Biomedical Commons^™

The Anti-Angiogenic Effects Of Sparstolonin B, Henry Rhodes Bateman

Theses and Dissertations

Sparstolonin B (SsnB) is a novel bioreactive compound isolated from Sparganium stoloniferum, an herb historically used in Traditional Chinese Medicine as an anti-tumor agent. SsnB has demonstrated anti-inflammatory properties, inhibiting Toll-like receptor mediated inflammation in isolated macrophages and in mice. Angiogenesis, the process of new capillary formation from existing blood vessels, is dysregulated in many pathological disorders, including atherosclerosis, diabetic retinopathy, and tumor growth. The goal of the project was to investigate the anti-angiogenic effects of SsnB.

The first part of the project utilized in vitro functional assays to study how SsnB affected endothelial cells. SsnB inhibited endothelial cell tube …

Development Of Proteomic Characterization And Speciation Techniques Utilizing Tryptic Peptides With Maldi-Tof Ms And Lc-Esi Ms-Ms, Jennifer Marie Kooken

Theses and Dissertations

The characterization of microbes which can be opportunists and pathogens (e.g., methicillin resistant Staphylococcus aureus (MRSA)) is important in understanding and potentially treating diseases caused by various bacterial species. Common genera found in the human skin micro-biome include Micrococcus and Staphylococcus, but there only a limited number of tests to differentiate these genera and/or species. My research reflects methods development from distinguishing one closely related genera from another and then expanded to species identification. Tryptic peptides were analyzed by MALDI TOF MS and the mass profiles compared with those of a reference strain in both genus and species identification. Aconitate …

Linking Obesity To Colorectal Cancer: Recent Insights Into Plausible Biological Mechanisms, Catherine Guffey

Theses and Dissertations

Obesity has emerged as a leading environmental risk factor for the development of CRC. However, the mechanisms underlying this relationship have not yet been fully explained. Recent literature has focused on 1) inflammatory processes, 2) adipokines, and 3) estrogen. Obesity-enhanced inflammation is largely orchestrated by increases in adipose tissue macrophages leading to the secretion of TNF-alpha, MCP-1, and IL-6, all of which are linked to CRC. Adiponectin is decreased with obesity and has been reported to be negatively associated with CRC, while leptin, which is increased, is positively associated with the disease. Estrogen has been shown to influence CRC, although …

Investigation Of Start Domain Proteins In Human Luteinized Cells And Cos-1 Cells, Bo Shi

Theses and Dissertations

After the luteinizing hormone surge of the menstrual cycle, the ovarian follicular granulosa and theca cells terminally differentiate to form the luteal cells of the corpus luteum. During this process known as luteinization, granulosa cells begin to synthesize large quantities of progesterone, a hormone essential for pregnancy. The rate limiting step for the de novo synthesis of pregnenolone (the precursor to progesterone) is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process mediated by STARD1. STARD1 contains a C-terminal lipid binding domain holding one molecule of cholesterol, and an N-terminal domain targeting STARD1 to the …

Osteon-Mimetic Nanocomposite Materials For Bone Regeneration, Ozan Karaman

Theses and Dissertations

The limitations of large bone defect regeneration has brought the focus of Bone Tissue Engineering research on fabricating three-dimensional bone-mimetic grafts that could enhance osteogenesis and vascularization. Osteons composed of apatite-deposited aligned collagen nanofiber layers are the fundamental building blocks of cortical bone. In natural cortical bone, mineralization is mediated by extracellular matrix (ECM) proteins with amino acid sequences rich in glutamic acid. This dissertation is focused on the establishment of a novel biomimetic approach to engineer scaffolds for healing large bone defects.

In the first part, we investigated the effect of calcium phosphate (CaP) deposition on aligned surface-modified nanofibers …

Characterizing Hypoxia And Its Behavioral Effects In 3-Dimensional Cell Aggregates, Matthew Lorincz Skiles

Theses and Dissertations

Cell transplantation can be considered a regenerative therapy, an intervention which attempts to replace or restore the function of compromised tissue by harnessing innate properties of cells that cannot be replicated artificially. For such therapies to succeed, it will be necessary to understand and closely match the physiological conditions that govern cell behaviors in vivo. One important factor is low oxygen tension, termed hypoxia, which is often overlooked in vitro. Because oxygen insufficiency can lead to cell death, hypoxia has traditionally been viewed as a negative condition. However, hypoxia can also serve as a potent regulator of crucial cell behaviors …

Mass Spectrometry And Tandem Mass Spectrometry Characterization Of Protein Patterns, Protein Markers And Whole Proteomes For Pathogenic Bacteria, Jennifer Intelicato-Young

Theses and Dissertations

There have been many recent reviews published on MALDI-TOF MS (matrix assisted laser desorption/ionization time-of-flight) MS (mass spectrometry) for identification of bacteria particularly with relevance to clinical microbiology. MALDI-TOF MS is now a mature technique for bacterial identification with great promise. The purpose of this review is to put into perspective MALDI-TOF MS and other widely used mass spectrometry methods for characterization of proteins. MALDI-TOF MS is used for rapid determination of a mass pattern of proteins for bacterial characterization; these proteins

are generally not identified. Alternatively, after gel separation, MALDI TOF-TOF MSMS (tandem mass spectrometry) or on-line LC-ESI MS-MS …

