Laboratory and Basic Science Research Commons^™

Characterizing Hypoxia, Neutrophil Persistence And Revascularization In The Murine Db/Db Model Of Type Ii Diabetic Impaired Skin Healing, Michael R. Grynyshyn

Electronic Thesis and Dissertation Repository

Impaired skin healing represents a significant clinical burden. In the diabetic, inflammatory aberrations, hypoxia and insufficient angiogenesis all result in negative wound healing outcomes - repeated infections, poor perfusion and ultimately amputation. Previous research has reported comparable levels of neutrophils in closed wounds up to 4-12 weeks old. Our study interest was in investigating the dynamics of hypoxia resolution, neutrophil persistence and angiogenic response in the db/db model. Contrary to our hypothesis, we observed significantly higher hypoxic load in the wild types at days 3 and 7. Additionally, we observed significantly elevated neutrophil numbers at day 7 db/db wound bed …

Erk Required For Lipopolysaccharide-Induced Tlr4 Internalization In Macrophages, Sara M. Reyna, Phoebe Fang-Mei Chang

Research Symposium

Background: Insulin resistance is associated with low circulating levels of lipopolysaccharide (LPS). Binding of LPS to Toll like receptor 4 (TLR4) leads to the internalization and trafficking of TLR4 resulting in activation of downstream signaling pathways. TLR4 internalization in macrophages leads to the activation of pro-inflammatory signaling pathways and production of factors linked to the development of insulin resistance. The extracellular signal-regulated kinase 1 and 2 (ERK1 and 2) are activated downstream of TLR4 and are associated with insulin resistance. We hypothesized that ERK1 and ERK2 regulate TLR4 internalization in macrophages when exposed to LPS.

Methods: We examined whether inhibition …

Immunomodulatory Effects Of Resolvin D2 In A Model Of Infection, Prem Yugandhar Kadiyam Sundarasivarao

Graduate School of Biomedical Sciences Theses and Dissertations

Dysregulated hyperinflammatory host immune response to underlying bacterial infections is a characteristic of sepsis. In sepsis, bacteria often trigger abnormal hyperinflammatory responses which can cause multiple organ failure and if sustained can lead to an immunosuppressive phase where the host is susceptible to secondary infections caused by opportunistic bacteria like Pseudomonas aeruginosa (P. aeruginosa). In our studies, we used a 2-hit model of cecal ligation and puncture (CLP) followed by P. aeruginosa secondary lung infection to investigate cellular and molecular mechanisms in the beneficial action of resolvin D2 (RvD2). Resolvins of the D-series are a group of fatty acids known …

Cul3 Negatively Regulates Nlrp12-Mediated Inhibition Of The Canonical Nf-Κb Signaling Pathway, Inyeong Lee

MSU Graduate Theses

Nod-like receptor family pyrin domain-containing protein 12 (NLRP12) is mainly known for its inhibitory function on NF-κB signaling in innate immune cells, and more recently, for its ability to regulate chemokine signaling and ubiquitination of the immune receptor RIG-I. Through a yeast 2-hybrid screen, the Lupfer lab previously discovered that NLRP12 interacts with other ubiquitin-associated proteins including Cullin 3 (CUL3) and RING finger protein 2 (RNF2). This research was conducted to mainly investigate the interaction between NLRP12 and CUL3 in human cells and examine the role in regulating NF-κB signaling. Previously, co-immunoprecipitation, followed by western blot analysis, and confocal microscopy …

Modulation Of Glucose Homeostasis By Nucleotide P2y2 Receptor And Biological Sex, Hailee Anne Marino

MSU Graduate Theses

Recent insights into the pathological role of Nucleotide P2Y₂ receptor suggest P2Y₂R involvement in high fat diet-induced obesity and potentiates insulin resistance. However, these recent insights do not demonstrate how P2Y₂R modulates glucose homeostasis under physiological conditions. Further, it remains unknown how sex biological factors influence P2Y₂R receptor signaling in the regulation of glucose homeostasis. The research objective for the present study is to elucidate the novel roles of P2Y₂ in fasting blood glucose and glucose tolerance (basal insulin sensitivity) under resting conditions in males and females. We expected that under physiological …

Multi-Generational Effects Of ∆9-Tetrahydrocannabinol Exposure On Gene Expression In Liver Tissue, Kayla Lovitt

