Life Sciences Commons^™

Predictive And Prognostic Biomarkers And Tumor Antigens For Targeted Therapy In Urothelial Carcinoma, Aditya Eturi, Amman Bhasin, Kevin Zarrabi, William Tester

Department of Medical Oncology Faculty Papers

Urothelial carcinoma (UC) is the fourth most prevalent cancer amongst males worldwide. While patients with non-muscle-invasive disease have a favorable prognosis, 25% of UC patients present with locally advanced disease which is associated with a 10-15% 5-year survival rate and poor overall prognosis. Muscle-invasive bladder cancer (MIBC) is associated with about 50% 5 year survival when treated by radical cystectomy or trimodality therapy; stage IV disease is associated with 10-15% 5 year survival. Current therapeutic modalities for MIBC include neoadjuvant chemotherapy, surgery and/or chemoradiation, although patients with relapsed or refractory disease have a poor prognosis. However, the rapid success of …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

Elucidating Neuroinflammation In Multiple Sclerosis By Network Analysis, Nora C. Welsh

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a heterogeneous disease, differing on many variables, including disease course, sex, and overall activity. Key characteristics of the disease encompass demyelination, axonal damage, neuronal loss, glial cell activation, and the infiltration of peripheral immune cells. Molecular proxies of these functions are secreted proteins, including cytokines and immunoglobulins, which, in the central nervous system (CNS), can be secreted into the cerebrospinal fluid (CSF). A detailed analysis of these secreted proteins can offer insights into the evolving immunological and neurodegenerative features as the disease progresses. To understand the dynamic biological processes involved in MS, I used network analysis …

The Dose-Response Effect Of Aerobic Exercise On Inflammation In Colon Cancer Survivors, Justin C. Brown, Stephanie L.E. Compton, Jeffrey A. Meyerhardt, Guillaume Spielmann, Shengping Yang

School of Medicine Faculty Publications

Background; Physical activity after surgical resection for colon cancer is associated with significantly longer disease-free survival. Inflammation is hypothesized to mediate the association between physical activity and disease-free survival in colon cancer. Methods; In this exploratory analysis of a randomized dose-response trial, 39 colon cancer survivors who completed standard therapy were stratified by cancer stage and randomized in a 1;1;1 ratio to one of three treatment groups for 24 weeks of usual-care control, 150 min/wk of moderate-intensity aerobic exercise (low-dose), or 300 min/wk of moderate-intensity aerobic exercise (high-dose). Inflammation outcomes included high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL6), and soluble tumor …

Development Of Synthetic Glycobiomarkers For The Follow-Up Of Chagas Disease Chemotherapy And Serological And Molecular Assays For Evaluation Of Trypanosoma Cruzi Infections In The U.S-Mexico Border, Igor L. Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan parasite Trypanosoma cruzi, affects 7-8 million people worldwide. Lately, the disease has been spread to nonendemic countries and regions, like the U.S. and Europe. The disease can be divided into two phases: the acute and chronic phases, which continue for years or even decades. There are two available drugs for CD treatment: benznidazole (BNZ) and nifurtimox (NFX). These drugs are highly effective in the acute phase but less efficient in the chronic stage. Other limitations of these drugs are their toxicity, leading to serious adverse events and premature treatment termination. Newer clinical trial …

Identification Of Circulating Proteins Associated With General Cognitive Function Among Middle-Aged And Older Adults, Adrienne Tin, Alison E Fohner, Qiong Yang, Jennifer A Brody, Gail Davies, Jie Yao, Dan Liu, Ilana Caro, Joni V Lindbohm, Michael R Duggan, Osorio Meirelles, Sarah E Harris, Valborg Gudmundsdottir, Adele M Taylor, Albert Henry, Alexa S Beiser, Ali Shojaie, Annabell Coors, Annette L Fitzpatrick, Claudia Langenberg, Claudia L Satizabal, Colleen M Sitlani, Eleanor Wheeler, Elliot M Tucker-Drob, Jan Bressler, Josef Coresh, Joshua C Bis, Julián Candia, Lori L Jennings, Maik Pietzner, Mark Lathrop, Oscar L Lopez, Paul Redmond, Robert E Gerszten, Stephen S Rich, Susan R Heckbert, Thomas R Austin, Timothy M Hughes, Toshiko Tanaka, Valur Emilsson, Ramachandran S Vasan, Xiuqing Guo, Yineng Zhu, Christophe Tzourio, Jerome I Rotter, Keenan A Walker, Luigi Ferrucci, Mika Kivimäki, Monique M B Breteler, Simon R Cox, Stephanie Debette, Thomas H Mosley, Vilmundur G Gudnason, Lenore J Launer, Bruce M Psaty, Sudha Seshadri, Myriam Fornage

