Pharmacy and Pharmaceutical Sciences Commons^™

The Short And Sweet On Sodium-Glucose Cotransporter Inhibitors And Glucagon-Like Peptide-1 Receptor Agonists In Heart Failure, Jose L. Batista, Tracy Makuvire, Jonathan D. Davis, Salvatore Carbone

EVMS School of Health Professions Faculty Publications

Heart failure (HF) affects 6 million people in the US, and type 2 diabetes (T2D) is a significant risk factor for HF. Since 2008, regulatory agencies have required cardiovascular safety trials for new T2D therapies, and these have consistently demonstrated the cardiovascular benefits of glucose-lowering drugs. Sodium-glucose cotransporter inhibitors (SGLTi) and glucagon-like peptide-1 (GLP-1) receptor agonists (RAs)/glucose-dependent insulinotropic polypeptide (GIP) reduce major adverse cardiovascular events and deaths, regardless of diabetes status, and improve cardiorespiratory fitness. SGLTis, such as dapagliflozin and empagliflozin, benefit patients with reduced and preserved ejection fraction, significantly reducing HF hospitalizations and cardiovascular deaths. The DAPA-HF and EMPEROR-Reduced …

Association Of Prenatal Exposure To Phthalates And Phenols With Adverse Pregnancy Outcomes, Misa Hayasaka, Diana Aboukhater, George Saade, Tetsuya Kawakita

Department of Obstetrics & Gynecology Faculty Publications

OBJECTIVE:

To evaluate the association between prenatal exposures to phthalates and phenols and adverse pregnancy outcomes, including preterm birth (PTB), small-for-gestational-age (SGA) birth weight, and gestational diabetes mellitus (GDM).

METHODS:

This study analyzed data from the Environmental Influences on Child Health Outcomes consortium, which harmonized longitudinal data on more than 30,000 pregnancies and 57,000 children from 69 cohorts across the United States and Puerto Rico. Pregnancy outcomes included PTB, SGA, and GDM, identified from medical records or self-reports. Generalized estimating equations models with Poisson distribution and robust variance were used to estimate relative risks (RRs) and 95% CIs per interquartile …

A Case Displaying The Importance Of Jak1 And Jak2 Gene Transcription In Antifungal Defense Against Coccidioidomycosis, Jennifer K. Priessnitz, Taylor Colore, Nelson Nicolasora

Department of Medicine Faculty Publications

This case report explores the consequences of ruxolitinib via inhibition janus kinase 1 (JAK1) and JAK2 pathways in the context of fungal defense in a patient diagnosed with pulmonary coccidioidomycosis during ruxolitinib therapy for polycythemia vera. The patient experienced a relapse of pulmonary coccidioidomycosis after antifungal treatment was discontinued while continuing ruxolitinib use. This case illustrates the heightened risk of discontinuing antifungal therapy in endemic regions, emphasizing the critical need for continued monitoring. Furthermore, this case underscores the vital role of the JAK1 and JAK2 signaling cascade, particularly the interferon-gamma (INF-γ)-JAK1 and JAK2-signal transducer and activator of transcription 1 (STAT) …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

The Significance Of Aldehyde Dehydrogenase 1 In Cancers, Anh L. Nguyen, Caroline O. B. Facey, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

The goal of this paper is to discuss the role of ALDH isozymes in different cancers, review advances in ALDH1-targeting cancer therapies, and explore a mechanism that explains how ALDH expression becomes elevated during cancer development. ALDH is often overexpressed in cancer, and each isoform has a unique expression pattern and a distinct role in different cancers. The abnormal expression of ALDHs in different cancer types (breast, colorectal, lung, gastric, cervical, melanoma, prostate, and renal) is presented and correlated with patient prognosis. ALDH plays a significant role in various cellular functions, such as metabolism, oxidative stress response, detoxification, and cellular …

Specifically Targeting Muc16 For Fluorescence-Guided Surgery Of Pancreatic Ductal Adenocarcinoma, Kathryn M. Muilenburg

Theses & Dissertations

Pancreatic cancer is a lethal disease with a low 5-year survival rate and a high rate of resection recurrence. However, surgery remains the only treatment with curative potential for pancreatic cancer. Many factors such as high desmoplasia, a lack of intraoperative imaging, and micrometastatic disease contribute to the high rate of incomplete resections in pancreatic cancer. Fluorescence-guided surgery (FGS) is a potential intraoperative tool for application in surgical resection. FGS works through passive or active targeting of a free dye or dye-containing moiety (e.g. antibody, peptide, and nanoparticles) to specifically fluoresce the tumor compared to the surrounding normal, fibrotic, and …

The Revised Cdc Chronic Pain Guidelines And Payer Opioid Analgesic Policies In Michigan, Victoria Tutag Lehr, Cynthia L. Arfken

