Life Sciences Commons^™

Behavioral Insights Into Nociceptor Function: A Systematic Approach To Understanding Postsurgical And Neuropathic Pain Mechanisms In Rats, Max Odem

Dissertations & Theses (Open Access)

Postsurgical and neuropathic pain are each clinically common, and often associated with ongoing pain. Ongoing pain has been linked to ongoing activity (OA) in human C-fiber nociceptors. Preclinical studies using rodent neuropathic models have concentrated on allodynia driven by OA generated in non-nociceptive Aβ fibers, but little attention has been paid to postsurgical pain in sham controls or to C-fiber nociceptor OA promoting ongoing pain.

Operant assays that reveal negative motivational and cognitive aspects of voluntary pain-related behavior may be particularly sensitive to pain-related alterations. In the mechanical conflict (MC) test, rodents can freely choose to escape from a brightly …

The Role Of Non-Neuronal Acetylcholine In Urogenital Chlamydial Infection, Jessica R. Lockhart

Electronic Theses and Dissertations

Chlamydia trachomatiscauses a bacterial sexually transmitted infection, Chlamydia, that is often chronic and casues reproductive complications in women. We hypothesized that Chlamydia infection increases local acetylcholine (ACh) production, which regulates the host’s inflammatory response to the infection. Female mice infected with C. muridarumwere sacrificed at days 3, 9, 15, and 21 post-infection, genital tract tissues harvested, and immunohistochemistry performed to enumerate ACh-producing cells. Infection increased the number of ACh-producing cells in cervical tissue at days 3,15, and 21 post-infection (pi), uterine tissue at day 3 and 9 pi, and ovarian tissue day 3, 15, and 21 pi. These …

White Matter Inflammation And Executive Dysfunction: Implications For Alzheimer Disease And Vascular Cognitive Impairment, Alexander Levit

Electronic Thesis and Dissertation Repository

White matter integrity is crucial to healthy executive function, the cognitive domain that enables functional independence. However, in the ageing brain, white matter is highly vulnerable. White matter inflammation increases with age and Alzheimer disease (AD), which disrupts the normal function of white matter. This may contribute to executive dysfunction, but the relationship between white matter inflammation and executive function has not been directly evaluated in ageing nor AD. White matter is also particularly vulnerable to cerebrovascular disease, corresponding with the common presentation of executive dysfunction in vascular cognitive impairment (VCI). Thus, white matter may be an important substrate by …

Repair And Adaptation Of Aged Skeletal Muscle To Nonpathological Muscle Damage: The Influence Of Macrophage Polarization, Jacob R. Sorensen

Theses and Dissertations

The age-related loss of skeletal muscle mass and function is accompanied by a decline in regenerative capacity. The processes that facilitate healthy muscle repair are complex, involving several phases of degradation and rebuilding of muscle tissue and the surrounding microenvironment. Specifically, myogenic progenitor cells known as satellite cells are the most influential in repairing damaged muscle tissue. Following injury, satellite cells become activated and migrate, proliferate and fuse with mature skeletal muscle fibers to restore homeostasis to the tissue. However, satellite cells do not act in isolation, a robust inflammatory response is necessary to facilitate successful and rapid healing. Macrophages …

Neutrophil Extracellular Traps And Vascular Barrier Injury, Jamie E. Meegan

USF Tampa Graduate Theses and Dissertations

Sepsis is a life-threatening inflammatory condition with high morbidity and mortality rates. Though improvements to diagnosis and management of sepsis have been made, the complexity of the disease process and an incomplete understanding of its endpoint mechanisms have prevented major breakthroughs for early diagnosis and treatment. Representing a common endpoint in a number of inflammatory injuries including sepsis, endothelial barrier dysfunction causes fluid leakage and leukocyte infiltration that leads to tissue damage and multiple organ failure. Therefore, elucidating mechanisms of endothelial barrier regulation is needed to further develop targeted therapies in inflammatory disease.

