Relationship between bullying victimization and perpetration, academic achievement and screen time among primary and secondary school students / 中国学校卫生

Objective@#The study aims to determine the latent class of roles in bullying victimization and perpetration among primary and secondary school students and to explore its relationship with academic achievement and screen use, to provide a reference for developing preventive measures and intervention plans.@*Methods@#A total of 29 099 students at grade 5,6,7,8,10, and 11 from Shenzhen were surveyed through convenient cluster sampling method by Olweus Bully/Victim Questionnaire. The latent class analysis was used for classifying bully/victim category.@*Results@#The latent class analysis revealed three classes, the noninvolvement group (low response rate at all items, 80.9%), the bullying victimization group (low response rate at bullying and high response rate at victimization items, 15.9%), and the bullying victimization and perpetration group (high response rate at all items,3.3%). Boys were more likely than girls to belong to the bullying victimization and perpetration at all study sections ( OR =0.83,0.74, 0.47 , P <0.05). Transfer students were at higher risk to be in the bullying victimization group in elementary and middle school ( OR = 1.21 ,1.21), while they were more likely to fall into the bullying victimization and perpetration group in high school ( OR =2.65)( P < 0.05). Students with poor academic performance were more likely to be in the bullying victimization group at all sections ( OR = 0.98 ,0.98,0.98) and in the bullying victimization and perpetration group at elementary and middle school ( OR =0.97, 0.98)( P < 0.05 ). Students spending longer time on screen had elevated risk in the bullying victimization group ( OR =1.06,1.04,1.08, P < 0.05 ).@*Conclusion@#Students with poor academic achievement and prolonged screen time are at higher risks to be involved in bullying victimization and perpetration. Collaboration between home and school are needed to preventing bullying victimization perpetration.

Recent advances in novel anticancer agents targeting β-catenin/TCF4 interaction for molecular cancer therapeutics / 药学学报

Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

Development of a fluorescence polarization-based high-throughput screening assay to identify antagonists targeting β-catenin/TCF4 interaction / 药学学报

To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrapTM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L-1 FITC-TCF4 and 100 nmol·L-1 β-catenin. Under these optimized conditions, a high Z´factor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.

Effect of hemoglobin on blood-brain barrier in rat models after intracerebral hemorrhage / 中华神经医学杂志

Objective To investigate the effect of hemoglobin on structure and function of blood-brain barrier (BBB) in rat models after intracerebral hemorrhage.Methods One hundred and eight male SD rats were randomized into normal control group (n=12),intracerebral hemoglobin injection group (Hb group,n=48) and sham-operated group (n=48); according to the different observation time points,rats in the Hb group and sham-operated group were divided into 4 subgroups (6 and 24 h,3 and 7 d after the injection,n=1 2).Histological changes and iron deposition of the brain tissues were examined with HE staining and iron staining,respectively.BBB permeability was evaluated by the permeation of Evens blue.The expressions of claudin-5 and ZO-1 in perihematomal brain tissues were detected by immunofluorescence staining and real-time fluorescence quantitative PCR.Results Evident edema and necrosis were observed in the perihematomal zone of Hb group,and iron deposition was found 3 and 7 days after the injection.The permeation of Evens blue in Hb group was significantly increased as compared with that in sham-operated group (P＜0.05).Immunofluorescence staining indicated that expressions ofclaudin-5 and ZO-1 were low and discontinuous in Hb group; the mRNA expression levels of claudin-5 and ZO-1 in Hb group were significantly lower than those in the sham-operated group (P＜0.05).Conclusion After intracerebral hemorrhage,Hb may induce the damage of BBB and participate in the course of brain edema.

Effects of hemoglobin level on Rho kinase of endothelial cells and tight junction protein claudin-5 in blood-brain barrier of rats after intracerebral hemorrhage / 中华神经医学杂志

Objective To explore the effects of hemoglobin level on Rho kinase Ⅱ of endothelial cells and tight junction protein clandin-5 in blood-brain barrier (BBB) of rats after intracerebral hemorrhage (ICH).Methods Male SD rats were randomized into normal control group (n=18) and hemoglobin inducement group (n=72); hemoglobin inducement group was divided into 4 subgroups (24 and 48 h,and 3 and 7 d after surgery,n=18).Rat ICH models in the hemoglobin inducement group were established by hemoglobin injection into the brain tissues.The expression ofRho kinase Ⅱ of endothelial cells and phosphorylated myosin light chain protein in BBB were observed by immunohistochemical staining,and BBB permeability was evaluated by Evans Blue dye; The protein and mRNA expressions of claudin-5 in the perihematomal brain tissues were detected by immunofluorescence staining and real-time quantitative PCR.Results Immunohistochemical staining indicated that expressions of Rho kinase Ⅱ of endothelial cells and phosphorylated myosin light chain in BBB of normal control group were rare,and those in the hemoglobin inducement group were high; as compared with that in the normal control group,mean optical density of Rho kinase Ⅱ and phosphorylated myosin light chain proteins in the endothelial cells of BBB in hemoglobin inducement group increased significantly at 48 h and 3 d after inducement (P＜0.05).The permeation of Evans Blue in hemoglobin inducement group significantly increased (P＜0.05).Immunofluorescence staining showed that the expression of clandin-5 in hemoglobin inducement group was uncontinuous and low as compared with that in the normal control group at 24 and 48 h and 3 d after inducement.PCR showed that the mRNA expression of claudin-5 in hemoglobin inducement group was significantly lower than that in the normal control group at 24 and 48 h and 3 and 7 d after the inducement (P＜0.05).Conclusion After intracerebral hemorrhage,hemoglobin can lead to increased expression of phosphorylated myosin light chain,and reduce the expression of tight junction protein claudin-5 of BBB by increasing the expression ofRho kinase Ⅱ in endothelial cells of BBB,which may be an important mechanism in the disruption of BBB and the occurrence of brain edema after intracerebral hemorrhage.

Distribution and expression changes of tight junctional protein JAM-1 in rat models after intracerebral hemorrhage / 中华神经医学杂志

[Objective]To explore the distribution and expression changes of tight junctional protein JAM-1 in rat models after intracerebral hemorrhage (ICH) and their significance.[Methods]One hundred and twenty-eighty healthy male SD rats were randomly divided into normal control group (n=16) and ICH group (n=112),and the ICH models were induced by stereotactically injecting 75 uL autologous blood into the right caudate nucleus.Seven time points after ICH (6,12,24 and 48 h,and 3,7 and 14 d after ICH,16 rats for each time point) were chosen.BBB permeability was evaluated by Evans blue dye extravasation.The distribution and expression of JAM-1 were detected by immunofluorescence and real-time quantitative PCR.[Results] As compared with that in the normal control group,BBB permeability in the ICH group significantly increased at 24 and 48 h,and 3 and 7 d after ICH (P＜0.05).JAM-1 expression decreased at blood vessels at 12,24 and 48 h after ICH,and JAM-1 expressed at the circulatingleukocytes3 dafterlCH,and abundant JAM-1 positive cells around hematoma were noted in the ED-l-positve macrophages 7 d after ICH.JAM-I mRNA significantly decreased at 12,24 and 48 h after ICH,and significantly increased 7 d after ICH as compared with that in the normal control group (P＜0.05).[Conclusion] JAM-1 experssion changes not only participate in regulation of BBB permeability but also play roles in inflammatory insult after ICH.