Journal Articles

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Identification Of Early Diagnostic And Predictive Biomarkers Of Cisplatin-Induced Acute Kidney Injury Using Metabolomics, Yong Jin Lim

Electronic Thesis and Dissertation Repository

Cisplatin is an effective chemotherapeutic agent used for the treatment of a wide variety of solid tumors and hematologic cancers. Despite its effectiveness, cisplatin is associated with several toxic effects to non-cancerous tissues. Nephrotoxicity is the main dose-limiting toxicity in cisplatin therapy, manifesting as acute kidney injury (AKI) in approximately one-third of patients receiving cisplatin. AKI is defined as an abrupt decline in kidney function and is associated with several short- and long-term adverse outcomes, including chronic kidney disease, cardiovascular disease, and mortality. AKI is currently diagnosed by increased serum creatinine (SCr) concentrations. However, SCr is a marker of functional …

Mutational And Expression Analysis Of Fbxw7 Gene In Colorectal Cancer Patients Among North Indian Population, Laraib Uroog

Research Symposium

Background: Colorectal cancer is the third most common cancer worldwide with the incidence rate of 1.8 million (10.2%) (GOBOCON-2018). CRC is endemic to Kashmir Valley due to both, kangri use and non-veg food habit. The current study was designed to explore the possible correlation between that FBXW7 and colorectal cancer progression.

Methods: FBXW7 gene mutations and expression was analyzed in 173 colorectal carcinoma tissues along with the adjacent non-cancerous matched tissues using polymerase chain reaction-single stranded confirmation polymorphism assay. Gene expression analysis was conducted using qRT-PCR, western blot and IHC.

Results: In total, six mutations were found …

The Use Of Prognostic Markers To Predict Disease Progression And Clinical Outcome In Monoclonal Gammopathy Of Undetermined Significance, Smouldering Multiple Myeloma And Multiple Myeloma., Róisín C. Mcmonagle

International Undergraduate Journal of Health Sciences

Multiple Myeloma (MM) is an incurable plasma cell malignancy with a complex and incompletely understood molecular pathogenesis. Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smouldering Multiple Myeloma (SMM) precede MM, with variable risks and rates of disease progression. The continuing high relapse and death rate in MM cases has prompted research into more accurate prognostic markers to predict progression from MGUS and SMM to MM, as well as identify MM cases with aggressive disease, in order to begin early, targeted and effective therapeutic intervention. Many studies have focused on utilising current markers more effectively, including M-protein, serum-free light chain ratio, …

Construction And Performance Optimization Of Bioconjugated Nanosensors For Early Detection Of Breast Cancer And Pro-Inflammatory Diseases, Pooja Gaikwad

Dissertations, Theses, and Capstone Projects

In recent years, nanosensors have emerged as a tool with strong potential in medical diagnostics. Single-walled carbon nanotube (SWCNT) based optical nanosensors have notably garnered interest due to the unique characteristics of their near-infrared fluorescence emission, including tissue transparency, photostability, and various chiralities with discrete absorption and fluorescence emission bands. Additionally, the optoelectronic properties of SWCNT are sensitive to the surrounding environment, which makes them suitable for in vitro and in vivo biosensing. Single-stranded (ss) DNA-wrapped SWCNTs have been reported as optical nanosensors for cancers and metabolic diseases. Breast cancer and cardiovascular diseases are the most common causes of death …

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Biological Sciences: Faculty Publications

