Tumor invasion and metastasis are the main causes of mortality in patients with hepatocellular carcinoma (HCC). Thus, the effective inhibition of these tumorigenic processes is critical in order for HCC therapy to be effective. Previous studies have demonstrated that Notch1 is associated with metastasis in several human malignancies. However, the exact molecular mechanisms underlying the Notch1-mediated induction of the invasion of HCC cells remain poorly understood. In the present study, we demonstrate that, compared to the normal liver cell line, L02, Notch1 is highly expressed in the human HCC cell lines, HepG2 and MHCC97H. Using small interfering RNA (siRNA), we knocked down the expression of Notch1 in the cell lines. Notch1 expression in the HCC cell lines was also measured following transfection with siRNA using RT-PCR and western blot analysis. In addition, a migration and invasion assay was performed to determine the effects of Notch1 knockdown on cell migration and invasion. Our results demonstrated that the downregulation of Notch1 by small interfering RNA (siRNA) significantly inhibited the migration and invasion of both HCC cell lines. Additionally, we demonstrated that the knockdown of Notch1 in both HCC cell lines increased both the total expression of phosphatase and tensin homolog (PTEN) and its phosphorylated form. By contrast, focal adhesion kinase (FAK) and phospho-FAK expression was decreased following Notch1 depletion. Taken together, our data suggest that targeting Notch1 may be a useful therapeutic approach to inhibiting the metastasis of HCC cells.
Background: Breathing exercises can improve the symptoms of patients with gastroesophageal reflux disease (GERD), but their specific effect and function are disputed. To evaluate and conduct a meta-analysis on the effect of breathing exercises on patients with GERD.Methods: A literature search for randomized controlled trials (RCTs) and prospective studies on the effects of employing breathing exercises on patients with GERD was conducted of all major online English databases (PubMed, Embase, the Cochrane library, CENTRAL, Web of Science, AMED, and CINAHL).After the systematic review of all the studies according to inclusion and exclusion criteria, we analyzed the extracted data through meta-analysis by using RevMan 5.3 software.Results: This thesis analyzes 7 studies (including three RCTs), which together involved 194 patients and 16 healthy volunteers. The primary outcomes of these studies included GERD symptoms, esophageal manometry, esophageal pH monitoring, laryngoscopic findings, and acid suppression usage. The results of meta-analysis indicate that breathing exercises can improve pressure generated by the lower oesophageal sphincter (LES), and a statistically significant difference was observed. The possible mechanism behind this is the enhancement of the anti-regurgitation barrier [especially crural diaphragm (CD) tension].Conclusions: To some extent, breathing exercises can relieve the symptoms of patients with GERD.
Background:The aim of the present study was to investigate the antitumor properties of N-(N-[3,5difluorophenacetyl]-1-alanyl)-S-phenylglycine t-butyl ester (DAPT) against hepatocellular carcinoma (HCC), as well as the underlying mechanism. Methods: Immunohistochemistry and quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay were used to determine the expression of Notch1 in HCC tissues. The expression of Notch1 in 3 HCC cell lines was evaluated by qRT-PCR and Western blot. The proliferation ability of cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony formation assays. Flow cytometry and Transwell assay were used to check the apoptosis and migration of HepG2 cells, respectively. Western blot was used to determine the expression level of Notch1, Hes1, Phosphatase and tensin homolog (PTEN), protein kinase B1 (AKT1), phosphorylated AKT1, mammalian target of rapamycin (mTOR), phosphorylated mTOR, intracellular adhesion molecule-1, vascular cell adhesion protein 1, matrix metalloproteinase (MMP)-2, MMP-9, and focal adhesion kinase in cells and tumor tissues. A HepG2 xenograft experiment was conducted to evaluate the in vivo antitumor properties of DAPT. Results: Notch1 was found to be significantly upregulated in both HCC tissues and cell lines. DAPT significantly inhibited the proliferation and migration of HepG2 cells in a dose-dependent manner, accompanied by the suppression of Notch1/Hes1 signaling, inactivation of AKT/mTOR signaling, downregulation of MMPs, and decreased expression of adhesion molecules. The activation of Notch1/ Hes1 or AKT/mTOR signaling removed the inhibitory effect of DAPT on the proliferation and migration of HepG2 cells, as well as the inhibitory properties of DAPT on the expression of MMPs and adhesion molecules. The antitumor properties and regulatory effect of DAPT against the extracellular matrix (ECM) and Hes1/PTEN/AKT/mTOR signaling were verified by the HepG2 xenograft experiments. Conclusions: DAPT could suppress the proliferation and migration of HCC by regulating the ECM and inhibiting the Hes1/PTEN/AKT/mTOR signaling pathway.
The great development of energy storage technology and energy storage materials will make an important contribution to energy saving, reducing emissions and improving energy utilization efficiency. Mobile thermal energy storage (M-TES) technology finds a way to realize value for low-grade heat sources far beyond the demand side. In this paper, an indirect-contact M-TES container is studied using the computational fluid dynamics (CFD) method. By optimizing the heat exchange tube bundle layout and the installed fin structure of the shell and tube type M-TES container, a method of enhancing the charging and discharging efficiency is identified. The peripheral distribution mode of the heat exchanger tubes improves the efficiency of heat charging by 12.6% compared with the traditional uniform layout. The installation of the Y-shaped fins can improve the heat charging efficiency by 8.3%, better than straight fins. Compared with the horizontal installation of Y-shaped fins, the vertical installation of Y-shaped fins is preferred to improve the heat charging efficiency of the M-TES container.
MicroRNA (miRNA/miR)-3677 has been indicated to be negatively associated with the survival of patients with hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas database. However, as a novel miRNA, the role of miR-3677-5p in HCC has remained to be elucidated. In the present study, the expression of miR-3677-5p was assessed in HCC tissues and cell lines using reverse transcription-quantitative PCR. Survival analysis was performed using Kaplan-Meier curves. Furthermore, the prognostic significance of miR-3677-5p was evaluated using Cox regression analysis. The effects of miR-3677-5p on cell proliferation, as well as migration and invasion capacities, were analyzed using Cell Counting Kit-8, crystal violet and Transwell assays. The results demonstrated that the level of miR-3677-5p expression was upregulated in human HCC tissues and cell lines and that miR-3677-5p expression was closely associated with tumor size, TNM stage and vascular invasion. Furthermore, high miR-3677-5p expression was significantly associated with unfavorable clinical prognosis for patients with HCC. Overexpression of miR-3677-5p was indicated to significantly promote the proliferation, migration and invasion of HCC cells, whereas knockdown of miR-3677-5p was observed to have an inhibitory effect. In conclusion, the present study demonstrated that miR-3677-5p acts as an oncogene that has a critical role in the regulation of HCC proliferation and progression. Hence, miR-3677-5p may serve as a valuable prognostic biomarker and may be developed as a promising therapeutic target for HCC. miR-3677-5p promotes the proliferation, migration and invasion of hepatocellular carcinoma cells and is associated with prognosis
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