Medicine and Health Sciences Commons^™

Bilirubin Hepatic And Intestinal Transport And Catabolism: Physiology, Pathophysiology, And Benefits, Zachary A. Kipp, Sally N. Pauss, Genesee J. Martinez, Terry D. Hinds, Jr., Wang-Hsin Lee

Pharmacology and Nutritional Sciences Faculty Publications

Bilirubin, a metabolite derived from heme degradation, has traditionally been regarded as a waste product and a marker of liver injury. However, increasing evidence suggests that bilirubin also functions as a hormone, and reduced levels are associated with metabolic dysfunction. Studies have shown a strong association between low circulating bilirubin levels and an increased risk of metabolic disorders and cardiovascular disease. To advance bilirubin-based treatment strategies, it is essential to elucidate the mechanisms underlying bilirubin transport and metabolism. Therefore, we provide an in-depth discussion of bilirubin production and its subsequent fates, with a particular focus on the transport between the …

Cd47: An Immunoregulatory Nexus In Liver And Gastrointestinal Disorders, Josephine Otuagomah, Alana Newcomb, Taesik Gwag, Shuxia Wang

Pharmacology and Nutritional Sciences Faculty Publications

Cluster of differentiation 47 (CD47) is a widely expressed transmembrane protein that serves as a critical immunoregulatory checkpoint in both homeostatic and pathological conditions of the digestive system. It interacts with signal regulatory protein alpha to send a ‘do not eat me’ signal, thereby preventing phagocytosis and shaping immune responses. Beyond immunity, CD47 also influences cell death, growth and metabolism through interactions with integrins and thrombospondin-1. Recent studies implicate CD47 as a central nexus in the pathogenesis of diverse liver and gastrointestinal disorders, including metabolic dysfunction-associated steatotic liver disease, metabolic dysfunction-associated steatohepatitis, inflammatory bowel disease, liver ischaemia-reperfusion injury, drug-induced liver …

Gut Microbiome, Neuroinflammation, And Fetal Alcohol Spectrum Disorders: Insights From Rodent Models, Abdulrahman M. Busayli, Wenhua Xu, Ghaidaa A. Raffah, Gang Chen

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorder (FASD) is a significant public health issue that affects children. It results from ethanol exposure during pregnancy, leading to considerable physical, neurodevelopmental, behavioral, and cognitive deficits. The exact mechanism is not well understood. Recently, considerable attention has been focused on the influence of gut microbiome on brain development through the gut–brain axis. Changes in the gut microbiome resulting from ethanol exposure may contribute to the pathology of FASD, potentially involving neuroinflammation. This literature review summarizes the existing research and primary animal studies on the impact of early ethanol exposure on the gut microbiome, neuroinflammation, brain development, …

Calcineurin/Nfat Inhibitors Maintain Cognition In A Preclinical Prevention Study In An Aging Canine Model Of Alzheimer Disease, Lorena Sordo, Margo F. Ubele, Kathy Boaz, Jennifer L. Mefford, Erin Dehnart Jones, Katie L. Mccarty, Hollie Y. Van Rooyen, Jeffrey R. Smiley, Stasia A. Bembenek Bailey, Jessica A. Perpich, Beverly Meacham, David K. Powell, Frederick Bresch, Jacob W. Crump, Michael J. Phelan, Jessica A. Noche, Craig E. Stark, László G. Puskás, Christopher M. Norris, Elizabeth Head

Pharmacology and Nutritional Sciences Faculty Publications

Brain signaling of calcineurin (CN) and nuclear factor of activated T-cells (NFAT) transcription factor increases in Alzheimer disease (AD) and is associated with synaptic loss, neurodegeneration, neuroinflammation, amyloid-β (Aβ) production, and cognitive decline. CN/NFAT inhibitors ameliorate these neuropathologies in mouse models of AD. Further, chronic use of tacrolimus in transplant patients reduces risk of AD. Beagles naturally develop Aβ plaques and cognitive dysfunction. We evaluated the impact of FDA-approved CN inhibitor, tacrolimus, and experimental NFAT inhibitor, Q134R, on cognitive outcomes during a three-year prevention study in 37 middle-aged beagles. While beagles treated with CN/NFAT inhibitors showed differences in the pattern …

