Life Sciences Commons^™

Pneumocystis Infection Alters The Activation State Of Pulmonary Macrophages, Jessica M. Deckman, Cathryn J. Kurkjian, Joseph P. Mcgillis, Theodore J. Cory, Susan E. Birket, Linda M. Schutzman, Brian S. Murphy, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Recent studies show a substantial incidence of Pneumocystis jirovecii colonization and infection in patients with chronic inflammatory lung conditions. However, little is known about the impact of Pneumocystis upon the regulation of pulmonary immunity. We demonstrate here that Pneumocystis polarizes macrophages towards an alternatively activated macrophage-like phenotype. Genetically engineered mice that lack the ability to signal through IL-4 and IL-13 were used to show that Pneumocystis alternative macrophage activation is dependent upon signaling through these cytokines. To determine whether Pneumocystis-induced macrophage polarization would impact subsequent immune responses, we infected mice with Pneumocystis and then challenged them with Pseudomonas aeruginosa 14 …

Increased Ros Production In Non-Polarized Mammary Epithelial Cells Induces Monocyte Infiltration In 3d Culture, Linzhang Li, Jie Chen, Gaofeng Xiong, Daret K. St. Clair, Wei Xu, Ren Xu

Markey Cancer Center Faculty Publications

Loss of epithelial cell polarity promotes cell invasion and cancer dissemination. Therefore, identification of factors that disrupt polarized acinar formation is crucial. Reactive oxygen species (ROS) drive cancer progression and promote inflammation. Here, we show that the non-polarized breast cancer cell line T4-2 generates significantly higher ROS levels than polarized S1 and T4R cells in three-dimensional (3D) culture, accompanied by induction of the nuclear factor κB (NF-κB) pathway and cytokine expression. Minimizing ROS in T4-2 cells with antioxidants reestablished basal polarity and inhibited cell proliferation. Introducing constitutively activated RAC1 disrupted cell polarity and increased ROS levels, indicating that RAC1 is …

Effect Of Endoplasmic Reticulum Stress On Vascular Smooth Muscle Cells And Its Regulation Of Sm22Α, Neeraja Priyanka Annam

Wayne State University Dissertations

Background: The vascular smooth muscle cells(VSMC) possess the ability to differentiate into a synthetic phenotype in response to stress. This phenotypic modulation may be accompanied by inflammatory or osteogenic response in chronic stress. The synthetic state is characterized by low levels of contractile markers unlike the differentiated state.

Hypothesis: Endoplasmic reticulum (ER) stress causes phenotypic modulation in VSMCs leading to apoptosis. Many transcription factors induced by ER stress contribute to the downregulation of Sm22α. Perturbation in cytoskeletal dynamics exacerbates the ER stress response.

Methods: Ex-vivo culture was used to establish importance of Sm22 in ER stress. In vitro analysis was …

P120 Catenin Regulates Inflammation In Macrophage, Xiaoqing Guan

Wayne State University Dissertations

Objective: p120 catenin (p120ctn) has been reported to play a critical role in maintenance of the stability of adherens junctions. It also has potential anti-inflammatory effects in epithelial and endothelial cells. This research was designed to evaluate the effects of p120ctn on inflammatory responses in human macrophages upon LPS stimulation, as well as the possible mechanism by which p120ctn regulates LPS-induced proinflammatory response in macrophages. Methods: THP-1 cells were induced to differentiate into macrophages by PMA. The isoforms of p120ctn were identified via RT-PCR and Western blot. The expression of p120ctn was examined by Western blot in THP-1 derived macrophages …

Cell Free Dna As A Marker Of Training Status In Weightlifters, Jeremy A. Gentles, William G. Hornsby, Christine L. Coniglio, Andy R. Dotterweich, Jon A. Miller, Charles A. Stuart, Michael H. Stone

ETSU Faculty Works

The purpose of this investigation was to elucidate the changes in cf-DNA as it relates to fluctuations in resistance training workloads and intensities. The relationship between cell free DNA (cf-DNA), C-reactive protein (CRP), creatine kinase (CK), testosterone (T), cortisol (C), testosterone-cortisol ratio (T:C), body mass and body composition were also examined. Eight weightlifters (5 males and 3 females, age = 25 ± 3.5 yr, body mass = 88.3 ± 22.7 kg, height = 173.8 ±8.4 cm) volunteered to participate in this study. Venous blood samples, body mass and body composition were taken six times, each corresponding to the end of …

