Physiology Commons^™

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …

The Importance Of Translationally Evaluating Steroid Hormone Contributions To Substance Use, Erin E. Maher, Ashley Strzelecki, Jessica J. Weafer, Cassandra D. Gipson

Markey Cancer Center Faculty Publications

Clinically, women appear to be more susceptible to certain aspects of substance use disorders (SUDs). The steroid hormones 17β-estradiol (E2) and progesterone (Pg) have been linked to women-specific drug behaviors. Here, we review clinical and preclinical studies investigating how cycling ovarian hormones affect nicotine-, cocaine-, and opioid-related behaviors. We also highlight gaps in the literature regarding how synthetic steroid hormone use may influence drug-related behaviors. In addition, we explore how E2 and Pg are known to interact in brain reward pathways and provide evidence of how these interactions may influence drug-related behaviors. The synthesis of this review demonstrates the critical …

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …

Chronic Environmental Circadian Disruption Increases Atherosclerosis And Dyslipidemia In Female, But Not Male, Apolipoproteine-Deficient Mice, Jeffrey M. Chalfant, Deborah A. Howatt, Victoria B. Johnson, Lisa R. Tannock, Alan Daugherty, Julie S. Pendergast

Saha Cardiovascular Research Center Faculty Publications

Shift work chronically disrupts circadian rhythms and increases the risk of developing cardiovascular disease. However, the mechanisms linking shift work and cardiovascular disease are largely unknown. The goal of this study was to investigate the effects of chronically shifting the light-dark (LD) cycle, which models the disordered exposure to light that may occur during shift work, on atherosclerosis. Atherosclerosis is the progressive accumulation of lipid-filled lesions within the artery wall and is the leading cause of cardiovascular disease. We studied ApolipoproteinE-deficient (ApoE−/−) mice that are a well-established model of atherosclerosis. Male and female ApoE−/− mice were housed in control 12L:12D …

Prevention Of Doxorubicin-Induced Cardiotoxicity By A Coumestan Analogue, Psoralidin, Mujtaba H. Shah, Myia Aiges, Kota V. Ramana

Annual Research Symposium

Natural phenolic compound Psoralidin limits cardiotoxicity associated with Doxorubicin

Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei

Markey Cancer Center Faculty Publications

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …

Enhancing The Quality Of Life For Senior Citizens: A Facilitator’S Guidebook For Mindful Music And Movement, Shannon Sexton

Mindfulness Studies Theses

Music appreciation and enjoyment enhance well-being throughout the lifespan. The challenges and constraints that people experience as they age can lead to lack of access to music, decreased physical activity, and fewer avenues for creative expression. Group music and movement interventions created for older populations offer opportunities for social connection and improved quality of life. Mindful practices add further benefit when combined with these interventions. Current available programs are scarce and most often do not encompass mixed modalities. In addition, the benefits of these programs do not show long-term sustainability. The purpose of this thesis is to explore the effects …

Late Onset Sheehan Syndrome 23 Years After Post-Partum Hemorrhage, Igbayilola Dosunmu, Ali Tariq Alvi, Sarah Kaufman, Ayesha Malik

East Florida Division GME Research Day 2023

Please see supplemental content for full abstract with figures and references.

Sheehan syndrome is defined as ischemic necrosis of pituitary gland following massive postpartum hemorrhage leading to panhypopituitarism. It has an insidious course with multitude of presentations. The majority of cases remain undiagnosed for many years after the delivery with average time following postpartum hemorrhage to diagnosis of Sheehan syndrome is believed to be almost 13 years according to one study. Here, we present a unique case of late onset of Sheehan syndrome 23 years after the last childbirth which was complicated by hemorrhage. To our knowledge, this is the …

Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

The Effects Of Exercise Training On Glucose Homeostasis And Muscle Metabolism In Type 1 Diabetic Female Mice, Caitlin O'Neill, Erica J. Locke, Darren A. Sipf, Jack Thompson, Erin Drebushenko, Nate Berger, Brooke Segich, Stephen C. Kolwicz Jr.

Health Sciences Faculty Publications

Although exercise training is an important recommendation for the management of type 1 diabetes (T1D), most of the available research studies predominantly focus on male subjects. Given the importance of sex as a biological variable, additional studies are required to improve the knowledge gap regarding sex differences in T1D research. Therefore, the purpose of this study was to examine the role of exercise training in mediating changes in glucose homeostasis and skeletal muscle metabolism in T1D female mice. Female mice were injected with streptozotocin (STZ) to induce T1D. Two weeks after STZ injection, control (CON) and STZ mice were exercise …

The Role Of The Hypoxia-Inducible Factor 2 In Pancreatic Cancer: Mechanisms Of Tumor Immunosuppression And Intestinal Radioprotection, Carolina Garcia Garcia

