Objective To investigate the mechanism of E26 transformation-specific sequence 4(ETV4)affecting the proliferation and migration of colon cancer cells through the nuclear factor-κB(NF-κB)signaling pathway.Methods The expression level of ETV4 in normal colon tissues and cancer tissues was analyzed by the user-friendly interactive cancer transcriptome data analysis resource(UALCAN)database.Reverse transcription quantitative polymerase chain reaction(qRT-PCR)and Western blot were used to detect the expression level of ETV4 in normal intestinal epithelial cells and colon cancer cell lines.After silencing ETV4 in SW480 cells,qRT-PCR and Western blot were per-formed to detect the expression of ETV4 to assess transfection efficiency;colony formation and Tran-swell assays were conducted to explore the effects of ETV4 silencing on the proliferation and migration of colon cancer cells;the Western blot was used to detect the effects of ETV4 silencing on the protein expression of protein 65(p65)and phosphorylated protein 65(p-p65)in the NF-κB pathway.Results The UALCAN database analysis revealed high expression of ETV4 in colon cancer tissues.The qRT-PCR and Western blot showed that ETV4 expression was significantly higher in the colon cancer cell lines SW480,Lovo,Caco-2,and SW620 than in normal intestinal epithelial cells HIEC-6,with the highest expression in SW480 cells(P＜0.001).Colony formation and Transwell assay results indicated that silencing ETV4 significantly inhibited the proliferation and migration of colon cancer SW480 cells(P＜0.001).Western blot results showed that silencing ETV4 significantly inhibited the expression of p-p65 protein in the cells(P＜0.001).Conclusion Silencing ETV4 may inhibit the activation of the NF-κB signaling pathway,thereby inhibiting the proliferation and migration of colon cancer cells.

Congenital hydrocephalus is a major neurological disorder with high rates of morbidity and mortality; however, the underlying cellular and molecular mechanisms remain largely unknown. Reproducible animal models mirroring both embryonic and postnatal hydrocephalus are also limited. Here, we describe a new mouse model of congenital hydrocephalus through knockout of β-catenin in Nkx2.1-expressing regional neural progenitors. Progressive ventriculomegaly and an enlarged brain were consistently observed in knockout mice from embryonic day 12.5 through to adulthood. Transcriptome profiling revealed severe dysfunctions in progenitor maintenance in the ventricular zone and therefore in cilium biogenesis after β-catenin knockout. Histological analyses also revealed an aberrant neuronal layout in both the ventral and dorsal telencephalon in hydrocephalic mice at both embryonic and postnatal stages. Thus, knockout of β-catenin in regional neural progenitors leads to congenital hydrocephalus and provides a reproducible animal model for studying pathological changes and developing therapeutic interventions for this devastating disease.
Animals ; Disease Models, Animal ; Hydrocephalus/genetics* ; Mice ; Mice, Knockout ; Neurons ; beta Catenin/genetics*

ObjectiveTo investigate the effect of imperatorin on liver damage， peroxidative stress and immune response in young rats with type I diabetes induced by streptozotocin （STZ）. MethodsTotally 50 BALB/c juvenile mice were equally divided into healthy control group， model group， model plus+3 mg/kg Imperatorin group， model+6 mg/kg Imperatorin group， and model+12 mg/kg Imperatorin group. Glucose tolerance test was used to detect fasting blood glucose， serum insulin and obesity index of mice in each group. Automatic biochemical analyzer was used to determine serum HDL， LDL， TG， TC content. HE staining was used to observe the degree of liver damage. TUNEL staining was used to observe cell apoptosis. SOD and MDA levels were detected by Kit， Box/Bcl-2， cleaved cas3/cas3， c-Myc expression levels in mitochondria by Western blot， and serum IL-6， TNF-α， IL-1β levels by ELISA. ResultsCompared with the model group， 12 mg/kg Imperatorin significantly reduced fasting blood glucose ［mean difference 5.3 mmol/L， 95% confidence interval （4.5， 6.1） mmol/L］， serum insulin ［mean difference 13.2 μU/L， 95% confidence interval （10.6， 15.8） μU/L］ and obesity index ［average difference 2.3 kg/m²， 95% confidence interval （2.1， 2.5） kg/m²］ all decreased. The content of SOD increased （P<0.05）， while the content of MDA was reduced （P<0.05）. The expression level of Bax/Bcl-2， and cleaved cas3/cas3 was down-regulated （P<0.05）， while the level of c-Myc was up-regulated （P<0.05）， and the content of IL-6， TNF-α and IL-1β was reduced （P<0.05）. ConclusionImperatorin can alleviate the liver damage， peroxidation and immune response in young rats with STZ-induced type I diabetes.

Objective::To explore the effect of Tongxie Yaofang on p38 mitogen activated protease(p38 MAPK), mitogen and stress protein kinase 1(MSK1), cyclic adenosine effector response element binding protein(CREB)mRNA and protein expression in colon tissue of diarrhea type irritable bowel syndrome (D-IBS) rat model with liver depression and spleen deficiency(GYPX), and interleukin-1β(IL-1β), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α), and the content of total superoxide dismutase (T-SOD) and malondialdehyde (MDA) in serum. Method::The 60 SPF Wistar rats were randomly divided into 6 groups, with 10 rats in each group. Except the normal group, rats in the other groups were given by gavage with folium sennae and chronic bondage to establish D-IBS with GYPX for 14 days. The low, medium, and high doses Tongxie Yaofang were administered to Tongxie Yaofang(2.25, 4.5, 9 g·kg^-1)gavage respectively. The piveronium bromide group was given piveronium bromide tablets suspension(0.02 g·kg^-1)gavage.The normal group group and model group were given the same volume normal saline for 21 days. After the last gavage for 18 hours, the heart blood was collected and the colon tissue was dissected. Real-time PCR was used to observe the expression of p38 MAPK, MSK1 and CREB mRNA in rat colon. Western blot was used to observe the expression of p38 MAPK, MSK1 and CREB protein. ELISA was used to observe the contents of IL-1β, IL-6 and TNF-α in colon. Hydroxylamine was used to observe the T-SOD level in serum, thiobarbituric acid(TBA)was used to observe the MDA content in serum. hematoxyl in-eosin(HE) staining was used to observe the morphological changes of colon tissues. Result::Compared with normal group, the expression of p38 MAPK, MSK1, CREB mRNA and the protein content of p38 MAPK, MSK1 and CREB in the colon tissue of model group rats increased significantly, while the content of IL-1β, IL-6 and TNF-α increased significantly(P<0.05). The level of serum T-SOD decreased significantly, and the content of MDA increased significantly(P<0.05). Compared with the model group, the medium and high dose group of Tongxie Yaofang significantly decreased the expression of p38 MAPK mRNA, content of p38 MAPK, CREB protein and IL-1β, IL-6, TNF-α in colon tissue(P<0.05). The level of serum T-SOD increased significantly, and the content of MDA decreased significantly(P<0.05). High dose group of Tongxie Yaofang can significantly decreased the expression of MSK1, CREB mRNA, content of MSK1 protein(P<0.05). Histopathological observation showed that no significant organic lesions were observed in the colonic morphology of each group of rats, which was consistent with the morphological characteristics of IBS. Conclusion::Tongxie Yaofang has a significant dose-effect relationship in the treatment of D-IBS rats with GYPX in a certain range, which may be related to its increases antioxidant stress and inhibit activation of p38 MAPK signaling pathway and reducing the level of downstream inflammatory factors.