An Investigation Of The Relationship Between Intervertebral Disc Puncture, Inflammation, And Tissue Mechanics Using A Rat-Tail Model., Brigitte Laird

Theses and Dissertations (Comprehensive)

Introduction: The intervertebral disc (IVD) is composed of the annulus fibrosus (AF), which surrounds and contains the nucleus pulposus (NP). It is hypothesized that when the IVD becomes injured, in the case of IVD herniation, a localized innate immune response is initiated. Although the presence of pro-inflammatory cytokines in injured IVDs has been well documented, the extent to which inflammation affects the mechanical properties of the IVD remains poorly understood. The purpose of this study was to determine the effect of IVD damage (via puncture) and inflammation (via lipopolysaccharide (LPS) exposure) on the mechanical and structural properties of the IVD. …

Oxidative Stress And Inflammation In Hepatic Diseases: Current And Future Therapy., Karina Reyes-Gordillo, Ruchi Shah, Pablo Muriel

Biochemistry and Molecular Medicine Faculty Publications

Liver disease is a highly prevalent disease that is one of the leading causes of death worldwide. The continuous exposure of the liver to some factors such as viruses, alcohol, fat, and biotransformed metabolites can cause hepatic injury, which can lead to inflammation and liver degeneration. When the injury is sustained for long time, it can cause chronic liver diseases (CLDs), which include a spectrum of disease states ranging from simple steatosis and steatohepatitis (steatosis with inflammation and hepatocyte injury and death) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Multiple evidences indicate that oxidative stress and inflammation are the most …

The Role Of Pparγ In Placental Development And Disease, Leena Kadam

Wayne State University Dissertations

The placenta in mammals forms the maternal fetal interface serving as the source of nutrition for the fetus throughout gestation. It comprises of two major trophoblast lineages: (i) the decidua invading extra-villous trophoblast (EVT) and (ii) the placenta residing villous trophoblast (VT). The EVT’s invade the maternal endometrium to establish pregnancy and secure blood-flow to the implantation site. The VT villous trophoblast forms the main maternal-fetal exchange surface and ensures nutrient and gas exchange to facilitate growth throughout pregnancy. Additionally, both lineages are involved in immunological functions such as maintaining allogenic tolerance and regulation of immune cell activation at the …

Clinicopathology And Molecular Determinants Underlying Benign Breast And Breast Cancer Lesions, Andreana Holowatyj Holowatyj

Wayne State University Dissertations

Despite converging incidence rates for breast cancers by race, disparities in mortality persist where black women suffer from poorer prognosis compared to white counterparts. To understand the clinical, demographic, and molecular characteristics underlying these disparities, we examined differences among patients with breast cancer to understand the role of human epidermal growth factor receptor 2 (HER2) status, age, and race/ethnicity among women diagnosed with hormone receptor-positive breast cancer, and disparities in surgical therapy among female patients with early stage young-onset breast cancer. Benign breast disease, another known risk factor for breast cancer, includes a histological spectrum of lesions, could contribute to …

The Role Of Inflammasomes In Asbestos-Induced Mesothelial To Fibroblastic Transition, Joyce K. Thompson

Graduate College Dissertations and Theses

Malignant Mesothelioma (MM) is a fatal disease with a low median survival between 8 to 12 months after diagnosis. MM has a long latency period (10-60 years), is causally related to asbestos exposure, and is refractory to all available modes of therapy. Despite the causal association between asbestos exposure and MM however, the mechanisms by which asbestos induces this deadly disease remain unclear. Chronic inflammation due to the presence of asbestos fibers is believed to play an important role in all aspects of MM pathogenesis, from development to progression and resistance. Chronic inflammation has been shown to promote dysregulated wound …

Accelerated Achilles Tendon Healing With Interleukin-1 Receptor Antagonist Protein In Rabbits, Marko Pecin, Mario Kreszinger, Snjezana Vukovic, Marija Lipar, Ozren Smolec, Berislav Radisic, Josip Kos

Turkish Journal of Veterinary & Animal Sciences

The current study describes the use of interleukin-1 receptor antagonist protein (IL-1Ra) as a possible strategy for optimizing tendon healing and repair by presenting histologically visible changes in rabbit Achilles tendon tissue after longitudinal tenotomy. The study was carried out on 26 Californian rabbits divided into two equal groups. One was the experimental IRAP (interleukin-1 receptor antagonist) group and the second one was the PBS (purified buffered saline) group. The PBS group was the control group. After longitudinal tenotomy in both groups of rabbits, in the IRAP group IL-1Ra was applied locally, whereas PBS was applied in the control group. …