Sepsis is characterized by a hyperinflammatory response …

Influences Of Antroquinonol And 4-Acetylantroquinonol B On Inflammatory Tumorigenesis In The Mcf-7 Breast Cancer Cell Line With Or Without Tnf-Α Stimulation, Ting-Chun Lin

Masters Theses

Breast cancer (BC) is one of the most common cancers among women worldwide that ~25% of new cancer cases diagnosed every year would be BC; moreover, ~15% of cancer deaths per year caused by BC makes it the leading cause of cancer death among women worldwide. To date, though the cause of a large proportion of BC are still unclear, recent studies have revealed that a supportive breast tissue microenvironment is critical for the development and progression of BC, especially the communication with immune cells within breast tissue. Therefore, breast inflammatory microenvironment is currently received a substantial attention in the …

Curcumin Inhibits The Ikk:Nf-Kappa B Pathway In Neural Fear Circuits, Miguel A. Briones

Dissertations, Theses, and Capstone Projects

The study of how the brain acquires fearful memories has attracted considerable experimental attention, due in part to the promise of discovering novel therapeutic approaches for psychiatric disorders that are characterized by unusually strong and persistent traumatic memories. In recent years, extensive research has focused on studying the neural and molecular mechanisms by which fear memories are acquired, stored, and retrieved in the brain. Once acquired, fear memories may be attenuated using one of 2 procedures: 1) fear extinction, which involves repeated presentation of the fear-arousing stimulus in the absence of an aversive consequence, or 2) interference with the reconsolidation …

The Role Of Membrane Excitability In Insulin Regulation, Christopher Howard Emfinger

Arts & Sciences Electronic Theses and Dissertations

In mammals, ATP-sensitive K+ (KATP) channels are essential regulators of insulin secretion from pancreatic islet [beta]-cells, illustrated by the finding that gain-of-function mutations in KATP channels (KATP-GOF) cause neonatal diabetes mellitus (NDM). However, variability in symptom severity and effectiveness of treatment is seen in NDM, even for those with the same mutation and in the same family. Short-term treatment of mice expressing KATP-GOF mutations in [beta]-cells (KATP-GOF mice) with the KATP blocker glibenclamide during disease onset results in two outcomes: one subset becomes severely diabetic (non-remitters), whereas the other subset remains below the glucose levels at which significant side effects …

Kdm6b Is Required For Self-Renewal Of Normal And Leukemic Mouse Stem Cells Under Proliferative Stress, Cates Mallaney

Arts & Sciences Electronic Theses and Dissertations

KDM6B (JMJD3) is one of two known epigenetic modifiers responsible for the removal of the repressive histone mark, histone-3 lysine-27 trimethylation (H3K27me3), and has been shown to play a role in development, differentiation, and inflammatory stress response. Unlike the other H3K27me3 demethylase, UTX (KDM6A), which is frequently mutated in hematopoietic malignancies, KDM6B is upregulated in a myriad of blood disorders. This suggests that it may have important functions in the pathogenesis of hematopoietic cancers. Here, we examined the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic …

Transcriptional Signatures Of Host Susceptibility In Urinary Tract Infections, Lu Yu

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTI) caused by uropathogenic Escherichia coli (UPEC) are common and highly recurrent. Two important non-behavioral risk factors for UTI in women are genetics and history of two or more episodes of previous UTI. However, specific mechanisms of how these two factors modulate host susceptibility to UTI remain unclear. Concordantly, inbred mice of various genotypes and with different infection histories exhibit different susceptibilities to acute and chronic bladder infection (cystitis), which recapitulates a range of clinical UTI outcomes observed in women. Early host-pathogen interactions have been shown to determine UTI outcomes in mouse models. Here, we used two …

The Effect Of Mechanical Load On Biomarkers Of Knee Joint Inflammation For Individuals Who Are Predisposed To Knee Cartilage Degeneration: An Exploratory Study, Alyssa Evans

Theses and Dissertations

Objective: Physical exercise decreases disability and pain associated with chronic articular cartilage degradation. However, understanding of the pathology is lacking. In this study, the levels of 17 biomarkers of inflammation and cartilage degradation were measured in synovial fluid (SF) before and after a 30-minute run in able-bodied and previously-injured individuals. Materials & Methods: Four able-bodied recreational runners (3 men and 1 woman: 24 ± 2 years, 68 ± 7 kg, and 173 ± 9 cm) and 4 recreational runners who had undergone a unilateral anterior cruciate ligament reconstruction (ACLr) (2 men and 2 women: 23 ± 1 years, 71 ± …

