The so-called "Trojan-horse" mechanism, in which nanoparticles are internalized within cells and then release high levels of toxic ions, has been proposed as a behavior in the cellular uptake of Ag nanoparticles (AgNPs). While several reports claim to have proved this mechanism by measuring AgNPs and Ag ions (I) in cells, it cannot be fully proven without examining those two components in both intra- and extracellular media. In our study, we found that even though cells take up AgNPs similarly to (microglia (BV-2)) or more rapidly than (astrocyte (ALT)) Ag (I), the ratio of AgNPs to total Ag (AgNPs+Ag (I)) in both cells was lower than that in outside media. It could be explained that H2O2, a major intracellular reactive oxygen species (ROS), reacts with AgNPs to form more Ag (I). Moreover, the major speciation of Ag (I) in cells was Ag(cysteine) and Ag(cysteine)2, indicating the possible binding of monomer cysteine or vital thiol proteins/peptides to Ag ions. Evidence we found indicates that the Trojan-horse mechanism really exists.
BackgroundThe epithelial-to-mesenchymal transition (EMT) process results in a loss of cell-cell adhesion, increased cell mobility, and is crucial for enabling the metastasis of cancer cells. Recently, the enzyme SIRT1 has been implicated in a variety of physiological processes; however, its role in regulating oral cancer metastasis and EMT is not fully elucidated. Here, we propose a mechanism by which the enzyme sirtuin1 (SIRT1) regulates the EMT process in oral cancer by deacetylating Smad4 and repressing the effect of TGF-β signaling on matrix metalloproteinase-7 (MMP7).MethodsThe roles of SIRT1 in tumor cell migration/invasion and metastasis to the lungs were investigated using the Boyden chamber assay and orthotopic injections, respectively. RNA interference was used to knockdown either SIRT1 or Smad4 expression in oral squamous cell carcinoma (OSCC) cell lines. Immunoblotting, zymographic assays, and co-immunoprecipitation were used to examine the effects of SIRT1 overexpression on MMP7 expression and activity, as well as on SIRT1/ Smad4 interaction.ResultsWe found that compared with normal human oral keratinocytes (HOKs), SIRT1 was underexpressed in OSCC cells, and also in oral cancer tissues obtained from 14 of 21 OSCC patients compared with expression in their matched normal tissues. Overexpression of SIRT1 inhibited migration of OSCC cells in vitro, as well as their metastasis to the lung in vivo. Furthermore, up-regulation of SIRT1 in metastatic OSCCs significantly inhibited the migration and invasion abilities of OSCC cells, while concomitantly increasing the expression of E-cadherin, and decreasing the expressions of mesenchymal markers. We also identified Smad4, a TGF-β-activated transcription factor, as a direct target protein for SIRT1. Overexpression of SIRT1 in OSCC cells led to decreased levels of acetylated Smad4, and inhibition of TGF-β-induced signaling. By associating and deacetylating Smad4, SIRT1 enzyme can influence MMP7 expression, MMP enzyme activity, and consequently, cell migration, invasion, and tumor metastasis in OSCCs.ConclusionsThese findings provide a valuable insight into the potential role of the SIRT1 enzyme in regulating cell migration and invasion in oral squamous cell carcinoma. Our findings suggest the SIRT1/Smad4/MMP7 pathway as a target for oral cancer driven by EMT.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-4598-13-254) contains supplementary material, which is available to authorized users.
Although research has documented the positive effects of family-based prevention programs, the field lacks specific information regarding why these programs are effective. The current study summarized the effects of family-based programs on adolescent substance use using a component-based approach to meta-analysis in which we decomposed programs into a set of key topics or components that were specifically addressed by program curricula (e.g., parental monitoring/behavior management, problem solving, positive family relations, etc.). Components were coded according to the amount of time spent on program services that targeted youth, parents, and the whole family; we also coded effect sizes across studies for each substance-related outcome. Given the nested nature of the data, we used hierarchical linear modeling to link program components (Level 2) with effect sizes (Level 1). The overall effect size across programs was .31, which did not differ by type of substance. Youth-focused components designed to encourage more positive family relationships and a positive orientation toward the future emerged as key factors predicting larger than average effect sizes. Our results suggest that, within the universe of family-based prevention, where components such as parental monitoring/behavior management are almost universal, adding or expanding certain youth-focused components may be able to enhance program efficacy.
BackgroundDespite the documented and well known patient benefits of ACP, the completion of ACP, only a minority of patients, during the advanced or EOL stage of their illnesses, receive such care. The misconceptions about ACP for healthcare providers, such as nurses, might become potential barriers to the effective implication of ACP. Also, from the transcultural perspective, it is evident essential to explore Taiwanese nurses’ attitudes, knowledge, and actions of ACP. The purposes of this study were to explore the implication of ACP or hospice care for nurses caring for non-cancer chronic illness patients at a regional teaching hospital in Taiwan; and, to identify predictors of those nurses’ knowledge, attitudes, and actions toward ACP.MethodsThis cross-sectional study with a purposive sample of 218 nurses was conducted at a teaching hospital in southern Taiwan. Structured questionnaires were employed and data were analyzed with descriptive statistics, t-test, one-way ANOVAs, Pearson’s correlation and multiple regressions.Results16.1% of Taiwanese physicians actively initiated ACP issues or conversations with patients or their family members. Nurses’ attitudes toward ACP were fairly positive but their knowledge about ACP was insufficient and actions of ACP were not positively executed. The predictors of ACP-Knowledge (ACP-K) included position title, education hours and lacking of educational training. The predictors of ACP-Attitude (ACP-A) included ACP-K and “fear of patient or family member not accepting”, whereas ACP-A, position title, “patients do not feel necessary” and “not sure physician’s concern” were the predictors of ACP-Act.ConclusionContinuous education and training for nurses regarding ACP needs to be improved by taking those predictors found in this current study into account, and more studies on the nurse’s role in ACP also should be further examined.Trial registrationKAFGH 106–012. Date of registration 1 May 2017.
Crafting Engaging Science Environments is a high school chemistry and physics project-based learning intervention that meets Next Generation Science Standards performance expectations. It was administered to a diverse group of over 4,000 students in a randomized control trial in California and Michigan. Results show that treatment students, on average, performed 0.20 standard deviations higher than control students on an independently developed summative science assessment. Mediation analyses show an indirect path between teacher- and student-reported participation in modeling practices and science achievement. Exploratory analyses indicate positive treatment effects for enhancing college ambitions. Overall, results show that improving secondary school science learning is achievable with a coherent system comprising teacher and student learning experiences, professional learning, and formative unit assessments that support students in “doing” science.
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