Adolescents’ And Parents’ Perspectives On Using The Medsmarxt Families Intervention In Emergency Departments For Opioid Medication Safety Education: Mixed Methods Study, Olufunmilola Abraham, Sara Nadi, Irene Hurst

Pharmacy Practice and Science Faculty Publications

Background: The opioid crisis has significantly impacted adolescents and their families. This is attributed in part to increased opioid prescriptions in pediatric emergency departments (EDs) due to acute pain conditions and injuries. Although EDs frequently prescribe opioids, no effective preventative interventions have been implemented to educate adolescents and their families on safe opioid use. This study evaluates the MedSMA℞T Families intervention, which consists of an engaging serious game, Adventures in PharmaCity, and a personalized Family Medication Safety Plan (FMSP) with the aim of reducing opioid misuse and promoting opioid medication safety. The MedSMA℞T Families intervention was developed to educate adolescents …

Barriers To And Facilitators Of Buprenorphine Dispensing For Opioid Use Disorder: Evidence From Focus Groups In Appalachian Kentucky, Douglas R. Oyler, Dustin K. Miracle, Hannah Hesener, Laura Stinson, Monica Roberts, Adrienne Matson, Patricia R. Freeman

Pharmacy Practice and Science Faculty Publications

Background: As efforts to increase buprenorphine prescribing continue to intensify, pharmacy dispensing plays an important role in access to essential medications for opioid use disorder. Existing survey research suggests stigma and regulatory concerns are barriers to pharmacists dispensing buprenorphine, but facilitators are less clear, as are in-depth perceptions of pharmacists regarding buprenorphine.

Objective: To assess barriers and facilitators to buprenorphine dispensing in Appalachian Kentucky using a series of focus groups with pharmacy employees.

Methods: Between September and October 2023, 5 structured focus groups were conducted with a total of 19 pharmacists and pharmacy technicians across a mixture of high- and …

Impact Of Fast Advancement And Early Fortification Of Enteral Feedings In Preterm Infants, A Retrospective, Observational Study., Enrique Gomez-Pomar, Holly Clarke, Jamie Adams

Pediatrics Faculty Publications

UNLABELLED: We aimed to evaluate the outcomes and growth of preterm infants at a Neonatal Intensive Care Unit that focuses on early initiation, fast advancement, and early fortification of enteral feeds.

METHODS: Retrospective study conducted at a community hospital level III NICU. Extensive feeding data and outcomes were collected by utilizing a NutritionIQ software application, NICUtrition®. Infants born between 26- and 34-weeks gestational age were included, whereas infants with congenital defects, deceased or with incomplete data were excluded. Frequency and descriptive statistical analysis were conducted using chi-square and Fisher's exact test. Unadjusted odds ratios were computed for categorical variables and …

Rcpneoperu Trial: A Cluster Randomized Pilot Trial To Assess Traditional Neonatal Resuscitation Compared To Partially Virtual Training In Remote Areas., Carlos A Delgado, Enrique Gómez Pomar, Pablo Velásquez, Víctor Sánchez, Roberto Shimabuku, Luis Huicho

Pediatrics Faculty Publications

OBJECTIVE: To assess the effects of a neonatal resuscitation training program using traditional training and partial distance learning.

METHOD: Through an open cluster-randomized trial, the authors compared a traditional approach involving face-to-face theory and practice sessions using information and communication technology to offer theory and distance examination, followed by face-to-face practice. Twelve health facilities were allocated by blocked randomization. Comparisons were made adjusting for clustering in qualitative and quantitative data. The primary outcome was the percentage of infants with heart rates ≥100 per minute at the second minute after birth. The authors performed a cluster-level analysis for cluster randomized trials, …

Congenital Malignant Ectomesenchymoma Presenting As A Neck Mass In A Newborn, Ianna S. C. Blanchard, Ravi C. Bhavsar, Ashley M. Olszewski, Nathan R. Shelman, John A. D'Orazio, Prasad Bhandary, Thitinart Sithisarn

Pediatrics Faculty Publications

Background: Malignant Ectomesenchymoma (MEM) is a rare, aggressive soft tissue neoplasm with both neuroectodermal and mesenchymal differentiation. Congenital cases are extremely uncommon, posing significant diagnostic and therapeutic challenges.