Michigan Journal of Public Health

Abstract

The 2016 publication of A Guideline for Prescribing Opioids for Chronic Pain by the Centers for Disease Control and Prevention motivated commercial and Medicaid payers to restrict their opioid prescribing policies including the imposition of hard limits on opioid daily dosages and duration. One result of these policies was an increase in abrupt opioid discontinuation and rapid tapering events for patients receiving long-term opioid therapy. Responding to this misapplication of the 2016 guideline, the 2022 revised guidelines emphasized individualized opioid therapy and exclusion of certain chronic diseases. However, it is not known if the payers changed their policies to …

Effectiveness Of Pharmacist-Managed Oncology Ambulatory Care For Patients With Non–Small Cell Lung Cancer In Taiwan, Ding-Cheng Liu, Chuan-Lun Hung, Yi-Wen Chen, Li-Na Kuo, Yen-Chun Hsin, Chun-Nan Kuo

Journal of Food and Drug Analysis

Non-small cell lung cancer (NSCLC) is commonly treated with tyrosine kinase inhibitors (TKIs). However, adverseevents from such treatment can lead to treatment discontinuation and additional medical expenditures. Ambulatory carefrom oncology pharmacists in patient education and symptom management can benefit patients with NSCLC. In thisstudy, we evaluated the effectiveness of an oncology pharmacy service at a medical center in Taiwan. We retrospectivelyenrolled 137 patients with NSCLC who initiated treatment with afatinib, gefitinib, or erlotinib between January 2017 andDecember 2021; 40 of them utilized the oncology pharmacy service (intervention group), and the remaining 97 did not(nonintervention group). To determine the effectiveness of …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

A Conjugate Of An Egfr-Binding Peptide And Doxorubicin Shows Selective Toxicity To Triple-Negative Breast Cancer Cells, Phi-Phung Than, Shih-Jing Yao, Emad Althagafi, Kamaljit Kaur

Pharmacy Faculty Articles and Research

Selective targeting of cancer cells via overexpressed cell-surface receptors is a promising strategy to enhance chemotherapy efficacy and minimize off-target side effects. In this study, we designed peptide 31 (YHWYGYTPERVI) to target the overexpressed epidermal growth factor receptor (EGFR) in triple-negative breast cancer (TNBC) cells. Peptide 31 is internalized by TNBC cells through EGFR-mediated endocytosis and shares sequence and structural similarities with human EGF (hEGF), a natural EGFR ligand. Unlike hEGF, peptide 31 does not induce cell migration in TNBC cells. A novel conjugate of peptide 31 with doxorubicin (Dox) retains selectivity for TNBC cells and exhibits significant toxicity comparable …

How Low Can We Go: Evaluation Of A Pharmacist-Led Weight Loss Management Program, Kelly Rubi, Elaina Rosario, Sara Panella, Jacqualine Igwe, Maria Pulido, Faaria Quadri

Nursing & Health Sciences Research Journal

Background: Obesity is a major health challenge that is associated with several health risks, including diabetes and hypertension. The purpose of this project was to evaluate the impact of clinical pharmacists on the therapy optimization of GLP-1 receptor agonists (GLP-1RAs) in a weight management program. Methods: This project evaluated a quality improvement initiative through a retrospective chart review that included patients who were treated with semaglutide or liraglutide between October 2022 and July 2023, with body mass indices (BMI) of 27 kg/m2 or greater with at least one weight-related comorbidity or a BMI greater than or equal to 30 kg/m2. …

Impact Of An Interdisciplinary Team On Patients Seen At A Heart Failure Clinic, Nilda Pelegrino, Faaria Quadri, Elaina Rosario, Jacqualine Igwe, Sandra Chaparro, Lourdes Labrada, Sara Panella, Maria Pulido, Stephen Breazeale, Zhenwei Zhang

Nursing & Health Sciences Research Journal

Background: Heart failure is a complex clinical syndrome that requires the involvement of interdisciplinary teams to address patient needs and optimize therapy. Interdisciplinary teams, including physicians, advanced practice practitioners, and pharmacists, play a crucial role in implementing guideline-directed medical therapy and addressing barriers to self-care that ultimately improve patients’ overall survival. This study assessed the impact of an interdisciplinary team on patients’ heart failure outcomes compared to patients solely managed by clinical cardiologists. Methods: This was a single-center retrospective chart review study of Baptist Health patients seen at the heart failure clinic. The study compared patients seen by an interdisciplinary …

