Anatomy Commons^™

Intersections Of Art And Medicine, Lina Adwer

EMET Projects

No abstract provided.

Endothelin-1 In The Failing Fontan: Pathobiology, Precision Therapeutics, And Future Trial Design, Iman Maiza

Department of Pediatrics Faculty Publications

The Fontan circulation, devised as definitive palliation for single-ventricle congenital heart disease, imposes systemic venous hypertension, loss of pulmonary arterial pulsatility, and restricted preload reserve. These hemodynamic trade-offs progressively injure the pulmonary vasculature, liver, and lymphatic system, producing late morbidities including elevated pulmonary vascular resistance, Fontan-associated liver disease (FALD), protein-losing enteropathy, and arrhythmias. Endothelin-1 (ET-1), a potent vasoconstrictor and profibrotic mediator, plausibly unifies these complications. Mechanistic studies demonstrate ET-1 upregulation in failed Fontan lungs, activating PLC–Ca²⁺, RhoA/ROCK, and MAPK/ERK cascades to drive vasoconstriction and remodeling. In cirrhotic livers, ET-1 localizes to stellate cells, promoting contraction and fibrogenesis, mechanisms biologically relevant …

Neurotensin Drives Theca Cell Migration During Ovulation In Primates, Jessica S. Miller, Megan A. G. Sage, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Theca cells are a critical steroidogenic cell type of the ovarian follicle and corpus luteum. The ovulatory luteinizing hormone (LH) surge (or human chorionic gonadotropin (hCG)) stimulates theca cell relocation from the stroma surrounding the dominant follicle to full integration into the developing corpus luteum. Luteinizing hormone/human chorionic gonadotropin also stimulates granulosa cells to produce local mediators of ovulation, including the peptide neurotensin (NTS). To determine if hCG-stimulated NTS regulates theca cell relocation within the ovulatory follicle, vehicle or an NTS receptor antagonist was injected into a macaque dominant follicle, and ovaries were removed 48 h after hCG administration. Additional …

P38 Mapk Is Involved In Epigenetic Regulation Of Fibrotic Genes In Replication Induced Senescence In Lung Fibroblasts, Shan Zhu, Jennifer Q. Zhou, Kan Wang, Ming-Lei Guo, Yan Sanders

Department of Biomedical and Translational Sciences Faculty Publications

Fibroblast activation is essential for tissue repair following injury; however, prolonged activation drives pathological fibrosis. Idiopathic pulmonary fibrosis (IPF), a progressive and age-associated lung disease, is characterized by aberrant fibroblast activation, with increasing evidence implicating senescent and near-senescent fibroblasts in its pathogenesis. However, the underlying mechanisms remain poorly defined. In this study, we investigated whether histone modification is involved in TGF-β1 treated lung fibroblasts and contributes to the fibrotic phenotype. Human IMR90 lung fibroblasts at low and high population doubling levels (LPDL and HPDL), as well as primary IPF fibroblasts, were used in this study. In response to TGF-β1, both …

Dysregulation Of Alternative Splicing Patterns In The Ovaries Of Reproductively Aged Mice, Adnan T. Alsamaraee, Vanessa L. Correll, Julius O. Nyalwidhe, Pavla Brachova, Nehemiah S. Alvarez

Department of Biomedical and Translational Sciences Faculty Publications

Female reproductive aging is characterized by progressive deterioration of ovarian function, yet the molecular mechanisms driving these changes remain incompletely understood. Here, we used long-read direct RNA-sequencing to map transcript isoform changes in mouse ovaries across reproductive age. Comparing young and aged mice after controlled gonadotropin stimulation, we identified widespread alternative splicing changes, including shifts in exon usage, splice site selection, and transcript boundaries. Aged ovaries exhibited increased isoform diversity, favoring distal start and end sites, and a significant rise in exon skipping and intron retention events. Many of these age-biased splicing events altered open reading frames, introduced premature stop …

Brief Pulses Of High-Level Fluid Shear Stress Enhance Metastatic Potential And Rapidly Alter The Metabolism Of Cancer Cells, Amanda N. Pope, Devon L. Moose, Guy O. Hudson, Hank R. Weresh, Marion R. Dykstra, Aabha Y. Joshi, Patrick Breheny, Eric B. Taylor, Michael D. Henry

Department of Biomedical and Translational Sciences Faculty Publications

Circulating tumor cells (CTCs) face challenges to their survival, including mechanical and oxidative stresses that are different from cancer cells in solid primary and metastatic tumors. The impact of adaptations to the fluid microenvironment of the circulation on the outcome of the metastatic cascade is not well understood. Here, we find that cancer cells exposed to brief pulses of high-level fluid shear stress (FSS) exhibit enhanced invasiveness and anchorage-independent proliferation in vitro and enhanced metastatic colonization/tumor formation in vivo. Cancer cells exposed to FSS rapidly alter their metabolism in a manner that promotes survival by providing energy for cytoskeletal remodeling …

