Cells Commons^™

Cell-Free Mitochondrial Dna (Mtdna) Triggers Vascular Dysfunction Via Toll-Like Receptor 9 (Tlr9)-Dependent Activation Of Inflammasomes, Mohin Amin

Senior Theses

Hypertension is the leading global risk factor for mortality and is closely associated with vascular inflammation and dysfunction. Damaged mitochondria release cell-free mitochondrial DNA (cf-mtDNA), which activates toll-like receptor 9 (TLR9). The binding of TLR9 to mtDNA activates the NLRP3 inflammasome pathway, promoting the release of pro-inflammatory cytokines via gasdermin D (GSDMD), therefore worsening inflammation. However, the mechanisms linking mitochondrial injury to inflammation-induced vascular dysfunction remain unclear. We hypothesize that cf-mtDNA triggers TLR9-dependent NLRP3 inflammasome activation contributing to vascular and endothelial dysfunction. To assess that, adult male C57BL/6 were exposed to 28 consecutive days of chronic unpredictable stress (CUS) or …

Evolving Solutions For Red Blood Cell Preservation, Ali Alkafaji, Charles A. Elder, Mohammad Zaidi, Kavin Parthiv, Michael A. Menze

The Cardinal Edge

In emergencies such as natural disasters, armed conflicts, or during outer space missions, the availability of transfusable blood can mean the difference between life and death. Red blood cells (RBCs) must be stored at +4 ± 2 °C and have a shelf life of just 42 days, which makes maintaining a stable blood supply during adverse conditions extraordinarily challenging. This challenge was especially apparent during the COVID-19 pandemic when hospitals faced severe blood shortages. Freeze-drying, or lyophilization, offers a promising avenue to extend the shelf life of RBCs for transfusion during crises. However, a significant hurdle in dry preservation is …

The Myopia Epidemic: Integrating Genetic, Environmental, And Epigenetic Pathways To Define A Critical Window For Intervention, Pranavika Balaji

Undergraduate Research Posters

Myopia, or nearsightedness, has increased rapidly worldwide and is now a major public health concern caused by both genetic and environmental factors. Current understanding shows that too much near work, limited time spent outdoors, and prolonged screen use contribute to abnormal eye growth in individuals who may already have a genetic predisposition. At the molecular level, epigenetic changes and shifts in DNA activity, often influenced by environmental conditions, affect the signaling pathways that regulate eye development and may help explain why myopia is increasingly common among children. This paper synthesizes recent environmental, genetic, and epigenetic research to explain how these …

Enhancing Cataract Surgery Outcomes: Optimal Use Of Pre- And Post-Operative Eye Drops, Keith Skolnick M.D., Anu Valiaveedu

Mako: NSU Undergraduate Student Journal

Many preoperative and postoperative cataract patients struggle with comprehending the use of prescription medication as directed. Language barriers and low health literacy levels are major factors contributing to improper use of prescriptions. To increase patients comprehension, the Fort Lauderdale Eye Institute employed an educational intervention consisting of a live presentation and an instructional video. Results found that 44% of patients were hesitant to ask questions to clinical staff, 32% felt overwhelmed, and nearly 70% lacked confidence in using their prescribed eye drops. Following the intervention, 91% of patients reported increased confidence in their medications, and most indicated that the video …

Exploring Hepatic Stellate Cell-Driven Fibrosis: Therapeutic Advances And Future Perspectives, Alka Singh, Ansab Akhtar, Prashant Shukla

School of Medicine Faculty Publications

BACKGROUND AND PURPOSE: Liver fibrosis, a progressive liver disease arising from viral or metabolic causes, poses a major global health challenge due to its potential progression to cirrhosis and hepatocellular carcinoma. Due to the complex aetiology and epidemiology of liver fibrosis, most therapies fail in the clinic, and very few drugs have been approved by the US FDA. APPROACH: This review highlights the pathophysiological features of liver fibrosis, with a focus on novel targets in hepatic stellate cells (HSCs), key players in the fibrogenesis process, to develop successful therapeutic approaches using both pharmacological agents and active targeting strategies. The review …

