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Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono May 2023

Synthesis, Characterization And Biological Evaluation Of Polyarginine Derived Bone-Targeting Peptides, Gina L. Antuono

Seton Hall University Dissertations and Theses (ETDs)

Osteoblast-targeting peptides in the treatment of bone disease is a new and novel approach to offering effective treatment of various cancers and can be used in bio-medical, medicinal chemistry and biotechnology applications. By targeting adhesion proteins produced by osteoblast cells, certain cancers which migrate and metastasize to the bone may be more effectively treated. An osteoblast-targeting peptide composed of Ser-Asp-Ser-Ser-Asp (SDSSD) which selectively binds to osteoblast cells via periostin has recently been identified. This peptide was functionalized with polyurethane, generating nanomicelles which encapsulated RNA for the therapeutic treatment of osteoporosis. This study has served as the basis for the research …


Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown Dec 2022

Bis-Indolyl Compounds And The Induction Of Apoptosis In T98g Glioblastoma Multiforme Cells, Margot C. Brown

Seton Hall University Dissertations and Theses (ETDs)

1,1-bis(3’idolyl)-1(aryl)methane compounds (BIM compounds) have been shown to have anti-cancer properties in colon cancer, bladder cancer, and leukemia cells. The purpose of this work was to determine if BIM compounds could be an effective treatment of glioblastoma multiforme. Sulforhodamine B (SRB) assays showed that 20µM of the BIM compounds could inhibit cellular proliferation of the T98G glioblastoma multiforme cell line over 72 hours. Then immunoblotting was used to analyze the molecular pathway induced by BIM compounds. An increase in the expression of both BAX and cleaved caspase 3 suggest BIM compounds activate programmed cell death, or apoptosis in glioblastoma cells. …


Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez Sep 2021

Clinically Relevant Dosage Of Vancomycin Does Not Negatively Impact Periosteum Derived Osteoblast Precursor Cellular Functions, Alexis Hernandez

Seton Hall University Dissertations and Theses (ETDs)

Surgical site infections (SSI) can develop post-operatively and carry significant clinical and financial implications. SSI can carry a cost of up to $30,000 per case, as well as an estimated 6 day longer hospitalization. Patients with Type II Diabetes (DM) have an increased susceptibility to infection and suffer from poor bone healing overall. Therefore, diabetic patients who have undergone orthopedic surgery risk both an increased chance of developing an SSI as well as suboptimal bone healing. Vancomycin and other antibiotics have traditionally been used prophylactically to prevent infection, however the effect of vancomycin on bone healing in a diabetic population …


A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti Dec 2020

A Functional Three-Dimensional Microphysiological Model Of Myeloma Bone Disease, Richard Visconti

Seton Hall University Dissertations and Theses (ETDs)

Multiple myeloma (MM) is a hematologic cancer caused by a mature B cell neoplasm, or plasmacytoma, that infiltrates the skeleton at several sites. The disease is characterized by uninhibited transformed plasma cell proliferation that disrupts skeletal homeostasis leading to decreased bone modeling and increased bone resorption. Osteolytic lesions (OL) or voids left in the bone, remain long after the treatment of the cancer and indicate disease progression to myeloma bone disease (MBD). Current combinatorial MM therapies inhibit malignant plasma cell proliferation, slow the progression towards MBD, and increase the mean five-year survival rate, but do little to improve osteoblastic function …


Cd11b+ Depletion Of Bone Marrow Derived Macrophages Negatively Affects Bone Fracture Healing, Sarah Hozain Apr 2020

Cd11b+ Depletion Of Bone Marrow Derived Macrophages Negatively Affects Bone Fracture Healing, Sarah Hozain

Seton Hall University Dissertations and Theses (ETDs)