Localization And Functional Exploration Of Leiomodin-2'S C-Terminal Binding Sites, Mason D. Summers, Madison Little, Robert P. Young, Brayan Osegueda, Alan Palma Guillen, Garry E. Smith Jr., John R. Cart, Vitold E. Galkin, Alla S. Kostyukova

Department of Biomedical and Translational Sciences Faculty Publications

Striated muscle contraction occurs through interactions between overlapping myosin-based thick and actin-based thin filaments within the sarcomere. For effective contraction to occur, the length of the thin filament must be maintained to ensure sufficient overlap with the thick filament. The proteins leiomodin and tropomodulin compete for binding at the pointed ends of thin filaments to regulate their length, using their homologous N-terminal actin and tropomyosin binding sites. Leiomodin also contains a region called the C-terminal extension, absent in tropomodulin. In this region, the cardiac isoform (leiomodin-2) contains additional actin-binding sites that enable it to bind along the sides of thin …

Stat4-Dependent Regulation Of Neuroinflammation In Atherosclerosis, Natalie Stahr, Alina K. Moriarty, Shelby D. Ma, W. Coles Keeter, Woong-Ki Kim, Larry D. Sanford, Elena V. Galkina

Department of Biomedical and Translational Sciences Faculty Publications

Atherosclerosis is linked to an increased risk of cognitive decline, with chronic inflammation being a common feature of both pathologies. IL-12 activates STAT4 to regulate myeloid cell functions, and blockade of this pathway alleviates cognitive impairment in Alzheimer's models. However, the mechanisms connecting vascular pathology to neuroinflammation remain unclear. Here, we examine whether STAT4 functions as a common mediator of neuroinflammation in atherosclerosis. We demonstrate that LysM^Cre-specific STAT4 deficiency ameliorates deficits in long-term memory in low-density lipoprotein-deficient (Ldlr^-/-) mice fed a high-fat diet (HFD-C). STAT4 deficiency moderately reduces Ser199-phosphorylated Tau burden. Atherosclerosis alters brain immune …

Yk-4-250 Mitigates Gastrointestinal Radiation Syndrome And Promotes Overall Survival Following Partial Body Radiation Injury, Vidya P. Kumar, Yali Kong, Kan Wang, Asa R. Britton-Jenkins, Stanton Dulan, Landon L. Moore, Debra Saunders, Randal May, Rheal Towner, Sanchita P. Ghosh, Courtney W. Houchen, Milton L. Brown

Department of Biomedical and Translational Sciences Faculty Publications

Acute gastrointestinal radiation syndrome (GI-ARS) is a significant health threat following high-dose ionizing radiation (IR) exposure, leading to severe morbidity and mortality. The syndrome is characterized by gastrointestinal tissue damage caused by angiotensin II (Ang II) and reactive oxygen species (ROS), resulting in impaired GI function, systemic bacteremia, multi-organ failure, and eventual death. Dysregulation of the renin-angiotensin system (RAS) via Ang II exacerbates ROS production through activation of the Angiotensin II type 1 receptor (AT1R). This underscores the need for agents capable of both scavenging ROS and inhibiting AT1R activity. To address this, we developed YK-4-250, a Tempol-conjugated angiotensin receptor …

Lipid And Foam Cell Accumulation As Novel Pathological Features Of Benign Prostatic Hyperplasia, Dita Julianingsih, Samara V. Silver, Thaissa Horne, Kasun Gunawardena, Savannah Ward, Alicia Malewska, Douglas Strand, Julius Nyalwidhe, Ilya Sobol, Petra Popovics

Department of Biomedical and Translational Sciences Faculty Publications

Background

Benign prostatic hyperplasia (BPH) encompasses a heterogeneous set of pathological processes that instigate lower urinary tract symptoms (LUTS). Using a mouse model of steroid hormone imbalance-induced lower urinary tract dysfunction, we identified luminal lipid-laden foamy macrophages, although their presence and contribution to human pathology have not yet been established. The objective of this study was to determine whether luminal macrophages are associated with human BPH and to assess how lipid accumulation relates to underlying pathological features and clinical parameters.

