BackgroundMechanisms governing the metastasis of endometrial cancer (EC) are poorly defined. Recent data support a role for Enhancer-of-split and hairy-related protein 1 (SHARP1), a basic helix-loop-helix transcription repressor, in regulating invasiveness and angiogenesis of several human cancers. However, the role of SHARP1 in metastasis of EC remains unclear.MethodsHuman EC cell lines (Ishikawa and HEC-1B) were used. SHARP1 was upregulated by lentivirus transduction, while intracellular domain of NOTCH1 (ICN) were upregulated by transient transfection with plasmids. Effects of SHARP1 on cell migration and invasion were evaluated by wound healing assay and transwell invasion assay. Experimental metastasis assay were performed in nude mice. Effects of SHAPR1 on protein levels of target genes were detected by western blotting. Furthermore, the association between SHARP1 and the NOTCH1/EMT pathway was further verified in EC tissue specimens by immunohistochemical analysis.ResultsOverexpression of SHARP1 in EC cells inhibited cell migration, invasion, and metastasis. Exogenous SHARP1 overexpression affected the proteins levels of genes involved in EMT process and NOTCH1 signaling pathway. Upregulation of ICN in SHARP1-overexpressing Ishikawa cells induced cell migration and an EMT phenotype. Additionally, immunohistochemical analysis demonstrated that SHARP1 protein levels were lower in metastatic EC than in primary tumors, and statistical analysis revealed correlations between levels of SHARP1 and markers of EMT and NOTCH1 signaling pathway in human EC tissue specimen.ConclusionsThis work supports a role for SHARP1 in suppressing EMT and metastasis in EC by attenuating NOTCH1 signaling. Therefore, SHARP1 may be a novel marker for lymphatic metastasis in EC patients.
This study investigated the function of a chloride channel blocker, DIDS. Both in vitro and in vivo studies found that DIDS significantly inhibits lipopolysaccharide (LPS)-induced release of proin flammatory cytokines. Here, we show that DIDS inhibits LPS-induced inflammation, as shown by downregulation of inflammatory cytokines via inhibition of the TLR4/NF-κB pathway. Furthermore, we show that ClC-3siRNA transfection reduces LPS-induced pro-inflammation in Raw264.7 cells, indicating that ClC-3 is involved in the inhibitory effect of DIDS during LPS-induced cytokines release. In vivo, DIDS reduced LPS-induced mortality, decreased LPS-induced organic damage, and down-regulated LPS-induced expression of inflammatory cytokines. In sum, we demonstrate that ClC-3 is a pro-inflammatory factor and that inhibition of ClC-3 inhibits inflammatory induction both in vitro and in vivo, suggesting that ClC-3 is a potential anti-inflammatory target.
Objective To evaluate the effect of newly designed arthroscopic reconstruction of posterior cruciate ligament (PCL) using tibial tendon bolt. Methods The effects of embedded tendon pin were observed by X‐ray of knee joint. From October 2010 to September 2015, 51 PCL injury patients who met the inclusion criteria were enrolled in this retrospective study. The arthroscopically assisted reconstruction of the PCL with tibial tendon bolt was performed on all patients. Visual Analog Scale (VAS) pain score, Tegner activity score, Lysholm score, International Knee Documentation Committee (IKDC) assessment, posterior drawer test (PDT), and KT‐1000 activity score were evaluated preoperatively and at 1‐year postoperative and 3‐year postoperative. Results The preoperative, 1‐year postoperative, and 3‐year postoperative IKDC score (15.8% ± 14.8%, 89.6% ± 5.8%, and 86.8% ± 5.4%), Lysholm score (17.4 ± 10.7, 91.2 ± 2.8, and 88.2 ± 3.1), VAS score (5.8 ± 1.2, 1.3 ± 0.5, and 0.6 ± 0.5), Tegner activity score (1.2 ± 0.8, 8.1 ± 0.8, and 7.4 ± 0.8), and KT‐1000 score (15.6 ± 3.6, 4.5 ± 2.4, and 5.4 ± 1.8) were obtained. There were significant differences in these outcomes among preoperative, 1‐year postoperative, and 3‐year postoperative (all P < 0.0001). After 1‐ and 3‐year surgery, 31 (60.8%) and 26 (51.0%) patients had the negative PDT, indicating that the PCL injury was improved. There were no postoperative complications. Conclusion The application of tendon pin fixed by tibial inlay 8‐shaped tibial tunnel to reconstruct PCL was an effective, simple, and safe surgical procedure for PCL injury.
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