Myeloperoxidase-Mediated Protein Lysine Oxidation Generates 2- Aminoadipic Acid And Lysine Nitrile In Vivo, Hongqiao Lin, Bruce S. Levison, Jennifer A. Buffa, Ying Huang, Xiaoming Fu, Zeneng Wang, Valentin Gogonea, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

Recent studies reveal 2-aminoadipic acid (2-AAA) is both elevated in subjects at risk for diabetes and mechanistically linked to glucose homeostasis. Prior studies also suggest enrichment of protein-bound 2-AAA as an oxidative post-translational modification of lysyl residues in tissues associated with degenerative diseases of aging. While in vitro studies suggest redox active transition metals or myeloperoxidase (MPO) generated hypochlorous acid (HOCl) may produce protein-bound 2-AAA, the mechanism(s) responsible for generation of 2- AAA during inflammatory diseases are unknown. In initial studies we observed that traditional acid- or basecatalyzed protein hydrolysis methods previously employed to measure tissue 2-AAA can artificially generate …

Th1 Cells In Cancer-Associated Inflammation, Güneş Di̇nç Akbulut, Di̇dem Özkazanç, Güneş Esendağli

Turkish Journal of Biology

The immune system is not only evolved to protect the body from pathogens, but it also recognizes and eliminates cancer cells. CD4+ helper T (Th) lymphocytes are central intercessors differentiated according to the character of physiological or pathological status. Generation of type 1 Th (Th1) cells is primarily associated with a pathological insult that must be removed through immune elimination. Upon interacting with other immune and transformed cells, Th1 cells can hamper cancer progression. Therefore, it is a major obstacle for tumor cells to become insensitive or resistant to Th1-oriented actions. The organism employs various mechanisms to return to a …

Maternal Fatty Acid And Inflammatory Status During Pregnancy Are Related To Infant Heart Rate And Heart Rate Variability, Merritt Leanne Drewery

LSU Doctoral Dissertations

Early life heart rate (HR) and heart rate variability (HRV) reflect autonomic maturation. Intervention with n-3 long chain polyunsaturated fatty acids (LCPUFAs) during pregnancy favorably affects fetal HR and HRV; similar observations have been reported with infant n-3 LCPUFA intake. Infant HR and HRV have not been assessed in relation to maternal fatty acid status during pregnancy. Further, exposure to intrauterine inflammation may underlie these observations, although this hypothesis has not been tested. The aim of this observational study was to explore associations between maternal fatty acid and inflammatory status during pregnancy and infant HR and HRV. Simple linear and …

Effects Of Dietary Supplementation Of Scutellaria Baicalensis Extract During Early Lactation On Milk Production Of Dairy Cattle, K. Olagaray, Michael Brouk, F. Robert, E. Dupuis, B. Bradford

Kansas Agricultural Experiment Station Research Reports

Multiparous Holstein cows (n = 122) were used in a randomized block design to determine the effect of short-term and long-term postpartum administration ofScutellaria baicalensisextract (SBE) on 305-day milk yield, 120-day milk component yield, and early lactation milk markers of inflammation and metabolic function. Treatments were (1) control, (2) short-term (5-day) administration of the SBE (SBE5), and (3) longterm (60-day) administration of the SBE (SBE60). Treatments were included in a treatment pellet that was identical to the control pellet in ingredient source and composition except for the extract, and both pellets were provided via an automated milking system. …

The Role Of Human Msc Derived Exosomes In The Treatment Of Periodontal Diseases, Sonia S. Talegaonkar

Theses and Dissertations

Periodontal disease affects 47% of Americans over 30. Characterized by microbial dysbiosis and unregulated inflammation, severe periodontitis causes degradation of bone and soft tissue around teeth. Current treatments have limited regenerative outcomes and frequent reinfection by harmful bacteria. Human mesenchymal stem cells (hMSCs) have been shown to promote wound healing and tissue regeneration. Many therapeutic benefits of hMSCs are due to their secretome products, like exosomes. Our long-term goal is to develop periodontal therapies with hMSC exosomes. The objectives of this study were to determine the effect of hMSC-derived exosomes on cellular activity of hMSCs and investigate whether hMSC exosome …