Methods

Whole-mount tissue sections from simple prostatectomy specimens and prostates from healthy donors were used to evaluate the association of …

The Effects Of Abused Drugs On Ferroptosis Pathways: Potential Therapeutic Targets For Substance Use Disorders, Tamara Bouchard, Brooke Russell, Liam Liyang Guo, Tina Nguyen, Yan Cheng, Yan Y. Sanders, Ming-Lei Guo

Department of Biomedical and Translational Sciences Faculty Publications

Substance use disorders (SUDs) remain major public health concerns worldwide, particularly in developed countries. SUDs are characterized by persistent neuroinflammation and synaptic dysfunction in the brain. Despite decades of extensive investigation, the detailed mechanisms underlying SUDs remain elusive. Ferroptosis is a highly regulated cell death process deeply affected by iron metabolism, lipid peroxidation, reactive oxygen species (ROS) production, and antioxidant systems. It has been implicated in multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, and ischemic stroke. Recently, emerging evidence has highlighted the role of ferroptosis in drug-induced pathological changes. Various types of abused substances including alcohol, cocaine, …

Microfluidic Encapsulation Of Sorafenib-Loaded Zif-8 Nanoparticles In Ph-Responsive Alginate Microparticles For Oral Chemotherapy Of Hepatocellular Carcinoma, Mojdeh Mirshafiei, Zahra Mahmoudi, Mehdi Mehrpouya, Mahdi Mahmoudi, Masoud Rezaeian, Mona Navaei-Nigjeh, Zahra Katoli, Lobat Tayebi

Electrical & Computer Engineering Faculty Publications

Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related mortality. Sorafenib is the current first-line oral therapy; however, its therapeutic efficacy is limited by poor aqueous solubility, low bioavailability, and gastrointestinal instability. This study aimed to develop a pH-responsive nano-in-microparticle delivery system using a single-step droplet-based microfluidic process to protect sorafenib in the gastric environment and achieve controlled release for enhanced oral chemotherapy. Sorafenib-loaded ZIF-8 nanoparticles (SZ NPs) were synthesized and characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FTIR) spectroscopy, Energy-dispersive X-ray (EDX) spectroscopy, and X-ray diffraction (XRD), exhibiting a mean diameter of about 72 nm and …

Depemokimab: A Twice Yearly Anti-Il 5 Biologic For Chronic Rhinosinusitis With Nasal Polyps (Crswnp) - A Narrative Review, Marn Joon Park, Joseph K. Han, Kent K. Lam

Department of Otolaryngology (ENT) Faculty Publications

Depemokimab is a monoclonal antibody that targets interleukin-5 with enhanced binding affinity and an extended terminal elimination half‑life of 6-8 weeks. The unique pharmacodynamic features of depemokimab enable sustained suppression of type 2 inflammation with twice‑yearly subcutaneous dosing. This narrative review provides details of depemokimab's molecular profile, pharmacokinetics, and pharmacodynamics and results regarding the clinical efficacy and safety of depemokimab from recently published Phase 3 clinical trials for the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). In 528 severe adult CRSwNP patients (ANCHOR‑1/‑2 trials), depemokimab achieved Δ total endoscopic nasal polyp score by -0.70 (p <  .001) and Δ nasal obstruction verbal response scale by -0.24 (p = .003) at week 52, compared to placebo. Twice‑yearly 100 mg depemokimab provides durable eosinophil suppression and with a safety profile comparable to placebo in Phase 3 trials for CRSwNP. Future work should refine biomarkers and assess comparative cost‑effectiveness and long‑term adherence, safety, and effectiveness.

Comparative Spatial Biology: A Cross-Species Analysis Of Canine Oral Cancers As Models For Human Disease, Ram Pradhyumnan

Honors Undergraduate Theses

Oral squamous cell carcinoma (OSCC), one of the most common malignancies of the oral cavity, remains a clinically challenging disease due to its aggressive behavior, late-stage diagnosis, and limited improvements in therapeutic outcomes over recent decades. A significant barrier to progress in OSCC research and treatment is the lack of suitable preclinical models that recapitulate the complexity and natural progression of the disease. Most current models—including cell lines, xenografts, and genetically engineered mice—fail to capture key features such as the spatial organization of tumor epithelium, interactions with an intact immune system, and the stepwise evolution from normal mucosa to invasive …

Magnesium-Based Metal Matrix Nanocomposite Implants And Nanobubble-Based Delivery Systems: Integrated Strategies For Bone Loss Treatment With Cytocompatibility Evaluation, Lucas José Martinho Bizuti

Honors Undergraduate Theses

This thesis intends to investigate the development of different multimodal therapeutic strategies for combating bone loss. Most specifically, this paper will emphasize the utilization of Magnesium-Based Metal Matrix Nanocomposite Implants (MMNC) and Nanobubble-Based Delivery Systems as options for future treatment focus. The effects of biodegradable magnesium implants were evaluated for cytotoxicity and cytocompatibility via Hematoxylin and Eosin, and Masson’s Trichrome staining, as well as radiological images. The Nanobubble-Based Delivery System is being developed and optimized as a delivery system to target osteoclast activity. This paper focused on optimizing experimental parameters, which include Rotational speeds for nanobubble stimulation under microgravity conditions …

Relationships Between Quadriceps Neuromuscular Function And Time From Surgery Following Acl Reconstruction Are Sex-Specific, Tatiana Restrepo