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 …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Evaluating Tirzepatide's Therapeutic Potential In Mitigating Obesity-Associated Comorbidities, Zaneh Kahook, Talaya Jones, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: The study aims to explore the therapeutic potential of dual GIP/GLP-1 agonist tirzepatide in managing obesity and its associated manifestations, including obstructive sleep apnea (OSA), hidradenitis suppurativa (HS), and obesity-associated cancer (OAC) risks. Background: OSA and HS are the associated comorbidities noted in persons with obesity. Obesity has been associated with an increased risk of cancers, such as breast cancer. Reducing obesity could improve these conditions. Tirzepatide has demonstrated efficacy in reducing body weight, but its benefits in obesity-related conditions and cancer risk need further investigation. Methods: Data was synthesized from peer-reviewed literature on tirzepatide. Additional sources were identified …

Recent Developments In Tirzepatide's Role In Reducing Cardiovascular Disease Risk Factors In Adults With Type 2 Diabetes, Talaya Jones, Zaneh Kahook, Carina Bryan, Mayur Parmar

HCA-NSU MD Research Day

Objective: This literature review aims to investigate recent developments in tirzepatide’s ability to lessen CVD risk factors for adults with increased risk of major adverse cardiovascular events. Background: Tirzepatide is an FDA - approved medication primarily used to treat adults with type 2 diabetes mellitus (T2DM) by reducing A1C and chronic weight management, however its efficacy for reducing CVD risk factors is under examination. Methods: This review synthesizes data from recent early findings published by the pharmaceutical company, which has not yet undergone peer review, alongside existing literature on tirzepatide. Additional sources were identified through a systematic search of PubMed, …

Effects Of Sex And Estrous Cycle On Extended-Access Oxycodone Self-Administration And Cue-Induced Drug Seeking Behavior, Bhumiben P Patel, Jessica A Loweth

Rowan-Virtua School of Osteopathic Medicine Departmental Research

INTRODUCTION: Increasing evidence indicates that sex is a factor that impacts the abuse liability and relapse vulnerability of prescription opioids like oxycodone. However, while women are more likely than men to be prescribed and to use these drugs, the impact of sex and ovarian hormones on prescription opioid use and relapse vulnerability remains unclear. Accurately assessing these measures is complicated by the fact that chronic opioid exposure can lower ovarian hormone levels and cause cycle irregularities.

METHODS: Adult male and female Sprague-Dawley rats self-administered oxycodone (0.1 mg/kg/infusion) under extended-access conditions (6 h/day, 10 days) followed by forced abstinence. Separate groups …

Predicting And Monitoring Immune Checkpoint Inhibitor Therapy Using Artificial Intelligence In Pancreatic Cancer, Guangbo Yu, Zigeng Zhang, Aydin Eresen, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Vahid Yaghmai, Zhuoli Zhang

Pharmacy Faculty Articles and Research

Pancreatic cancer remains one of the most lethal cancers, primarily due to its late diagnosis and limited treatment options. This review examines the challenges and potential of using immunotherapy to treat pancreatic cancer, highlighting the role of artificial intelligence (AI) as a promising tool to enhance early detection and monitor the effectiveness of these therapies. By synthesizing recent advancements and identifying gaps in the current research, this review aims to provide a comprehensive overview of how AI and immunotherapy can be integrated to develop more personalized and effective treatment strategies. The insights from this review may guide future research efforts …

Hepatotoxicity Induced By Immune Checkpoint Inhibitors, Flaviu Muresan, Olga Hilda Orasan, Angela Cozma, Madalina Daiana Bancos, Lorena Ciumarnean, Mircea Vasile Milaciu, Tinca Codruta Pocol, Nicoleta Valentina Leach, Teodora Gabriela Alexescu, Ovidiu Vasile Fabian, George Ciulei, Mirela Georgiana Perne

Journal of Mind and Medical Sciences

Immune checkpoint inhibitors (ICIs) are an effective immunotherapeutic approach for cancers affecting the lung, skin, kidney, mammary gland, or certain hematologic malignancies. Regarding the prognosis of these oncological conditions, treatments with ICIs open new therapeutic perspectives with benefits for both patients and healthcare providers. A drawback of immune checkpoint inhibition is the occurrence of immune-related adverse events that can involve a wide range of organs, such as the liver. Given widespread usage of immunotherapy, the number of patients who suffer from this unwanted condition has increased. Hepatopathy induced by ICIs can be severe and can even lead to death. Detecting …

Lower Urinary Tract Symptoms, Depression And Sleep Problems; A Triple Whammy For Patients’ Health-Related Quality Of Life, Muhammad Salman, Amer Hayat Khan, Syed Azhar Syed Sulaiman, Jeffery David Hughes, Junaid Habib Khan, Yusra Habib Khan, Tauqeer Hussain Mallhi

Bulletin of Faculty of Pharmacy Cairo University

Introduction: Lower urinary tract symptoms (LUTS) are characterized by voiding, storage and post-micturition symptoms. LUTS can have detrimental effects on various facets of patients’ quality of life. Therefore, this study was aimed to evaluate the association of LUTS with depression and sleep disturbances, and their impact on patients’ health-related quality of life (HRQOL).

