RESUMO
The Cancer/Testis Antigen (CTA), Prostate-associated Gene 4 (PAGE4), is a stress-response protein that is upregulated in prostate cancer (PCa) especially in precursor lesions that result from inflammatory stress. In cells under stress, translocation of PAGE4 to mitochondria increases while production of reactive oxygen species decreases. Furthermore, PAGE4 is also upregulated in human fetal prostate, underscoring its potential role in development. However, the proteins that interact with PAGE4 and the mechanisms underlying its pleiotropic functions in prostatic development and disease remain unknown. Here, we identified c-Jun as a PAGE4 interacting partner. We show that both PAGE4 and c-Jun are overexpressed in the human fetal prostate; and in cell-based assays, PAGE4 robustly potentiates c-Jun transactivation. Single-molecule Förster resonance energy transfer experiments indicate that upon binding to c-Jun, PAGE4 undergoes conformational changes. However, no interaction is observed in presence of BSA or unilamellar vesicles containing the mitochondrial inner membrane diphosphatidylglycerol lipid marker cardiolipin. Together, our data indicate that PAGE4 specifically interacts with c-Jun and that, conformational dynamics may account for its observed pleiotropic functions. To our knowledge, this is the first report demonstrating crosstalk between a CTA and a proto-oncogene. Disrupting PAGE4/c-Jun interactions using small molecules may represent a novel therapeutic strategy for PCa.
Assuntos
Antígenos de Neoplasias/metabolismo , Próstata/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Ativação Transcricional , Regiões 3' não Traduzidas/genética , Antígenos de Neoplasias/química , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Transferência Ressonante de Energia de Fluorescência , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Mutação , Próstata/embriologia , Próstata/crescimento & desenvolvimento , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Ligação Proteica , Conformação Proteica , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-jun/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Estresse FisiológicoRESUMO
Background: The use of a rubber dam is more important than ever in today's COVID-19 era to limit cross infections. In children, the placement of the metal clamp to retain the rubber dam is perceived to be painful and often requiring a local anesthetic injection. This dissuades many clinicians from placing the rubber dam. Hence, this study evaluated the pain response of children to a SoftClamp™ compared to the conventional metal clamp. Materials and Methods: This was a randomized controlled, equal allocation ratio, split-mouth clinical trial. Forty-two children aged between 8 and 12 years, having two permanent mandibular molars in need of sealants, were divided into Groups A and B (metal clamp and SoftClamp™, respectively). The pain response was recorded using both an objective and a subjective scale i.e., the Faces Legs Activity Cry Consolability (FLACC) scale and the Wong Baker Faces Pain Rating Scale (WBFPRS). The level of significance was set at 5% (P < 0.05). The pain response recorded from the WBFPRS and the FLACC scale for the metal and the SoftClamp™ were analyzed using the Wilcoxon signed rank test. The difference in pain response between genders and between two age groups (below and above 10 years of age) was analyzed using the Mann-Whitney U-test. Results: The children reported mild discomfort to clamp placement in both the scales. The P values for the FLACC and WBFPRS scores comparing the pain response to the metal and SoftClamp™ were 0.311 and 0.149, respectively. Conclusion: There was no significant difference in the pain response of children to both the clamps. Good rubber dam application practices in children through the use of behavior guidance and a proper topical anesthesia technique may play a far more important role regardless of the clamp used. But the SoftClamp™, with its more child friendly appearance could be a viable alternative to the metal clamp in children.