Hematoma formation and inflammation occurs during the beginning stages of fracture repair, which require the presence of innate cells such as macrophages. Macrophages are subdivided into proinflammatory, M1, or anti-inflammatory, M2, phenotypes with different functions, cytokine profiles, and surface markers. In this study, in vitro and in vivo models were used to deplete M1 macrophages, using Mac-1 Sap conjugated antibody (Mac1SAP), to determine the effects on fracture healing. In vitro study, primary macrophages isolated from mice femoral bone marrow were harvested and differentiated into M1 macrophages (+LPS), M2 macrophages (+IL-4), or undifferentiated then treated with either vehicle or 10pM Mac1SAP. …


Vanadium Compounds Modulate Osteoblast Proliferation And Function, Bryan Sosa Aug 2019

Vanadium Compounds Modulate Osteoblast Proliferation And Function, Bryan Sosa

Seton Hall University Dissertations and Theses (ETDs)

Osteoblastogenesis is an essential part of the bone healing process. Insulin has been shown to improve bone healing in both normal and diabetic bone healing models. In addition, insulin mimetic compounds such as Zinc chloride (ZnCl2) and Vanadyl acetylacetonate (VAC) have also been shown to improve bone healing in these models as well. The purpose of this study was to determine the effects of vanadium compounds VAC and Vanadium (II) sulfate (VSO4) in osteoblast proliferation and function. In addition the mechanisms by which growth and function are facilitated by these Vanadium compounds were also evaluated. In …


Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale Jul 2019

Comparison Of Nickel And Cobalt Induced Hypoxic Cell Models Using Cell Proliferation Assay, Melissa Delcasale

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is an imbalance in oxygen delivery and oxygen consumption, ultimately affecting cell survival. Low levels of oxygen diminish adenosine triphosphate synthesis resulting from a decline in oxidative phosphorylation in the mitochondria, therefore inducing apoptosis and cell death. To create a hypoxia mimicked environment, we used hypoxia mimetic compounds cobalt and nickel to treat human neuroblastoma (NMB) cells. Using hypoxic mimic human neuronal cell models, we examined and compared the effects of compound-induced hypoxia on NMB cell proliferation. The cells were treated with 100mM and 300mM concentrations of each compound at 24- and 48-hour intervals. To investigate cell proliferation, the …


Zinc Chloride Enhanced Chondrogenesis Is Vegf Dependent, Gilbert M. Sharp Iv Jun 2019

Zinc Chloride Enhanced Chondrogenesis Is Vegf Dependent, Gilbert M. Sharp Iv

Seton Hall University Dissertations and Theses (ETDs)

Researchers have begun investigating whether insulin mimetics such as ZnCl2 could promote bone healing in both non-diabetic and diabetic fracture healing similarly to insulin. Our research focused on understanding the mechanism by which ZnCl2 affects chondrogenesis, an important component of bone fracture healing. The increases in proteoglycan deposition and cell proliferation seen in our data may be a result of ZnCl2 induction of the IGF-1 pathway. When the VEGF pathway was inhibited in ZnCl2- or insulin-treated cells significant decreases in proteoglycan deposition occurred on day 7 and 14 (P=0.007 for ZnCl2, P=0.028 for insulin) when compared to controls. This data …


Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney Sep 2018

Characterization Of The Protective Role Of Th17 Cells In An Fc Receptor-Targeted Vaccine Strategy Against Fracisella Tularensis Infection, Kyle Devenney

Seton Hall University Dissertations and Theses (ETDs)

Using a murine model, we have previously showed that targeting an inactivated form of F.tularensis (iFt) bacteria to Fcg receptors by utilizing an IgG2a, anti-LPS monoclonal antibody (mAb) provides 100% protection against a lethal dose with the live vaccine strain (LVS). The binding of anti-LPS monoclonal antibodies and iFt create an immune complex (mAb-iFt) allowing the Fc-region of the antibody to target Fc receptors expressed on antigen presenting cells, leading to a more robust and effective processing and presentation of the bacterial antigens. Although the resulting protective response generated relies on both humoral and cell-mediated immunity, in our study we …


Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera Aug 2017

Examining The Role Of Hres On The Regulation Of Opioid Receptor Gene Expression In Neuronal Cells Undergoing Hypoxic Mimic Condition, Alberto Herrera

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a condition of inadequate oxygen supply, which can induce cell death. Using human neuronal cells treated with a hypoxia memetic compound, desferoxamine (DFO), a hypoxic cell model system was created. Our lab reported previously that treatment with DFO resulted in the decrease of cell viability. However, there were still surviving neurons. The surviving cells did not exhibit significant morphological changes, as compared to the control cells, under confocal microscopy analysis using annexin-V-FLUOS and propidium iodide staining, indicating that they were not at apoptotic or necrotic stages. These surviving neurons, therefore, developed adaptive responses under hypoxic challenge. Several changes …


Platelets Prime Hematopoietic-Vascular Niche To Drive Angiocrine-Mediated Liver Regeneration, Koji Shido May 2017

Platelets Prime Hematopoietic-Vascular Niche To Drive Angiocrine-Mediated Liver Regeneration, Koji Shido

Seton Hall University Dissertations and Theses (ETDs)

A critical function for blood vessels is that they secrete paracrine factors necessary for development, homeostasis and repair of the rest of all organs. Among them, the liver is a highly vascular organ, and can undergo regeneration after injury. This liver regeneration process is governed by dynamic interplay between hepatocytes and non-parenchymal cells, liver sinusoidal endothelial cells (LSECs). However, how factors produced from LSECs triggered by injury remains to be defined. Following mouse in vivo liver injury model, activated platelets deploy stromal cell-derived factor 1 and vascular endothelial growth factor A to stimulate CXCR7+ LSECs, orchestrating hepatic regeneration. Upon injection …


Human Neuroblastoma Adaptation To Cobalt Chloride-Induced Hypoxia, Conor Mcauliffe Apr 2017

Human Neuroblastoma Adaptation To Cobalt Chloride-Induced Hypoxia, Conor Mcauliffe

Seton Hall University Dissertations and Theses (ETDs)

Hypoxia is a frequent characteristic of the solid tumor microenvironment, which occurs when cancer cells lack adequate access to oxygen. By selecting for cells that can adapt to and grow in low oxygen conditions, tumor hypoxia contributes to a more aggressive and invasive cancer phenotype that portends a poor clinical outcome. While many aspects of the cellular response to hypoxia have been explored, the roles of some factors have not been fully explained. Cell signaling factors, including signal transducer and activator of transcription 3 (STAT3), the mu opioid receptor (MOR), and the delta opioid receptor (DOR), as well as changes …


Chemical Induced Hypoxia Differentially Affects Gene Expression In Human Neuronal Cells, Natasha V. Pavlichko May 2014

Chemical Induced Hypoxia Differentially Affects Gene Expression In Human Neuronal Cells, Natasha V. Pavlichko

Seton Hall University Dissertations and Theses (ETDs)

Previously, our laboratory used desferoxamine (DFO), to generate hypoxic conditions (a low oxygen condition) which decreased human neuronal cell viability, but some cells still survived. These surviving neurons showed no morphological changes when compared to the non-treated group. However, the alteration of several intracellular events were detected, such as an increase of hypoxia inducible factor 1 (HIF-1) mRNA levels, a decrease of human mu opioid receptor (hMOR) message, and no change of human delta opioid receptor (hDOR) receptor message. Western blot analysis showed the Janus kinase (JAK)/ Signal Transducers and Activators of Transcription (STAT) pathway was activated and an increase …


Investigations On The Effects Of Palmitate On Neuronal Cells, Ryan Gelsinger Apr 2014

Investigations On The Effects Of Palmitate On Neuronal Cells, Ryan Gelsinger

Seton Hall University Dissertations and Theses (ETDs)

