Medical Specialties Commons^™

Co-Occurrence Of Autism Spectrum Disorder And Attention-Deficit/Hyperactivity Disorder With Idiopathic Hypersomnia: Data From The Hypersomnia Foundation Registry, Sophie Sevan Mikkelsen

Honors Undergraduate Theses

In recent years, hypersomnia patients and researchers alike have increasingly discussed the possibility of heightened comorbidities, or co-occurrences, of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) with the central disorders of hypersomnolence: idiopathic hypersomnia (IH) and narcolepsy (N). While a few scarce studies have investigated a link between ADHD and N, there has been no research on the co-occurrence of these conditions with IH. This study, using data from the Hypersomnia Foundation’s CoRDS Patient Registry, is the first to identify self-reported rates of ASD and ADHD diagnoses by people with idiopathic hypersomnia. Four chi-square tests were conducted to determine …

Assessment Of Forensic And Clinical Criteria Of Orbital Blowout Fractures For Use In Bioarchaeological Analysis, Dylan E. Ornot

Honors Undergraduate Theses

Orbital blowout fractures are a particular facial fracture occurring within the inner eye orbits of the face caused by blunt force trauma to the eyeball or the lower orbital rim. This fracture is common in modern clinical contexts due to physical assaults, but examining this fracture in skeletal material can also provide insights into the patterns of interpersonal violence within the fields of bioarchaeology and forensic anthropology. Issues with analyzing this fracture in skeletal material arise due to the clinical assessment practices of blowout fractures, where medical practitioners are highly focused on the soft tissue presentations of the fracture in …

Dance Movement Therapy For Pediatric Oncology Patients And Its Effect On Cancer Therapy-Related Symptoms, Victoria M. Trautwein

Honors Undergraduate Theses

Background: Pediatric cancer patients are susceptible to emotional distress, depression, anxiety, and physical symptoms impacting their quality of life. Dance movement therapy is a non-pharmacological method that has been shown to improve feelings of depression, anxiety, emotional, somatic symptoms, and overall quality of life. While much of cancer research is dedicated to finding cures, it is also important to focus on identifying methods for improving the symptoms and quality of life for pediatric cancer patients.

Aim: The purpose of the literature review is to examine studies that show the effects of dance movement therapy on pediatric oncology patients’ cancer-treatment related …

Unraveling The Effects Of The Covid-19 Pandemic On Staphylococcus Aureus Carriage: A Comparative Research Of Pre- And Post-Pandemic Samples, Catherine G. Johnston

Honors Undergraduate Theses

The COVID-19 pandemic brought about significant changes in the epidemiology of Staphylococcus aureus carriage and disease. This study aims to assess these changes by leveraging respiratory samples collected from a longstanding cohort, comparing the genomic characteristics of S. aureus isolates from pre- and post-pandemic periods. We analyzed S. aureus genomes and phenotypically determined macrolide resistance to characterize population structure, antibiotic resistance, and virulence profiles. Changes in S. aureus carriage rates, macrolide resistance, disease occurrence, and population structure between samples collected pre- and post-pandemic were examined. By using respiratory samples, chart reviews, and risk factor questionnaires of 498 children from a …

Ai And Radiologist Assessments On The Prevalence Of Tmj Osteoarthritis Using Radiographic Images: A Comparative Study, Louloua Mourad, Nayer Abo El Saad, Yehia El Mahallawy

International Arab Journal of Dentistry

Objectives: This study aims to address the significant discomfort and functional impairment associated with temporomandibular joint osteoarthritis (TMJ OA), which negatively impacts the quality of life. It emphasizes the importance of prompt diagnosis and explores the potential of an Artificial Intelligence (AI) system to enhance TMJ OA diagnosis.

Methods: The prevalence of TMJ OA was evaluated using 3 diagnostic tools: the gold standard, the AI model, and an examiner. In total, 132 patients who performed 190 cone-beam computed tomography (CBCT) images were included.

