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Expression of microRNA in Alveolar Macrophages Deficient in PPARy
(East Carolina University, 2014)
The nuclear transcription factor Peroxisome proliferator-activated receptor gamma (PPARgamma) is a negative regulator of macrophage activation and inflammatory mediators. Alveolar macrophages of healthy individuals constitutively express PPARgamma Decreased activity and expression of PPARgamma are observed in the alveolar macrophages from patients suffering from inflammatory conditions such as pulmonary alveolar proteinosis (PAP) and sarcoidosis. These finding suggest that PPARf× activity may have an integral role in maintaining lung homeostasis. This study tested the hypothesis that microRNA expression would be dysregulated in murine alveolar macrophages deficient in PPARgamma. microRNA (miR) are small non-coding RNA molecules that post-transcriptionally regulate the expression of messenger RNA. Evaluation of microRNA in the murine model of PAP, the GM-CSF-KO mouse, demonstrates the elevation of miR-27a and miR-27b which target PPARgamma. The deficiency of PPARgamma and the lipid transporters ABCA1 and ABCG1 have been shown to contribute to the pathology of PAP. The microRNA miR-33-3p and miR-33-5p, which target these lipid transporters, were also elevated in GM-CSF-KO mice. Pulmonary granulomas comparable to those observed in pulmonary sarcoidosis are induced by instillation of multiwall carbon nanotubes (MWCNT) in C57Bl/6 mice. These animals have decreased PPARgamma activity and show elevated expression of miR-27a and miR-27b. It was also observed that the expression of the transporters ABCA1 and ABCG1 were decreased in MWCNT instilled mice. Expression of miR-33-3p and miR-33-5p was elevated in MWCNT instilled animals. The expression of microRNA that affects the activity of NF-£eB is also elevated in both murine models. We next investigated the use of PPARgamma agonist rosiglitazone on the expression of microRNA and messenger RNA. The use of rosiglitazone altered the expression of microRNA in both GM-CSF-KO and C57Bl/6+MWCNT mice. Rosiglitazone treatment altered the expression of the lipid transporter ABCA1and ABCG1 in C57Bl/6+MWCNT mice. The elevation of proinflammatory cytokines was also observed. Taken together, these observations support the hypothesis that PPARgamma activity effects the microRNA and gene expression in alveolar macrophages which is critical to overall lung homeostasis. Understanding the relationship between PPARgamma and microRNA in alveolar macrophage biology will provide insight into the regulation of the lung environment and possible therapeutic targets. ...
Modeling of Non-Small Cell Lung Cancer Volume Changes during CT-Based Image Guided Radiotherapy: Patterns Observed and Clinical Implications
(2013)
Background. To characterize the lung tumor volume response during conventional and hypofractionated radiotherapy (RT) based on diagnostic quality CT images prior to each treatment fraction. Methods. Out of 26 consecutive ...
Catalpol Modulates Lifespan via DAF-16/FOXO and SKN-1/Nrf2 Activation in
(2015)
Catalpol is an effective component of rehmannia root and known to possess various pharmacological properties. The present study was aimed at investigating the potential effects of catalpol on the lifespan and stress tolerance ...
The Potential Role of Magnetic Resonance Spectroscopy in Image-Guided Radiotherapy
(2014-05)
Magnetic resonance spectroscopy (MRS) is a non-invasive technique to detect metabolites within the normal and tumoral tissues. The ability of MRS to diagnose areas of high metabolic activity linked to tumor cell proliferation ...
Late gastrointestinal tissue effects after hypofractionated radiation therapy of the pancreas
(2015-09)
Background
To consolidate literature reports of serious late gastrointestinal toxicities after hypofractionated radiation treatment of pancreatic cancer and attempt to derive normal tissue complication probability (NTCP) ...
A Tri-Modality Image Fusion Method for Target Delineation of Brain Tumors in Radiotherapy
(2014)
Purpose
To develop a tri-modality image fusion method for better target delineation in image-guided radiotherapy for patients with brain tumors.
Methods
A new method of tri-modality image fusion was developed, ...
Formative Evaluation for a Healthy Corner Store Initiative in Pitt County, North Carolina: Assessing the Rural Food Environment, Part 1
(2013)
Introduction
Obesity prevalence in the rural United States is higher than in urban or suburban areas, perhaps as a result of the food environment. Because rural residents live farther from supermarkets than their urban- ...
Breaking Patterns of Environmentally Influenced Disease for Health Risk Reduction: Immune Perspectives
(2010-08)
Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or “pattern” of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, ...
Association of Perfluoroalkyl Substances, Bone Mineral Density, and Osteoporosis in the U.S. Population in NHANES 2009-2010
(2015-06)
Background
Perfluoroalkyl substances (PFASs), including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), are detectable in the ...
Course of Depressive Symptoms and Treatment in the Longitudinal Assessment of Bariatric Surgery (LABS-2) Study
(2014-05)
Objective
To examine changes in depressive symptoms and treatment in the first three years following bariatric surgery.
Design and Methods
The Longitudinal Assessment of Bariatric Surgery-2 is an observational ...