Honors Undergraduate Theses

Anterior cruciate ligament reconstruction (ACLR) is associated with persistent quadriceps dysfunction, including muscular weakness and altered spinal and cortical excitability. While recovery has been widely studied, most investigations focus on isolated domains and fixed postoperative time points. Emerging evidence suggests females often experience slower or less complete quadriceps recovery compared to males, yet the time-dependent nature of these sex-specific outcomes remains unclear. The purpose of this study is to examine whether relationships between time since ACLR and quadriceps neuromuscular outcomes differ by sex across muscular, spinal, and cortical domains. Adults aged 18–35 with a history of primary, unilateral ACLR were …

Microarray Analysis Of Human Abdominal Aortic Aneurysm With Emphasis On Cardiovascular Genes Revealed Differentially Expressed Genes, Song Lu, Li Ping Li, John V. White, Xiaoying Zhang, Ifeyinwa Nwaneshiudu, Adaobi Nwaneshiudu, Nectaria Ntaoula, John Gaughan, Dimitri S. Monos, Wan-Lu Lin, Charalambos C. Solomides, Emilia L. Oleszak, Chris D. Platsoucas

Biological Sciences Faculty Publications

Background/Aim: We examined gene expression profiles in abdominal aortic aneurysm (AAA) lesions vs. normal aortas by cDNA microarray and real-time quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR).

Materials and Methods: Phosphorus (32P)-labeled cDNA from AAA specimens (mean AAA size 6.65 cm) and normal aortas were hybridized with a 588-gene microarray primarily of the cardiovascular system. The results were validated by qRT-PCR.

Results: A total of 35 out of the 588 genes were differentially expressed, with either log2 ratio of AAAs/controls ≥1 (upregulated; 20 genes) or ≤−1 (downregulated; 15 genes) in AAA lesions vs. normal aorta, and 25 of these were significantly …

Balloon Aortic Valvuloplasty As A Bridge Therapy In Acute Valve Syndrome: A Narrative Review Of Evidence Gaps And Future Directions, Omar Saleh, Omar Jafar, Nicholas Valle, Shirish Yasa, Saleh Mostafa, Raymond L. Benza, Deepak R. Talreja, Benjamin D. Peterson, Matthew R. Summers

Department of Medicine Faculty Publications

Acute valve syndrome (AVS) represents a high-acuity, decompensated presentation of severe aortic stenosis (AS), often manifesting as acute heart failure, cardiogenic shock, or cardiac arrest. Transcatheter aortic valve replacement (TAVR) remains the only durable therapy for severe AS in patients with prohibitive surgical risk, yet AVS patients may be too unstable for standard preprocedural planning. Balloon aortic valvuloplasty (BAV) has re-emerged as a bridge strategy that can provide rapid hemodynamic stabilization and permit subsequent valve replacement. Registry analyses report lower mortality in emergent TAVR compared with BAV, but these comparisons are confounded by procedural indication and unmatched AS severity. Smaller …

Nanosecond Pulsed Electric Fields For Extracellular Vesicle Engineering: From Electro-Exocytosis To Cargo Modulation, Art Neal, Teresa Graham, Mohamadmahdi Samandari, Arash Ghorbannia, Anca Dobrian, Stephen J. Beebe, Ruben M. L. Colunga-Biancatelli

Bioelectrics Publications

Extracellular vesicles (EVs), including small extracellular vesicles (sEVs) and medium/large extracellular vesicles (MVs), have emerged as promising therapeutic vectors and diagnostic biomarkers across various branches of biomedicine. However, the clinical translation of EV-based technologies remains constrained by persistent challenges in manufacturing: insufficient yield from primary cell sources, limited control over cargo composition, and the absence of scalable, standardized production platforms. Nanosecond pulsed electric fields (nsPEF) represent an emerging biophysical approach that can address several of these limitations. Unlike conventional electroporation, which targets the plasma membrane using microsecond-to-millisecond pulses, nsPEF delivers ultrashort (1–300 ns), high-amplitude (10–300 kV/cm) pulses that penetrate intracellularly …

Comparative Analysis Of Left Ventricular Sympathetic Axons In Shr And Wky Rats, Parker R. Tyson

Honors Undergraduate Theses

Hypertension is a leading cause of cardiovascular morbidity and mortality and is strongly associated with dysregulation of the sympathetic nervous system, which plays a central role in controlling heart rate, vascular tone, and blood pressure. Although increased sympathetic activity has been widely documented in hypertensive disease, the precise structural organization of sympathetic innervation within the hypertensive heart remains incompletely characterized. This study investigates whether chronic hypertension is associated with structural remodeling of sympathetic axons in the left ventricle by comparing autonomic innervation patterns between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Hearts were collected following transcardial perfusion …