Case Presentation: We report a case of a full-term male neonate presenting with a large congenital neck mass and respiratory distress at birth. Imaging revealed a lobulated, heterogeneously enhancing mass in the left submandibular region with a mass effect on the airway. Open biopsy and gross resection on day six of life confirmed MEM with rhabdomyoblastic and neuroectodermal differentiation. Post-surgical staging classified the tumor as Stage I, Clinical Group II. Despite initial …

A 40-Week Phase 2b Randomized, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating The Safety And Efficacy Of Memantine In Amyotrophic Lateral Sclerosis, Salman Bhai, Todd Levine, Dan Moore, Robert Bowser, Andrew J. Heim, Maureen Walsh, Aziz Shibani, Zachary Simmons, James Grogan, Namita A. Goyal, Raghav Govindarajan, Yessar Hussain, Tania Papsdorf, Tiffany Schwasinger-Schmidt, Nick Olney, Kim Goslin, Michael Pulley, Edward J. Kasarskis, Michael Weiss, Susan W. Katz, Suzan Moser, Duaa Jabari, Omar Jawdat, Jeffrey Statland, Mazen M. Dimachkie, Richard Barohn, Neuromuscular Study Group And Western Als Consortium Memantine Als Study Group

Neurology Faculty Publications

Introduction: Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with no known cure, limited treatment options with minimal benefits, and significant unmet need for disease modifying therapies.

Aims: This study investigated memantine's impact on ALS progression, with an additional focus on the effects of memantine on cognitive and behavioral changes associated with the disease.

Methods: A randomized, double-blind, placebo-controlled clinical trial was conducted from December 2018 to September 2020. ALS patients were enrolled in-person and remotely across 13 sites in the United States. Participants were randomized to memantine (20 mg twice daily) or placebo in a 2:1 ratio …

Interaction Between Riluzole Treatment And Dietary Glycemic Index In The Disease Progression Of Amyotrophic Lateral Sclerosis, Ikjae Lee, Hiroshi Mitsumoto, Seonjoo Lee, Edward J. Kasarskis, Michael Rosenbaum, Pam Factor-Litvak, Jeri W. Nieves

Neurology Faculty Publications

Objective: We examined whether riluzole treatment modifies the associations between the dietary glycemic index (GI) and load (GL) and disease progression in amyotrophic lateral sclerosis (ALS).

Methods: Sporadic ALS patients in the Multicenter Cohort Study of Oxidative Stress who completed a baseline food frequency questionnaire were included (n = 304). Interactions between baseline riluzole treatment and GI/GL on functional decline and tracheostomy-free survival were examined using linear regression and Cox proportional hazard models adjusted for covariates. Age, sex, disease duration, diagnostic certainty, body mass index, bulbar onset, revised ALS functional rating scale (ALSFRS-r) total score, and forced vital capacity, from …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer’S Disease Detection And Monitoring, Melissa E. Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah E. Pape, Juan Fortea, Nicholas J. Ashton, Chinedu Udeh-Momoh, Sid E. O’Bryant, Dwight German, Florin Despa, Mark Mapstone, Henrik Zetterberg

Neurology Faculty Publications

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer’s Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

A Case Study In Program Evaluation, Soma Dutta

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Program evaluation is a systematic process of assessing a program’s design, implementation, and outcomes to determine its effectiveness, efficiency, and impact, guiding data-driven improvements and decision-making. The Centers for Disease Control and Prevention (CDC) Evaluation Framework provides a structured approach to assessing public health programs, ensuring they are effective, accountable, and continuously improving. By systematically applying this framework, evaluations can provide actionable insights that inform program improvements, guide resource allocation, and ensure that evaluations are practical and meaningful to all stakeholders involved (Centers for Disease Control and Prevention, 2024).

