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HSDM Theses and Dissertations

Mostrando recursos 1 - 10 de 10

  1. Pro-Resolving Maresins in Inflammation: New Pathway and Mechanisms With Oral Pathogens

    Wang, Chin-Wei
    Objectives The aim of this thesis was to study the biosynthesis of Maresin 1 (MaR1) in human macrophage and to investigate the potential defect of this pathway in patients with localized aggressive periodontitis as well as the role of MaR1 in regulating phagocyte functions and leukocyte-platelet aggregation using LAP as a disease model. Methods Human recombinant enzyme (12-lipoxygenase and soluble epoxide hydrolyse) and synthetic intermediates were used to investigate the maresin pathway by LC/MS/MS-based lipid mediator (LM) metabololipidomics. Human macrophage 12-LOX sequence was crosschecked with platelet-type 12-LOX. Enzyme expression levels in human myeloid mononuclear lineage were determined with flow cytometry. Peripheral blood was...

  2. Experimental Evaluation of Discoid Domain Receptor 2 as an Ideal Target for Development of Disease-Modifying Osteoarthritis Drugs

    Manning, Lauren Brooke
    Abstract: Osteoarthritis (OA) affects 250 million people worldwide. Currently, no targets for disease-modifying osteoarthritis drugs exist. Matrix metalloproteinase-13 (MMP-13) would make it an ideal target; however, its broad biological effects restrict its application as a target enzyme of inhibitory drugs in the treatment of OA. The expression and activation of discoidin domain receptor 2 (DDR2) is increased in human OA tissues and mouse models of OA and was co-localized with elevated expression of MMP-13 in degenerative articular cartilages. In healthy articular cartilage, DDR2 is kept inactivated by the pericellular matrix, which separates the receptor from its ligand, type II collagen. Once...

  3. Comprehensive Optical Assessment of Peri-Implant Mucosa

    Gil, Mindy S.
    Esthetic outcomes with implants begin with proper implant placement, but the predictability of the peri-implant esthetic outcome is also affected by patient’s pre-existing or reconstructed local tissue. An unpleasant optical phenomenon where the peri-implant mucosa appears gray has been documented in the literature. However, it’s etiology and solutions have not yet been fully investigated. The overall goal of this project is to perform comprehensive optical examination and to establish the clinical guideline to achieve optimal peri-implant mucosa. A. Specific Aim 1: Assess the optical properties of the peri-implant mucosa. A total of 40 patients who has a healthy, single bone level...

  4. Attenuation of the Progression of Articular Cartilage Degeneration by Inhibition of Tgf-β1 Signaling in a Mouse Model of Osteoarthritis

    Chen, Rebecca Y.
    Background The goal of this study is to understand role of transforming growth factor beta 1 (TGF-β1) in development of osteoarthritis (OA). Results from studies indicate that the genetic inactivation of Smad-3, or the disruption of the interaction of Tgf-β1 with its receptor Tgf-β type II receptor (Tgfbr2), in germline cells results in OA-like knee joints in mice at one month of age. However, other studies suggest that the increased expression of Tgf-β1 in mature knee joints causes OA in animal models. A human genetic study reports that a two-nucleotide deletion, 741-742del AT, and/or a nucleotide change, 859C>T or 782C>T in...

  5. A Comprehensive Assessment of Soft Tissue Esthetics

    Grieco, Peter C.
    This thesis investigated the efficacy of two techniques, digital spectrophotometry and narrow-band endoscopy, in observing and describing gingival tissue in a patient population. The efficacy of existing gingival restorative materials in mimicking the optical qualities of the participant pool was also investigated using spectrophotometric analysis. The spectrophotometric analysis examined the ability of a digital, non-contact, full-tooth spectrophotometer (Crystaleye; Olympus, Japan) to evaluate objectively gingival color, thickness, and translucency in 100 participants drawn from the patient population of a dental school. Color metrics of gingival soft tissue were obtained from all teeth in the maxillary sextant in the participant population and...

  6. Impact of Resolvin E1 on Experimental Periodontitis and Periodontal Biofilm

    Lee, Chun-Teh
    Objective: The goal of this project was to determine the impact of local inflammation on changes in the subgingival biofilm composition in ligature-induced periodontitis in rats using the specialized pro-resolving mediator (SPM), resolvin E1 (RvE1). Materials and Methods: The impact of RvE1 on the microbiota of ligature-induced periodontitis was assessed in two separate experiments; treatment of established periodontitis and prevention of ligature-induced periodontitis. In the treatment study, eighteen rats were separated into four groups comprising no ligature, ligature alone (no treatment), ligature with topical RvE1 treatment (ligature+RvE1) and, ligature with topical vehicle treatment (ligature + Vehicle). 3-0 silk ligatures were tied...

  7. A Comparison of Zirconia CAD/CAM to Conventionally Fabricated Single Implant Restorations in the Esthetic Zone

    Borzangy, Sary
    Objective: This project aimed to determine whether single tooth implant restorations fabricated with CAD/CAM zirconia abutments/porcelain fused to zirconia crowns reveal different biological and esthetic outcomes compared with prefabricated anatomic titanium abutments/porcelain fused to metal crowns in the esthetic zone. Materials and Methods: Thirty patients who needed a single implant restoration in the esthetic zone were included in the study. Twenty-nine patients completed screening, baseline, crown insertion, one-month, six-month and one-year follow-up visits. At the screening visit, the patients were randomly allocated into two groups: the prefabricated anatomic titanium abutments/ porcelain fused to metal crown (Ti) group and the CAD/CAM zirconia...

  8. Immune Reconstitution of B Cells Following Allogeneic Hematopoietic Cell Transplantation

    Aboalela, Ali Anwar
    Objectives: Graft versus host disease (GVHD), infections and disease relapse continue to be major complications of allogeneic hematopoietic cell transplantation (HCT). B cell abnormalities have been associated with these complications, and the objective of these studies was to identify and quantify abnormalities of B cell recovery after allogeneic HCT. Methods: Flow cytometry was used to analyze peripheral blood from healthy donors (HD) and samples obtained at 1, 2, 3, 6, 9, 12, 18, 24, 30, and 36 months post HCT. A panel of 8 fluorophore-conjugated monoclonal antibodies specific for B cell surface markers was used to identify levels of total B...

  9. Halofuginone Prevents the Progression of Osteoarthritis

    Khoynezhad, Shirin
    Background: Halofuginone (HF) is a natural product that has been shown to have therapeutic benefits in a variety of pathologic conditions, from cancer to autoimmune diseases. These beneficial effects are mainly through inhibition of pro-inflammatory cytokines. Inflammatory cytokines have been recently shown to exert a crucial role in development of osteoarthritis and one of their most important targets is Matrix metallopeptidase-13 (MMP-13). In this preclinical study, we investigated the effect of HF on the progression of Osteoarthritis. Methods: The effect of adding HF ± IL-1β/TNF-α on mRNA expression of MMP-13 on the C28/I2 Chondrocytes was evaluated with qPCR in vitro....

  10. Role of the Transcription Factor Zinc Finger Protein 521 on Runx2 Acetylation

    Bahadoran, Mahshid
    Runx2 is a transcription factor that has a crucial role in the development of bone; haploinsufficiency of Runx2 leads to the autosomal-dominant disorder, cleidocranial dysplasia (CCD) characterized by various skeletal abnormalities. Zinc finger protein 521 (Zfp521) is a transcription factor that is expressed in several cell types including bone. Recent studies demonstrated that Zfp521 interacts with Runx2 and regulates osteoblast maturation at least in part by repressing the transcriptional activity of Runx2; furthermore, it was demonstrated that the repression of Runx2 by Zfp521 involves the recruitment of HDAC3. The interaction of Runx2 with HDAC3 is strongly enhanced by Zfp521. Zfp521...

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