Background Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …

Comparative Polar And Lipid Plasma Metabolomics Differentiate Kshv Infection And Disease States, Sara R. Privatt, Camila Pereira Braga, Alicia Johnson, Salum J. Lidenge, Luke Berry, John R. Ngowi, Owen Ngalamika, Andrew G. Chapple, Julius Mwaiselage, Charles Wood, John T. West, Jiri Adamec

School of Biological Sciences: Faculty Publications

Background Kaposi sarcoma (KS) is a neoplastic disease etiologically associated with infection by the Kaposi sarcoma-associated herpesvirus (KSHV). KS manifests primarily as cutaneous lesions in individuals due to either age (classical KS), HIV infection (epidemic KS), or tissue rejection preventatives in transplantation (iatrogenic KS) but can also occur in individuals, predominantly in sub-Saharan Africa (SSA), lacking any obvious immune suppression (endemic KS). The high endemicity of KSHV and human immunodeficiency virus-1 (HIV) co-infection in Africa results in KS being one of the top 5 cancers there. As with most viral cancers, infection with KSHV alone is insufficient to induce tumorigenesis. …

Biomarkers In Borrelia Burgdorferi Infected Triple-Negative Breast Cancer Cells, Sambuddha Paul

Master's Theses

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Although some studies have attempted to identify new biomarkers and therapies, only a few have shown promise in clinical trials. In the context of cancer development, infectious agents rank as the third major risk factor, contributing to approximately 15-20% of cancer cases, according to the American Cancer Society. Hence, the identification of biomarkers associated with infection-originated cancer is crucial for enhancing cancer prevention, early detection, diagnosis, and treatment. Borrelia burgdorferi, the causative agent of Lyme disease, has been linked to TNBC …

Hsp70 And Hsp22 As Toxicity Bioreporters In Drosophila Melanogaster, Zakkary Hudson

Electronic Theses, Projects, and Dissertations

Of the over 80,000 chemicals used commercially in the United States, few have had sufficient safety and toxicological information collected. To further reduce animal usage, methods that will lessen reliance upon traditional animal toxicology testing and increase the usage of alternative, high throughput toxicology screening methods are being explored. One such method is the utilization of biomarkers and bioreporters in model organisms such as Drosophila melanogaster. The biomarkers, HSP22 and HSP70 have been successfully utilized in various studies involving Drosophila melanogaster bioreporter constructs to evaluate chemical toxicity. In this study, both an in vivo and in vitro HSP22 and …

Sources Of Volatile Aromatic Congeners In Whiskey, Thomas J. Kelly, Christine O'Connor, Kieran N. Kilcawley

Articles

Whiskey’s complex and diverse flavor stems from a range of reactions that create congeners that are primarily dependent upon the cereal source/mash bill and each stage of the process: malting, mashing, fermentation, distillation, and cask maturation. Therefore, in theory, the congener profile of a whiskey is a summation of its ingredients and the specific parameters of each stage of the manufacturing process. Congener profiles have been used as biomarkers for quality and authentication; however, to date, insufficient information has been published in relation to the extensive profiling of congeners associated with specific whiskey styles/types or the intra-and inter-variability within brands, …

Biomarker Identification For Breast Cancer Types Using Feature Selection And Explainable Ai Methods, David E. La Rosa Giraud

Honors Undergraduate Theses

This paper investigates the impact the LASSO, mRMR, SHAP, and Reinforcement Feature Selection techniques on random forest models for the breast cancer subtypes markers ER, HER2, PR, and TN as well as identifying a small subset of biomarkers that could potentially cause the disease and explain them using explainable AI techniques. This is important because in areas such as healthcare understanding why the model makes a specific decision is important it is a diagnostic of an individual which requires reliable AI. Another contribution is using feature selection methods to identify a small subset of biomarkers capable of predicting if a …

Revisiting The 2018 Corsica Oil Spill - A Preliminary Case Study Of Ecosystem Recovery From Pahs In Yelkouan Shearwater (Puffinus Yelkouan), Makenna Mahrer