Role Of Microrna-155 In A Mouse Model Of Colon Cancer., Claire Mitchell Midyette

Theses and Dissertations

Colorectal cancer remains the third most common malignancy and the fourth most common cause of cancer mortality worldwide. Dysregulated miRNA levels are associated with several types of malignancies and may serve as important biomarkers and/or therapeutic targets in colorectal cancer. We examined the role of miRNA-155 on tumorigenesis and associated symptoms using a well-characterized mouse model of colorectal cancer. C57BL/6 wild-type mice and miRNA-155-/- mice (n=7-13 group) were given a single injection of AOM (10mg/Kg) followed by 3 cycles of DSS (2% in the water for 1 week followed by 2 weeks of plain water). A C57BL/6 wild-type group that …

Effect Of Physiological Oxygen Levels On Osteogenic Differentiation Of Adipose-Derived Stem Cells, Suchit Sahai

Theses and Dissertations

Regenerative medicine presents exciting strategies for healing critical-size bone defects through the implantation of cells and biocompatible scaffolds. Most in vitro studies are performed in atmospheric oxygen conditions (~20%), which do not accurately mimic the CSD microenvironment. Due to damage to the vasculature at CSDs, oxygen levels fall into the hypoxic range (<5%), which can impact viability, proliferation and differentiation of the cells employed for bone regeneration. Understanding the cellular responses to hypoxia has grown primarily from study of individual molecular factors. The master regulator of adaptive responses to low oxygen availability is the nuclear factor, hypoxia-inducible factor-1. HIF-1 is a heterodimeric protein, stable below 6% O2 condition in the nucleus and has been shown to play a role in angiogenic-osteogenic coupling. We have developed a responsive, fluorescent, hypoxia detection system and determined whether HIF activity can be tracked in both 2-D and 3-D cultures. Adipose-derived stem cells (ASCs) were selected due to their broad utilization in tissue engineering strategies and characterized the influence of HIF signaling on its phenotype. The work done identified that of hypoxia impaired osteogenic differentiation of ASCs in both 2-D and 3-D cultures and HIF-1 did not mediate this effect. Ischemic preconditioning (IPC) strategy and varied protocols used represents a clinically feasible manipulation of cell preparation to help the survival of implanted ASCs and accelerate osteogenic differentiation at physiological oxygen levels.

Resveratrol Attenuates The Development Of Trans-Aortic Constriction (Tac) Induced Heart Failure In Mice, Prakash Kumar Gupta

Theses and Dissertations

Heart failure (HF) still remains the leading cause of morbidity and mortality and imposes severe global affliction and enormous cost on the healthcare system. Although current pharmacological therapies have shown to slow down the progression of HF, but seems to have reached their limits in improving overall patient prognosis. Thus, an immediate call for novel alternate therapies are needed which act independently as well as in conjunction with current treatment modality. Studies were performed in the well-established transverse aortic constriction (TAC) model of chronic pressure overload (PO) in mice. In the first series of studies, Male C57BL6 mice (26-28 g) …

High Fat Diet Induced Obesity In A Mouse Model For Colorectal Cancer, Kennerly Clinton Patrick

Theses and Dissertations

Obesity is widely correlated with the incidence of colorectal cancer (CRC). The exact mechanisms that link obesity to CRC risk have not yet been fully established, and only a limited number of animal models are available to study pathways involved in obesity-related colon carcinogenesis. The objective of this study was to determine the influence of HFD-induced obesity on AOM/DSS-mediated colorectal tumorigenesis, tumor proliferation, and symptom severity. Male C57BL/6 mice were fed a novel high fat diet, designed to mimic the standard American diet (12 % saturated fat & 28 % unsaturated fat), at 4 weeks of age until 16 weeks …

The Effect Of Αct-1 Peptide On Bone Marrow Stromal Cells Following Injury, Adam Clay Vandergriff

Theses and Dissertations

Connexin43 (Cx43) is a component of gap junctions and is involved in intercel- lular signaling following injury to tissues. The carboxyl terminus of Cx43 binds to the PDZ2 domain of ZO-1 in order to form gap junction plaques and connect to the cytoskeleton. A biomimetic peptide known as αCT-1, replicating the last 9 amino acids found in the carboxyl terminus of CX43, has been shown to improve wound healing by preferentially binding to the PDZ2 domain of ZO-1. A possible mecha- nism for its action is through the Epithelial-Mesenchymal Transformation (EMT). Scratch assays were performed on rat bone marrow stromal …

Microencapsulation Of A Connexin-43 Mimetic Peptide As A Novel Wound Healing Agent In An Ocular Injury Model, Keith Brian Moore

Theses and Dissertations

Corneal transplantation and related surgical procedures are areas of tissue replacement which have seen promising advances. Currently, cornea transplants are one of the most common surgical procedures, with approximately 40,000 occurring each year in the United States. Still, problems exist with a 20% rejection rate, post surgical infections, and the need for a constant supply of donors. The ability to safely and quickly heal and regenerate corneal epithelia fills an area of advancement in regenerative medicine, with implications reaching beyond the scope of vision therapies toward healing of a wide range of tissues and wounds. In vivo corneal wounds were …

Impact Of Physical Activity In The Prevention Of Colorectal Cancer, Sarah Ashley Barnes

Theses and Dissertations

This review evaluates the current understanding of research on the impact of physical activity in the prevention of colorectal cancer. Current biological mechanisms implicated in physical activity and colorectal cancer risk reduction are blood glucose regulation, insulin sensitivity, leptin and adiponectin profiles, inflammation as well as secreted protein acidic and rich in cysteine (SPARC), an exercise induced myokine. Recent literature indicates that 30-60 minutes of moderate to vigorous activity a day is effective against colorectal cancer development, and there is convincing evidence of aerobic exercise as differently beneficial in recruiting mechanisms identified as preventative against colorectal cancer. This article provides …