Results: The prevalence of TMJ OA was 62.11% using the gold standard, 63.68% using …

Improving Nutritional Delivery To Pediatric Patients On Continuous Renal Replacement Therapy, Jennifer Ruiz-Boada, Sarah Brunner, Tara Benton, Vimal Chadha

Presentations

INTRODUCTION: Continuous renal replacement therapy (CRRT) is used in critically ill children with acute renal failure. CRRT can lead to malnutrition by removing essential proteins and micronutrients. Malnutrition is associated with worse outcomes, including increased length of stay and mortality. CRRT guidelines suggest the importance of early nutrition and ensuring high protein intake. After evaluating our CRRT patients, we found sub-optimal adherence to the guidelines. This Quality Improvement project aimed to increase the percentage of patients achieving 75% of their goal protein and caloric intake by day 5 of CRRT initiation by 15% by August 2023. METHODS: A multidisciplinary group …

Role Of Wave3 As An Actin Binding Protein In The Pathology Of Triple Negative Breast Cancer, Lamyae El Khalki, Khalid Sossey-Alaoui

Faculty Scholarship

Breast cancer, a prevalent global health concern, has sparked extensive research efforts, particularly focusing on triple negative breast cancer (TNBC), a subtype lacking estrogen receptor (ER), progesterone receptor, and epidermal growth factor receptor. TNBC's aggressive nature and resistance to hormone-based therapies heightens the risk of tumor progression and recurrence. Actin-binding proteins, specifically WAVE3 from the Wiskott–Aldrich syndrome protein (WASP) family, have emerged as major drivers in understanding TNBC biology. This review delves into the intricate molecular makeup of TNBC, shedding light on actin's fundamental role in cellular processes. Actin, a structural element in the cytoskeleton, regulates various cellular pathways essential …

The Cancer-Associated Secretory Phenotype: A New Frontier In Targeted Therapeutics, Xiaochao Tan, Guan-Yu Xiao, Priyam Banerjee, Shike Wang, Jonathan M. Kurie

Markey Cancer Center Faculty Publications

Oncogenic mutations activate secretory programs that drive tumor progression and represent therapeutic targets. The clinical relevance of CASPs is underscored by their prevalence, their linkages to specific genetic and epigenetic contexts, the proven efficacy of secretory blockade in preclinical models, and the availability of assays to identify vulnerable patient populations.

Carfilzomib-Loaded Ternary Polypeptide Nanoparticles Stabilized By Polycationic Complexation, Preye Mike Agbana, Ji Eun Park, Piotr G. Rychahou, Kyung-Bo Kim, Younsoo Bae

Markey Cancer Center Faculty Publications

Carfilzomib (CFZ) is a second-generation proteasome inhibitor showing great efficacy in multiple myeloma treatment, yet its clinical applications for other diseases such as solid cancers are limited due to low aqueous solubility and poor biostability. Ternary polypeptide nanoparticles (tPNPs) are drug carriers that we previ- ously reported to overcome these pharmaceutical limitations by entrapping CFZ in the core of the nanopar- ticles and protecting the drugs from degradation in biological media. However, preclinical studies revealed that tPNPs would require further improvement in particle stability to suppress initial burst drug release and thus achieve prolonged inhibition of proteasome activity with CFZ …

Cd8+ T Cell Metabolic Flexibility Elicited By Cd28-Ars2 Axis- Driven Alternative Splicing Of Pkm Supports Antitumor Immunity, G. Aaron Holling, Colin A. Chavel, Anand P. Sharda, Mackenzie M. Lieberman, Caitlin M. James, Shivana M. Lightman, Jason H. Tong, Guanxi Qiao, Tiffany R. Emmons, Thejaswini Giridharan, Shengqi Hou, Andrew M. Intlekofer, Richard M. Higashi, Teresa W. M. Fan, Andrew N. Lane, Kevin H. Eng, Brahm H. Segal, Elizabeth A. Repasky, Kevin P. Lee, Scott H. Olejniczak

Markey Cancer Center Faculty Publications

Metabolic flexibility has emerged as a critical determinant of CD8+ T-cell antitumor activity, yet the mechanisms driving the metabolic flexibility of T cells have not been determined. In this study, we investigated the influence of the nuclear cap-binding complex (CBC) adaptor protein ARS2 on mature T cells. In doing so, we discovered a novel signaling axis that endows activated CD8+ T cells with flexibility of glucose catabolism. ARS2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing events. Among these effects, the CD28-ARS2 axis suppressed the expression of the …

Effect Of Mitochondrial Oxidative Stress On Regulatory T Cell Manufacturing For Clinical Application In Transplantation: Results From A Pilot Study, Roberto Gedaly, Gabriel Orozco, Lillie J. Lewis, Deepa Valvi, Fanny Chapelin, Aman Khurana, Giovanna E. Hidalgo, Aaron Shmookler, Aashutosh Tripathi, Cuiping Zhang, Joseph B. Zwischenberger, Francesc Marti

Markey Cancer Center Faculty Publications

The manufacturing process of regulatory T (Treg) cells for clinical application begins with the positive selection of CD25⁺ cells using superparamagnetic iron oxide nanoparticle (SPION)-conjugated anti-CD25 antibodies (spCD25) and immunomagnetic cell separation technology. Our findings revealed that the interaction of spCD25 with its cell target induced the internalization of the complex spCD25–interleukin-2 receptor. Accumulation of intracellular spCD25 triggered oxidative stress, causing delayed Treg expansion and temporary reduction in suppressor activity. This activation delay hindered the efficient generation of clinically competent cells. During this early phase, Treg cells exhibited elevated mitochondrial superoxide and lipid peroxidation levels, with a concomitant decrease …

Abnormal Regulation Of Mitochondrial Sphingolipids During Aging And Alzheimer’S Disease, Simone M. Crivelli, Zainuddin Quadri, Ahmed Elsherbini, Hemendra J. Vekaria, Patrick G. Sullivan, Wenbo Zhi, Pilar Martinez-Martinez, Stefka D. Spassieva, Erhard Bieberich

Markey Cancer Center Faculty Publications

During pathogenesis of Alzheimer’s disease (AD), mitochondria suffer alterations that lead to low energy production and reactive oxygen species formation. However, the mechanism of impaired mitochondria homeostasis in AD is not fully understood. We hypothesized that abnormal sphingolipid metabolism in mitochondria could be one of the contributing factors to mitochondrial dysfunction. Synaptic and non-synaptic mitochondria were isolated from 5xFAD and wild type (WT) mice at 3 and 7 months using Ficoll gradient ultracentrifugation, and their function was analyzed using Seahorse assay. Additionally, mitochondria were ana- lyzed using mass spectrometry for proteomics and sphingolipidomics analyses. Sphingolipid levels were also determined in …

The Carboxy Terminus Causes Interfacial Assembly Of Oleate Hydratase On A Membrane Bilayer, Christopher D. Radka, Christy R. Grace, Hale S. Hasdemir, Yupeng Li, Carlos C. Rodriguez, Patrick Rodrigues, Michael L. Oldham, M. Zuhaib Qayyum, Aaron Pitre, William J. Maccain, Ravi C. Kalathur, Emad Tajkhorshid, Charles O. Rock

Markey Cancer Center Faculty Publications

The soluble flavoprotein oleate hydratase (OhyA) hydrates the 9-cis double bond of unsaturated fatty acids. OhyA sub- strates are embedded in membrane bilayers; OhyA must remove the fatty acid from the bilayer and enclose it in the active site. Here, we show that the positively charged helix- turn-helix motif in the carboxy terminus (CTD) is responsible for interacting with the negatively charged phosphatidylgly- cerol (PG) bilayer. Super-resolution microscopy of Staphylo- coccus aureus cells expressing green fluorescent protein fused to OhyA or the CTD sequence shows subcellular localization along the cellular boundary, indicating OhyA is membrane- associated and the CTD sequence …

Cognitive Decline, Aβ Pathology, And Blood–Brain Barrier Function In Aged 5xfad Mice, Geetika Nehra, Sasivimon Promsan, Ruedeemars Yubolphan, Wijitra Chumboatong, Pornpun Vivithanaporn, Bryan J. Maloney, Anusorn Lungkaphin, Bjoern Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background

Patients with Alzheimer’s disease (AD) develop blood–brain barrier dysfunction to varying degrees. How aging impacts Aβ pathology, blood–brain barrier function, and cognitive decline in AD remains largely unknown. In this study, we used 5xFAD mice to investigate changes in Aβ levels, barrier function, and cognitive decline over time.

Methods

5xFAD and wild-type (WT) mice were aged between 9.5 and 15.5 months and tested for spatial learning and reference memory with the Morris Water Maze (MWM). After behavior testing, mice were implanted with acute cranial windows and intravenously injected with fluorescent-labeled dextrans to assess their in vivo distribution in the …

Extended Conformations Of Bifurcating Electron Transfer Flavoprotein Constitute Up To Half The Population, Possibly Mediating Conformational Change, Sharique A. Khan, Alan Hicks, Wellington C. Leite, James Byrnes, Biswajit Gorai, Maria-Andrea Mroginski, Hugh O'Neill, Anne-Francis Miller

Markey Cancer Center Faculty Publications

Electron transfer bifurcation enables biological systems to drive unfavourable (endergonic) electron transfer by coupling it to favourable (exergonic) transfer of a second electron. In electron transfer flavoproteins (ETFs), a domain-scale conformational change is believed to sever the favourable pathway after a single electron has used it, thereby preventing the energy dissipation that would accompany exergonic transfer of the second electron. To understand the conformation change that participates in turnover, we have deployed small-angle neutron scattering (SANS) and computational techniques to characterize the bifurcating ETF from Acidaminococcus fermentans (AfeETF). SANS data reveal an overall radius of gyration (Rg) of 30.1 ± …

Strategies For Improving The Performance Of Prediction Models For Response To Immune Checkpoint Blockade Therapy In Cancer, Tiantian Zeng, Jason Z. Zhang, Arnold Stromberg, Jin Chen, Chi Wang

Markey Cancer Center Faculty Publications

Immune checkpoint blockade (ICB) therapy holds promise for bringing long-lasting clinical gains for the treatment of cancer. However, studies show that only a fraction of patients respond to the treatment. In this regard, it is valu- able to develop gene expression signatures based on RNA sequencing (RNAseq) data and machine learning meth- ods to predict a patient’s response to the ICB therapy, which contributes to more personalized treatment strategy and better management of cancer patients. However, due to the limited sample size of ICB trials with RNAseq data available and the vast number of candidate gene expression features, it is …

Machine-Learning-Assisted Design Of Deep Eutectic Solvents Based On Uncovered Hydrogen Bond Patterns, Usman Lame Abbas, Yuxuan Zhang, Joseph Tapia, Md Selim, Jin Chen, Jian Shi, Qing Shao

Markey Cancer Center Faculty Publications

Non-ionic deep eutectic solvents (DESs) are non-ionic designer solvents with various applications in catalysis, extraction, carbon capture, and pharmaceuticals. However, discovering new DES candidates is challenging due to a lack of efficient tools that accurately predict DES formation. The search for DES relies heavily on intuition or trial-and-error processes, leading to low success rates or missed opportuni- ties. Recognizing that hydrogen bonds (HBs) play a central role in DES formation, we aim to identify HB features that distinguish DES from non-DES systems and use them to develop machine learning (ML) models to discover new DES systems. We first analyze the …

Tyrp1 Is The Mendelian Determinant Of The Axolotl (Ambystoma Mexicanum) Copper Mutant, Raissa F. Cecil, Lloyd Strohl, Maddie K. Thomas, James L. Schwartz, Nataliya Timoshevskaya, Jeramiah J. Smith, S. Randal Voss

Markey Cancer Center Faculty Publications

Several dozen Mendelian mutants have been discovered in axolotl (Ambystoma mexicanum) populations, including several that affect pigmentation. Four recessive mutants have been described in the scientific literature and genes for three of these have been identified. Here we describe and genetically dissect copper, a mutant with an albino-like phenotype known only from the pet trade. We performed a cross segregating copper and wildtype color phenotypes and used bulked segregant RNA-Seq to identify a region on chromosome 6 that was enriched for single-nucleotide polymorphisms (SNPs) between the color phenotypes. This region included Tyrosinase-like Protein 1 (Tyrp1), a melanin synthesis protein that …

Vaginal Lactobacillus Fatty Acid Response Mechanisms Reveal A Metabolite-Targeted Strategy For Bacterial Vaginosis Treatment, Paul C. Blainey, Seth M. Bloom, Douglas S. Kwon

Markey Cancer Center Faculty Publications

Bacterial vaginosis (BV), a common syndrome characterized by Lactobacillus-deficient vaginal microbiota, is associated with adverse health outcomes. BV often recurs after standard antibiotic therapy in part because antibiotics promote microbiota dominance by Lactobacillus iners instead of Lactobacillus crispatus, which has more beneficial health associations. Strategies to promote L. crispatus and inhibit L. iners are thus needed. We show that oleic acid (OA) and similar long-chain fatty acids simultaneously inhibit L. iners and enhance L. crispatus growth. These phenotypes require OA-inducible genes conserved in L. crispatus and related lactobacilli, including an oleate hydratase (ohyA) and putative fatty acid efflux pump (farE). …

Oxidative Stress Alters Mitochondrial Homeostasis In Isolated Brain Capillaries, Gopal V. Velmurugan, Hemendra J. Vekaria, Anika M. S. Hartz, Björn Bauer, William Brad Hubbard

Markey Cancer Center Faculty Publications

Background

Neurovascular deficits and blood-brain barrier (BBB) dysfunction are major hallmarks of brain trauma and neurodegenerative diseases. Oxidative stress is a prominent contributor to neurovascular unit (NVU) dysfunction and can propagate BBB disruption. Oxidative damage results in an imbalance of mitochondrial homeostasis, which can further drive functional impairment of brain capillaries. To this end, we developed a method to track mitochondrial-related changes after oxidative stress in the context of neurovascular pathophysiology as a critical endophenotype of neurodegenerative diseases.

Methods

To study brain capillary-specific mitochondrial function and dynamics in response to oxidative stress, we developed an ex vivo model in which …

Elevated Free Cholesterol Levels Due To Impaired Reverse Cholesterol Transport Are A Risk Factor For Polymicrobial Sepsis In Mice, Qian Wang, Ling Guo, Dan Hao, Misa Ito, Chieko Mineo, Philip W. Shaul, Xiang-An Li

Markey Cancer Center Faculty Publications

Dysregulated lipid metabolism is commonly observed in septic patients, but how it contributes to sepsis remains largely unknown. Reverse cholesterol transport (RCT) is crucial for regulating cholesterol metabolism in circulation. During RCT, high-density lipoprotein collects cholesterol from peripheral tissues and transports it to the liver’s scavenger receptor BI (SR- BI), where SR-BI mediates the uptake of cholesteryl esters (CEs) from high-density lipoprotein for excretion via bile. In this study, we utilized AlbCreSR-BIfl/fl mice, a model with impaired RCT, to investigate the impact of RCT on sepsis. We found that AlbCreSR-BIfl/fl mice were significantly more susceptible to cecal ligation and puncture …

Nudcl2 Is Required For Cytokinesis By Stabilizing Rcc2 With Hsp90 At The Midbody, Xiaoyang Xu, Yuliang Huang, Feng Yang, Xiaoxia Sun, Rijin Lin, Jiaxing Feng, Mingyang Yang, Jiaqi Shao, Xiaoqi Liu, Tianhua Zhou, Shanshan Xie, Yuehong Yang