RESUMO
Background: The primary maxillary molars occasionally remain sensitive during operative procedures even post the buccal supraperiosteal injection. This could be due to the widely flared palatal roots receiving accessory innervation from the palatal nerves. Identifying inadequate anesthesia upfront using the electric pulp test (EPT) would give vital information to the clinician on the need of a supplemental palatal injection. Aim: The aim of this study was to assess and evaluate the reliability of the EPT as an indicator of pulpal anesthesia in primary maxillary molars. Methodology: Fifty one primary maxillary molars were subjected to the EPT following a buccal supraperiosteal injection. During the operative procedure, the " Face Legs Activity Cry Consolability" (FLACC) scores were recorded. The outcome of the EPT was correlated with the results of the FLACC score using Pearson's Chi-square test.Results: The EPT results were correlated to the FLACC scores. Five out of the 10 primary maxillary second molars which responded to the EPT scored 0 on the FLACC scale. The remaining 5 teeth scored 1 on the FLACC scale. The P value was 0.056 which was not statistically significant. This infers that the EPT is not a reliable tool to assess the adequacy of pulpal anesthesia in primary maxillary second molars. Conclusion: From the results of the present study, it can be concluded that the EPT is not a reliable tool to be used as an indicator of pulpal anesthesia in primary maxillary molars.
Assuntos
Anestesia Dentária , Anestésicos Locais , Humanos , Anestesia Local/métodos , Reprodutibilidade dos Testes , Polpa Dentária , Anestesia Dentária/métodosRESUMO
Removing dissolved metals from urban storMwater may be required to protect aquatic species in particular watersheds. This research examined the adsorption of zinc and copper on 12 granular activated carbons, of which six were obtained commercially and six were produced by thermal activation of agricultural byproducts in the laboratory. Batch studies were used to obtain single solute distribution coefficients at pH 7. Copper distribution coefficients were higher than those for zinc on each of the 12 adsorbents. Granular activated carbon (GAC) produced from nutshells was less effective than that produced from rice materials (straw and hulls). The rice-derived GACs had the highest zinc distribution coefficients, and the commercial GACs typically exhibited higher copper distribution coefficients. Distribution coefficients for zinc and copper typically were higher for the materials tested in this study than in previous research, possibly because of the lower dissolved metal concentrations used, which were chosen to represent highway stormwater. Adsorption isotherms were obtained for zinc and copper adsorption on one commercial GAC and on activated rice hulls in buffered laboratory water and in highway stormwater. The constituents in stormwater caused a reduction in sorption of zinc and copper of up to 80%. The results suggest that 1 kg of activated rice hulls could treat up to 7 m3 of stormwater for zinc or 46 m3 of copper before exhaustion at the 90th percentile dissolved concentrations in California highway stormwater. The higher stormwater concentration and lower GAC affinity of zinc means that this constituent typically will limit adsorption system design for removal of multiple metals from stormwater.
Assuntos
Carbono/química , Cobre/química , Chuva/química , Purificação da Água/métodos , Água/química , Zinco/química , Adsorção , Cidades , Metais/químicaRESUMO
STUDY OBJECTIVES: Nocturnal bruxism is associated with gastroesophageal reflux disease (GERD), and GERD is strongly associated with obstructive sleep apnea (OSA). Gender and ethnic differences in the prevalence and clinical presentation of these often overlapping sleep disorders have not been well documented. Our aim was to examine the associations between, and the symptoms associated with, nocturnal GERD and sleep bruxism in patients with OSA, and to examine the influence of gender and ethnicity. METHODS: A retrospective chart review was performed of patients diagnosed with OSA at an academic sleep center. The patients completed a sleep questionnaire prior to undergoing polysomnography. Patients with confirmed OSA were evaluated based on gender and ethnicity. Associations were determined between sleep bruxism and nocturnal GERD, and daytime sleepiness, insomnia, restless legs symptoms, and markers of OSA severity in each group. RESULTS: In these patients with OSA, the prevalence of nocturnal GERD (35%) and sleep bruxism (26%) were higher than the general population. Sleep bruxism was more common in Caucasians than in African Americans or Hispanics; there was no gender difference. Nocturnal GERD was similar among all gender and ethnic groups. Bruxism was associated with nocturnal GERD in females, restless legs symptoms in all subjects and in males, sleepiness in African Americans, and insomnia in Hispanics. Nocturnal GERD was associated with sleepiness in males and African Americans, insomnia in females, and restless legs symptoms in females and in Caucasians. CONCLUSION: Patients with OSA commonly have comorbid sleep bruxism and nocturnal GERD, which may require separate treatment. Providers should be aware of differences in clinical presentation among different ethnic and gender groups.