7 downregulated its expression. We also saw decreased CD127 expression during inflammation in vivo. Overall, upregulation …

Engineered Nls-Chimera Downregulates Expression Of Aggregation-Prone Endogenous Fus, Miyuki Hayashi, Amandeep Girdhar, Ying-Hui Ko, Kevin Kim, Jacquelyn Depierro, Joseph R. Buchler, Nikhita Arunprakash, Aditya Bajaj, Gino Cingolani, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Importin β-superfamily nuclear import receptors (NIRs) mitigate mislocalization and aggregation of RNA-binding proteins (RBPs), like FUS and TDP-43, which are implicated in neurodegenerative diseases. NIRs potently disaggregate RBPs by recognizing their nuclear localization signal (NLS). However, disease-causing mutations in NLS compromise NIR binding and activity. Here, we define features that characterize the anti-aggregation activity of NIR and NLS. We find that high binding affinity between NIR and NLS, and optimal NLS location relative to the aggregating domain plays a role in determining NIR disaggregation activity. A designed FUS chimera (FUS_IBB), carrying the importin β binding (IBB) domain, is …

Immunoactive Signatures Of Circulating Trna- And Rrna-Derived Rnas In Chronic Obstructive Pulmonary Disease, Megumi Shigematsu, Takuya Kawamura, Deepak Deshpande, Yohei Kirino

Computational Medicine Center Faculty Papers

Chronic obstructive pulmonary disease (COPD) is the most prevalent lung disease, and macrophages play a central role in the inflammatory response in COPD. We here report a comprehensive characterization of circulating short non-coding RNAs (sncRNAs) in plasma from patients with COPD. While circulating sncRNAs are increasingly recognized for their regulatory roles and biomarker potential in various diseases, the conventional RNA sequencing (RNA-seq) method cannot fully capture these circulating sncRNAs due to their heterogeneous terminal structures. By pre-treating the plasma RNAs with T4 polynucleotide kinase, which converts all RNAs to those with RNA-seq susceptible ends (5′-phosphate and 3′-hydroxyl), we comprehensively sequenced …

Aars Online: A Collaborative Database On The Structure, Function, And Evolution Of The Aminoacyl-Trna Synthetases, Jordan Douglas, Haissi Cui, John J. Perona, Oscar Vargas-Rodriguez, Henna Tyynismaa, Claudia Alvarez Carreño, Jiqiang Ling, Lluís Ribas De Pouplana, Xiang-Lei Yang, Michael Ibba, Hubert Becker, Frédéric Fischer, Marie Sissler, Charles W. Carter Jr., Peter Wills

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The aminoacyl-tRNA synthetases (aaRS) are a large group of enzymes that implement the genetic code in all known biological systems. They attach amino acids to their cognate tRNAs, moonlight in various translational and non-translational activities beyond aminoacylation, and are linked to many genetic disorders. The aaRS have a subtle ontology characterized by structural and functional idiosyncrasies that vary from organism to organism, and protein to protein. Across the tree of life, the 22 coded amino acids are handled by 16 evolutionary families of Class I aaRS and 21 families of Class II aaRS. We introduce AARS Online, an interactive Wikipedia-like …

Clinical Practice Guideline-Inconsistent Chemotherapy-Induced Vomiting Prophylaxis In Pediatric Cancer Patients In Community Settings: A Children's Oncology Group Study, Aaron J. Sugalski, Allison C. Grimes, Michelle M. Nuño, Subhash Ramakrishnan, Melissa P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra M. Walsh, Andrea R. Wrightson, Lolie C. Yu, Susan K. Parsons, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described. Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG …

Improving Ligand Pharmacokinetics Via Bioisosteric Substitution Of Amides With 1, 2, 3-Triazoles While Maintaining Dopamine D4 Receptor Selectivity And Potency, Mohammad Alkhatib

Theses and Dissertations

Several neurophysiological functions, such as attention, cognition, and emotional regulation, are regulated by the binding of dopamine on G-Protein coupled receptors. D4Rs are mainly located in the prefrontal cortex and the hippocampus and are known to have a key role in decision-making, memory formation, cognition, and attention. Administration of D4Rs- selective ligands during the preclinical studies enhance the outcomes and the results in animal models suffering from neuropsychiatric disorders, including ADHD, substance use disorders (SUD), and Alzheimer's disease. Recently, we reported a group of D4R-selective ligands with different efficacies depending on their phenylpiperazine ring scaffold to illustrate D4R function during …

