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The aim was to assess the influence of local application of curcumin-loaded nanoparticles on an experimental model of periodontal repair. Periodontitis was induced by ligatures on both lower first molars of rats. After 15 days, ligatures were removed ("treatment") and animals were randomly allocated to three experimental groups (n = 8/group): (i) 0.05 mg/ml curcumin-loaded nanoparticles, (ii) empty nanoparticles (vehicle control), and (iii) sterile saline (negative control). Experimental treatments were administered locally on days 0, 3, 5, 7, 9, and 11 after ligature removal. Animals were euthanized at 7 and 14 days. Bone repair was assessed by microcomputer tomography (µCT). Histological sections were stained with hematoxylin/eosin (H/E), Picrosirius Red, and Masson's trichrome. Expression of Runx-2 was studied by immunohistochemistry. Gene expression of Itgam, Arg1, and Inos was assessed by RT-qPCR. At 7 days, there was increased gene expression of Itgam and Arg1 and of the relative expression of Arg1/Inos in curcumin-treated animals, but no difference in any other outcomes. At 14 days, curcumin-loaded nanoparticles significantly increased bone repair and collagen content, as well as the number of osteocytes, percentage of extracellular matrix, and expression of Runx2. The results demonstrate that local administration of curcumin-loaded nanoparticles enhanced tissue repair in an experimental model of periodontal repair. Nanoparticle-encapsulated curcumin enhances early post-treatment repair of periodontal tissues.

In oral squamous cell carcinoma (OSCC), macrophages are the most abundant immune cell type in the tumor microenvironment (TME). Macrophage infiltration is inversely proportional to prognosis and disease survival, particularly when these tumor-associated macrophages (TAM) assume an M2-like phenotype. This phenotype is determined by cues from the microenvironment, especially tumor cell-secreted molecules, and is associated with increased production of extracellular-matrix-degrading enzymes, angiogenic molecules and immunosuppressing cytokines. This study investigates, in vitro and in vivo, the relative contribution of OSCC cell-secreted transforming growth factor beta (TGF-β) on the phenotype of macrophages and on macrophage-facilitated tumor invasion. TCGA database shows a positive correlation between high expression of TGFB1 and macrophage infiltrate in Head and neck squamous cell carcinoma (HNSCC). THP-1 derived-macrophages were exposed to the secretome of two OSCC cell lines using two strategies to block the effects of neoplastic cell-secreted TGF-β: pre-treatment with a TGF-β receptor type I kinase inhibitor (LY364947) and antibody-mediated depletion. RT-qPCR, ELISA and flow cytometry determined macrophage phenotype after exposure to conditioned medium (CM) from H-314 (TGF-β

Made available in DSpace on 2021-06-25T10:54:06Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-06-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Objective: This study aimed to assess the effect of a novel synthetic chalcone, Chalcone T4, on a murine model of periodontitis and on RANKL-induced osteoclastogenesis in vitro. Background: Chalcones are natural compounds with anti-inflammatory properties, and its synthetic analogs with enhanced biological effects have potential as therapeutic agents. Periodontitis is characterized by chronic inflammation of the periodontium and alveolar bone resorption. Safe and effective anti-inflammatory agents can have an important additive effect in the treatment in this disease. Methods: Periodontitis was induced via the installation of a ligature around the first molar. Rats (n = 32) received Chalcone T4 (5 and 50 mg/kg) or distilled water by gavage daily for 15 days. Outcomes assessed were bone resorption (μCT), TNF-α production (ELISA), cellular infiltrate, and collagen content (stereometric analysis, CD45+ cells by immunohistochemistry), and activation of NFATc1 and NF-kB (immunohistochemistry). In vitro, RAW 264.7 were treated with Chalcone T4 and stimulated with RANKL for assessment of osteoclast differentiation (actin ring staining) and activity (pit assay). Results: Chalcone T4 significantly reduced periodontitis-associated bone resorption, as well as the cellular infiltrate, while increasing the collagen content. Production of TNF-α, infiltration of CD45-positive cells, and NF-kB activation were markedly reduced. In vitro, chalcone T4 inhibited both osteoclast differentiation and activity. Conclusion: Chalcone T4 significantly inhibited alveolar bone resorption and inflammation in vivo and RANKL-induced osteoclastogenesis in vitro, suggesting a therapeutic role for this compound in the treatment of periodontitis. Department of Diagnosis and Surgery School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Physiology and Pathology School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Chemistry and Environmental Sciences São Paulo State University (UNESP) Department of Diagnosis and Surgery School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Physiology and Pathology School of Dentistry at Araraquara São Paulo State University (UNESP) Department of Chemistry and Environmental Sciences São Paulo State University (UNESP) FAPESP: 2018/17047-3