An Investigation Into Fatigue Management: Effects Of Two Different Loading Protocols On Markers Of Inflammation And The Endocrine Response, Jake Bernards

Electronic Theses and Dissertations

The purposes of this dissertation were to 1) determine the effectiveness of the neutrophillymphocyte ratio (NLR) as an athlete monitoring tool in resistance training and 2) determine if repetition maximum or relative intensity loading scheme is superior in managing fatigue through the hormonal, inflammatory, and performances response throughout a 10-week periodized resistance training program. Results from the dissertation give merit to continued research regarding the use of NLR as a monitoring tool to help determine the degree of recovery. Furthermore, results from this dissertation lead to questioning the effectiveness of using a repetition maximum (RM) loading scheme within a periodized …

An Evaluation Of Alzheimer's Disease-Related Pathology In Two Different Models Of Diabetes In Immune-Challenged Mice, Andrew Scott Murtishaw

UNLV Theses, Dissertations, Professional Papers, and Capstones

Obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome are related disorders with wide-ranging and devastating effects that can be observed throughout the body. One important and understudied organ of damage is the brain. Clinical and epidemiological studies have found that T2DM, and more specifically hyperinsulinemia, significantly increases the risk of cognitive decline and increases the likelihood of Alzheimer’s disease (AD) and other forms of dementia in the elderly. Insulin has slightly different functions in the peripheral body than in the central nervous system and the dysregulation of these functions may contribute to the onset and progression of late-life neurodegenerative …

The Role Of T Cells In Muscle Damage Protective Adaptation, Michael Roger Deyhle

Theses and Dissertations

Skeletal muscle is prone to damage from a range of stimuli. The muscle repair process that ensues is complex, involving several phases and requiring the participation of many different cell types. Among the cells involved are various immune cells including neutrophils, macrophages, monocytes, and eosinophils. More recently, T cells were added to this list of immune cells known to participate in effective muscle repair from traumatic injuries in mice. We recently published data showing that T cells also accumulate in human muscle following contraction-induced damage. These data suggested that T cells might be involved an adaptation known as the repeated …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Dissecting The Molecular Mechanism Of Early Tumor Dissemination In Non-Small Cell Lung Cancer, Xingtong Liu

Dissertations & Theses (Open Access)

Lung cancer is the most common cause of cancer related death in the United States and worldwide. It has been shown that 30%-55% of patients with early stages of non-small cell lung cancer (NSCLC) developed and died of recurrence after curative resection, suggesting that tumor cell dissemination occurred early in those patients before surgery. However, molecular evidence, underline mechanisms and risk factors for the NSCLC relapse remain largely unknown. Addressing these questions will be critical for the development of strategies to stratify the risk of recurrence and approaches to reduce these risks. My thesis focused on dissecting the molecular basis …

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …

Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai

Arts & Sciences Electronic Theses and Dissertations

Peripheral Treg cells (pTreg cells) maintain immune homeostasis at mucosal interfaces, where they can develop upon activation of naïve CD4+ T cells by bacteria antigen. However, the cellular and molecular requirements that govern their differentiation in inflamed and homeostatic contexts require further elucidation. To circumvent uncertainties in existing methods of distinguishing pTreg cells from thymic Treg cells (tTreg cells), we analyzed monoclonal cell populations of CT2 and CT6 transgenic (Tg) cells that develop into pTreg cells in response to different species of endogenously presented Helicobacter antigen. In our comprehensive assessment of multiple intestinal inflammatory models, including infections and physical injury, …

Biological Clocks, Inflammation, And Multiorgan Damage In Sickle Cell Disease, Morayo Adebiyi

Dissertations & Theses (Open Access)

Sickle cell disease (SCD) is a dangerous condition caused by a genetic mutation on the human beta-globin gene that contributes to erythrocyte sickling, the hallmark of the disease. Previous metabolomics studies have confirmed that elevated sphingosine kinase 1 (SphK1) mediates sphingosine-1-phosphate (S1P) production to promote erythrocyte sickling. S1P signals via five S1P receptors (S1PR) regulates several pathophysiological functions.

