Medical Toxicology Commons^™

The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary

Electronic Theses and Dissertations

The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current …

Neprilysin Is A Mediator Of Alternative Renin-Angiotensin-System Activation In The Murine And Human Kidney, Oliver Domenig, Arndt Manzel, Nadja Grobe, Eva Königshausen, Christopher C. Kaltenecker, Johannes J. Kovarik, Susan B. Gurley, Dunja Van Oyen, Marlies Antlanger, Michael Bader, Daisy Motta-Santos, Jose Carlos Santos, Robson A. Santos, Khalid M. Elased, Marcus D. Säemann, Ralf A. Linker, Marko Poglitsch

Pharmacology and Toxicology Faculty Publications

Cardiovascular and renal pathologies are frequently associated with an activated renin-angiotensin-system (RAS) and increased levels of its main effector and vasoconstrictor hormone angiotensin II (Ang II). Angiotensin-converting-enzyme-2 (ACE2) has been described as a crucial enzymatic player in shifting the RAS towards its so-called alternative vasodilative and reno-protective axis by enzymatically converting Ang II to angiotensin-(1-7) (Ang-(1-7)). Yet, the relative contribution of ACE2 to Ang-(1-7) formation in vivo has not been elucidated. Mass spectrometry based quantification of angiotensin metabolites in the kidney and plasma of ACE2 KO mice surprisingly revealed an increase in Ang-(1-7), suggesting additional pathways to be responsible for …

Micellular Electrokinetic Chromatography For Studying Amyloid Beta Oligomer Membrane Affinity, Andrew Bryson

Biomedical Engineering Undergraduate Honors Theses

Amyloid Beta (Aβ) was the major focus of this study. It is a peptide that is present in the brain with a high tendency to self-aggregate. When this protein aggregates, it forms oligomers and protofibrils which in turn are deposited as senile plaques in the brain. The reason for the concern with these plaques is their association with the neurological disorder Alzheimer’s disease. It has been found that the most dangerous oligomers are formed in a portion of the plasma membrane known as lipid rafts. The purpose of this study was to understand how micelles affect the aggregation properties of …

Injury-Induced Microvesicle Particle Release In Keratinocyte Cell Line And Abdominoplasty Skin, Katherine E. Fahy, Langni Liu, Christina E. Borchers, Christine M. Rapp, Mike Kemp, Richard Simman, Ji C. Bihl, Jeffrey B. Travers

Pharmacology and Toxicology Faculty Publications

No abstract provided.

Endothelial Progenitor Cells And Neural Progenitor Cells Synergistically Protect Cerebral Endothelial Cells From Hypoxia/Reoxygenation-Induced Injury Via Activating The Pi3k/Akt Pathway, Jinju Wang, Yusen Chen, Yi Yang, Xiang Xiao, Shuzhen Chen, Cheng Zhang, Bradley S. Jacobs, Bin Zhao, Ji C. Bihl, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Background

Protection of cerebral endothelial cells (ECs) from hypoxia/reoxygenation (H/R)-induced injury is an important strategy for treating ischemic stroke. In this study, we investigated whether co-culture with endothelial progenitor cells (EPCs) and neural progenitor cells (NPCs) synergistically protects cerebral ECs against H/R injury and the underlying mechanism.

Results

EPCs and NPCs were respectively generated from inducible pluripotent stem cells. Human brain ECs were used to produce an in vitro H/R-injury model. Data showed: 1) Co-culture with EPCs and NPCs synergistically inhibited H/R-induced reactive oxygen species (ROS) over-production, apoptosis, and improved the angiogenic and barrier functions (tube formation and permeability) in …

Uvb Generates Microvesicle Particles Via Platelet-Activating Factor-Receptor Signaling: A Novel Pathway By Which A Skin-Specific Stimulus Exerts Systemic Effects, Jeffrey B. Travers, Christine M. Rapp, Katherine E. Fahy, Christina E. Borchers, Richard Simman, Langni Liu, Yanfang Chen, Ji C. Bihl

Pharmacology and Toxicology Faculty Publications

Though Ultraviolet B radiation (290-320 nm; UVB) exerts profound systemic effects, it is absorbed only in the epidermis. One important question in photobiology is how UVB signals are emanated from the epidermis. Microvesicle particles (MVP) are small (200-1000nm diameter) membrane-bound vesicles released by numerous cell types and can be found in the circulation. MVP can contain both nuclear and cytoplasmic components and are thought to provide a mechanism by which cells transmit signals systemically. Though various stressors have been demonstrated to generate MVP, the ability of UVB to exert this effect has not been demonstrated. Previous studies from ours and …

Analyses Of Endothelial Cells And Endothelial Progenitor Cells Released Microvesicles By Using Microbead And Q-Dot Based Nanoparticle Tracking Analysis, Jinju Wang, Yun Zhong, Xiaotang Ma, Xiang Xiao, Chuanfang Cheng, Yusen Chen, Ifeanyi Iwuchukwu, Kenneth J. Gaines, Bin Zhao, Shiming Liu, Jeffrey B. Travers, Ji C. Bihl, Yanfang Chen

Pharmacology and Toxicology Faculty Publications

Accurate analysis of specific microvesicles (MVs) from biofluids is critical and challenging. Here we described novel methods to purify and detect MVs shed from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads with fluorescence quantum dots (Q-dots) coupled nanoparticle tracking analysis (NTA). In the in vitroscreening systems, we demonstrated that 1) anti-CD105 (EC marker) and anti-CD34 (EPC marker) conjugated-microbeads had the highest sensitivity and specificity for isolating respective MVs, which were confirmed with negative controls, CD41 and CD235a; 2) anti-CD144 (EC marker) and anti-KDR (EPC marker) conjugated-Q-dots exhibited the best sensitivity and specificity for their respective …

The Novel Methods For Analysis Of Exosomes Released From Endothelial Cells And Endothelial Progenitor Cells, Jinju Wang, Runmin Guo, Yi Yang, Bradley S. Jacobs, Suhong Chen, Ifeanyi Iwuchukwu, Kenneth J. Gaines, Yanfang Chen, Richard Simman, Guiyuan Lv, Keng Wu, Ji C. Bihl

Pharmacology and Toxicology Faculty Publications

Exosomes (EXs) are cell-derived vesicles that mediate cell-cell communication and could serve as biomarkers. Here we described novel methods for purification and phenotyping of EXs released from endothelial cells (ECs) and endothelial progenitor cells (EPCs) by combining microbeads and fluorescence quantum dots (Q-dots®) techniques. EXs from the culture medium of ECs and EPCs were isolated and detected with cell-specific antibody conjugated microbeads and second antibody conjugated Q-dots by using nanoparticle tracking analysis (NTA) system. The sensitivities of the cell origin markers for ECs (CD105, CD144) and EPCs (CD34, KDR) were evaluated. The sensitivity and specificity were determined by using positive …

Microvascular Endothelial Cells-Derived Microvesicles Imply In Ischemic Stroke By Modulating Astrocyte And Blood Brain Barrier Function And Cerebral Blood Flow, Qunwen Pan, Caixia He, Hua Liu, Xiaorong Liao, Bingyan Dai, Yanfang Chen, Yi Yang, Bin Zhao, Ji C. Bihl, Xiaotang Ma

Pharmacology and Toxicology Faculty Publications

Background

Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage.

Results

EMVs prepared from ECs cultured in normal condition (n-EMVs) or …

The Role Of Pxr And Ikkβ Signaling In Cardiometabolic Disease, Robert N. Helsley

Theses and Dissertations--Pharmacology and Nutritional Sciences

Cardiovascular disease (CVD) is the leading cause of death worldwide and is partially attributed to perturbations in lipid metabolism. Xenobiotics, such as pharmaceutical drugs and environmental chemicals, have been associated with increased risk of CVD in multiple large-scale human population studies, but the underlying mechanisms remain poorly defined. We and others have identified several xenobiotics as potent agonists for the pregnane X receptor (PXR), a nuclear receptor that can be activated by numerous drugs as well as environmental and dietary chemicals. However, the role of PXR in mediating the pathophysiological effects of xenobiotic exposure in humans and animals remains elusive. …