Dissertations and Theses (Open Access)

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with dismal prognosis. The only curative option for patients is surgery, but over 80% of patients are not surgical candidates. Unfortunately, PDAC is resistant to the three remaining options. PDAC is characterized by a profoundly hypoxic and immunosuppressive stroma, which contributes to its therapeutic recalcitrance. Alpha-smooth muscle actin+ (αSMA+) cancer-associated fibroblasts (CAFs) are the most abundant stromal component, as well as mediators of stromal deposition. The hypoxia-inducible factors (HIF1 and HIF2) coordinate responses to hypoxia, yet, despite their known association to poor patient outcomes, their functions within the PDAC tumor microenvironment (TME) …

Renal Cell Carcinoma Of Pelvic Kidney With Atypical Nodal Metastasis: A Diagnostic Challenge, Roshan-E-Shahid Rana, Muhammad Hammad Ather

Section of Urology

Ectopic pelvic kidney is a known congenital anomaly; however, the presence of renal cell carcinoma (RCC) in an ectopic kidney is rare with the evidence available in the form of a few case reports only. In this case report, we present a case of metastatic RCC in the pelvic kidney which became a diagnostic challenge because of atypical contrast-enhanced computed tomographic (CT) characteristics and unusual pattern of lymph node involvement including cervical lymph node in the absence of visceral metastasis. Because of its unusual location and uncertain vascular anatomy, ectopic kidney poses a surgical challenge. Owing to the rarity of …

Role Of Lipid-Lowering Therapy In Peripheral Artery Disease, Agastya Deepak Belur, Aangi J. Shah, Salim S. Virani, Mounica Vorla, Dinesh K. Kalra

Office of the Provost

Atherosclerosis is a multifactorial, lipoprotein-driven condition that leads to plaque formation within the arterial tree, leading to subsequent arterial stenosis and thrombosis that accounts for a large burden of cardiovascular morbidity and mortality globally. Atherosclerosis of the lower extremities is called peripheral artery disease and is a major cause of loss in mobility, amputation, and critical limb ischemia. Peripheral artery disease is a common condition with a gamut of clinical manifestations that affects an estimated 10 million people in the United States of America and 200 million people worldwide. The role of apolipoprotein B-containing lipoproteins, such as LDL and remnant …

The Effects Of Vitamin D Supplementation On Athletic Performance And Injury Prevention, Amani Adeeb Abushamma

Journal of Sports Medicine and Allied Health Sciences: Official Journal of the Ohio Athletic Trainers Association

Vitamin D supplementation has numerous effects on athletic performance and plays a significant role in preventing an athlete’s risk of getting injuries. Vitamin D has an impact on numerous physiological functions such as: bone health, muscle function, inflammatory response, and immune function. An athlete’s bone and muscle health are essential for maximum performance and career success. A bone fracture due to vitamin D deficiency can delay an athlete’s training and ultimately inhibit obtaining a collegiate scholarship and/or contract. A cross sectional study found that more than half of athletic trainers did not view 25-hydroxyvitamin D(25[OH]) testing and vitamin D supplementation …

Diabetes-Related Outcomes Following Use Of Basal-Bolus Insulin Vs Premixed Insulin In A Va Population With Type 2 Diabetes: A Retrospective Chart Review., Ravisha Bai, Kavita Batra, Charmaine Yap, Kenneth Izuora

School of Medicine Faculty Presentations

No abstract provided.

Linking Spinal Cord Circuits With Upper Limb Sensorimotor Control In Adults With Cerebral Palsy, Saihari Dukkipati

Theses & Dissertations

Cerebral palsy (CP) is the most common neurological disorder originating in childhood, but most of the people living with CP are currently adults. While people with CP continue to get older, the amount of research focused on adults has been rather limited. The early childhood insults leading to CP are thought to originate in the brain, but the effects on the entire neuromuscular system across the lifespan have only recently started to be explored. Of note, recent neuroimaging evidence suggests that the cervical spinal cord structure is atypical in adults with CP. However, it is largely unclear how the neurophysiological …

Psychological Trauma Alters T-Lymphocyte Inflammation And Redox Through Sympathetic Mechanisms, Safwan K. Elkhatib

Theses & Dissertations

Posttraumatic stress disorder (PTSD) is a devastating psychiatric disorder characterized by distinctive symptom clusters, including intrusive memories (i.e., flashbacks), avoidance of related stimuli, affective changes, and hyperarousal. Strikingly, patients with PTSD face a significantly increased risk for a number of inflammation-driven pathologies, ranging from cardiovascular to autoimmune disease. Yet, the exact etiology of this increased risk remains unknown. The immune system is known to be strongly influenced by the sympathetic nervous system, and sympathetic overactivity is a hallmark of PTSD. Lymphoid organs, such as the spleen, are richly innervated by sympathetic nerve fibers which terminate near adaptive immune …

