Medical Pharmacology Commons^™

Fluoroquinolone Use And Risk Of Pneumothorax In Adults Hospitalized With Community Acquired Pneumonia: A Retrospective Cohort Study, Steven Yi B. S., Saurav Sumughan B.S., Jessica Cobb M. D., Erika J. Yoo

Department of Medicine Faculty Papers

Objectives: The objective of this study is to examine the relationship between fluoroquinolone exposure and pneumothorax risk in patients hospitalized with pneumonia.

Methods: This retrospective cohort study used the TriNetX US Collaborative Network. We defined two mutually exclusive cohorts of hospitalized adults based on exposure to antibiotic classes commonly used to treat community acquired pneumonia: fluoroquinolone (ciprofloxacin, moxifloxacin, levofloxacin, and ofloxacin) versus nonfluoroquinolone (amoxicillin, azithromycin, ceftriaxone, and doxycycline). Patients with connective tissue disorders were excluded. The primary outcome was the occurrence of pneumothorax within 60 days. We used Cox proportional hazards regression to estimate hazard ratios (HRs) adjusted for demographics, …

Pharmacologic Interventions To Reduce Cardiopulmonary Bypass Induced Inflammation In Cardiac Surgery: A Scoping Review, Wyatt Anderson

Student Works

ABSTRACT

1. Structured summary

Background

Cardiopulmonary bypass (CPB) is essential in cardiac surgery but can trigger a systemic inflammatory response that contributes to postoperative complications. The scoping review conducted has a purpose to map the existing literature on pharmacologic interventions to mitigate CPB related inflammation. While several interventions demonstrated potential anti-inflammatory effects, findings were inconsistent, and no standardized pharmacologic approach is currently agreed upon.

Methods

This scoping review followed PRISMA-ScR guidelines.Both PubMed, and CINAHL were screened for studies published between 2000 and 2024 that evaluated pharmacologic interventions aimed at reducing CPB related inflammation. After screening and duplicate removal, 10 studies met …

Pharmacological Treatment Options For Vasoplegia Syndrome During And After Cardiopulmonary Bypass: A Scoping Review, Bradley Darby

Student Works

ABSTRACT

2: Structured summary

Background

Vasoplegia Syndrome (VS) is a form of distributive shock that is characterized by profound hypotension, low systemic vascular resistance, and high to normal cardiac output during/after cardiopulmonary bypass. VS is associated with increased mortality, morbidity, and length of stay in the intensive care unit.

Objective

The main objectives of this scoping review are to note the available treatment options, characterize potential risk factors, and identify gaps in knowledge for vasoplegia syndrome during and after cardiopulmonary bypass.

Method

This scoping review utilized the Preferred Reporting Items for Systematic reviews and MetaAnalyses extension for Scoping Reviews (PRISMA-ScR) …

Role Of Plants And Phytochemicals In Promoting Proliferation And Osteogenic Differentiation Of Dental Mesenchymal Stem Cells: A Comprehensive Review, Hala El-Zahar, Essam Abdel-Sattar, Marwa Yousry Moustafa Issa, Shereen N. Raafat, Noha Swilam

Dentistry

Abstract Objectives Dental mesenchymal stem cells (MSCs) represent a promising source for regenerative medicine due to their accessibility and capacity to differentiate into osteoblasts and other lineages. Osteogenic differentiation of dental MSCs is essential for bone formation and is regulated by multiple signaling pathways, cytokines, growth fac‑ tors, and transcription factors. This review aims to summarize the effects of plant-derived extracts and phytochemicals on the proliferation and osteogenic differentiation of dental MSCs. Methods In this review, an extensive literature search was conducted covering studies from the past 10 years, using different online databases (SCOPUS, Google Scholar, PubMed, Web of Science, …

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.