CMC Senior Theses

Polycyclic aromatic hydrocarbons (PAHs) are a specific class of persistent organic pollutants (POPs) heavily associated with crude oil, and pose genotoxic and physiological threats to marine life when released into the aquatic environment during a petroleum spill. This study seeks to understand the residual impacts of the 2018 Corsica oil spill on Puffinus yelkouan (Yelkouan Shearwater), a seabird endemic to the Mediterranean basin, using the species as a bioindicator for contamination in the region. Though classified by the IUCN Red List as ‘vulnerable,’ this species remains grossly understudied in present monitoring literature. This study made use of blood samples and …

Detectable Ctdna At The Time Of Treatment Cessation Of Ipilimumab And Nivolumab For Toxicity Predicts Disease Progression In Advanced Melanoma Patients, Lydia Warburton, Anna Reid, Benhur Amanuel, Leslie Calapre, Michael Millward, Elin Gray

Research outputs 2022 to 2026

Background: Immune checkpoint inhibition (ICI) has led to unprecedented outcomes for melanoma patients but is associated with toxicity. ICI resumption after high grade irAEs poses a significant challenge in the clinical management of melanoma patients and there are no biomarkers that can help identify patients that might benefit from resuming treatment. This study aims to determine if circulating tumor DNA (ctDNA) levels at the time of treatment-limiting irAE could guide treatment decisions in this clinical context. Methods: This is a retrospective exploratory biomarker study from 34 patients treated with combination ICI for stage IV melanoma. Patients had a treatment-limiting toxicity …

Understanding SjöGren's Syndrome As A Systemic Autoimmune Disorder, Gaietchyne Chery

Legacy Theses & Dissertations (2009 - 2024)

Sjögren’s syndrome is an autoimmune condition characterized by a dysfunction in the lachrymal and salivary glands which results in dry eyes and dry mouth. Since its first description in 1892, the disease is one of the most common autoimmune diseases after lupus erythematosus and rheumatoid arthritis in the United States. Despite its high prevalence in the general population, Sjögren’s syndrome remains hard to diagnose due to the wide range of symptoms associated with the disease that is also shared by other conditions. Furthermore, the mechanisms behind the pathogenesis are not properly understood even though multiple factors have been proposed to …

Contrasting Particle Fluxes And Composition In A Submarine Canyon Affected By Natural Sediment Transport Events And Bottom Trawling, Sarah Paradis, Marta Arjona-Camas, Miguel Goñi, Albert Palanques, Pere Masqué, Pere Puig

Research outputs 2022 to 2026

Submarine canyons are important conduits of sediment and organic matter to deep-sea environments, mainly during high-energy natural events such as storms, river floods, or dense shelf water cascading, but also due to human activities such as bottom trawling. The contributions of natural and trawling-induced sediment and organic matter inputs into Palamós Canyon (NW Mediterranean) were assessed from three instrumented moorings deployed in the axis and northern flank of the canyon covering the trawling closure (February) and the trawling season (March-December) of 2017. During the trawling closure, large sediment fluxes with high contents of labile marine organic matter content were registered …

Integrated Dna Copy Number And Expression Profiling Identifies Igf1r As A Prognostic Biomarker In Pediatric Osteosarcoma., Aaron M Taylor, Jiayi M Sun, Alexander Yu, Horatiu Voicu, Jianhe Shen, Donald A Barkauskas, Timothy J Triche, Julie M Gastier-Foster, Tsz-Kwong Man, Ching C Lau

Faculty Research 2022

Osteosarcoma is a primary malignant bone tumor arising from bone-forming mesenchymal cells in children and adolescents. Despite efforts to understand the biology of the disease and identify novel therapeutics, the survival of osteosarcoma patients remains dismal. We have concurrently profiled the copy number and gene expression of 226 osteosarcoma samples as part of the Strategic Partnering to Evaluate Cancer Signatures (SPECS) initiative. Our results demonstrate the heterogeneous landscape of osteosarcoma in younger populations by showing the presence of genome-wide copy number abnormalities occurring both recurrently among samples and in a high frequency. Insulin growth factor receptor 1 (IGF1R) is a …