The Bourbon County Health Department (BCHD) has implemented a Physical Activity …

A Case Study In Program Evaluation: Evaluation Of The Bourbon County Physical Activity Initiative, Michaela D. Amburgey

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

This evaluation examines the Bourbon County Physical Activity Initiative, which aims to increase physical activity levels in Bourbon County, Kentucky. The initiative includes increased access to exercise opportunities, community events, and an incentive-based activity tracking system. This evaluation assesses the program’s implementation, effectiveness, and provides recommendations for improvement. By utilizing evaluation findings, public health practitioners can enhance decision-making, optimize resource allocation, and improve population health outcomes.

Bones And Brains: The Association Between Osteoporosis And Depression, Mason Taylor

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Introduction: Osteoporosis and depression are two public health problems that are increasing in prevalence. Previous studies have found a positive association between the two variables in women and men and women together, but there is a gap when looking at men. Therefore, it was important to investigate the odds of depression in men, women, and men and women together to make comparisons by sex.

Methods: 1,602 participants aged 65 and older were included in the study from the National Health and Nutrition Examination Survey (NHANES) 2017 – March 2020 Pre-Pandemic dataset. One unadjusted and seven adjusted models were created for …

Evaluation Of The Bourbon County Health Department Physical Activity Program, Walker S. Hancock

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Bourbon County has a low physical activity rate. A program has been implemented to increase rates of physical activity. An evaluation has been performed using the CDC’s 6-step program evaluation process framework.

According the the framework, two recommendations were made. The first one is to increase access to parks or exercise facilities for those outside of Paris city limits. The second one is to increase the number of indoor facilities for people to use during the cold, winter months.

A Case Study In Program Evaluation: Evaluation Of A Program To Increase Physical Activity, Megan M. Harper

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Public health revolves around 3 core functions: assessment, policy development, and assurance.¹ For public health initiatives to have long-term success, we must determine if the intended effects of those programs are met in the beginning stages of program development and implementation; thus, program evaluation relates to the core function of assessment. The Centers for Disease Control and Prevention (CDC) developed a framework to facilitate this process and enable subsequent informed decisions on how to improve public health programs, which relates to policy development.² The CDC framework is comprised of 6 interconnected steps and 4 groups of standards; together, …

Understanding The Impact Of Pharmacist Prescriptive Authority On Hiv Pre-Exposure Prophylaxis At The State Level, Cameron G. King

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

HIV transmission, with relative risk reductions of up to 99%. However, real world data have revealed that even with large increases in PrEP use, new HIV diagnoses may only slightly decline. This disparity suggests that access to PrEP may be suboptimal, especially among high-risk subgroups, who are often hard to maintain on the continuum of HIV care. Pharmacists, because of their accessibility, trusted role in their communities, and growing scope of practice, could serve as an intervention point to improve access to PrEP.

A previously validated algorithm using National Drug Codes (NDCs) and the International Classification of Disease, 10^{th …}

How Sleep Disorders And Sleep Duration Impact Memory, Alexandria J. Sims

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

INTRODUCTION: Sleep duration and sleep disorders can cause changes in memory function as populations age. Previous studies have shown that disordered sleep is associated with increased risk of cognitive dysfunction and long and short sleep durations can cause memory impairment. This study studies aims to find if there is an association between sleep disorders and sleep duration and the impacts on memory.

METHODS: In this study, 3,478 participants aged 60 year and older from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 dataset were included in adjusted and unadjusted models, comparing the sleep disorders and sleep duration exposures to …

Environmental And Behavioral Determinants Of Congenital Defects: An Ecologic Study In Kentucky, Amelia G. Floyd

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Congenital defects are a significant contributor to infant morbidity and mortality. The multifactorial etiology of such defects presents complex challenges for public health. This ecologic study investigates the association between environmental and behavioral exposures and congenital defects rates at the county level in Kentucky from 2010 to 2019. The Kentucky Department for Public Health, Office of Vital Statistics, provided all relevant defect data. County-level exposure data was collected from multiple sources.

