RESUMO
The historic outbreak of the novel coronavirus (SARS CoV-2) sent concern and even panic around the world due to the unknown nature of this disease. As a result, the US implemented a whole-of government approach to tackle the outbreak of this deadly virus. The national and global impact of an uncontrolled COVID-19 outbreak, threatens the US healthcare system and our way of life with potential to cause riveting economic and national security instability. As a result of the health impact on American society, the US military must also take precaution to preserve and defend our nation's fighting force. This charge has created a unique opportunity for military medicine to take the lead at the front line to combat this biologic viral threat.
Assuntos
COVID-19/prevenção & controle , Odontologia/organização & administração , Controle de Infecções/instrumentação , Controle de Infecções/organização & administração , Medicina Militar/organização & administração , COVID-19/epidemiologia , COVID-19/transmissão , Humanos , Equipamento de Proteção Individual , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Cancer-Associated Fibroblasts (CAFs) are the most prominent stromal cell type in breast tumors. CAFs promote tumor growth and metastasis by multiple mechanisms, including by mediating tumor-promoting inflammation. Immune modulation in the tumor microenvironment plays a central role in determining disease outcome. However, the functional interactions of CAFs with immune cells are largely unknown. Here we report a novel signaling axis between fibroblasts, cancer cells and immune cells in breast tumors that drives an immunosuppressive microenvironment, mediated by CAF-derived Chi3L1. We demonstrate that Chi3L1 is highly upregulated in CAFs isolated from mammary tumors and pulmonary metastases of transgenic mice, and in the stroma of human breast carcinomas. Genetic ablation of Chi3L1 in fibroblasts in vivo attenuated tumor growth, macrophage recruitment and reprogramming to an M2-like phenotype, enhanced tumor infiltration by CD8+ and CD4+ T cells and promoted a Th1 phenotype. These results indicate that CAF-derived Chi3L1 promotes tumor growth and shifts the balance of the immune milieu towards type 2 immunity. Taken together, our findings implicate fibroblast-derived Chi3L1 as a novel key player in the complex reciprocal interactions of stromal cells that facilitate tumor progression and metastasis, and suggest that targeting Chi3L1 may be clinically beneficial in breast cancer.
Assuntos
Neoplasias da Mama/patologia , Fibroblastos Associados a Câncer/fisiologia , Proteína 1 Semelhante à Quitinase-3/fisiologia , Tolerância Imunológica , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Movimento Celular , Polaridade Celular , Feminino , Neoplasias Pulmonares/secundário , Macrófagos/fisiologia , Camundongos , Neovascularização FisiológicaRESUMO
CLINICAL RELEVANCE: Surface alterations of dental restorations can result in increased plaque biofilm. This leads to increased risk of premature restoration failure. Smokeless tobacco, in common use by some US military personnel, represents a potential source for surface alteration. If smokeless tobacco causes an untoward effect, selection of a more resistant restorative material could increase restoration longevity, thus minimizing lost work time and costs associated with replacement of failed restorations. PURPOSE: Comparatively assess the effect of smokeless tobacco/salivary substitute mixture on altering surface roughness of amalgam, composite resin, and resin modified glass ionomer (RMGI) restorations. MATERIALS AND METHODS: Sixty cubic restorations (3 groups of 20) were fabricated using a 4 mm by 3 mm Teflon mold. One examiner assessed the restorations at time points representing zero days, one day, one week, 2 weeks, one month, and 3 months. The data obtained were collected using a surface profilometer, measured in micrometers. Data were statistically analyzed using 2-way analysis of variance (ANOVA) test. A difference was significant if P< .05. RESULTS: Confidence levels with a 95% overall rating received a clinically acceptable classification. The 2-way ANOVA test detected significant differences between baseline, one day, one week, 2 weeks, one month, and 3-month data for surface roughness (P<.05). With respect to time and restoration type, results proved statistically significant with P<.0001. All restorations were statistically significant with respect to change in surface roughness with RMGIs showing the greatest surface roughness alteration. CONCLUSION: Smokeless tobacco mixed with a salivary substitute altered restoration surface roughness over time. Resin-modified glass isonomer restorations demonstrate the greatest alteration of surface roughness, with amalgam restorations showing the least. Amalgam remains the preferential restorative material in patients who use smokeless tobacco.
Assuntos
Resinas Acrílicas/análise , Resinas Compostas/análise , Amálgama Dentário/análise , Dióxido de Silício/análise , Tabaco sem Fumaça/efeitos adversos , Humanos , MilitaresRESUMO
The hybrid prokaryotic lipo-beta-lactamase mature and precursor proteins spontaneously form an intramolecular disulphide bond when oxidized in vitro. When expressed in Saccharomyces cerevisiae (in vivo) the lipo-beta-lactamase precursor is in a reduced form whereas the majority of the mature protein is oxidized. The results indicate that in yeast, the lipo-beta-lactamase precursor is first processed (the signal peptide is removed) and then oxidized to form a disulphide bond in the mature protein. Reduced-mature lipo-beta-lactamase was found to reach the yeast periplasm and the process depends on endoplasmic reticulum (ER) entry even though the protein is not oxidized. This result is remarkable since in eukaryotes, disulphide bond formation occurs in the ER. Oxidized mature lipo-beta-lactamase can also be released from the sphaeroplast into the yeast periplasm. Mutant lipo-beta-lactamase genes in which cysteine residue 131 was changed to either tyrosine or threonine, were efficiently processed and secreted in yeast, which is consistent with the finding that reduced-mature non-mutant lipo-beta-lactamase can be secreted. We discuss the possibility that the folding mechanism of lipo-beta-lactamase in vitro may be fundamentally different from the process in the eukaryotic system of S. cerevisiae.