Medical Biotechnology Commons^™

Identification Of Proteins With Immune Stimulatory Activities From The Culture Filtrates Of Nontuberculous Mycobacteria, Christian Albert Agyei Acheampong

Biotechnology Theses

Nontuberculous mycobacteria (NTM) are the mycobacterial species other than Mycobacterium tuberculosis, which causes tuberculosis, and Mycobacterium leprae, which causes leprosy. Diseases caused by NTM are on the rise in the United States and are steadily becoming a significant public health problem globally, particularly in developed countries. Despite the ability of NTM pathogens to interact with the host immune system, the proteins responsible for eliciting host immune responses remain unidentified, making the accurate and timely diagnosis of the disease a challenge. In this study, we tested the hypothesis that NTM strains secrete proteins that stimulate immune responses. Our study …

Human Osteosarcoma Cell Line That Overexpresses Cd4/Ccr5 Or Cd4/Cxcr4 To Study Hiv-Host Interactions, Harry Baffour Awuah

Biotechnology Theses

Human immunodeficiency virus type 1 (HIV-1) entry into host cells occurs through interactions between the viral surface envelope glycoprotein (Env) and the host receptor CD4, and co-receptors CCR5 or CXCR4. However, understanding these interactions in membrane contexts remains limited due to low receptor and coreceptor densities in commonly used cell models. To address this, we developed cellular systems with elevated CD4 expression and either CCR5 or CXCR4. Human osteosarcoma cells (HOS), which lack endogenous surface expression of HIV receptor (CD4) and co-receptors (CCR5 or CXCR4), were engineered via lentiviral transduction to overexpress CD4 and either CCR5 or CXCR4. Cells were …

The Influence Of Myocardin Effector Genes On The Tgf-Beta Smad3 Signaling Pathway In Human Pleural Mesothelial Cells, Hema Chandra Hrushi Dusharla

Biotechnology Theses

Pleural Fibrosis (PF) involves excessive extracellular matrix (ECM) deposition, mainly by myofibroblasts, leading to pleural thickening and impaired lung function. Pleural mesothelial cells (PMCs) contribute via mesothelial and mesenchymal transition (MesoMT), triggered by cytokines like TGF-β. Our lab identified Myocardin (MyoCD), a transcriptional co-activator of cardiac and smooth muscle, is a master regulator of pleural fibrosis through interactions with serum response factor (SRF) and Smad2/3 transcription factors which initiate fibrosis signaling. RNA sequencing and qPCR analysis revealed that silencing MyoCD decreased the expression of CTNNB1, MDFI, and Tspan2. MDFI emerged as a potent candidate, as this gene affecting the expression …

The Role Of Myocardin And Its Effector Proteins In Tgf-Β Induced Cytoskeletal Remodeling Of Ipf Fibroblasts, Khadijat Abolore Olawuyi

Biotechnology Theses

Idiopathic pulmonary fibrosis (IPF) is characterized by thickening and stiffness around the air sacs. Approved treatments like nintedanib and pirfenidone slow disease progression in IPF and often have tolerability issues. More research is needed to fully grasp the mechanisms behind abnormal cytoskeletal changes in lung cells, notably fibroblasts and epithelial cells, and their role in fibrosis progression. Previous studies suggest that myocardin expression and function, traditionally limited to smooth/cardiac development in physiology, become active in pathophysiological conditions like pleural fibrosis. Myocardin's role in liver and kidney fibrosis is known, but its involvement in IPF is unclear. To get more insights, …

Targeting Brd4 In The Treatment Of Pleural Fibrosis, Joy Adewumi

Biotechnology Theses

Pleural fibrosis (PF) is a respiratory disorder that refers to the thickening and scarring of the pleura. Currently, there is a lack of pharmaceutic treatment options for PF. Pleural mesothelial to mesenchymal transition (MesoMT) is a critical process that contributes to the development of PF. Bromodomain-containing protein 4 (BRD4), a transcriptional and epigenetic regulator, has recently been implicated in a wide range of lung injuries. However, whether BRD4 is involved in regulating MesoMT and the development of PF remains unclear and was explored in this study. Primary human pleural mesothelial cells (HPMCs) were used to test the role of BRD4 …

Effects Of Interleukin-22 (Il-22) On Necroptosis, Inflammatory Responses, And Metabolism Of Mycobacterium Tuberculosis Stimulated Type 2 Diabetes Mellitus Mouse Macrophages, Bismark Owusu-Afriyie

Biotechnology Theses

Mycobacterium tuberculosis (Mtb) infects one-third of the world’s population and causes nearly 1.3 million deaths per year. Limited information is available about the immune responses during Mtb infection in type 2 diabetic hosts. Our laboratory developed an experimentally induced type 2 diabetes (T2DM) model in wild-type C57BL/6 mice and found that IL-22 and type 3 innate lymphoid cells (ILC3s) reduce inflammation and mortality of Mtb-infected T2DM mice. Our laboratory also found that Mtb-infected alveolar macrophages (AMs) from T2DM mice undergo necroptosis compared to Mtb-infected AMs of non-T2DM mice. In the current study, we determined whether …

Functional Impact Of Ethyl-Β-D-Glucuronide On Mycobacterium Tuberculosis Stimulated Lung Macrophages, Charles Inaku

Biotechnology Theses

Chronic alcohol abuse has been shown to alter immune defense mechanisms in humans and mice which makes the host susceptible to infections, including Mycobacterium tuberculosis (Mtb) infection. However, limited information is available on the mechanisms involved in alcohol-mediated host immune system dysfunction.

In this study, we determined the effects of ethyl-β-d-glucuronide (EtG), an alcohol-derived metabolite, on immune response of mice lung macrophages. We measured cytokine and chemokine production by gamma-irradiated mtb (γ-mtb) stimulated mice lung macrophages in the presence or absence of EtG. We also determined the effect of EtG on the metabolic state of γ-mtb stimulated mice lung macrophages. …

Aryl Hydrocarbon Receptor Regulation Of Induction Of Inflammatory Mediators By Organic Dust Extract In Lung Epithelial Cells, Maxine Stenhouse

Biotechnology Theses

Previous studies have indicated a link between respiratory symptoms and diseases and organic dust exposure in agricultural workers. The aryl hydrocarbon receptor (AhR), a transcription factor activated by a wide variety of exogenous and endogenous compounds, is known to be involved in the metabolism of toxic chemicals and recently in the modulation of immune and inflammatory responses. To better understand mechanisms of pathogenesis of respiratory symptoms and diseases, the role of AhR in the regulation of induction of inflammatory mediators by poultry organic dust extract in airway epithelial cells was studied. The role of AhR was studied by investigating the …