Many studies have demonstrated that increased levels of free fatty acids (FFAs) are associated with increased apoptosis in hepatocytes, podocytes, myocytes, and pancreatic islet cells. However, the effects of FAAs on neuronal cell function are not well characterized. In this study, mouse neuroblastoma cells from the Neuro-2a (N2a) cell line were treated with either bovine serum albumin (BSA) or different concentrations of BSA-conjugated palmitate (PA) and examined cell viability using MTT assay. Concentrations of PA at or above 200 μM in the growth media were associated with a decrease in cell viability. In order to examine whether N-acetylcysteine (NAC) or …


Somatostatin Receptor Subtype 2 Is Functionally Expressed In Raw264.7 Cells, Matthew Sung Jun 2007

Somatostatin Receptor Subtype 2 Is Functionally Expressed In Raw264.7 Cells, Matthew Sung

Seton Hall University Dissertations and Theses (ETDs)

Chronic inflammation left unchecked can be quite harmful to the tissue with the pro-inflammatory stimulus. It is marked by the recruitment and activation of leukocytes, including lymphocytes and macrophages with their subsequent proliferation and reactive oxygen species release. Macrophages are also one of the primary players in propagating the inflammatory response as they secrete pro-inflammatory cytokines to sustain local tissue responses. Current therapies for chronic inflammation include non-steroidal anti­ inflammatory drugs and glucocorticoids; however, both have various side effects and setbacks. Somatostatin is an endogenous hormone which inhibits cellular secretion and proliferation throughout the body. Somatostatin receptor activation is mediated …


Characterization Of Migrating Cells From Ventricular Zone (Vz) To Distant Limbic Structures After Multiple Neonatal Seizures, Melissa Corcia Jan 2005

Characterization Of Migrating Cells From Ventricular Zone (Vz) To Distant Limbic Structures After Multiple Neonatal Seizures, Melissa Corcia

Seton Hall University Dissertations and Theses (ETDs)

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Molecular Pharmacology Of Somatostatin Receptors, Fredric C. Mazza Aug 2003

Molecular Pharmacology Of Somatostatin Receptors, Fredric C. Mazza

Seton Hall University Dissertations and Theses (ETDs)

Somatostatin (somatotropin release inhibitory factor, SRIF), inhibits animal cell secretion and proliferation. SRIF is transcribed from a single gene as a 1 t 6 amino acid that in precursor is cleaved a cell specific manner into two distinct peptides, SRIF-14 and SRIF-28. Each binds with high affinity to all five known SRIF-receptor subtypes (sst, - ssts) and several of these receptor subtypes are endogenously expressed in the AtT-20 cell, a murine pituitary corticotroph. SRIF receptors belong to the G protein-coupled family of integral membrane receptors. Within the SRIF receptor family, it has been shown that the sst, receptor subtype exists …


Lipopolysaccharide Induced Septicemia In Chronic Morphine Treated Rats, Frank Ocasio Aug 2003

Lipopolysaccharide Induced Septicemia In Chronic Morphine Treated Rats, Frank Ocasio

Seton Hall University Dissertations and Theses (ETDs)

Opiate-addicts have been known to show increased susceptibility to bacterial infection. Lipopolysaccharide (LPS), which is a cell wall component in gram-negative bacterial, is a potent stimulator of inflammation. We investigated how treatment with morphine alters LPS-induced inflammatory responses in the rat. Chronic morphine exposure alone elevated serum endotoxin levels. Animals treated with morphine and LPS (250 µglkg) developed hypothermia, decreased mean arterial pressure (MAP), increased plasma thrombin anti-thrombin III (TAT) complex, and approximately 67% exhibited progressive intramicrovascular coagulation. Morphine also enhanced LPS­ induced leukocyte endothelial adhesion (LEA), suppressed leukocyte flux and corticosterone production, and elevated interleukin- I�, tumor necrotic factor-a, …


Dipyridamole Reduces Oxidative Stress In Human Coronary Artery Endothelial And Hela Cell Models, Matthew E. Giangrante Jan 2002

Dipyridamole Reduces Oxidative Stress In Human Coronary Artery Endothelial And Hela Cell Models, Matthew E. Giangrante

Seton Hall University Dissertations and Theses (ETDs)

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