Translational Medical Research Commons^™

Oncofetal Reprogramming: A New Frontier In Cancer Therapy Resistance, Anh Nguyen, Molly Lausten, Bruce M. Boman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Oncofetal reprogramming has recently emerged as a critical concept in translational cancer research, particularly for its role in driving therapeutic resistance across a variety of malignancies. This biological process refers to a pattern of gene expression that is restricted to embryogenesis, but becomes expressed again in a subpopulation of cancer cells. These genes are typically suppressed after embryogenesis, and their aberrant re-expression in tumors endows cancer cells with stem-like properties and enhanced adaptability. The goal of this review is the following: (i) comprehensively examine the multifaceted nature of oncofetal reprogramming; (ii) elucidate its underlying molecular mechanisms, including its regulators and …

Editorial: Advancing Musculoskeletal Health: Bridging Basic And Clinical Research On Biomechanical Properties Of Joints, Ligaments, Tendons, And Associated Structures, Xin Jin, Snehal S. Shetye, Mengcun Chen

Center for Translational Medicine Faculty Papers

No abstract provided.

Synergistic Anti-Tumor Activity Of Ciclopirox Olamine And Metformin In Triple-Negative Breast Cancer, Yakun Wu, Hui Lyu, Congcong Tan, Margaret E. Larsen, Shou Ching Tang, Shile Huang, Bolin Liu

School of Graduate Studies Faculty Publications

No abstract provided.

Volumetric Wear Analysis Of Polyethylene Orthopedic Liners Using Point Clouds, Gabriel Landi

Dartmouth College Master’s Theses

In vivo wear of ultra-high molecular weight polyethylene (UHMWPE) orthopedic bearings represents a major problem in shoulder and knee arthroplasty, with significant amounts of devices failing due to the complication itself, and even more due to associated reasons for retrieval, including aseptic loosening. However, quantification of UHMWPE wear has largely been limited to linear and in vitro volumetric analyses, obscuring the understanding of the amount of clinically relevant material loss. This study proposes new methods to measure articular, rim, and backside surfaces of retrieved shoulder and knee UHMWPE liners, centered around the coordinate measuring machine (CMM)-based collection of high density …

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

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, …

Synthesis And Characterization Of Glass-Ceramic Nanoparticles And Nanobubbles For Integration Into Bone Regenerative Biomaterials, Sun Latt

Honors Undergraduate Theses

Osteoporosis affects over 200 million individuals worldwide and is characterized by an imbalance between osteoclastic bone resorption and osteoblastic bone formation, leading to fragility fractures that significantly diminish quality of life. Current clinical bone cements, such as poly(methyl methacrylate), are limited by poor osseointegration, toxic monomers, and an inability to address the underlying pathophysiology of osteoporosis. This work presents the synthesis, characterization, and systematic in vitro evaluation of a sol-gel-derived, magnesium-incorporated glass-ceramic (GC) nanoparticle within the CaO-MgO-SiO₂ system for incorporation into a novel hydrogel bone cement and bioresorbable magnesium implants. XRD confirmed a biphasic amorphous-crystalline diopside composition, and TEM …

A Chicken Model For Non-Invasive Diagnosis Of Infant Developmental Dysplasia Of The Hip (Ddh) Using Acoustic Transmission Measurements, Aliza Shah

Honors Undergraduate Theses

Developmental dysplasia of the hip (DDH) is a condition characterized by abnormal development and stability of the hip joint. In a healthy infant, the femoral head (ball) fits securely within the acetabulum (socket of the pelvis), allowing for proper joint function. In DDH, the relationship is disrupted, ranging from mild acetabular dysplasia to partial (subluxation) or complete dislocation of the femoral head. This condition represents a range of structural abnormalities that develop during early growth. The integrity of the hip joint is essential for physical mobility, and disruption of this structure can lead to significant functional impairment. DDH may result …

Use Of Transcranial Magnetic Stimulation As An Assessment Of Corticospinal Excitability In Individuals With Persistent Postural Perceptual Dizziness, Elizabeth Cornforth

Theses and Dissertations

Persistent postural-perceptual dizziness (PPPD) is a common, disabling, chronic vestibular disorder whereby individuals experience symptoms of non-vertiginous dizziness, unsteadiness, and sway or rocking that are present most hours of the day, most days of the week. Individuals with PPPD have been noted to have an increased burden of dizziness and reduced quality of life compared to other dizziness diagnoses. The cause of PPPD is not well understood which can lead to years of diagnostic testing, failed therapies, and poor symptom management. It is important to understand PPPD pathophysiology so that optimal treatment interventions can be developed for this disorder to …

Oral Pathogens Reprogram Endothelial Barrier And Angiotensin-Converting Enzyme2/Endothelial Nitric Oxide Synthase-Nitric Oxide Signaling To Promote Blood Pressure Dysregulation, Ming-Shou Hsieh, Tung-Nien Hsu, Chin-Sheng Huang, Ting-Yi Renn, Kuang-Tai Kuo, Kuo-Yao Lin, Wei Jen Chang

Journal of Dental Sciences

Background/purpose: Although periodontal disease is associated with an increased risk of hypertension, the endothelial mechanisms linking oral inflammation to vascular dysfunction remain unclear. We investigated whether Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) can directly disturb endothelial homeostasis and whether macrophage–endothelial crosstalk further worsens endothelial injury.

Materials and methods: Human umbilical vein endothelial cells (HUVECs) were exposed to Pg-LPS alone or co-cultured (transwell system) with Pg-LPS-primed human monocytic cells -derived macrophages. Endothelial dysfunction was assessed through nitric oxide (NO) production, endothelial nitric oxide synthase (eNOS) phosphorylation, inflammatory and adhesion molecule expression, as well as junctional and cytoskeletal changes. Macrophage …

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 …