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- Clinical and Translational Science Faculty Publications (61)
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Articles 1 - 30 of 119
Full-Text Articles in Translational Medical Research
The Functional Significance Of Plk1 Phosphorylation Of Nrf2 In Prostate Cancer Progression, Maria Nur
The Functional Significance Of Plk1 Phosphorylation Of Nrf2 In Prostate Cancer Progression, Maria Nur
Theses and Dissertations--Toxicology and Cancer Biology
Prostate cancer progression and therapeutic resistance are closely linked to alterations in redox homeostasis and cell cycle regulation. Nuclear factor erythroid 2–related factor 2 (NRF2) is a master regulator of antioxidant responses, yet the mechanisms integrating cell cycle signaling with NRF2 activity in prostate cancer remain poorly defined. In this study, we identify polo‑like kinase 1 (PLK1) as a novel regulator of NRF2 through direct phosphorylation at serine 253 (S253). Using bioinformatic prediction, mass spectrometry, in vitro kinase assays, and cell‑based analyses, we demonstrate that PLK1 phosphorylates NRF2 at S253 in a cell cycle–dependent manner, with maximal phosphorylation during mitosis. …
The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton
The Immune Hangover: Understanding The Influence Of Alcohol Use, Abstinence, And Post-Abstinence Drinking On Monocyte Plasticity, Madison B. Blanton
Theses and Dissertations--Pharmacy
Alcohol consumption is widespread in the United States, with 80% of individuals aged 12 and older reporting alcohol use and 1-in-4 engaging in risky drinking behaviors. Alcohol misuse heightens susceptibility to infections and delays wound healing, indicating a disrupted immune system. Previous studies show alcohol rewires immune cells, especially monocytes and macrophages, which play critical roles in tissue homeostasis and host defense.
Using a rhesus macaque model of ethanol self-administration, we demonstrate that after 6-months of drinking, monocytes exhibit decreased cytokine production and significant transcriptomic changes, indicating a hypo-inflammatory state. In contrast, 12-months of chronic alcohol use induces hyperinflammatory responses, …
Biomechanical Effects Of Exercise-Based Interventions In Chronic Nonspecific Low Back Pain: A Systematic Review And Meta-Analysis, Lara De Vecchi Machado
Biomechanical Effects Of Exercise-Based Interventions In Chronic Nonspecific Low Back Pain: A Systematic Review And Meta-Analysis, Lara De Vecchi Machado
Theses and Dissertations--Kinesiology and Health Promotion
Chronic nonspecific low back pain (CNLBP) is the leading cause of years lived with disability worldwide and represents a complex, multifactorial, and heterogeneous condition. It is characterized by substantial interindividual variability in muscle activation patterns, lumbo-pelvic coordination, and movement strategies. Although exercise is widely recommended as a first-line intervention and its clinical benefits are well established, the biomechanical mechanisms underlying functional improvement remain fragmented in the literature and are rarely synthesized quantitatively.
This dissertation conducted a systematic review with meta-analysis to investigate the biomechanical effects of exercise-based interventions in individuals with CNLBP. A total of 39 studies were included and …
Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein
Leveraging Clinical Standards To Improve The Translational Relevance Of Therapies For Experimental Spinal Cord Injury, Aaron L. Silverstein
Theses and Dissertations--Neuroscience
Efforts to improve treatment of spinal cord injury (SCI) often use animals to develop effective therapeutics, intending to improve the survival and the quality of life of persons with SCI. Over half of all SCIs in the United States occur at the cervical level and often cause locomotor deficits and life-threatening breathing dysfunction. Thus, my dissertation is focused on this important patient population.
After beginning with a description of translational research and surveying SCI from a clinical standpoint, I turned to describe experimental models of cervical SCI and more detailed neuroimmunological findings relevant to my work. Then, I conducted a …
The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True
The Impact Of Maternal Environmental Exposures On The Immune Landscape Of The Maternal-Fetal Interface, Heather E. True
Theses and Dissertations--Pharmacy
Maternal environmental exposures and inflammation are known to impact fetal development in utero as well as increase the risk for chronic diseases later in life. Therefore, it is essential that we understand how the maternal environment alters placental structure and immune function.
Therefore, we isolated fetal (chorionic villous) tissues from the placentas of healthy pregnant participants (control) and those with inflammatory conditions, including SARS-COV-2 infection, pregravid obesity, and opioid use disorder. Isolated placental leukocytes were subjected to a series of assays to uncover the phenotypic, functional, and transcriptional (single-cell RNA-sequencing) landscape of placental immune cells. Additional placental tissues were subjected …
Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan
Impact Of Hyperthermia And Mitomycin C On Heat Shock Proteins, Mismatch Repair Proteins, And Cytotoxicity In Colon Cancer, Anna M. Reagan
Theses and Dissertations--Clinical and Translational Science
Cytoreductive surgery and heated intraperitoneal chemotherapy (HIPEC) is a treatment used for primary peritoneal malignancy or metastases, including colon cancer. We aimed to explore the effects of hyperthermia and/or mitomycin C (MMC) on mismatch repair (MMR) proteins and heat shock proteins (hsps) and the potential for post-HIPEC treatment with pembrolizumab treatment. Colon cancer cells were treated with hyperthermia and/or MMC for 90 minutes. Subcellular fractionation and immunofluorescent imaging were performed to identify protein abundance and localization of MSH2, MLH1, hsp70, and hsp27. Proteomics analysis was performed for HT29 cells. HT29 cells and patient-derived organoids (PDOs) underwent simulated HIPEC and treatment …
Enhancing Public Health Surveillance: Development And Validation Of Machine Learning Models For Suspected Opioid Overdose Detection In Emergency Medical Services Data, Peter J. Rock
Theses and Dissertations--Clinical and Translational Science
The ongoing opioid overdose crisis in the United States requires timely and accurate surveillance systems to inform public health responses. Traditional public health surveillance methods rely on hospital discharge data and death certificates, which suffer from significant reporting delays and miss cases where patients refuse hospital transportation. Emergency Medical Services (EMS) data presents a promising alternative with advantages in timeliness and case ascertainment but lacks validated definitions for suspected opioid overdose (SOO).
This dissertation addresses this critical gap through the development, validation, and fairness assessment of machine learning models with natural language processing (ML-NLP) for identifying SOOs in EMS data. …
Students Participating As Ambassadors For Research In Kentucky (Spark): A Health Equity Undergraduate Research Training Program, Ariel A. Arthur, Rebecca L. Delacerda Allen, Fidelis Y. Sesenu, Maxwell A. Groznik, Carrie B. Oser, Madeline Dunfee, Philip A. Kern, Nancy Schoenberg
Students Participating As Ambassadors For Research In Kentucky (Spark): A Health Equity Undergraduate Research Training Program, Ariel A. Arthur, Rebecca L. Delacerda Allen, Fidelis Y. Sesenu, Maxwell A. Groznik, Carrie B. Oser, Madeline Dunfee, Philip A. Kern, Nancy Schoenberg
UK CARES Faculty Publications
The Students Participating as Ambassadors for Research in Kentucky (SPARK) program provides novel health equity research training and targeted mentorship for undergraduates, particularly those from groups underrepresented in the biomedical and behavioral research and workforce. SPARK aims to address inadequate diversity in the medical and scientific research fields by providing comprehensive research mentorship and skill-building. Unlike most existing research training programs that are brief, focus on laboratory research, or are limited to graduate students and junior faculty, SPARK delivers a 16-month intensive behavioral and population health science training, equipping students with needed tools to conceptualize, plan, execute, and analyze their …
Key To Success: A Comprehensive Examination Of Support Personnel In School-Based Speech-Language Telepractice, Hannah Douglass
Key To Success: A Comprehensive Examination Of Support Personnel In School-Based Speech-Language Telepractice, Hannah Douglass
Theses and Dissertations--Rehabilitation Sciences
In the school setting, the telepractice team primarily consists of the clinician and a support person known as a telefacilitator. Though telepractice is an accepted method for delivering school-based speech-language therapy, many barriers to the integration of telepractice as routine care persist. A major barrier is clinicians' acceptance of telehealth. However, there has been limited investigation of factors that influence clinician acceptance. Another barrier is related to support personnel. Telefacilitators have been shown to be an integral part of the telepractice program. Yet there are significant gaps in knowledge regarding the roles and responsibilities, staffing and management, and barriers/facilitators to …
Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph
Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph
Theses and Dissertations--Medical Sciences
Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …
Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow
Theses and Dissertations--Clinical and Translational Science
Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …
Moving Toward And Accessing Adult-Oriented Rehabilitation Therapy Services For Adults With Lifelong Disabilities: A Tale Of Three Studies, Catherine Gohrband
Moving Toward And Accessing Adult-Oriented Rehabilitation Therapy Services For Adults With Lifelong Disabilities: A Tale Of Three Studies, Catherine Gohrband
Theses and Dissertations--Rehabilitation Sciences
The aim of this dissertation was to explore how adults with a Lifelong Disability (LLD) access and experience rehabilitation therapy services across their lives. Many LLD diagnoses such as cerebral palsy and spina bifida are considered non-progressive; however, there are common challenges that occur as people with LLD become adults, including increased pain, fatigue, and functional loss. Literature addressing the needs of people with LLD to access adult-oriented medical providers has focused primarily on medical transitions, which have described the processes for pediatric patients moving to adult-oriented settings from pediatric settings. Few studies have addressed the rehabilitation therapy needs of …
Developing Ecologically Valid Clinical Tools For Persons With Tbi: Understanding The Role And Impact Of Distractions, Deanna Pinnow
Developing Ecologically Valid Clinical Tools For Persons With Tbi: Understanding The Role And Impact Of Distractions, Deanna Pinnow
Theses and Dissertations--Rehabilitation Sciences
There is a critical need for the development of ecologically valid clinical tools to assess real-life cognitive functioning in persons impacted by traumatic brain injury (TBI). Chronic cognitive impairments that are exacerbated by distractions are one of the core factors contributing to poor home and community re-integration post injury. Simulation-based digital platforms (i.e., virtual reality, augmented reality, and mixed reality) have become potential solutions for eliciting real-world cognitive performance in clinical settings. Yet, there is a paucity of research investigating the role and impact of distractions on cognition. As a result, there is no clear framework of measuring distractions to …
Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren
Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren
Theses and Dissertations--Pharmacology and Nutritional Sciences
Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …
Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali
Theses and Dissertations--Clinical and Translational Science
Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …
Relative Adrenal Insufficiency In Sepsis, Dan Hao
Relative Adrenal Insufficiency In Sepsis, Dan Hao
Theses and Dissertations--Pharmacology and Nutritional Sciences
Sepsis is a leading cause of death in children. Glucocorticoid (GC) therapy had been strongly recommended for the pediatric sepsis (grade 1A). However, the recommendation was changed to grade 2C in 2020 due to weak evidence. Relative adrenal insufficiency (RAI) is a condition characterized by impaired inducible glucocorticoid (iGC) production in response to stress. It develops in 32.8% of pediatric septic patients. Unfortunately, little is known about the pathogenesis of RAI in pediatric sepsis, and whether GC therapy should be based on the status of RAI is controversial. In this study, we utilized 21-day-old SF1CreSRBIfl/fl mice as the first …
Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac
Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac
Theses and Dissertations--Physiology
Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.
First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …
Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna
Leveraging Cell-Substrate Adhesion And Cell Migratory Properties In Skeletal Muscle Constructs And Cancer Metastasis Assays, Lauren E. Mehanna
Theses and Dissertations--Chemical and Materials Engineering
Volumetric muscle loss (VML) remains one of the few skeletal muscle injuries without a reliable and repeatable treatment. In large volume muscle injuries, muscle fibers as well as the surrounding connective tissue are damaged, preventing therapeutic muscle stem cells, called myogenic progenitor cells (MPCs), from reaching the injury site and initiating repair. There is a clinical need to rapidly fabricate in vitro muscle tissue constructs that mimic the native tissue organization, with aligned myotubes, for insertion and integration at the patient’s injury site. In this dissertation, we utilize the MPC’s natural propensity to close gaps across an injury site to …
Potential Benefits Of Combined Statin And Metformin Therapy On Resistance Training Response In Older Individuals, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Marcas M. Bamman, Charlotte A. Peterson, Phillip A. Kern
Potential Benefits Of Combined Statin And Metformin Therapy On Resistance Training Response In Older Individuals, Douglas E. Long, Kate Kosmac, Cory M. Dungan, Marcas M. Bamman, Charlotte A. Peterson, Phillip A. Kern
Clinical and Translational Science Faculty Publications
Metformin and statins are currently the focus of large clinical trials testing their ability to counter age-associated declines in health, but recent reports suggest that both may negatively affect skeletal muscle response to exercise. However, it has also been suggested that metformin may act as a possible protectant of statin-related muscle symptoms. The potential impact of combined drug use on the hypertrophic response to resistance exercise in healthy older adults has not been described. We present secondary statin analyses of data from the MASTERS trial where metformin blunted the hypertrophy response in healthy participants (>65 years) following 14 weeks …
Evaluating Simulation-Based Tobacco Treatment Scenarios For Providers Delivering Treatment For People Living With Mental Illnesses, Chizimuzo T. C. Okoli, Janet Otachi, Sarret Seng, Bassema Abufarsakh, Lovoria B. Williams
Evaluating Simulation-Based Tobacco Treatment Scenarios For Providers Delivering Treatment For People Living With Mental Illnesses, Chizimuzo T. C. Okoli, Janet Otachi, Sarret Seng, Bassema Abufarsakh, Lovoria B. Williams
Clinical and Translational Science Faculty Publications
Background: People living with mental illnesses (PMI) experience elevated tobacco use and related morbidity and mortality. Despite the availability of effective and safe tobacco treatments along with evidence that PMI are motivated and able to quit successfully, few Mental and behavioral healthcare providers (MHPs) engage PMI in such treatment. MHPs may lack the confidence or skills to engage their clients in tobacco treatment. Currently, there are limited training modalities to prepare MHPs in delivering tobacco treatment for PMI. However, animated scenario-based simulated encounters can bridge this gap to effectively provide tailored MHP training to enhance treatment delivery. Hence, the purpose …
Tumor Suppressor Par-4 Regulates Complement Factor C3 And Obesity, Nathália Araujo, James Sledziona, Sunil K. Noothi, Ravshan Burikhanov, Nikhil Hebbar, Saptadwipa Ganguly, Tripti Shrestha-Bhattarai, Beibei Zhu, Wendy S. Katz, Yi Zhang, Barry S. Taylor, Jinze Liu, Li Chen, Heidi L. Weiss, Daheng He, Chi Wang, Andrew J. Morris, Lisa A. Cassis, Mariana N. Nikolova‑Karakashian, Prabhakara R. Nagareddy, Olle Melander, B. Mark Evers, Phillip A. Kern, Vivek M. Rangnekar
Tumor Suppressor Par-4 Regulates Complement Factor C3 And Obesity, Nathália Araujo, James Sledziona, Sunil K. Noothi, Ravshan Burikhanov, Nikhil Hebbar, Saptadwipa Ganguly, Tripti Shrestha-Bhattarai, Beibei Zhu, Wendy S. Katz, Yi Zhang, Barry S. Taylor, Jinze Liu, Li Chen, Heidi L. Weiss, Daheng He, Chi Wang, Andrew J. Morris, Lisa A. Cassis, Mariana N. Nikolova‑Karakashian, Prabhakara R. Nagareddy, Olle Melander, B. Mark Evers, Phillip A. Kern, Vivek M. Rangnekar
Clinical and Translational Science Faculty Publications
Prostate apoptosis response-4 (Par-4) is a tumor suppressor that induces apoptosis in cancer cells. However, the physiological function of Par-4 remains unknown. Here we show that conventional Par-4 knockout (Par-4-/-) mice and adipocyte-specific Par-4 knockout (AKO) mice, but not hepatocyte-specific Par-4 knockout mice, are obese with standard chow diet. Par-4-/- and AKO mice exhibit increased absorption and storage of fat in adipocytes. Mechanistically, Par-4 loss is associated with mdm2 downregulation and activation of p53. We identified complement factor c3 as a p53-regulated gene linked to fat storage in adipocytes. Par-4 re-expression in adipocytes or c3 deletion reversed …
Regulatory T Cells Control Effector T Cell Inflammation In Human Prediabetes, Rui Liu, Gabriella H. Pugh, Erin Tevonian, Katherine Thompson, Douglas A. Lauffenburger, Philip A. Kern, Barbara S. Nikolajczyk
Regulatory T Cells Control Effector T Cell Inflammation In Human Prediabetes, Rui Liu, Gabriella H. Pugh, Erin Tevonian, Katherine Thompson, Douglas A. Lauffenburger, Philip A. Kern, Barbara S. Nikolajczyk
Clinical and Translational Science Faculty Publications
A disparate array of plasma/serum markers provides evidence for chronic inflammation in human prediabetes, a condition that is most closely replicated by standard mouse models of obesity and metaflammation. These remain largely nonactionable and contrast with our rich understanding of inflammation in human type 2 diabetes. New data show that inflammatory profiles produced by CD4+ T cells define human prediabetes as a unique inflammatory state. Regulatory T cells (Treg) control mitochondrial function and cytokine production by CD4+ effector T cells (Teff) in prediabetes and type 2 diabetes by supporting T helper (Th)17 or Th1 cytokine production, respectively. These data suggest …
Overcoming Resistance To Sg-Aris In Castration-Resistant Prostate Cancer, Chaohao Li
Overcoming Resistance To Sg-Aris In Castration-Resistant Prostate Cancer, Chaohao Li
Theses and Dissertations--Toxicology and Cancer Biology
Prostate cancer (PCa) ranks as the most diagnosed type of cancer and the second leading cause of death in men. Androgen receptor (AR) signaling plays a pivotal function in promoting the survival and progression of PCa. Therefore, medication for PCa mainly focuses on the inhibition of AR pathway, which is termed androgen deprivation therapy (ADT). However, the disease eventually progresses and develops to a lethal stage called castration-resistant prostate cancer (CRPC) that is characterized by resistance to canonical ADT. To deal with this situation, several second-generation AR inhibitors (SG-ARIs) have been created that have better efficacy against AR, including Enzalutamide …
Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino
Regulation Of Skeletal Muscle Plasticity By The Gut Microbiome, Taylor R. Valentino
Theses and Dissertations--Physiology
Recent evidence suggests that the gut microbiome could play a role in skeletal muscle plasticity, providing novel treatments for muscle wasting diseases and/or performance enhancements. I first sought to determine if the gut microbiome is necessary for skeletal muscle adaptation to exercise. Forty-two, four-month old, female C57Bl/6J underwent nine weeks of weighted wheel running or remained in cage with a locked wheel, without or without the administration of antibiotics (treated). In response to wheel running, I found that antibiotic depletion of the microbiome led to a blunted hypertrophic response in the soleus muscle as measured by normalized muscle wet weight …
Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson
Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson
Clinical and Translational Science Faculty Publications
Background: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer’s disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.
Methods: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.
Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif
Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif
Physiology Faculty Publications
Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …
Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian
Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian
Surgery Faculty Publications
Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.
Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …
Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson
Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson
Physiology Faculty Publications
BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.
METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.
RESULTS: Single-cell …
Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg
Covid-19 And The Impact On Rural And Black Church Congregants: Results Of The C-M-C Project, Lovoria B. Williams, Anita F. Fernander, Tofial Azam, Maria L. Gomez, Junghee Kang, Cassidy L. Moody, Hannah Bowman, Nancy E. Schoenberg
Clinical and Translational Science Faculty Publications
The COVID‐19 pandemic has had devastating effects on Black and rural populations with a mortality rate among Blacks three times that of Whites and both rural and Black populations experiencing limited access to COVID‐19 resources. The primary purpose of this study was to explore the health, financial, and psychological impact of COVID‐19 among rural White Appalachian and Black nonrural central Kentucky church congregants. Secondarily we sought to examine the association between sociodemographics and behaviors, attitudes, and beliefs regarding COVID‐19 and intent to vaccinate. We used a cross sectional survey design developed with the constructs of the Health Belief and Theory …
The Use Of Mechanotherapy To Promote The Recovery From Disuse Atrophy In Aging Rat Skeletal Muscle, Zachary Hettinger
The Use Of Mechanotherapy To Promote The Recovery From Disuse Atrophy In Aging Rat Skeletal Muscle, Zachary Hettinger
Theses and Dissertations--Rehabilitation Sciences
The combination of age and disuse-related skeletal muscle atrophy predisposes older adults to reduced mobility, loss of independence, and poor quality of life. Poor health outcomes resulting from periods of disuse in older adults are exacerbated by an inability to fully recover, ultimately accelerating geriatric populations towards further functional decline. Aged-related changes to skeletal muscle viscoelastic properties, specifically of muscle extracellular matrix (ECM) stiffness, may not only impact how muscle responds during recovery, but also to interventions intended to augment recovery. Remodeling of muscle ECM in the aged may therefore benefit muscle mass recovery, yet therapies focused on ECM remodeling …