Descriptive and geospatial analyses revealed substantial geographic variability, with notable high defect rates in northeastern Kentucky. Negative binomial regression models identified behavioral and socioeconomic factors to be the strongest …

Assessing The Impact Of A Physical Activity Program In Bourbon County Using The Cdc Evaluation Framework, Abigail Lay

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Physical inactivity is a significant public health concern, contributing to increased risks of chronic diseases such as obesity, cardiovascular disease, and diabetes (Centers for Disease Control and Prevention [CDC], 2022). To address this issue, communities across the United States have implemented physical activity programs to promote healthier lifestyles, including Bourbon County. This project evaluates the impact of a physical activity program in Bourbon County, KY, using the CDC Framework for Program Evaluation to assess its effectiveness, sustainability, and areas for improvement (CDC, 1999).

The primary objective of this evaluation is to determine whether the program has successfully increased participants' physical …

Changes In Local Public Health System Characteristics Before And After The Implementation Of Ohio’S Public Health Accreditation Board Policy For Local Public Health Departments., Christine Lynn Vazquez

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The Public Health Accreditation Board is a nationally recognized nonprofit organization that manages a series of programs including the national public health accreditation program. Public health accreditation is awarded to health departments that achieve a set of nationally recognized goals and standards for departments to adopt. The state of Ohio initiated policy requiring that Local Health Departments to achieve accreditation by 2018. In result, Ohio has the largest number of accredited local health departments. This study looked at the local health departments in Ohio responses to the National Longitudinal Survey of Public Health Systems to understand if services provided improved …

Evaluating Hiv Testing Strategies And Screening In The University Of Kentucky’S Target 4 Project, Emily E. Wagoner

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

The University of Kentucky’s Target 4 project aims to expand HIV testing and provide accessible, confidential services throughout Kentucky, focusing on individuals at highest risk for HIV and Hepatitis C. In December 2023, the Target 4 project implemented a new, expanded HIV screening form, increasing the number of questions from seven to eighteen. This study analyzes the impact of the new screening form on risk factor identification and HIV positivity rates in Region 9, a 16-county area in central Kentucky, from September 2021 to November 2023. Data from 11,187 encounters before the implementation of the new screening form and 2,585 …

Evaluating The Acceptability Of Ptsd Treatment Among Justice-Involved Women In Kentucky With Histories Of Opioid Use, Jesse P. Mccann

Theses and Dissertations--Psychology

Rates of trauma and PTSD as well as histories of opioid use are high among justice-involved women, particularly in Kentucky. However, there are many barriers to receiving treatment. There is a pressing need for brief, trauma-focused interventions that can be more feasibly delivered in jail or prison settings as well as by community clinicians serving women on probation or parole. This study explores the acceptability of treatment for PTSD, particularly Written Exposure Therapy (WET), among justice-involved women on probation or parole with a history of illicit or nonmedical prescription opioid use. The research aims to deepen our understanding of factors …

Cognitive Rehabilitation Of Brain Tumor Survivors: A Systematic Review, Rabeet Tariq, Hafiza Fatima Aziz, Shahier Paracha, Nida Zahid, Timothy J. Ainger, Farhan A. Mirza, Syed Ather Enam

Neurology Faculty Publications

Background Cognitive decline is commonly seen in brain tumor (BT) patients and is associated with a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors.

