Search

Despite widespread recognition that conspiracy theories carry the potential for serious harm, relatively little research has investigated possible antidotes to conspiracy beliefs. Previous theorizing posits that belief in conspiracy theories is driven in part by existential motives related to a sense of control and social motives aimed at maintaining a positive image of oneself and one's ingroup. Using electoral contests as the context, we investigated whether the act of voting (i.e., addressing existential motives) and seeing one's preferred candidate win (i.e., addressing social motives) were associated with a reduction in conspiracy beliefs. In two two-wave studies of high-profile U.S. elections, we measured endorsement of conspiracy beliefs before the election and after the results were known, thereby tracking change in conspiracy belief endorsement over time. Both Study 1 (2020 U.S. Presidential election) and Study 2 (2021 Georgia Senate runoff election) showed a significant decrease in conspiracy beliefs among people who supported the winning candidate, consistent with the importance of social motives. The findings highlight the merits of one's political ideology receiving support and recognition for potentially abating conspiracy beliefs. [ABSTRACT FROM AUTHOR]

The epithelial–mesenchymal transition (EMT) is a key process in tumor invasion and migration. Transforming growth factor-βs (TGF-βs) are multifunctional growth factors and powerful modulators of the EMT. Here, we investigated the relationship between TGF-β expression and invasion by treated triple-negative breast cancer (TNBC) cells. Our results show that invasion capacity of TNBC cells was markedly higher than that of non-TNBC cells. In addition, EMT-related gene signatures, including vimentin (vim), fibronectin (FN), snail, and slug were highly expressed in TNBC cells. Interestingly, our results show that TGF-β1 and β2 mRNA expression levels were higher in TNBC cells than those in non-TNBC cells. Thus, we examined the effect of the TGF-β receptor I/II inhibitor LY2109761 on EMT-related gene expression and cell motility. Our data show that vim, FN, and slug mRNA expression levels dose-dependently decreased in response to LY2109761. TNBC cell motility also decreased in response to LY2109761. Finally, we investigated the effect of LY2109761 on TGF-β1 or TGF-β2-induced E-cadherin (E-cad), vim, and FN mRNA and protein expression. The reduction in E-cad and induction of vim and FN expression by TGF-β1 or TGF-β2 were completely reversed by LY2109761 treatment in HCC1806 TNBC cells. Taken together, we demonstrated that elevated TGF-β expression triggers invasion and migration by TNBCs through the EMT process. Inhibiting the TGF-β signaling pathway is considered a promising therapeutic strategy for treating TNBC. [ABSTRACT FROM AUTHOR]

Abstract: The regulatory function of caveolin-2 in cell cycle regulation by insulin was investigated in human insulin receptor-overexpressed rat 1 fibroblast (Hirc-B) cells. Insulin increased induction of the caveolin-2 gene in a time-dependent manner. Direct interaction between ERK and caveolin-2 was confirmed by immunoprecipitation and phosphorylated ERK increased the specific interaction in response to insulin. That insulin induced their nuclear co-localization over time was demonstrated by immunofluorescence microscopy. Insulin increased the S phase in the cell cycle by 6-fold. When recombinant caveolin-1 was transiently expressed, a decrease in the S phase was detected by flow-cytometry. The results indicate that the up-regulation of caveolin-2 in response to insulin activates the downstream signal cascades in the cell cycle, chiefly the increased phosphorylation of ERK, the nuclear translocation of phosphorylated ERK, and the subsequent activation of G0/G1 to S phase transition of the cell cycle. The results also suggest that DNA synthesis and the activation of the cell cycle by insulin are achieved concomitantly with an increase in the interaction between caveolin-2 and phosphorylated ERK, and the nuclear translocation of that complex. Taken together, we conclude that caveolin-2 positively regulates the insulin-induced cell cycle through activation of and direct interaction with ERK in Hirc-B cells. [Copyright &y& Elsevier]

WNT5A is abnormally increased in a variety of cancers including breast cancer and has an adverse effect on the prognosis. However, the biological function of WNT5A is not fully known in HER2-positive (HER2+) breast cancer. Using public clinical data, we analyzed disease-free survival (DFS) and distant metastasis-free survival (DMFS). Here, we found that abnormal WNT5A induction is a correlation with the poor prognosis of HER2+ breast cancer. WNT5A expression was also decreased by pan-HER inhibitor neratinib but not by trastuzumab. In addition, WNT5A augmented cell invasiveness of HER2+ breast-cancer cells. To find WNT5A-induced metastatic-related factors, we did a human cytokine array. The levels of GM-CSF and CXCL8 were significantly increased by WNT5A. CXCL8 also accelerated cell invasiveness in HCC1954 breast-cancer cells. The expression of CXCL8 induced by WNT5A has been significantly reduced by MEK inhibitor, binimetinib. Finally, we studied the effect of CXCR2 antagonist, SB225002, to verify the relevance of CXCL8 in WNT5A-induced cell invasion. As expected, we found that WNT5A-induced cell invasion is completely inhibited by SB225002. Taken together, we have demonstrated that WNT5A directly mediates cell invasion through the induction of CXCL8 and ultimately affects the survival rate of HER2+ breast cancer. [ABSTRACT FROM AUTHOR]

Background: Berberine (BBR) is one of the major alkaloids, and it has been reported to have a variety of pharmacologic effects, including inhibition of cell cycle progression. Here, we investigated the effect of BBR on the MMP-1 and MMP-9 expressions, which are predictors of metastasis and invasion in breast cancer cells. Methods: MMP-1 and MMP-9 mRNA expressions were analyzed by real-time PCR. The levels of MMP-1 protein and PKC-α phosphorylation were detected by Western blotting. MMP-9 protein expression was detected by gelatin zymography. Cell cycle was analyzed by FACS analysis. PKC-α knock-down was examined by PKC-α siRNA transfection. Results: The basal levels of both the MMP-1 and MMP-9 mRNA expressions were decreased by BBR treatment in a dose-dependent manner. In contrast, TPA, which is a tumor promoter, significantly increased the levels of the MMP-1 and MMP-9 mRNA and protein expressions in the MCF-7 breast cancer cells. We also observed that the TPA-induced MMP-1 and MMP-9 mRNA and protein expressions were prevented by BBR treatment. In addition, the TPA-induced MMP-1 and MMP-9 expressions were completely decreased by Go6983 and PKC-α siRNA, respectively. TPA-induced PKC-α phosphorylation was dose-dependently decreased by BBR treatment. Conclusion: The TPA-induced PKC-α phosphorylation is suppressed and then the MMP-1 and MMP-9 expressions are also inhibited by berberine. Therefore, we suggest that berberine may be used as a candidate drug for the inhibition of metastasis of human breast cancer. [Copyright &y& Elsevier]

Fibronectin (FN), an extracellular matrix ligand, plays a pivotal role in cell adhesion, migration, and oncogenic transformation. Aberrant FN expression is associated with poor prognoses in various types of cancer, including breast cancer. In the current study, we investigated the relationship between FN induction and HER2 expression in breast cancer cells. Our results showed that the level of FN expression increased in response to HER family ligands, EGF and TGF-α in a time- and dose-dependent manner. On the other hand, EGF-induced FN expression decreased in response to trastuzumab, which is a HER2-targeted monoclonal antibody. However, EGF-induced FN expression was not affected by trastuzumab in JIMT-1 breast cancer cells, which are trastuzumab insensitive cells. Next, we introduced the HER2 gene into MDA-MB231 cells to verify the relationship between FN and HER2. The level of FN expression significantly increased in HER2-overexpressed MDA-MB231 cells. In contrast, the induction of FN by HER2 was significantly decreased in response to trastuzumab treatment. In addition, the induction of FN by HER2 was down-regulated by the MEK 1/2 specific inhibitor, U0126. Using conditioned culture media of vec- and HER2-overexpressed MDA-MB231 cells, we observed the cell morphology, adhesion, and invasion of MDA-MB231 cells. Interestingly, in conditioned culture media of HER2-overexpressed MDA-MB231 cells, the cell morphology was altered, and adhesion and invasion of MDA-MB231 cells significantly increased. In addition, our results showed that recombinant human FN augmented cell adhesion and invasion of MDA-MB231 cells while these inductions decreased in response to an FN inhibitor. Therefore, we demonstrated that the induction of FN by HER2 triggers cell adhesion and invasion capacities. [ABSTRACT FROM AUTHOR]

Abstract: Students’ learning has been the center of schooling. This study examined the contribution of situational interest motivation and cognitive engagement in workbooks to student achievement in learning health-related fitness knowledge. Situational interest, performance on solving workbook problems, and knowledge gain in cardio-respiratory fitness and benefits were measured in 670 third-grade students from 13 randomly selected urban elementary schools. Structural equation modeling and regression curve estimation analyses revealed that situational interest contributed little to workbook performance and knowledge gain. Performance on solving workbook problems contributed significantly to knowledge gain. The results also show that skipping workbook tasks had stronger negative impact on knowledge gain than performing the tasks incorrectly, suggesting the importance of engaging students in the learning process by attempting the workbook tasks. The findings reinforced the value of using workbooks to facilitate cognitive knowledge learning in physical education, but raised questions about the direct function of situational interest on engaging students in cognitive learning. [Copyright &y& Elsevier]