Honors Theses

Cannabis is the most commonly used, cultivated, and trafficked illicit drug worldwide. Increased availability and acceptance of cannabis and cannabinoid-containing products provide the necessity for understanding how these substances influence aging. In this study, zebrafish (Danio rerio) were exposed to concentrations of Δ⁹-tetrahydrocannabinol (THC) (0.08, 0.4, 2 µM) during embryonic-larval development, the effects on aging were measured 30 months later and in the offspring of the exposed fish (F1 generation. We observed results indicating a biphasic and hormetic effect. Treatment with the lowest concentration of THC significantly increased egg production, while higher concentrations resulted in impaired …

The Impact Of E-Cigarette Smoking On Pulmonary Responses To Maximal Exercise, Chelsea N. Robinson

Masters Theses, 2020-current

Electronic cigarettes (e-cigarettes) have emerged as popular alternatives to smoking conventional tobacco, particularly in a younger demographic. However, there is emerging and conflicting evidence on the magnitude of airway damage with e-cigarette usage. While evaluating airway health can be challenging, using a stimulus such as exercise may be used to elucidate the effects of e-cigarettes on the pulmonary system. Purpose: To determine the impact of an acute maximal exercise on changes in pulmonary function (i.e. bronchodilation and bronchoconstriction) in young adult exclusive e-cigarette smokers (S) compared to nonsmokers (NS). We hypothesized that S will have lower post-exercise bronchodilation after an …

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Chronic Low Intensity Continuous And Interval Training Prevent Heart Failure-Related Coronary Artery Stiffness, An Ouyang

Theses and Dissertations--Kinesiology and Health Promotion

Heart failure (HF) induced by aortic pressure over-load is associated with increased coronary artery stiffness. Perivascular adipose tissue (PVAT) and advanced glycation end products (AGE) both promote arterial stiffness. However, the mechanisms by which coronary PVAT promotes arterial stiffness and the efficacy of exercise to prevent coronary stiffness are unknown. The present study hypothesized both chronic continuous and interval exercise training would prevent coronary artery stiffness associated with inhibition of PVAT secreted AGE. Yucatan mininature swine were divided into four groups: control-sedentary (CON), aortic-banded sedentary heart failure (HF), aortic-banded HF continuous exercise trained (HF+CONT), and aortic-banded HF interval exercise trained …

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 …

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 …

Lps-Induced Inos Mrna And The Pro-Apoptotic Signaling Pathway In Leukocytes Of Fit And Unfit Males, Tiffany M. Zuniga

Theses and Dissertations

Overexpression of the enzyme iNOS induces apoptotic cellular death by increasing indices of pro-inflammation and oxidative stress. Aerobic physical activity has been known to have anti- inflammatory benefits and reduce oxidative stress. Purpose: Therefore, this study aimed to examine the impact of aerobic fitness on LPS-induced iNOS mRNA expression and the relationship of this expression with indices of oxidative stress, pro-inflammation and apoptosis in isolated leukocytes. Methods: Whole blood samples from aerobically fit and unfit males were stimulated with and without LPS. Thereafter, iNOS mRNA expression and MDA, TNF-α and p53 concentrations were analyzed. Results: iNOS mRNA expression levels following …

Aging, Inflammation, And Gut Microbiota In Mice, Jody Demeo

Honors Projects

Inflammation and gut microbiota are two areas of study that can be linked to aging in the body. As a person ages, systemic inflammation tends to increase, and changes in microbiota in the gastrointestinal system occur as well.

Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield

Electronic Theses and Dissertations

Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the …

Receptor Of Advanced Glycation Endproducts (Rage) Is Positively Correlated With Tumor Necrosis Factor-Α In Adolescents With Obesity, Tasnim Rahman, Daniel H. Conrad, Anshu Gupta

Undergraduate Research Posters

Introduction: Obesity in childhood is associated with an increased prevalence of diabetes and other traditional cardiometabolic risk factors, suggesting an epidemic of premature cardiovascular disease among today’s youth. Glycotoxins, known as advanced glycationend products (AGE’s), activating via the membrane-bound receptors (mRAGE), have been implicated in the pathophysiology of inflammation, (increased tumor necrosis factor-α [TNF-α ]), insulin resistance and vascular dysfunction in adults, but the role of RAGE in the early stages of metabolic disorders is unknown. In this study, we assessed relationship of cardiometabolicrisk factors, mRNA expression of TNF-α and RAGE in peripheral monocytes in adolescents with obesity.

Methods: Thirty …