Integrative Analysis Of Clinical And Epigenetic Biomarkers Of Mortality, Tianxiao Huan, Steve Nguyen, Elena Colicino, Carolina Ochoa-Rosales, W David Hill, Jennifer A Brody, Mette Soerensen, Yan Zhang, Antoine Baldassari, Mohamed Ahmed Elhadad, Tanaka Toshiko, Yinan Zheng, Arce Domingo-Relloso, Dong Heon Lee, Jiantao Ma, Chen Yao, Chunyu Liu, Shih-Jen Hwang, Roby Joehanes, Myriam Fornage, Jan Bressler, Joyce B J Van Meurs, Birgit Debrabant, Jonas Mengel-From, Jacob Hjelmborg, Kaare Christensen, Pantel Vokonas, Joel Schwartz, Sina A Gahrib, Nona Sotoodehnia, Colleen M Sitlani, Sonja Kunze, Christian Gieger, Annette Peters, Melanie Waldenberger, Ian J Deary, Luigi Ferrucci, Yishu Qu, Philip Greenland, Donald M Lloyd-Jones, Lifang Hou, Stefania Bandinelli, Trudy Voortman, Brenner Hermann, Andrea Baccarelli, Eric Whitsel, James S Pankow, Daniel Levy

Journal Articles

DNA methylation (DNAm) has been reported to be associated with many diseases and with mortality. We hypothesized that the integration of DNAm with clinical risk factors would improve mortality prediction. We performed an epigenome-wide association study of whole blood DNAm in relation to mortality in 15 cohorts (n = 15,013). During a mean follow-up of 10 years, there were 4314 deaths from all causes including 1235 cardiovascular disease (CVD) deaths and 868 cancer deaths. Ancestry-stratified meta-analysis of all-cause mortality identified 163 CpGs in European ancestry (EA) and 17 in African ancestry (AA) participants at p < 1 × 10

Metagenome-Wide Associations And Metabolic Modeling To Predict The Biomarkers For Colorectal Cancer, Nagavardhini Avuthu

Theses & Dissertations

Colorectal cancer (CRC) is the most common malignancy and the second most common cause of cancer-related deaths in the world. It is a multifactorial disease mediated by genetic, environmental, and lifestyle factors. Over time, the accumulation of genetic and epigenetic changes results in the activation of oncogenes and deactivation of tumor suppressor genes in the colon and rectal region which finally leads to tumor development. The gut microbiome is the main factor linking the effects of diet and environmental factors to host metabolism. Several studies showed the dysbiosis of gut microbiota in CRC patients with an increased proportion of pathogenic …

Molecular And Behavioral Impacts Of Treated Wastewater Effluent On Fish, Peter Schumann

Theses and Dissertations

Currently, most studies that focus on the sublethal impacts of contaminants of emerging concern (CECs) such as pharmaceuticals utilize a single-compound approach, whereas these compounds always occur as complex mixtures in the environment. Wastewater treatment plants (WWTPs) are a major contributor to the formation of these mixtures as current treatment technologies inadequately remove many chemical pollutants. There is a paucity of knowledge on the neurological impacts due to exposure to complex CEC mixtures resulting from the discharge of treated WWTP effluent into aquatic environments. This knowledge gap leaves incomplete assessments of the hazards and risks from exposure to treated effluent …

Effect Of Basal Diet And Black Raspberry Supplementation On Gene Biomarkers Of "Leaky Gut" In A Mouse Model Of Colitis-Associated Colorectal Cancer, Eliza Catherine Stewart

Undergraduate Honors Capstone Projects

Colorectal cancer is currently the second leading cause of cancer death in the world. The risk of developing colorectal cancer increases significantly in individuals who suffer from colitis, which is inflammation of the colon lining, seen in Irritable Bowel Disease. The term “leaky gut” is often used to describe increased intestinal permeability and is closely related to colitis. Leaky gut is associated with dysbiosis of the gut microbiota, which can occur through diet. This dysbiosis leads to prolonged inflammation and affects genes that encode for proteins involved in the tight junctions between cells. Compromised intestinal integrity allows for translocation of …

Liquid Biopsies For Type 2 Diabetes Mellitus: Biomarkers For Disease Risk And Diagnosis, Stephanie Chidester