Markey Cancer Center Faculty Publications

Cytokinesis is required for faithful division of cytoplasmic components and duplicated nuclei into two daughter cells. Midbody, a protein-dense organelle that forms at the intercellular bridge, is indispensable for success- ful cytokinesis. However, the regulatory mechanism of cytokinesis at the midbody still remains elusive. Here, we unveil a critical role for NudC-like protein 2 (NudCL2), a co-chaperone of heat shock protein 90 (Hsp90), in cytokinesis regulation by stabilizing regulator of chromosome condensation 2 (RCC2) at the midbody in mam- malian cells. NudCL2 localizes at the midbody, and its downregulation results in cytokinesis failure, multinu- cleation, and midbody disorganization. Using iTRAQ-based …

Rnf20 Contributes To Epigenetic Immunosuppression Through Cdk9- Dependent Lsd1 Stabilization, Bo Dong, Xinzhao Wang, Xiang Song, Jianlin Wang, Xia Liu, Zhiyong Yu, Yongkun Zhou, Jiong Deng, Yadi Wu

Markey Cancer Center Faculty Publications

Cyclin- dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9- mediated phosphorylation. This CDK9- and RNF20- dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus, and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD- 1 in vivo …

Putting Biomonitors To Work: Native Moss As A Screening Tool For Solid Waste Incineration, Sarah Jovan, Eleonore Jacobson, Jason M. Unrine, Nasser Jalili‑Jahani, Bruce Mccune

Markey Cancer Center Faculty Publications

Solid waste incineration (SWI) can release numerous air pollutants although the geographic reach of emissions is not routinely monitored. While many studies use moss and lichens for biomonitoring trace elements, including around SWIs, few investigate the complex, multi-element footprint expected from SWI emissions. This study develops using native moss as a screening tool for SWI while also informing community concerns about an aging incinerator in rural Oregon, USA. Trained community volunteers helped collect 36 composite samples of epiphytic moss (Orthotrichum s.l.) along a 32-km transect from the SWI. We used ICP-MS to measure 40 elements in moss, including 14 rare …

Enhancing Translation: A Need To Leverage Complex Preclinical Models Of Addictive Drugs To Accelerate Substance Use Treatment Options, Christa Corley, Ashley Craig, Safiyah M. Sadek, Julie A. Marusich, Samar N. Chehimi, Ashley M. White, Lexi J. Holdiness, Benjamin C. Reiner, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Preclinical models of addictive drugs have been developed for decades to model aspects of the clinical experience in substance use disorders (SUDs). These include passive exposure as well as volitional intake models across addictive drugs and have been utilized to also measure withdrawal symptomatology and potential neuro- behavioral mechanisms underlying relapse to drug seeking or taking. There are a number of Food and Drug Administration (FDA)-approved medications for SUDs, however, many demonstrate low clinical efficacy as well as potential sex differences, and we also note gaps in the continuum of care for certain aspects of clinical ex- periences in individuals …

Biliverdin Reductase-A Integrates Insulin Signaling With Mitochondrial Metabolism Through Phosphorylation Of Gsk3Β, Chiara Lanzillotta, Antonella Tramutola, Simona Lanzillotta, Viviana Greco, Sara Pagnotta, Caterina Sanchini, Silvia Di Angelantonio, Elena Forte, Serena Rinaldo, Alessio Paone, Francesca Cutruzzolà, Flavia Agata Cimini, Ilaria Barchetta, Maria Gisella Cavallo, Andrea Urbani, D. Allan Butterfield, Fabio Di Domenico, Bindu D. Paul, Marzia Perluigi, Joao M.N. Duarte

