242 research outputs found
Exploiting PI 3 K /m TOR signaling to accelerate epithelial wound healing
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99096/1/odi12070.pd
Identificação de subcentros de emprego: o caso do Município de São Paulo, Brasil
Theoretical models concerned with multiple centers have been brought to the debate on sprawling urban employment. However, empirical methods that identify these centers are not a specific focus of the specialized literature. The purpose of this paper is to apply a new empirical methodology in the identification and characterization of urban employment subcenters (Small Business Districts, SBD) using the case of the Municipality of São Paulo. To this end, we adopted a two-step approach, developing: 1) Exploratory Spatial Data Analysis and 2) Spatial Hedonic Price Model. As a result, we found seven regions that can be considered SBDs.Modelos teóricos preocupados com centros múltiplos foram trazidos para o debate sobre o espraiamento do emprego urbano. No entanto, os métodos empíricos que identificam esses centros não são um foco específico da literatura especializada. O objetivo deste artigo é aplicar uma nova metodologia empírica na identificação e caracterização de subcentros de emprego urbano (Pequenos Distritos Comercial, SBD) utilizando o caso do Município de São Paulo. Para tanto, adotamos uma abordagem em duas etapas, desenvolvendo: 1) Análise Exploratória de Dados Espaciais e 2) Modelo de Preço Hedônico Espacial. Como resultado, encontramos sete regiões que podem ser consideradas SBDs
Teremos que trocar energia por comida? Análise do impacto da expansão da produção de cana-de-açúcar sobre o preço da terra e dos alimentos
Cyclin D 1‐induced proliferation is independent of beta‐catenin in H ead and N eck C ancer
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106775/1/odi12124.pd
BMI-1 expression increases in oral leukoplakias and correlates with cell proliferation
Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective: To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology: This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results: A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions: These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC
Characterization of macrophages infiltrating periâ implantitis lesions
ObjectivesThe mechanisms involved in the initiation and progression of periâ implantitis lesions are poorly understood. It was the aim to determine the content and activation status of macrophages present in human periâ implantitis lesions and compare the current findings with the macrophage polarization associated with periodontitis lesions.Material and MethodsA total of 14 patients were studied in this investigation. Seven were soft tissue biopsies from dental implants affected by periâ implantitis that required explantation. Seven biopsies were from chronic periodontal disease. Immunofluorescence stains were performed using biomarkers to identify macrophages (CD68+) undergoing M1 polarization (iNOS+) and M2 polarization (CD206+), along with Hoechst 33,342 to identify DNA content. All samples were stained and photographed, and doubleâ positive cells for CD68 and iNOS or CD68 and CD206 were quantified.ResultsAll periâ implantitis biopsies examined revealed a mixed population of macrophages undergoing M1 polarization and M2 polarization. Further analysis demonstrated the coâ expression of iNOS and CD206, which indicates the presence of a heterogenic immune response on periâ implantitis lesions. Macrophage polarization in periâ implantitis lesions presents a distinct pattern than in periodontitis. We observed a significant increase in the population of M1 macrophages on periâ implantitis samples compared to periodontal disease samples.ConclusionOur results demonstrate that periâ implantitis has higher numbers of macrophages displaying a distinct macrophage M1 polarization signature compared to periodontitis lesions. This pattern may explain, in part, the distinct nature of periâ implantitis progression vs. periodontitis in humans.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154542/1/clr13568_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154542/2/clr13568.pd
Characterization of macrophage polarization in periodontal disease
AimTo explore the M1/M2 status of macrophage polarization from healthy, gingivitis, and periodontitis patient samples.Materials and methodsGingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with haematoxylin and eosin staining. Immunofluorescence was performed using a combination of CD68 (macrophages), iNOS (M1), and CD206 (M2) in order to acquire changes in macrophage polarization at a singleâ cell resolution. Macrophages were quantified under microscopy using narrow wavelength filters to detect Alexa 488, Alexa 568, Alexa 633 fluorophores, and Hoechst 33342 to identify cellular DNA content.ResultsGingivitis and periodontitis samples showed higher levels of macrophages compared with healthy samples. Unexpectedly, periodontitis samples displayed lower levels of macrophages dispersed in the stromal tissues compared with gingivitis samples; however, it remained higher than healthy tissues. The polarization of macrophages appears to be reduced in periodontitis and showed similar levels to those observed in healthy tissues.ConclusionsOur study found that gingivitis and periodontitis differ from each other by the levels of macrophage infiltrate, but not by changes in macrophage polarization.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150506/1/jcpe13156_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150506/2/jcpe13156.pd
Periodontal disease affects oral cancer progression in a surrogate animal model for tobacco exposure
For decades, the link between poor oral hygiene and the increased prevalence of oral cancer has been suggested. Most recently, emerging evidence has suggested that chronic inflammatory diseases from the oral cavity (e.g., periodontal disease), to some extent, play a role in the development of oral squamous cell carcinoma (OSCC). The present study aimed to explore the direct impact of biofilm‑induced periodontitis in the carcinogenesis process using a tobacco surrogate animal model for oral cancer. A total of 42 Wistar rats were distributed into four experimental groups: Control group, periodontitis (Perio) group, 4‑nitroquinoline 1‑oxide (4‑NQO) group and 4NQO/Perio group. Periodontitis was stimulated by placing a ligature subgingivally, while oral carcinogenesis was induced by systemic administration of 4NQO in the drinking water for 20 weeks. It was observed that the Perio, 4NQO and 4NQO/Perio groups presented with significantly higher alveolar bone loss compared with that in the control group. Furthermore, all groups receiving 4NQO developed lesions on the dorsal surface of the tongue; however, the 4NQO/Perio group presented larger lesions compared with the 4NQO group. There was also a modest overall increase in the number of epithelial dysplasia and OSCC lesions in the 4NQO/Perio group. Notably, abnormal focal activation of cellular differentiation (cytokeratin 10‑positive cells) that extended near the basal cell layer of the mucosa was observed in rats receiving 4NQO alone, but was absent in rats receiving 4NQO and presenting with periodontal disease. Altogether, the presence of periodontitis combined with 4NQO administration augmented tumor size in the current rat model and tampered with the protective mechanisms of the cellular differentiation of epithelial cells
Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma
IntroductionAlterations of the epigenome may influence cancer initiation and progression. At the cellular level, histones are key regulators of chromatin accessibility and gene transcription; thus, the inhibition of histone deacetylase enzymes (HDACs) constitutes an attractive target for therapy. In this study, we investigated the effects of the HDAC inhibitor entinostat on oral squamous cell carcinoma (OSCC).Materials and MethodsWe tested the effects of entinostat on OSCC cell lines. Cell viability and growth were analyzed using MTT assay. Cell cycle analysis, cell apoptosis, cancer stem cell (CSC) content, and the concentration of reactive oxygen species (ROS) in OSCC tumor cells were assessed using flow cytometry. The expression of histones and cell cycle regulatory proteins was examined by Western blot.ResultsThe administration of entinostat resulted in reduced proliferation of OSCC cells, followed by cell cycle arrest at the G0/G1 phase, as well as substantial tumor apoptosis. We found an increase in ROS production and significant reductions in CSCs. We also found that entinostat caused increased acetylation histone H3 and histone H4, and changes in the expression of cell cycle‐associated proteins such as p21.ConclusionThis study indicates that entinostat is a potential novel therapeutic agent for OSCC by halting tumor proliferation, inducing cytotoxicity and intracellular ROS, and attacking the CSCs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162762/2/jop13039.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162762/1/jop13039_am.pd
Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis
Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-β/IκBα/ NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem
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