Dissertations

Background: Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in the United States. There is a critical need for earlier and more effective screening and diagnostic tools. Innovative liquid biopsy technologies may play a key role in meeting this need. Liquid biopsies are a non-invasive, adjunctive tool for determining diagnosis, prognosis, and therapeutic response. This dissertation focuses on two potential applications of liquid biopsy technologies to T2DM: (1) epigenome-wide association studies to identify epigenetic markers of risk for T2DM, and (2) extracellular vesicle (EV)-based biomarker studies to identify and detect markers associated with T2DM development and progression. Dissertation studies: …

Spatiotemporal Dynamics Of Clonal Selection And Diversification In Normal Endometrial Epithelium., Manako Yamaguchi, Hirofumi Nakaoka, Kazuaki Suda, Kosuke Yoshihara, Tatsuya Ishiguro, Nozomi Yachida, Kyota Saito, Haruka Ueda, Kentaro Sugino, Yutaro Mori, Kaoru Yamawaki, Ryo Tamura, Sundaramoorthy Revathidevi, Teiichi Motoyama, Kazuki Tainaka, Roel G W Verhaak, Ituro Inoue, Takayuki Enomoto

Faculty Research 2022

It has become evident that somatic mutations in cancer-associated genes accumulate in the normal endometrium, but spatiotemporal understanding of the evolution and expansion of mutant clones is limited. To elucidate the timing and mechanism of the clonal expansion of somatic mutations in cancer-associated genes in the normal endometrium, we sequence 1311 endometrial glands from 37 women. By collecting endometrial glands from different parts of the endometrium, we show that multiple glands with the same somatic mutations occupy substantial areas of the endometrium. We demonstrate that "rhizome structures", in which the basal glands run horizontally along the muscular layer and multiple …

An Artifact In Intracellular Cytokine Staining For Studying T Cell Responses And Its Alleviation., Zheng Gong, Qing Li, Jiayuan Shi, Guangwen Ren

Faculty Research 2022

Intracellular cytokine staining (ICS) is a widely employed ex vivo method for quantitative determination of the activation status of immune cells, most often applied to T cells. ICS test samples are commonly prepared from animal or human tissues as unpurified cell mixtures, and cell-specific cytokine signals are subsequently discriminated by gating strategies using flow cytometry. Here, we show that when ICS samples contain Ly6G⁺ neutrophils, neutrophils are ex vivo activated by an ICS reagent - phorbol myristate acetate (PMA) - which leads to hydrogen peroxide (H₂O₂) release and death of cytokine-expressing T cells. This artifact …

Examining The Effects Of Exercise-Induced, Physical Stress Overtraining On Stress Biomarkers In Adolescent, C57bl/6 Mice, Curtis Scotty Davis

Theses, Dissertations and Capstones

Exercise has long been established as a therapeutic modality to improve health and related physical fitness, sports performance, and injury/risk reduction in both adults and adolescents (Haff & Triplett, 2015; Kaminsky, 2010). Nonetheless, there is a lack of research investigating the negative effects of exercise overstress (i.e., overtraining syndrome) in these populations, particularly adolescents (Brenner & American Academy of Pediatrics Council on Sports Medicine and Fitness, 2007; Matos & Winsley, 2007). The objective of this study was to examine hormone biochemical markers, anthropometric markers, and behavioral traits, which are associated with overtraining syndrome, in adolescent C57BL/6 mice. A total of …

Antioxidant Biomarkers And Nutraceutical Therapeutics In Neurodegeneration And Neurotrauma, Lilia A. Koza

Electronic Theses and Dissertations

Mild traumatic brain injury (mTBI), yielding a Glascow Coma Scale of 13-15, is the most commonly occurring severity of TBI. Pathology from mTBI consists of blood brain barrier disruption, neuroinflammation, oxidative stress, excitotoxicity, mitochondrial dysfunction, protein aggregation, axonal degeneration, and resulting neuronal death. These processes deplete the body’s endogenous antioxidant system. We report a retrospective analysis of antioxidant blood biomarkers in patients with a history of mTBI from a local sports medicine clinic, Resilience Code. We found persistent sex-specific antioxidant depletions in mTBI patients associated with worsened symptomology.

Certain populations, such as athletes, are at high risk for repetitive mTBI …