Markey Cancer Center Faculty Publications

Brain insulin resistance links the failure of energy metabolism with cognitive decline in both type 2 Diabetes Mellitus (T2D) and Alzheimer’s disease (AD), although the molecular changes preceding overt brain insulin resistance remain unexplored. Abnormal biliverdin reductase-A (BVR-A) levels were observed in both T2D and AD and were associated with insulin resistance. Here, we demonstrate that reduced BVR-A levels alter insulin signaling and mitochondrial bioenergetics in the brain. Loss of BVR-A leads to IRS1 hyper-activation but dys- regulates Akt-GSK3β complex in response to insulin, hindering the accumulation of pGSK3βS9 into the mito- chondria. This event impairs oxidative phosphorylation and fosters …

Therapeutic Potential Of Berberine In Attenuating Cholestatic Liver Injury: Insights From A Psc Mouse Model, Yanyan Wang, Derrick Zhao, Lianyong Su, Yun-Ling Tai, Grayson W. Way, Jing Zeng, Qianhua Yan, Ying Xu, Xuan Wang, Emily C. Gurley, Xi-Qiao Zhou, Jinze Liu, Jinpeng Liu, Weidong Chen, Philip B. Hylemon, Huiping Zhou

Markey Cancer Center Faculty Publications

Background and aims

Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2 −/− mice) and eluci‑ date the underlying mechanisms.

Methods

Mdr2−/− mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical …

Mechanisms Of Γδ T Cell Accumulation In Visceral Adipose Tissue With Aging, Sujata Mukherjee, Maria E. C. Bruno, Jason Oakes, Gregory S. Hawk, Arnold Stromberg, Donald A. Cohen, Marlene E. Starr

Markey Cancer Center Faculty Publications

γδ T cells are resident in visceral adipose tissue (VAT) where they show an age- associated increase in numbers and contribute to local and systemic chronic inflammation. However, regulation of this population and mechanisms for the age-dependent accumulation are not known. In this study, we identified a progressive trend of γδ T cell accumulation in VAT over the lifespan in mice and explored physiological mechanisms contributing to accumulation. Using isochronic parabiotic pairs of wild-type (WT) and T cell receptor delta knockout (TCRδ KO) mice at young and old age, we confirmed that VAT γδ T cells are predominately a tissue-resident …

Pai-1 As A Critical Factor In The Resolution Of Sepsis And Acute Kidney Injury In Old Age, Maria E. C. Bruno, Sujata Mukherjee, Jamie L. Sturgill, Virgilius Cornea, Peng Yeh, Gregory S. Hawk, Hiroshi Saito, Marlene E. Starr

Markey Cancer Center Faculty Publications

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and levels positively correlate with disease severity and mortality. Our prior work demonstrated that PAI-1 in plasma is positively associated with acute kidney injury (AKI) in septic patients and mice. The objective of this study was to determine if PAI-1 is causally related to AKI and worse sepsis outcomes using a clinically-relevant and age-appropriate murine model of sepsis. Sepsis was induced by cecal slurry (CS)-injection to wild-type (WT, C57BL/6) and PAI-1 knockout (KO) mice at young (5–9 months) and old (18–22 months) age. Survival …

A Community-Engaged, Mixed-Methods Approach To Prioritizing Needs In A Statewide Assessment Of Community Cancer Needs, Jessica R. Thompson, Todd Burus, Caree R. Mcafee, Christine Stroebel, Madeline Brown, Keeghan Francis, Melinda Rogers, Jennifer Redmond Knight, Elaine Russell, Connie L. Sorrell, Elizabeth A. Westbrook, Pamela C. Hull

Markey Cancer Center Faculty Publications

Introduction Kentucky has the highest all-site cancer incidence and death rate in the US. In 2021, the University of Kentucky Markey Cancer Center convened a steering committee to conduct a statewide community cancer needs assessment (CNA). The goal of the final CNA phase was to gather community input on prioritizing Kentucky’s cancer-related needs and ways to address them. Methods In 2021, we recruited 162 people to participate in online concept mapping, a participatory mixed method, to explore connections and identify priority areas. Fifty-one community members and 111 organizational partners participated in survey-based activities to prioritize 80 items representing key CNA …