Zoliflodacin Versus Ceftriaxone Plus Azithromycin For Treatment Of Uncomplicated Urogenital Gonorrhoea: An International, Randomised, Controlled, Open-Label, Phase 3, Non-Inferiority Clinical Trial, Alison Luckey, Manica Balasegaram, Lindley A. Barbee, Teresa A. Batteiger, Helen Broadhurst, Stephanie E. Cohen, Sinead Delany-Moretlwe, Henry J.C. De Vries, Jodie A. Dionne, Katherine Gill, Chris Kenyon, Rossaphorn Kittiyaowamarn, Drew Lewis, John P. Mueller, Vimla Naicker, Seamus O'Brien, John P. O'Donnell, Nittaya Phanuphak, Elizabeth Spooner, Subasree Srinivasan, Stephanie N. Taylor, Magnus Unemo, Zinhle Zwane, Edward W. Hook, Zoliflodacin Phase 3 Study Group

School of Medicine Faculty Publications

Background Development of new treatments for gonorrhoea is a global public health priority. We aimed to evaluate the efficacy and safety of zoliflodacin versus ceftriaxone plus azithromycin in patients with uncomplicated urogenital gonorrhoea. Methods In this phase 3, multinational, randomised, controlled, open-label, non-inferiority clinical trial, participants aged 12 years and older with clinical suspicion of uncomplicated urogenital gonorrhoea were eligible for inclusion. The trial was done in 17 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA. Participating countries with high disease prevalence were identified for participation in the study. Sites selected for participation were led by …

Vestibular Migraine And Ssri Withdrawal: A Case Presentation, Grace Fairchild, Sarah Redding, Ashley Flagge

V&B Presentations

No abstract provided.

Kinase Signaling In Liver Disease Via Clinical-Trial-On-A-Pamchip: A Distinctive Methodology For Drug Mechanisms And Personalized Medicine, Zachary A. Kipp, Evelyn A. Bates, Genesee J. Martinez, Wang-Hsin Lee, Sally N. Pauss, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

The utilization of extensive datasets, such as those generated by DNA or RNA sequencing, has become a central focus in drug discovery and personalized medicine (PerMed). Nonetheless, these datasets are constrained by the absence of protein-functionality testing, which affects physiological responses. In this study, we employed PamGene PamStation technology to quantify protein function by kinase activity across more than 500 signaling pathways from patients with hepatocellular carcinoma (HCC). Using proteins derived from nine patients and five human HCC cell lines for drug discovery and the clinical trial-on-a-chip approach, we developed comprehensive PerMed scores from the PamStation data to differentiate individual …

Maesa Ramentacea Leaf Extract Protects Against Gentamicin-Induced Nephrotoxicity In Wistar Rats By Modulating Renal Oxidative Stress, Inflammation And Apoptosis, Fahmida Akter, Md Shafiqul Islam Sovon, Baizid Hossain, Md Ariful Islam, Subrato Das, Anik Biswas, Md Sohorab Uddin, Md Mahmudul Hasan

Faculty Publications

Background: Gentamicin-induced nephrotoxicity continues to be a significant clinical concern, while effective and safe protective options remain limited. The nephroprotective potential of Maesa ramentacea has not yet been explored. To address this gap, the present study investigated the ethanolic leaf extract of M. ramentacea (MR-LEE) for its effects on gentamicin-induced kidney injury in Wistar rats. Methods: GC-MS profiling was employed to identify bioactive metabolites. Rats were categorised into five groups: control, gentamicin (100 mg/kg), gentamicin combined with silymarin (100 mg/kg), gentamicin combined with MR-LEE (200 mg/kg) and gentamicin combined with MR-LEE (400 mg/kg). Renal biomarkers, oxidative stress indicators, inflammatory and …

A Ubiquitous Organophosphate Flame Retardant Disrupts Energy And Glucose Homeostasis In Mice, Krystal M. Sewell, Kelly Oriakhi, Sara Y. Ngo Tenlep, Megan L. Weaver, Mansura Shahad Bawa, Se-Hyung Park, Shubh Saraswat, Xiaohua D. Zhang, Robert N. Helsley, Samir Softic, Cetewayo S. Rashid

Pharmacology and Nutritional Sciences Faculty Publications

Organophosphate flame retardants (OPFRs) are used in many consumer products, and their presence in our environment raises concerns about potential health dangers. In humans, exposure to OPFRs, such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) is associated with metabolic disorders such as obesity, hyperglycemia, and insulin resistance. Our current study seeks to determine how TDCPP exposure affects body composition, glucose homeostasis, and energy balance in a rodent model. C57Bl/6 J mice were divided into two weight-matched groups and fed purified low phytoestrogen diets containing either 0.1 % DMSO (control) or TDCPP 415 mg/kg resulting in an approximate exposure of 50 mg/kg/day. Both male …

Contribution Of Metabolism-Independent Glucose Sensing To Metabolic Homeostasis, Nadia Rashid, Kavaljit H. Chhabra

Pharmacology and Nutritional Sciences Faculty Publications

Glucose sensing and signaling are central to cellular metabolic machinery for the regulation of metabolic homeostasis. Glucose sensing has been almost always assumed to be coupled with glucose metabolism; however, recent findings have unraveled metabolism-independent sensing mechanisms. Here, we discuss whether glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) may also function as glucose sensors independent of their roles in transporting glucose. Moreover, we review the emerging roles of G protein-coupled receptors (GPCRs) in sensing glucose and, consequently, initiating its signaling pathways in a cell-specific manner. Altogether, this review offers insights into the newly identified glucose sensing mechanisms and highlights the …

Anatomical Atlas Of Kinase Responsiveness To Weight Gain: Adipose Depot Reprogramming In Diet-Induced Adiposity, Wang-Hsin Lee, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Mei Xu, Terry D. Hinds, Jr.

Pharmacology and Nutritional Sciences Faculty Publications

Background/Objectives: Adipose tissue depots located at different anatomical sites exert differential functions in response to adiposity and glucose intolerance. These fat depots exhibit distinct metabolic signaling patterns that may influence pathological fat accumulation, thereby affecting the efficacy of anti-obesity interventions. Nonetheless, the mechanisms underpinning depot-specific signaling and pathway responsiveness remain insufficiently understood.

Methods: Kinase activity was characterized during the progression of adiposity across five adipose tissue depots in obese versus lean mice using the advanced PamGene kinome technology. Furthermore, kinase pathways in human preadipocytes and mouse 3T3-L1 preadipocytes were analyzed and compared with those in their differentiated, mature adipocytes. The …

Stim1-Dependent Treg Dysfunction Promotes Cardiometabolic Hfpef: Insights From Patients And Animal Studies, Balaji Srinivas, Alluri Kiran, Hongmei Peng, Jiang Xu, Paula Fortuno, Jennifer May, Ismail El Moudden, Nour-Eddine Rhaleb, John M. Herre, Raymond L. Benza, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Background

Heart failure with preserved ejection fraction (HFpEF) arises from chronic cardiometabolic and vascular stress and is increasingly recognized as an inflammatory syndrome with immune dysregulation. Regulatory T cells (Tregs) are critical modulators of cardiovascular inflammation, yet the mechanisms driving Treg dysfunction in HFpEF remain poorly defined. stromal interaction molecule 1 (STIM1)-dependent calcium signaling is a key stress-responsive pathway in immune cells; however, its role in Treg maladaptation during HFpEF remains unknown.

Methods

Circulating Tregs from patients with and without HFpEF were analyzed for abundance, STIM1 expression, and stress-associated signaling pathways. To establish causality, mice with Treg-specific deletion of STIM1 …

The Gut-Heart Axis: Exploring The Role Of The Gut Microbiome In Cardiovascular Health-A Focused Systematic Review, Yahya Makkieh, Haider Hussain Shah, Sakan Binte Imran, Shadman Mahmood Mahmood Khan Pathan, Anagha Chirayath Saju, Mounica Majooju, Aastha Garg, Tarun Naag, Rabeeul Islam, Cheeranthodika Fahima, Ramsha Ali

Electrical & Computer Engineering Faculty Publications

This focused systematic review examines the role of the gut microbiota in cardiovascular disease (CVD). The review explores mechanisms linking gut dysbiosis with CVD via microbial metabolites such as trimethylamine-Noxide (TMAO) and short-chain fatty acids (SCFAs), which affect inflammation, endothelial function, and lipid metabolism. Interventions including dietary modifications, probiotics, prebiotics, fecal microbiota transplantation, and pharmacological agents such as statins, rifaximin, and empagliflozin are evaluated for their impact on microbial composition and cardiovascular outcomes. Probiotic strains and fiber-rich diets demonstrated modest improvements in blood pressure, lipid profiles, and inflammatory markers. Studies revealed that gut microbiome alterations influence drug metabolism and bleeding …

Experience Of Using Anti-Cd 20 Therapies In Multiple Sclerosis Patients In Kenya, Eunice Nyambane, Tejal Patel, Jacqueline Mavuti, Juzar Hooker, Dilraj Sokhi

Internal Medicine, East Africa

Objective: The objective of the study was to evaluate the safety and efficacy of ocrelizumab (OCR) and rituximab (RTX) in multiple sclerosis.

Methods: This was a retrospective single-centre study. Ocrelizumab- and rituximab-treated patients were identified through the multiple sclerosis (MS) registry maintained at Aga Khan University Hospital Nairobi (AKUHN), Kenya. Adult patients aged 18–65 years old who fulfilled the McDonald 2017 diagnosis criteria and received treatment with either rituximab or ocrelizumab between January 2016 and June 2025 were retrospectively evaluated. Data collected at baseline included age, gender, first symptoms, disease duration since onset, MS phenotype, treatment duration, previous …

Inflammatory Co-Regulation Of Voltage-Gated Sodium Channels And Na,K-Atpase In Metastatic Breast Cancer, Steven D. Scahill, Kelly Jean Sherman, Dennis Paul

School of Graduate Studies Faculty Publications

Sodium regulation is a potentially major driver of cancer metastasis. Voltage-gated sodium channels (VGSCs) and Na,K-ATPase are sodium transporters that are upregulated in many advanced carcinomas and are implicated as metastatic drivers. However, little is known about what drives this overexpression, how these proteins influence metastatic behavior, or whether these complementary sodium transporters are co-regulated in cancer. Using sodium transporter regulation in healthy neurons as a model, the present study demonstrated that the inflammatory mediator tumor necrosis factor alpha (TNFα) affects the expression of VGSCs and Na,K-ATPase in an in vitro model of metastatic breast cancer. Acute TNFα challenge increased …

Topical Lidocaine For Pain Control With Intrauterine Device Insertion: Does It Work?, Piper Gaudet, Jahnavi Ramakrishnan, Fariha Azam

Physician Assistant Capstones, 2020-current

Objective: To evaluate whether topical lidocaine improves the subjective perception of pain during the insertion of an intrauterine device (IUD) in women of childbearing age, compared to a placebo. Design: Mini-systematic literature review. Methods: An initial search of PubMed, CINAHL, and Scopus was conducted using the terms "pain control," "IUD," and "lidocaine," yielding 49 articles, of which 31 were screened and 26 excluded based on pre-designated inclusion criteria. After assessing five articles for eligibility, three met the criteria and were evaluated using Duke University's Clinical Appraisal Worksheet and the Oxford Centre for Evidence-Based Medicine table to determine their level of …

The Need To Incorporate Polysubstance Use In Neuropsychopharmacology Research: Biological Lessons And New Opportunities, Max E. Joffe, Susan M. Ferguson, Nick W. Gilpin, Melissa A. Herman, Lori A. Knackstedt, Patrick A. Randall, Abigail G. Schindler, Mary M. Torregrossa, Jennifer A. Rinker

School of Medicine Faculty Publications

Critical evaluation and refinement of animal models is essential for neuroscientists to understand complex physiological and pathological processes related to psychiatric diseases. In general, preclinical studies modeling drug dependence and problematic substance use have been limited to the administration of a single substance; however, there is a growing appreciation that this approach has failed to capture the complexities of humans and has stifled translational efforts. Polysubstance use represents the overwhelmingly common patterns of alcohol and drug use in humans. For example, epidemiological studies generally determine that between 70–95 % of individuals with alcohol use disorder use tobacco daily, and upwards …

Endothelial-Derived Extracellular Vesicles During Exercise In Copd Patients, Samuel C Okpechi, Dorota Wyczechowska, Bennett Deboisblanc, Jessica L Johnson, Mohamed A Ghonim, Natalie Bauer, Hamid A Boulares, Matthew R Lammi

School of Medicine Faculty Publications

Introduction: There are no treatments directly targeting the pulmonary vasculature in chronic obstructive pulmonary disease (COPD), and further characterization of the underlying endothelial cell (EC) abnormalities could be helpful in drug development. Methods: We investigated the influence of exercise and the prostacyclin analog iloprost on extracellular vesicles derived from ECs (eEVs) in 15 moderate–severe COPD patients who were enrolled in a randomized, placebo-controlled crossover trial of iloprost. Results: Active smokers had a profile consistent with inflammatory-derived EVs, while exacerbation-prone COPD subjects had a profile consistent with apoptosis-derived eEVs. There were no significant effects of iloprost on eEV levels. However, there …

Disruption Of The Placenta–Brain Axis In Transgenic Mice Lacking Serotonin Transporter (Sert) In Trophoblast Cells, David T. Ellenberger, Zhen Lyu, Rosalind T. B. Herrington, Jessica A. Kinkade, Gustavo W. Leone, Ji Ying Sze, Nathan J. Bivens, R. Frank Baker, R. Michael Roberts, Trupti Joshi, Cheryl S. Rosenfeld

Biomedical Sciences

Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental–brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked …

Tlr2 Agonism Suppresses Myeloid Leukemogenesis By Reprogramming Leukemia Stem Cells, Michael E. Lawler, Jennifer S. Romer-Seibert, Michael S. Bowman, Ramkrishna Mitra, Christine M. Eischen, Robert L. Bowman, Sara E. Meyer

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

The consequences of activated innate immune signaling in acute myeloid leukemia (AML) is not well understood. Using ligands directed at the toll-like family receptors (TLR) in models of high-risk AML, we uncover that TLR2 ligands exert unique antileukemic effects that are distinct from other TLRs. Although TLR2 signaling broadly induces inflammatory gene expression in AML cells, at the single-cell level, cell-type-dependent, divergent transcriptional responses coordinate cellular outputs of proliferation, differentiation, cell death, and activation of immune cell function. TLR2 ligands were the only TLR agonists capable of extending survival of AML-bearing mice through leukemia stem cell (LSC) reprogramming that elevated …

Characterization Of Androctonus Mauritanicus Venom And In Vitro Screening Of Sars-Cov-2 Entry Inhibitors Candidates, Reda Chahir, Jacob Galan, Hicham Hboub, Ahmed Salim Lahlou, Salma Chakir, Hinde Aassila, Reda Ben Mrid, Najat Bouchmaa, Reto Stöcklin, Rachid El Fatimy, Naoual Oukkache

Human Genetics Publications

Animal venom, known for its complex biochemical composition, presents a valuable source of therapeutic molecules, particularly for antiviral applications. Despite this potential, the industrial use of venom remains limited, with fewer than a dozen venom-derived compounds reaching commercial markets. This study underscores the significance of exploring venom’s natural diversity as a reservoir for novel bioactive compounds that could drive innovative drug development. We investigated the venom of the Moroccan black scorpion Androctonus mauritanicus (Am), applying solid-phase extraction (SPE) and high-performance reversed-phase liquid chromatography (RP-HPLC) to fractionate the venom into 80 distinct samples. These fractions were subjected to detailed analysis …

Synthesis, Pharmacokinetic Studies, And Metabolite Analysis Of Meridianin C In Rats Using A Validated Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry Method, Liangyu Xu, Zhaogen Wu, Karna Ramachandraiah, Guihun Jiang, Guozhe Zhang

School of Graduate Studies Faculty Publications

Introduction: Meridianin C (MC) is a marine-derived indole alkaloid that has demonstrated kinase inhibitory and anti-tumor activities. Despite its diverse biological properties, no previous reports have systematically evaluated the in vivo quantitative analysis of MC and its metabolites. Methods: In this study, MC was synthesized following a previously reported procedure with slight modifications. A sensitive, accurate, and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method was developed to simultaneously detect MC and its five major metabolites (MC-1-N-O-GluA, MC-1-N-O-SO3H, MC-2′-N-O-GluA, MC-2′-N-O-SO3H, and MC-O-GluA-didehydration) in rat plasma. Rats received a single oral dose of MC (100 mg/kg), and pharmacokinetic analysis was …

Emerging Clinical Role Of Tavapadon, A Novel Dopamine Partial Agonist, In The Treatment Of Parkinson’S Disease, Alan D. Kaye, Bennett M. Ford, Brennan M. Abbott, Kalob M. Broocks, Sofia Novacic, Sahar Shekoohi

School of Medicine Faculty Publications

Tavapadon, a novel oral dopamine-D1R/D5R partial agonist, has been studied in recent years for the treatment of late-stage development Parkinson’s disease (PD). Levodopa, a dopamine precursor that currently remains the gold-standard first-line therapy for PD motor symptoms, serves as a benchmark against emerging dopaminergic agents. By selectively activating D1-family receptors on direct-pathway medium neurons, Tavapadon differs in that it delivers levodopa-level motor benefit while avoiding its many D2R/D3R-mediated adverse effects. In placebo-controlled trials, Tavapadon produced clear, clinically meaningful gains in motor function and day-to-day activities, as captured by the Unified Parkinson’s Disease Rating Scale (UPDRS). Recent late-stage results have revealed …

Deep Learning-Driven Proteomics Analysis For Gene Annotation In The Renin-Angiotensin System, Mortaza Eivazi, Kamran Hosseini, Shahin Alipanahi, Huijing Xia, Luke Restivo, Ayushi Patel, Mahdieh Gozali, Tahereh Ebrahimi, Amy Scarborough, Vahideh Tarhriz, Eric Lazartigues

School of Medicine Faculty Publications

The renin-angiotensin system (RAS) is central to cardiovascular diseases such as hypertension and cardiomyopathy, yet the functions of many RAS genes remain unclear. This study developed a multi-label deep learning model to systematically annotate RAS gene functions and elucidate their roles in biological pathways. A total of 39,463 RAS-related publications from PubMed and PMC were processed into text format. Feature matrices were generated using TF-IDF and token processing, followed by dimensionality reduction via Principal Component Analysis (PCA). A Multi-Layer Perceptron (MLP) was applied for multi-label classification, with performance evaluated using Precision, F1-Score, Ranking Loss, and ROC-AUC metrics. The model outperformed …

Subtype-Specific Her3 Enrichment In Basal-Like Breast Cancer Is Regulated Via The Gata2/Gata3–Foxa1 Axis, Congcong Tan, Hui Lyu, Sanbao Ruan, Yakun Wu, Margaret E. Larsen, Shou Ching Tang, Bolin Liu

School of Medicine Faculty Publications

Basal-like breast cancer (BLBC) is a major subtype of triple-negative breast cancer (TNBC), characterized by aggressive behavior, limited treatment options, and poor prognosis. While HER3 overexpression is frequently observed in TNBC and associated with poor outcomes, its subtype-specific expression and therapeutic potential remain unclear. Here, we demonstrated that HER3 signaling is selectively hyperactivated in BLBC compared to claudin-low breast cancer (CLBC) using transcriptomic profiling. Histone deacetylase inhibitors (HDACi), Romidepsin and Panobinostat, exerted potent antitumor effects on BLBC by selectively downregulating HER3 expression. HER3 levels were positively correlated with FOXA1, a key transcriptional activator. Mechanistically, we identified GATA2 and GATA3 as …