Methods: A cross-sectional survey was conducted among a clinical sample of calcium channel blocker-users (n = 410), recruited via convenient sampling. Outcomes were assessed using validated Urdu translated instruments [LUTS: International Prostate Symptom Score; sleep problems: Jenkins sleep evaluation questionnaire (JSEQ); depression: Center for Epidemiologic Studies Short …

Identification Of New Leads Against Ubiquitin Specific Protease-7 (Usp7): A Step Towards The Potential Treatment Of Cancers, Sumaira Javaid, Seema Zadi, Muhammad Awais, Atai-Tul Wahab, Humaira Zafar, Innokentiy Maslennikov, M. Iqbal Choudhary

Pharmacy Faculty Articles and Research

Ubiquitin-specific protease-7 (USP7) is an important drug target as it regulates multiple proteins and genes (such as MDM2 and p53) with roles in cancer progression. Its inhibition can hinder the function of oncogenes, increase tumor suppression, and enhance immune response. The current study was designed to express USP7 in a prokaryotic system, followed by screening of small molecules against it using biophysical methods, primarily STD-NMR technique. Among them, 12 compounds showed interaction with USP7 as inferred from NMR-based screening. These compounds further caused destabilization of USP7 by reducing its melting temperature (T_m) up to 6 °C in …

The Impact Of Pdcd4, A Translation Inhibitor, On Drug Resistance, Qing Wang, Hsin-Sheng Yang

Markey Cancer Center Faculty Publications

Programmed cell death 4 (Pdcd4) is a tumor suppressor, which has been demonstrated to efficiently suppress tumorigenesis. Biochemically, Pdcd4 binds with translation initiation factor 4A and represses protein translation. Beyond its role in tumor suppression, growing evidence suggests that Pdcd4 enhances the chemosensitivity of several anticancer drugs. To date, numerous translational targets of Pdcd4 have been identified. These targets govern important signal transduction pathways, and their attenuation may improve chemosensitivity or overcome drug resistance. This review will discuss the signal transduction pathways regulated by Pdcd4 and the potential mechanisms through which Pdcd4 enhances chemosensitivity or counteracts drug resistance.

Molecular Targets For Breast Cancer Therapy, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

"Breast cancer is by far the most common cancer in women, and for a while, it surpassed lung cancer as the most diagnosed cancer, regardless of gender, in 2020 [1]. Chemotherapy and hormone therapy are still the first line of treatment, despite extensive research in molecularly targeted drugs. Therefore, triple negative breast cancer (TNBC) is still known as the most challenging type for treatment due to the limited identified targets. Inherent and acquired resistance are still major hurdles in breast cancer therapy, which further highlights the importance of identifying new molecular targets in this battle. The inherent resistance of unresponsive …

Removal Of Common Antimicrobial Agents By Sustained Low- Efficiency Dialysis, Joanna Q. Hudson Pharmd, Bcps, Fasn, Fccp, Madelyn N. Hilgers Bs, Pharmd Candidate, Elvira O. Gosmanova Md

Faculty Publications

Adequate dosing of antimicrobials is paramount for treating infections in critically ill patients undergoing kidney replacement therapy; however, little is known about antimicrobial removal by sustained low-efficiency dialysis (SLED). The objective was to quantify the removal of cefepime, daptomycin, meropenem, piperacillin–tazobactam, and vancomycin in patients undergoing SLED. Adult patients ≥18 years with acute kidney injury (AKI) or end-stage kidney disease receiving one of the select antimicrobials and requiring SLED were included. Blood and dialysate flow rates were maintained at 250 and 100 mL/min, respectively. Simultaneous arterial and venous blood samples for the analysis of antibiotic concentrations were collected hourly for …

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 …

Intracellular Islatravir-Triphosphate Half-Life Supports Extended Dosing Intervals, Xiaowei Zang, Wendy Ankrom, Walter K. Kraft, Ryan Vargo, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t½) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 …

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 …

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 …

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 …

Antitumor Activity Of A Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting Lgr5 In Preclinical Models Of Neuroblastoma, Jianghua Tu, Yukimatsu Toh, Adela M Aldana, Jake J Wen, Ling Wu, Joan Jacob, Li Li, Sheng Pan, Kendra S Carmon, Qingyun J Liu

Faculty, Staff and Student Publications

Neuroblastoma (NB) is a cancer of the peripheral nervous system found in children under 15 years of age. It is the most frequently diagnosed cancer during infancy, accounting for ~12% of all cancer-related deaths in children. Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a membrane receptor that is associated with the primary tumor formation and metastasis of cancers in the gastrointestinal system. Remarkably, high levels of LGR5 are found in NB tumor cells, and high LGR5 expression is strongly correlated with poor survival. Antibody-drug conjugates (ADCs) are monoclonal antibodies that are covalently linked to cell-killing cytotoxins to deliver the payloads …