In the first chapter of this dissertation, I explored the role of S1PRs in SCD by utilizing pharmacologic and genetic tools. To determine the role of S1P-S1PRs signaling in SCD, I treated humanized Berkeley sickle mice (Berkeley HBS mice), with FTY720, a …

5-Lipoxygenase (5-Lox)-5-Lipoxygenase Activating Protein (Flap)-Nanodisc Complex: A Model For The 5-Lox-Flap Interaction, Erin Elizabeth Schexnaydre

LSU Doctoral Dissertations

Leukotrienes (LT) are lipid mediators of the inflammatory response that play important roles in diseases such as asthma and atherosclerosis. Leukotriene A4 (LTA₄) is synthesized from arachidonic acid (AA) by 5-lipoxygenase (5-LOX) with the help of 5-lipoxygenase activating protein (FLAP), a trimeric nuclear transmembrane protein. Exactly how 5-LOX and FLAP interact is not well understood, however FLAP is essential for the production of leukotrienes in vivo. I used nanodiscs (NDs), engineered membrane systems, as a tool to study the 5-LOX-FLAP interaction. FLAP was incorporated into NDs with a phospholipid composition to mimic of the nuclear membrane. Structural features …

Inflammation In The Pathogenesis Of Diabetic Retinopathy, Haoshen Shi

Wayne State University Dissertations

The general purpose of these studies is to investigate inflammation in diabetic retinopathy in an effort to identify key intervention points to develop as treatments. Firstly, we showed that the neuropeptide VIP displayed protective immunoregulatory effects on retinal endothelial cells cultured under high glucose conditions. This effect was carried out, in part through the VPAC2 receptor.

Next, we studied the β-adrenergic receptor agonist, Compound 49b, and its effect on the pro-resolving RvD1 pathway. Compound 49b was previously shown to suppress both inflammatory and apoptotic responses in DR. We demonstrated that Compound 49b rescued the high glucose-induced decrese in RvD1 and …

Lidocaine Attenuates An Induced Inflammatory Response, Stephanie Zack

Master's Theses

Inflammation is common to the pathogenesis of a variety of diseases. Therapeutics which can regulate and reduce damaging inflammation are therefore valuable in the treatment of inflammation and inflammatory diseases.

One commonly used analgesic, recently identified as limiting inflammation, is lidocaine. Additionally, alternative, less toxic therapeutics like the snake venom peptides, Zep 3 and Zep 4, are thought to have anti-inflammatory effects. Yet a well-defined mechanism or cellular target for lidocaine or Zep peptides' anti-inflammatory effects has not been proposed.

We aimed to determine whether lidocaine and Zep peptides reduce the release of the proinflammatory cytokine, IL-1β, from activated human …

Complexities Of Chronic Opioid Exposure, Maciej Gonek

Theses and Dissertations

Studies on repeated exposure to opioids have been carried out for decades yet the mechanisms for certain phenomena such as tolerance are still not fully understood. Furthermore, different medications, such as frequently prescribed benzodiazepines, or different disease states, such as HIV, have their own effects and interactions with chronic opioid exposure that are not fully understood. The overall objective of this dissertation was to investigate the complexities of chronic opioid exposure and how different disease states and medications may modulate the effects of chronic opioids. Our findings demonstrate that the administration of diazepam, at doses that are not antinociceptive or …

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Il-17 Drives Copper Uptake And Activation Of Growth Pathways In Colorectal Cancer Cells In A Steap4-Dependent Manner, Evan Martin

ETD Archive

Colorectal cancer is a disease characterized by abnormal, invasive cell growth beginning in the colon or rectum. The third most common type of cancer worldwide, approximately one million new cases of the disease are diagnosed across the globe annually, resulting in an estimated 700,000+ deaths. One major risk factor associated with development of colorectal cancer is the presence of chronic inflammation in the large intestine, also known as colitis. Inflammation is a complex immune response against harmful stimuli, characterized by symptoms including heat, redness, swelling and pain. One important molecular mediator of this process is interleukin 17 (IL-17), a pro-inflammatory …