Hsp90 Inhibitors Modulate Sars-Cov-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation And Barrier Dysfunction, Ruben Manuel Luciano Colunga Biancatelli, Pavel Solopov, Betsy W. Gregory, Yara Khodour, John D. Catravas

Bioelectrics Publications

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused more than 5 million deaths worldwide. Multiple reports indicate that the endothelium is involved during SARS-Cov-2-related disease (COVID-19). Indeed, COVID-19 patients display increased thrombophilia with arterial and venous embolism and lung microcapillary thrombotic disease as major determinants of deaths. The pathophysiology of endothelial dysfunction in COVID-19 is not completely understood. We have investigated the role of subunit 1 of the SARS-CoV-2 spike protein (S1SP) in eliciting endothelial barrier dysfunction, characterized dose and time relationships, and tested the hypothesis that heat shock protein 90 (HSP90) inhibitors would prevent and repair such injury. S1SP …

Inflammatory Bowel Disease Causing Retroperitoneal Varicosity Mimicking A Renal Artery Aneurysm: A Novel Case Report And Literature Review, Areez Shafqat, Shameel Shafqat, Belal Nedal Sabbah, Abdullah Shaik, Wael Khalil Alfehaid, Syed Shafqat Ul Islam

Medical College Documents

A 17-year-old female presented to our hospital complaining of bloody diarrhea 4-6 times per day for the past month. She was a known case of inflammatory bowel disease noncompliant to her medications. Abdominal computed tomography revealed an unusually dilated mass in the retroperitoneum at L2 vertebral level connecting the lumbar and left renal veins. The renal artery was visualized separately, and a diagnosis of communicating vein varicosity was made. This lesion can be misleading on imaging, hence our aim to disseminate our findings to practicing radiologists. The differential diagnosis of these lesions include retroperitoneal lymphadenopathy, renal artery aneurysms, and testicular …

Comparison Of Effects Of Sleep Fragmentation On Pro-Inflammatory Cytokine Il-1Β Of Male And Female Adult Mice, Manzar Rzayeva

Mahurin Honors College Capstone Experience/Thesis Projects

Sleep plays an essential role throughout the body by affecting the physiological function and regulation of many systems. One of these systems that receives effects as a result of the adequacy of sleep is the immune system. Previous studies have demonstrated effects of sleep fragmentation upon the immune system; however, sexual differences of these effects have not been studied in depth. To analyze these variances amongst the genders, male and female adult mice were subjected to acute sleep fragmentation (SF) for 24 hours in an automated SF cage that includes a bar sweeping across the cage every two minutes. Meanwhile, …

Pulmonary Capillary Recruitment And Distention In Mammalian Lungs: Species Similarities, David Langleben, Benjamin D. Fox, Stylianos E. Orfanos, Michele Giovinazzo, John D. Catravas

Bioelectrics Publications

Pulmonary arterial pressure rises minimally during exercise. The pulmonary microcirculation accommodates increasing blood flow via recruitment of pulmonary capillaries and, at higher flows, by distention of already perfused capillaries. The flow transition range between recruitment and distention has not been studied or compared across mammalian species, including humans. We hypothesised that the range would be similar. Functional pulmonary capillary surface area (FCSA) can be estimated using validated metabolic techniques. We reviewed data from previous studies in three mammalian species (perfused rabbit lungs and dog lung lobes, and exercising humans) and generated blood flow-FCSA curves over a range of flows. We …

Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook

Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …

Late-Life Exercise Mitigates Skeletal Muscle Epigenetic Aging, Kevin A. Murach, Andrea L. Dimet-Wiley, Yuan Wen, Camille R. Brightwell, Christine M. Latham, Cory M. Dungan, Christopher S. Fry, Stanley J. Watowich

Center for Muscle Biology Faculty Publications

There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22–24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle …

Role Of Meibum And Tear Phospholipids In The Evaporative Water Loss Associated With Dry Eye., Samiyyah M. Sledge

Electronic Theses and Dissertations

It is generally believed that the tear film lipid surface film inhibits the rate of evaporation (Revap) of the underlying tear aqueous. It is also generally believed that changes in the composition of the tear film lipid layer is responsible for an increase in Revap in patients with dry eye. Both of these ideas have never been proven. The purpose of the current studies was to test these ideas. Revap was measured in vitro gravimetrically. Lipid spreading was measured using Raman spectroscopy and microscopy. The influence of the following surface films on the Revap of the sub phase of physiologically …

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 …

Editorial: Perturbations In Metabolic Cues: Implications For Adverse Cardiac Function Leading To Sudden Cardiac Death, Brian P. Delisle, Ademuyiwa S. Aromolaran

Physiology Faculty Publications

No abstract provided.

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.