Methods The review was conducted in accordance with the PRISMA guidelines. The studies on CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying …

Tam Receptors Mediate The Fpr2-Driven Pain Resolution And Fibrinolysis After Nerve Injury, Beate Hartmannsberger, Adel Ben‑Kraiem, Sofia Kramer, Carolina Guidolin, Ida Kazerani, Kathrin Doppler, Dominique Thomas, Robert Gurke, Marco Sisignano, Pranav P. Kalelkar, Andrés J. García, Paula V. Monje, Michael Sammeth, Asma Nusrat, Alexander Brack, Susanne M. Krug, Claudia Sommer, Heike L. Rittner

Markey Cancer Center Faculty Publications

Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothe- lial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery. To this end, we analysed the nerve barrier property portfolio, pain behaviour battery and lipidomics for precursors of specialized pro-resolving meditators (SPMs) and their receptors in chronic constriction injury of the rat sciatic nerve to identify tar- gets for pain resolution by resealing the selected nerve barriers. Of the three nerve barriers—perineurium, capillaries and myelin—only capillary tightness specifically against larger molecules, such as fibrinogen, recuperated with …

Extracellular Vesicles Released By All Patients Contain Hne-Adducted Proteins: Implications Of Collateral Damage, Jenni Ho, Suriyan Sukati, Tamara Taylor, Sherry Carter, Brittany Fuller, Amy Marmo, Caryn Sorge, John A. D'Orazio, D. Allan Butterfield, Subbarao Bondada, Heidi Weiss, Daret K. St. Clair, Luksana Chaiswing

Markey Cancer Center Faculty Publications

Off-target neuronal injury is a serious side-effect observed in cancer survivors. It has previously been shown that pediatric acute lymphoblastic leukemia (ALL) survivors have a decline in neurocognition compared to healthy age-matched counterparts. Elevated oxidative stress has been documented to be a mediator in off- target tissue damage in cancer survivors. Early detection of oxidative stress markers may provide an opportunity to prevent off-target tissue damage. Extracellular vesicles (EVs) have surfaced as a potential diagnostic tool due to molecular cargo they contain. We investigated the potential for EVs to be a sensitive indicator of oxidative stress and off-target tissue damage …

Engaging Nurses In Effective Cost Of Care Conversations To Address Cancer-Related Financial Toxicity: Results From An Exploratory Survey, Jean Edward, Amanda T. Wiggins, Louis G. Baser, Haafsah Fariduddin, Joanna F. Doran, Monica F. Bryant, John August D'Orazio, Kimberly D. Northrip

Markey Cancer Center Faculty Publications

Few evidence-based trainings exist on how to equip healthcare providers, particularly nurses, with the skills to engage in cost of care conversations with patients/caregivers to mitigate the impact of cancer-related financial toxicity. This study evaluated a pilot training developed in collaboration with Triage Cancer® to prepare oncology nurses to identify and assist patients/caregivers facing financial and/or legal barriers to care. Ten pediatric oncology nurses completed the training and pre/post-surveys on behaviors related to financial and legal need screening, frequency and comfort level of answering questions, knowledge, and behavior changes, along with training evaluation questions. At baseline, six nurses reported never …

Pharmacological Or Genetic Inhibition Of Ltcc Promotes Cardiomyocyte Proliferation Through Inhibition Of Calcineurin Activity, Lynn A. C. Devilée, Abou Bakr M. Salama, Jessica M. Miller, Janice D. Reid, Qinghui Ou, Nourhan M. Baraka, Kamal Abou Farraj, Madiha Jamal, Yibing Nong, Todd K. Rosengart, Douglas A. Andres, Jonathan Satin, Tamer M. A. Mohamed, James E. Hudson, Riham R. E. Abouleisa

Markey Cancer Center Faculty Publications

Cardiomyocytes (CMs) lost during ischemic cardiac injury cannot be replaced due to their limited proliferative capacity. Calcium is an important signal transducer that regulates key cellular processes, but its role in regulating CM proliferation is incompletely understood. Here we show a robust pathway for new calcium signaling-based cardiac regenerative strategies. A drug screen targeting proteins involved in CM calcium cycling in human embryonic stem cell-derived cardiac organoids (hCOs) revealed that only the inhibition of L-Type Calcium Channel (LTCC) induced the CM cell cycle. Furthermore, overexpression of Ras-related associated with Diabetes (RRAD), an endogenous inhibitor of LTCC, induced CM cell cycle …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M. Kusminski, Terry D. Hinds Jr., Philipp E. Scherer

Markey Cancer Center Faculty Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …