ABSTRACT
As the most aggressive breast cancer, triple-negative breast cancer (TNBC) is still incurable and very prone to metastasis. The transform growth factor β (TGF-β)-induced epithelial-mesenchymal transition (EMT) is crucially involved in the growth and metastasis of TNBC. This study reported that a natural compound isotoosendanin (ITSN) reduced TNBC metastasis by inhibiting TGF-β-induced EMT and the formation of invadopodia. ITSN can directly interact with TGF-β receptor type-1 (TGFβR1) and abrogated the kinase activity of TGFβR1, thereby blocking the TGF-β-initiated downstream signaling pathway. Moreover, the ITSN-provided inhibition on metastasis obviously disappeared in TGFβR1-overexpressed TNBC cells in vitro as well as in mice bearing TNBC cells overexpressed TGFβR1. Furthermore, Lys232 and Asp351 residues in the kinase domain of TGFβR1 were found to be crucial for the interaction of ITSN with TGFβR1. Additionally, ITSN also improved the inhibitory efficacy of programmed cell death 1 ligand 1 (PD-L1) antibody for TNBC in vivo via inhibiting the TGF-β-mediated EMT in the tumor microenvironment. Our findings not only highlight the key role of TGFβR1 in TNBC metastasis, but also provide a leading compound targeting TGFβR1 for the treatment of TNBC metastasis. Moreover, this study also points out a potential strategy for TNBC treatment by using the combined application of anti-PD-L1 with a TGFβR1 inhibitor.
ABSTRACT
Objective To explore the relationship between aggressive behavior and attachment styles for adult prisoners.Methods A sample of 413 criminals filled out measures for Aggression Questionnaire and Adult Attachment Scale.Results There existed significant differences of anxiety,anger,hostility,physical attacks and the total score of AQ among different criminals type (F =2.80,5.80,5.15,16.82,10.69,P ＜ 0.001 or P ＜ 0.05).And there existed significant differences of anxiety,anger,hostility,physical attacks,verbal attacks and the total score of AQ among different adult attachment style (F =18.14,34,17,7,83,22,75,P ＜ 0.01).The close dimension of AAS was significantly negatively related with anger,hostility,physical attacks and the total score of AQ (r =-0.15--0.20,P ＜ 0.01).And the anxiety dimension of AAS was significantly positively related with anger,hostility,physical attacks,verbal attacks and the total score of AQ(r =0.30-0.52,P ＜ 0.01).Regression analysis found that anxiety dimension and close dimension of AAS were fairly effective variables in the prediction of the criminal attacks.Conclusion There are close relationships between aggressive behavior and adult attachment for criminals.The anxiety dimension and close dimension make a certain prediction to the criminal attacks.
ABSTRACT
A new chitosan derivative is prepared using chitosan.Ethyl chlorocarbonate was first introduced to the hydroxyl group of phthaloylchitosan through a nucleophilic reaction.Hydrazine was then added to recover the amino groups of chitosan and promote cross-linking.The structure of this new chitosan derivative was characterized by Fourier transform infrared (FT-IR) and proton nuclear magnetic resonance (1H NMR) spectroscopy,and its physical properties were determined by X-ray diffraction (XRD),differential scanning calorimetry (DSC),and thermogravimetric analysis (TGA).The thermal and chemical stabilities of the new derivative were improved compared with those of native chitosan.Assay of Escherichia coli adhesion on a film based on this chitosan derivative showed good adsorption and biofilm formation.