Perilous Consequences Of Chemotherapy Induced Alopecia In Afflicted Cancer Survivors: A Comprehensive State Of The Art Review, Salma A. Fereig, Mona Gamal Arafa, Ghada Mamdouh Elzaafarany, Mona Mohamed Ahmed Abdelmottaleb, John Youshia

Pharmacy

Due to researchers’ great efforts during previous and current centuries to cure cancer, a remarkable increase in the number of cancer survivors has been observed. However, side effects of chemotherapeutic agents greatly affect the quality of life of cancer cases, usually referred to as cancer stigma, the most psychologically traumatizing of which is chemotherapy-induced alopecia (anagen effluvium). Unfortunately, there is no preventive protocol for chemotherapy-induced alopecia to date. The only suggested technique is vasoconstriction by scalp cooling during and after chemotherapy sessions to minimize the absorption of cytotoxic agents within the hair follicle area; a technique that is not very …

Successful Treatment Of A Chronic Recurrent Expanding Hematoma Of The Thigh, Gianfranco Galantini, Bakhtawar Mushtaq, Jesse Ottaway, Charles Long

Abington Jefferson Health Papers

Chronic expanding hematoma (CEH) is a rare entity that poses diagnostic and therapeutic challenges due to persistent growth, risk of recurrence, and potential for blood loss anemia. The most common etiologies of CEH are trauma or surgery. It is thought to occur due to irritant effects of blood breakdown products, causing bleeding from capillaries in chronic granulation tissue. Although treatment of CEH is variable, complete surgical excision of the hematoma and its pseudocapsule is the gold standard. We present a case of a 15-year CEH that was initially treated with limited evacuation of the hematoma and cavity decortication, resulting in …

Complications And Influential Perioperative Factors Associated With Spaceoar Hydrogel Placement, Kerith Wang, Rishabh Simhal, Cassra Clark, Mark Mann, James Mark, Costas Lallas, Robert Den, Edouard Trabulsi

Department of Urology Faculty Papers

OBJECTIVE: To examine one academic institution's experiences with SpaceOAR placement, its associated complications, and periprocedural characteristics that affect outcomes for the purpose of quality improvement.

MATERIALS AND METHODS: We conducted a retrospective review of 233 patients who received SpaceOAR from four surgeons and one radiation oncologist between 2018 and 2021. Variables such as demographics, oncologic parameters, radiation plan, and radiographic assessment of hydrogel placement were recorded. The Charlson Comorbidity Index (CCI) was used to assess comorbidity risk. Mann-Whitney and Fisher's exact tests were performed to compare patients with and without complications.

RESULTS: Of the 233 patients who received SpaceOAR, 24 …

Keratin 17 Is A Prognostic And Predictive Biomarker In Pancreatic Ductal Adenocarcinoma, Lyanne Delgado-Coka, Lucia Roa-Peña, Sruthi Babu, Michael Horowitz, Emanuel Petricoin, Lynn Matrisian, Edik Blais, Natalia Marchenko, Felicia Allard, Ali Akalin, Wei Jiang, Md, Phd, Brent Larson, Andrew Hendifar, Vincent Picozzi, Minsig Choi, Kenneth Shroyer, Luisa Escobar-Hoyos

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

OBJECTIVES: To determine the role of keratin 17 (K17) as a predictive biomarker for response to chemotherapy by defining thresholds of K17 expression based on immunohistochemical tests that could be used to optimize therapeutic intervention for patients with pancreatic ductal adenocarcinoma (PDAC).

METHODS: We profiled K17 expression, a hallmark of the basal molecular subtype of PDAC, by immunohistochemistry in 2 cohorts of formalin-fixed, paraffin-embedded PDACs (n = 305). We determined a K17 threshold of expression to optimize prognostic stratification according to the lowest Akaike information criterion and explored the potential relationship between K17 and chemoresistance by multivariate predictive analyses.

RESULTS: …

Factors Associated With Recanalization And Reintervention Following Below Knee Polidocanol Endovenous Microfoam Ablation For Great Saphenous And Small Saphenous Veins, John Fang, Christian Fang, Andy Moyal, Enrico Ascher, Anil Hingorani, Natalie Marks

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Polidocanol endovenous microfoam (PEM) has been used to treat lower extremity venous reflux for almost one decade with specific advantages for below knee (BK) truncal veins where thermal ablation poses a risk of injury to adjacent nerves. The current literature of the BK segment often examines short-term outcomes with modest sample sizes. We aim to identify factors associated with recanalization and reintervention in this subset of patients.