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Seeking Into Cell-Free Therapies For Bone-Affected Lysosomal Storage Disorders, Andrés Felipe Leal, Harry Pachajoa, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Lysosomal storage disorders (LSDs) constitute a group of monogenic systemic diseases resulting from deficiencies in specific lysosomal enzymes that cause the intralysosomal accumulation of non- or partially degraded substrates, leading to lysosomal dysfunction. In some cases of LSDs, the bone is more severely affected, thus producing skeletal manifestations in patients. Current therapies, such as enzyme replacement therapy (ERT) and gene therapy (GT), show limited efficacy in correcting skeletal abnormalities. Increasing evidence suggests that microenvironmental disturbances also contribute significantly to disease pathogenesis. Therefore, therapeutic strategies targeting lysosomal dysfunction and microenvironmental dysregulation are needed. Mesenchymal stem-cell-derived extracellular vesicles (MSC-EVs) are emerging as …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Anti-Inflammatory And Antioxidant Effects Of Sea Urchin Spine Extract, Dina Magdy El Gamal

The Undergraduate Research Journal

Diadema savignyi spine extract in an experimental setup using L929 cell line in vitro. The cell metabolic activity of L929 cells is tested through an MTT assay. The sea urchin spine extract is applied to the cells in two concentrations: 100 μg/ml (136% viability) and 200 μg/ml (95% viability). The bioactive components of the sea urchin spine are identified via GC-MS, and the antioxidant and anti-inflammatory activities are evaluated using catalase assay (CAT), glutathione (GSH), and nitric oxide (NO) tests. Results show that the GC-MS identified bioactive components including the anti-inflammatory and anti-irritant bisabolol oxide and the pro-inflammatory oleic acid. …

Proposing An Rna Interference (Rnai)-Based Treatment For Human Immunodeficiency Virus (Hiv) By Analyzing The Post-Transcriptional Gene Targeting Of Sars-Cov-2, Hepatitis C Virus, And A549 Lung Cancer Cells, Arjun Jagdeesh

Undergraduate Research Posters

Human Immunodeficiency Virus (HIV) is a retrovirus that infects CD4+ T cell lymphocytes in humans, leading to the development of Acquired Immunodeficiency Syndrome (AIDS) if left untreated. While current treatment methods, including antiretroviral combination treatments, effectively limit HIV replication, HIV can evade these treatments due to its high mutation rate. Long-term antiretroviral treatment can also be toxic to patients, meaning patients would benefit from a new mechanism of HIV treatment. RNA interference (RNAi) is an antiviral pathway found in mammals, plants, and insects that involves a small-interfering RNA that is incorporated into a protein complex called the RNA-induced Silencing Complex …

Expansion On The Use Of The Novel Compound, Elp-004, Using A Mycobacterium Tuberculosis Experimentation Model, Kendyl Marie Berry

Graduate Theses, Dissertations, and Problem Reports (ETD)

Osteoarticular tuberculosis (OAT) is a bone degenerative disease that results in bone erosion, joint effusion, joint swelling, and sometimes, nerve compression. OAT occurs from the hematogenous dissemination of Mycobacterium tuberculosis (Mtb) bacilli spreading from the primary site of infection to the bones and joints; the primary site of infection tends to be the lungs as pulmonary tuberculosis infections are the most common. OAT can occur as the result of an active or latent infection. Latent infections result in OAT when bacilli are able to escape granulomas. The incidence of OAT is not as high as pulmonary infections, making up about …

Therapies For Mitochondrial Disorders, Kayli Sousa Smyth, Anne Mulvihill

SURE Journal: Science Undergraduate Research Experience Journal

Mitochondria are cytoplasmic, double-membrane organelles that synthesise adenosine triphosphate (ATP). Mitochondria contain their own genome, mitochondrial DNA (mtDNA), which is maternally inherited from the oocyte. Mitochondrial proteins are encoded by either nuclear DNA (nDNA) or mtDNA, and both code for proteins forming the mitochondrial oxidative phosphorylation (OXPHOS) complexes of the respiratory chain. These complexes form a chain that allows the passage of electrons down the electron transport chain (ETC) through a proton motive force, creating ATP from adenosine diphosphate (ADP). This study aims to explore current and prospective therapies for mitochondrial disorders (MTDS). MTDS are clinical syndromes coupled with abnormalities …

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …

Mutational And Biophysical Robustness In A Prestabilized Monobody, Peter G. Chandler, Li Lynn Tan, Benjamin T. Porebski, James S. Green, Blake T. Riley, Sebastian S. Broendum, David E. Hoke, Robert J. Falconer, Trent P. Munro, Malcolm Buckle, Colin J. Jackson, Ashley M. Buckle

Advanced Science Research Center

The fibronectin type III (FN3) monobody domain is a promising non-antibody scaffold, which features a less complex architecture than an antibody while maintaining analogous binding loops. We previously developed FN3Con, a hyperstable monobody derivative with diagnostic and therapeutic potential. Prestabilization of the scaffold mitigates the stability–function trade-off commonly associated with evolving a protein domain toward biological activity. Here, we aimed to examine if the FN3Con monobody could take on antibody-like binding to therapeutic targets, while retaining its extreme stability. We targeted the first of the Adnectin derivative of monobodies to reach clinical trials, which was engineered by directed evolution for …

Effects Of Alternative Chemotherapeutic Agents On Thyroid Cancer Cell Line Ml-1, Husref Rizvanovic

Graduate Theses/Dissertations

Though differentiated thyroid carcinomas have decent prognosis when detected early, radioactive iodine (RAI) resistant and advanced thyroid cancers are still difficult to treat with existing therapies. Better therapeutic agents are needed. Studies have shown that aggressive thyroid cancers (ML-1) express the extracellular matrix protein, matrix metalloproteinase (MMP-2). MMP-2 has been linked to metastasis and aggressiveness of several cancers and has been shown to play a crucial role in tumor invasion. Chlorotoxin is a selective MMP-2 receptor agonist, and Saporin is a well-known ribosome-inactivating protein used for anti-cancer treatment; however, these two agents have never been studied when conjugated together. I …

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are currently …

Family Strategies To Support Siblings Of Pediatric Hematopoietic Stem Cell Transplant Patients., Taylor E. White, Kristopher A. Hendershot, Margie D. Dixon, Wendy Pelletier, Ann Haight, Kristin Stegenga, Melissa A. Alderfer, Lydia Cox, Jeffrey M. Switchenko, Pamela Hinds, Rebecca D. Pentz

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: To describe the strategies families report using to address the needs and concerns of siblings of children, adolescents, and young adults undergoing hematopoietic stem cell transplant (HSCT).

METHODS: A secondary semantic analysis was conducted of 86 qualitative interviews with family members of children, adolescents, and young adults undergoing HSCT at 4 HSCT centers and supplemented with a primary analysis of 38 additional targeted qualitative interviews (23 family members, 15 health care professionals) conducted at the primary center. Analyses focused on sibling issues and the strategies families use to address these issues.

RESULTS: The sibling issues identified included: (1) feeling …

Taurine's Effect On Cocaine Reward And Neurogenesis In The Adolescent Male Rat Brain., Avery E. Villa-Gonzalez

Dissertations and Theses

Adolescence is a developmentally critical transition from childhood to adulthood including both maturation of the body and the brain. Neuroplastic changes result in dynamic organization of the brain during adolescence, leaving them vulnerable to development of mental illness and drug-seeking behavior. According to the United Nations Office on Drugs and Crime, the psychostimulant cocaine is the second most popular illicit drug in the world. Cocaine, amongst having many detrimental effects, has shown to also decrease hippocampal neurogenesis, resulting in decreased neuroplasticity and cognitive dysfunction. Previous students in our laboratory have shown that treatment of adult male rats with the essential …

Stem Cells As A Cure For Amyotrophic Lateral Sclerosis, Chaya K. Hirsch

The Science Journal of the Lander College of Arts and Sciences

Amyotrophic Lateral Sclerosis (ALS) is a fatal motor neuron disease which affects approximately 30,000 Americans at any given time (alsa.org, 2010). The etiology of this terminal disease unfortunately remains an unsolved mystery and has therefore severely limited the ability to find a cure. The use of stem cells to regenerate neurons has been vastly studied and have produced very promising results. However, its practicality as a cure or treatment for neurodegenerative diseases, such as ALS, is greatly compromised. Three different therapies involving stem cells were examined, Embryonic Stem Cells (ESC), induced pluripotent stem cells, (iPSC) and direct reprogramming of adult …

Cardiac Tissue Regeneration - The Use Of Stem Cells, Chavy Friedlander

The Science Journal of the Lander College of Arts and Sciences

The following is the introduction to the article: Cardiovascular disease is the leading cause of illness and fatality. Diseases such as coronary artery disease, myocardial infarction and subsequent congestive heart failure pose a serious problem to much of the population in the Unites States and all over the world. The heart’s compromised function that results from the above conditions is so influential as the heart has little capacity to repair its lost tissue; once the cardiac myocytes are destroyed its effects are amplified by a drastic decrease in cardiac function. Until recently with the advent of stem cell technology, researchers …