Hydrogen Sulfide Deficiency And Therapeutic Targeting In Cardiometabolic Hfpef: Evidence For Synergistic Benefit With Glp-1/Glucagon Agonism, Jake E. Doiron, Mahmoud H. Elbatreek, Huijing Xia, Xiaoman Yu, Natalie D. Gehred, Tatiana Gromova, Jingshu Chen, Ian H. Driver, Naoto Muraoka, Martin Jensen, Smitha Shambhu, W. H.Wilson Tang, Kyle B. Lapenna, Thomas E. Sharp, Traci T. Goodchild, Ming Xian, Shi Xu, Heather Quiriarte, Timothy D. Allerton, Alexia Zagouras, Jennifer Wilcox, Sanjiv J. Shah, Josef Pfeilschifter, Karl Friedrich Beck, Thomas M. Vondriska, Zhen Li, David J. Lefer

School of Graduate Studies Faculty Publications

Heart failure with preserved ejection fraction (HFpEF) presents significant treatment challenges. We assessed hydrogen sulfide (H2S) bioavailability in HFpEF patients and 2 animal models: the "2-hit" L-NAME + high-fat diet mouse model and ZSF1 obese rats. H2S levels were significantly reduced in patients and both models, linked to decreased cystathionine-γ-lyase expression and increased sulfide quinone oxidoreductase. Cystathionine-γ-lyase knockout worsened HFpEF, whereas pharmacological supplementation with an H2S donor improved diastolic function and reduced cardiac fibrosis. H2S supplement synergized with GLP-1/glucagon agonist and ameliorated HFpEF. These findings suggest that enhancing H2S bioavailability may provide a novel therapeutic strategy for HFpEF.

Nuak Kinases: Signaling Mechanisms And Therapeutic Applications, Nicole M. Cullen, Peter Rosston, Bakhtawar Tufail, Anne E. D'Armond, Ayushi Patel, Dara H. Khosravi, Bridgette M. Collins-Burow, Van T. Hoang, Elizabeth C. Martin, David H. Drewry, Matthew E. Burow, Suresh K. Alahari

School of Medicine Faculty Publications

The novel (nua) kinases 1 and 2 are two of 12 AMP-activated protein–related kinases whose signaling pathways are involved in cancer progression, as well as neurologic, fibrotic, and inflammatory diseases. Currently, there are 80 Food and Drug Administration-approved kinase inhibitors which target roughly 24 of the 500+ known human kinases, leaving most kinases underexplored, including NUAK1 and NUAK2. Thus, there is a critical need for selective inhibition of NUAK1 and NUAK2 signaling. Here, we review the protein structure, known upstream regulators and downstream targets, and expression profiles of NUAK1 and NUAK2 in cancerous compared to noncancerous tissue. We also delineate …

Topical Lifitegrast Therapy For Dry Eye Disease, Lama Assi, Salim C. Lutfallah, Tsz Wing Yim, Su Hsun Liu, Sharon J. Duffy, Jayne Weiss

School of Medicine Faculty Publications

Objectives: This is a protocol for a Cochrane Review (intervention). The objectives are as follows:. To assess the effectiveness and safety of topical lifitegrast therapy alone or in combination with artificial tears, compared with a placebo, artificial tears alone, or no treatment for dry eye disease.

Renal Denervation Improves Cardiac Function And Exercise Duration In A Miniswine Model Of Heart Failure With Preserved Ejection Fraction, David J. Lefer, Thomas E. Sharp, Amy L. Scarborough, Amelia G. Haydel, Sanjiv J. Shah, Zhen Li, Traci T. Goodchild

School of Medicine Faculty Publications

Aims: Overactivity of the sympathetic nervous system is a common underlying mechanism in development and progression of several heart failure with preserved ejection fraction (HFpEF) comorbidities. Decreasing renal sympathetic nerve activity using catheter-based renal denervation (RDN) systems have shown efficacy in treating resistant hypertension and cardiac dysfunction in heart failure with reduced ejection fraction. The purpose of this study was to determine if modulation of renal sympathetic nerve activity by RDN improves cardiac function and exercise tolerance in a clinically-relevant minipig model of cardiometabolic HFpEF. Methods and results: Multiple HFpEF comorbidities were induced in adult female Göttingen minipigs by mineralocorticoid …