METHODS: We performed a retrospective study of a prospectively maintained database of patients from a single institution who underwent 1% PEM ablation for BK great saphenous vein (GSV) and small saphenous vein …

A Comparison Of The Safety And Efficacy Of Tapinarof And Roflumilast Topical Therapies In The Management Of Mild-To-Moderate Plaque Psoriasis, Hira Ghani, Alicia Podwojniak, Isabella J Tan, Aarushi K Parikh, Bianca Sanabria, Babar Rao

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Psoriasis is an immune-mediated inflammatory skin disease. First-line topical treatments include steroids, calcineurin inhibitors, vitamin D analogs, and anthralin. Recently, novel topical therapeutics like tapinarof and roflumilast have emerged with unique anti-inflammatory mechanisms and promising efficacy profiles.

MATERIALS AND METHODS: This review utilized PubMed, SCOPUS, and Web of Science databases to identify recent studies on tapinarof and roflumilast. Criteria focused on efficacy, safety profiles, and therapeutic roles in psoriasis treatment.

RESULTS: Four primary literature articles were identified for tapinarof and five for roflumilast. Both drugs demonstrated strong efficacy with minimal adverse events in treating mild-to-moderate plaque psoriasis. Tapinarof showed …

Evaluating Efficacy Of Vedolizumab, Ustekinumab, And Golimumab In The Management Of Inflammatory Bowel Disease And The Combined Role Of Nutritional Therapy With Biologics: A Review, Shahed Kamal, Karan Varshney, Danielle Josefa F. Uayan, Fides Myles C. Caliwag

Ateneo School of Medicine and Public Health Publications

Inflammatory bowel disease (IBD), which encompasses both ulcerative colitis (UC) and Crohn’s disease (CD), is a major health burden worldwide. There are increasing concerns surrounding the impacts of this disease due to significant rises in the prevalence rates of IBD across the world. In consideration of the complexities of managing IBD along with this marked rise in prevalence and incidence, developing new forms of treatment for this condition has become a major priority. In recent years, a potential new form of treatment for IBD has emerged in the form of biologic therapies. While there is a high level of optimism …

Incorporating Solvation Thermodynamic Mapping In Computer-Aided Drug Design, Yeonji Ji

Dissertations, Theses, and Capstone Projects

Advancements in computational techniques have revolutionized structure-based drug design, substantially improving the efficiency and effectiveness of the drug discovery process by reducing time, costs, and labor requirements. These advancements include various methods, such as investigating small molecule ligands binding to proteins, exploring alternative protein conformations, and solvation mapping on the protein surfaces. Among these methods, understanding the correlation between protein-ligand binding and the role of solvation is important.

A fundamental concept in protein-ligand binding is shape and electrostatic complementarity, which is complicated by the inherent flexibility of proteins. In the absence of small molecule ligands, proteins are complementary to surface …

Exploiting The Heavy Chain Glycans For The Improvement Of Radioimmunoconjugates, Cindy Rodriguez

Dissertations, Theses, and Capstone Projects

Radiolabeled antibodies have become indispensable tools in nuclear medicine. However, the natural roles of antibodies within the immune system mean that they have several intrinsic limitations as a platform for radiopharmaceuticals. A handful of recent preclinical studies suggest that binding by FcR and particularly FcyRI can affect the pharmacokinetic profiles of 89Zr-labeled radioimmunoconjugates. Fc receptors (FcR) are responsible for many of the interactions between immunoglobulins (IgG) and immune cells. In biomedicine, this interplay is critical to the activity of several types of immunotherapeutics; however, relatively little is known about how FcRs affect the in vivo performance of radiolabeled antibodies. Antibodies …

A Pseudo-Surfactant Chemical Permeation Enhancer To Treat Otitis Media Via Sustained Transtympanic Delivery Of Antibiotics, Sophie S. Liu, Joanna M. White, Zhongmou Chao, Ruye Li, Shuxian Wen, Ally Garza, Wenjing Tang, Xiaojing Ma, Pengyu Chen, Susan Daniel

Health & Biomedical Sciences Faculty Publications

Chemical permeation enhancers (CPEs) represent a prevalent and safe strategy to enable non-invasive drug delivery across skin-like biological barriers such as the tympanic membrane (TM). While most existing CPEs interact strongly with the lipid bilayers in the stratum corneum to create defects as diffusion paths, their interactions with the delivery system, such as polymers forming a hydrogel, could compromise gelation, formulation stability, and drug diffusion. To overcome that challenge, we explore the differing interactions present with sodium dodecyl sulfate (SDS), an ionic surfactant and a common CPE, and methyl laurate (ML), a non-ionic counterpart with a similar length alkyl chain. …

July / August / September 2024, Randy Curry, Cindy Brooks

RURAL ROCKS

This is the July, August, and September issue of Rural Rocks from the SWOSU College of Pharmacy.