Effects Of Endophyte-Infected Tall Fescue Seed And Bromocriptine On Endocrine And Immune Function In Horses, Jessica Marie Hanneman

Theses and Dissertations--Veterinary Science

Consumption of endophyte-infected (E+) grasses has long been associated with health problems in animals. In cattle E+ tall fescue consumption leads to fescue toxicosis, and in horses it leads reproductive problems. The health-related issues associated with endophyte consumption have been attributed to the effects caused by the ergot alkaloids produced by the fungus. These ergot alkaloids are considered D2-like receptor agonists, and 5-HT2 serotonin and α-adrenergic receptor partial agonists. Many studies in humans, swine, cattle, and horses have identified that ergopeptines cause a decrease in prolactin production due to their dopaminergic activities. Additionally, these molecules have been found to cause …

Effect Of Tart Cherry Concentrate On Pain, Inflammation, And Strength, Natasha Kirkbride

Graduate Research Theses & Dissertations

The purpose of this double-blinded, randomized control study was to assess the impact of tart cherry concentrate on pain, inflammation, and strength in resistance-trained males (n = 24). Specifically, it analyzed the impact of tart cherry supplementation following an eccentric exercise protocol without the use of NSAIDs. Participants received their supplementation of either tart cherry concentrate (TC) or the placebo (PL) to consume over 8 consecutive days. Participants supplemented twice daily with either the TC concentrate (one ounce of concentrate mixed with water) or the placebo. On day 5 of the study, participants completed an eccentric knee extension exercise with …

Impact Of Aerobic Exercise On Monocyte Subset Receptor Expression And Macrophage Polarization, Anson M. Blanks

Theses and Dissertations

Atherosclerotic cardiovascular disease (CVD) is hallmarked by inflammatory immune activation, particularly by the induction of a response by monocytes. Classical (CD14⁺⁺CD16^-) are anti-inflammatory mediators under homeostatic conditions, while intermediate (CD14⁺⁺CD16⁺) and non-classical (CD14^LowCD16⁺⁺) monocytes promote inflammation following activation. Monocyte activation and functionality is dependent upon receptor expression and ligand production by a variety of cells, including monocytes. Alterations in the expression of surface receptors often have a direct impact upon monocyte function, such as the increased pro-inflammatory cytokine production in response to activation that accompanies elevated CD14 expression …

Modulation Of Cytokine Signaling In Optic Nerve Regeneration In Xenopus Laevis, Rupa Priscilla Choudhary

Legacy Theses & Dissertations (2009 - 2024)

The axons of the optic nerve, like other central nervous system (CNS) axons, tend to lose their capacity to regenerate following an injury in adult amniotes, but these axons are able to regenerate throughout life in anamniotes. In mammals, optic axon regeneration is promoted by inhibiting the increased expression in retinal ganglion cells of a cytokine signaling molecule, Suppressor of Cytokine Signaling 3 (SOCS3), that accompanies injury. In animals capable of regeneration, SOCS3 mRNA expression also increases dramatically in retinal ganglion cells after optic nerve injury, but somehow this increase is insufficient to block regeneration. To gain insights into how …

The Interaction Between Ceramide-1-Phosphate And Group Iva Cytosolic Phospholipase A2 And Its Role In Wound Healing, Patrick Macknight

Theses and Dissertations

The sphingolipid, ceramide-1-phosphate (C1P), directly binds and activates Group IVA cytosolic phospholipase A₂ (cPLA₂a) to generate eicosanoids. Due to the role of eicosanoids in wound healing, we choose to use our novel genetic mouse model expressing cPLA₂a with an ablated C1P interaction site (KI) to examine the cPLA₂a/C1P interaction in wound healing. Wound closure rate was not affected, but wound maturation was dramatically enhanced by loss of the C1P/cPLA₂α interaction based on the following findings. Wounds in KI mice displayed: i) increased infiltration of dermal fibroblasts into the wound environment; ii …