migration

摘要： Schisandrin B(Sch B)is a monomer with anti-cancer and anti-inflammatory effects,which are isolated from the plant Schisandra chinensis(Turcz)Baillon.We investigated the anti-gastric cancer(GC)effects of Sch B and its underlying molecular mechanisms.The Cell Counting Kit-8 assay was used to determine the effects of Sch B on the viability of GC and normal cell lines.Hoechst/propidium iodide staining and flow cytometry were used to assess the apoptosis induction of Sch B.Western blotting was used to evaluate the effects of Sch B on downstream apoptotic proteins.The DCFH-DA fluorescent probe was used to assess the regulatory effects of Sch B on reactive oxygen species(ROS)levels and related signaling pathways in GC cells.The results showed that Sch B could regulate the phosphorylation level of mitogen-activated protein kinase(MAPK)by upregulating ROS accumulation in gastric cancer cells,and then reduce the expression of nuclear factor kappa B(NF-κB)and phosphorylated transcription 3(p-STAT3).In addition,Sch B downregulated the cell cycle proteins cyclin-dependent kinase 2/4/6 and cyclin D1/E,and arrested cells in the G0/G1 phase.Moreover,it also inhibited cell migration,which was reversed with Nacetylcysteine pretreatment.In summary,Sch B has killing effects on GC cells by upregulating the production of intracellular ROS and regulating the MAPK/STAT3/NF-κB signaling pathway,leading to the migration arrest and apoptosis of GC cells.

摘要： Inhibiting retinal neovascularization is the optimal strategy for the treatment of retina-related diseases, but there is currently no effective treatment for retinal neovascularization. P-element-induced wimpy testis(PIWI)-interacting RNA(piRNA) is a type of small non-coding RNA implicated in a variety of diseases. In this study, we found that the expression of piR-1245 and the interacting protein PIWIL2 were remarkably increased in human retinal endothelial cells cultured in a hypoxic environment, and cell apoptosis, migration, tube formation and proliferation were remarkably enhanced in these cells. Knocking down piR-1245 inhibited the above phenomena. After intervention by a p-JAK2 activator, piR-1245 decreased the expression of hypoxia inducible factor-1α and vascular endothelial growth factor through the JAK2/STAT3 pathway. For in vivo analysis, 7-day-old newborn mice were raised in 75 ± 2% hyperoxia for 5 days and then piR-1245 in the retina was knocked down. In these mice, the number of newly formed vessels in the retina was decreased, the expressions of inflammationrelated proteins were reduced, the number of apoptotic cells in the retina was decreased, the JAK2/STAT3 pathway was inhibited, and the expressions of hypoxia inducible factor-1α and vascular endothelial growth factor were decreased. Injection of the JAK2 inhibitor JAK2/TYK2-IN-1 into the vitreous cavity inhibited retinal neovascularization in mice and reduced expression of hypoxia inducible factor-1α and vascular endothelial growth factor. These findings suggest that piR-1245 activates the JAK2/STAT3 pathway, regulates the expression of hypoxia inducible factor-1α and vascular endothelial growth factor, and promotes retinal neovascularization. Therefore, piR-1245 may be a new therapeutic target for retinal neovascularization.

摘要： Objective:The eukaryotic release factor 3a(eRF3a),a member of the eukaryotic peptide chain release factor family,is overexpressed in several types of cancer.This study aims to investigate the biological role and mechanism of eRF3a in the progression of liver cancer.

摘要： Objective:The aims of this study were to examine the prognostic value of SHP-1 in breast cancer,its roles in the regulation of breast cancer cell growth and metastasis,and the underlying mechanisms.Methods:Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan–Meier and multivariate Cox regression analyses.RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas.In vitro and in vivo assays were performed to elucidate the effects of SHP-1 on breast cancer cell proliferation and invasion.Confocal immunofluorescence and GST pulldown assays were used to demonstrate the interaction between SHP-1 and epidermal growth factor receptor,as well as its downstream pathways.Immunohistochemistry and The Cancer Genome Atlas database were used to investigate the clinical association between SHP-1 and EGFR in human breast cancer.Results:SHP-1 expression was associated with better survival in patients with breast cancer,whereas SHP-1 expression was negatively correlated with EGFR in human breast cancer.Ectopic SHP-1 expression significantly suppressed breast cancer cell proliferation,migration,and invasion.SHP-1 knockdown induced a more invasive phenotype and accelerated cell growth.Mechanistically,EGFR,a protein directly interacting with SHP-1,mediates the SHP-1-induced inactivation of Ras/Erk/GSK3βsignaling and its downstream effectors.Conclusions:SHP-1 is an important prognostic biomarker in patients with breast cancer,and the SHP-1-EGFR axis is a promising target for treatment.

摘要： BACKGROUND Mesh plug(MP)erosion into the intra-abdominal organs is a rare but serious long-term complication after inguinal hernia repair(IHR),and may lead to aggravation of symptoms if not treated promptly.It is difficult to diagnose MP erosion as there are no obvious specific clinical manifestations,and surgery is often needed for confirmation.In recent years,with the increased understanding of postoperative complications,MP eroding into the intra-abdominal organs has been a cause for concern among surgeons.CASE SUMMARY A 50-year-old man was referred to the Department of General Surgery with the complaint of abdominal pain in the right lower quadrant for 2 d.He had a surgical history of right open IHR and partial thyroidectomy performed 20 years and 15 years ago,respectively.Computed tomography revealed a circinate highdensity image with short segmental thickening of the ileum stuck to the abdominal wall,and no evidence of recurrent inguinal hernia.Laparoscopic abdominal exploration confirmed adhesion of the middle segmental portion of the ileal loop to the right inguinal abdominal wall;the rest of the small intestine was normal.Further exploration revealed migration of the polypropylene MP into the intraperitoneal cavity and formation of granulation tissue around the plug,which eroded the ileum.Partial resection of the ileum,including the MP and end-to-side anastomosis with an anastomat,was performed.CONCLUSION Surgeons should aim to improve their ability to predict patients at high risk for MP erosion after IHR.

摘要： BACKGROUND Colorectal cancer(CRC)is an extremely malignant tumor with a high mortality rate.Little is known about the mechanism by which forkhead Box q1(FOXQ1)causes CRC invasion and metastasis through the epidermal growth factor receptor(EGFR)pathway.AIM To illuminate the mechanism by which FOXQ1 promotes the invasion and metastasis of CRC by activating the heparin binding epidermal growth factor(HB-EGF)/EGFR pathway.METHODS We investigated the differential expression and prognosis of FOXQ1 and HB-EGF in CRC using the Gene Expression Profiling Interactive Analysis(GEPIA)website(http://gepia.cancer-pku.cn/index.html).Quantitative real-time polymerase chain reaction(qRT-PCR)and Western blotting were used to detect the expression of FOXQ1 and HB-EGF in cell lines and tissues,and we constructed a stable lowexpressing FOXQ1 cell line and verified it with the above method.The expression changes of membrane-bound HB-EGF(proHB-EGF)and soluble HB-EGF(sHB-EGF)in the lowexpressing FOXQ1 cell line were detected by flow cytometry and ELISA.Western blotting was used to detect changes in the expression levels of HB-EGF and EGFR pathway-related downstream genes when exogenous recombinant human HB-EGF was added to FOXQ1 knockdown cells.Proliferation experiments,transwell migration experiments,and scratch experiments were carried out to determine the mechanism by which FOXQ1 activates the EGFR signaling pathway through HB-EGF,and then to evaluate the clinical relevance of FOXQ1 and HB-EGF.RESULTS GEPIA showed that the expression of FOXQ1 in CRC tissues was relatively high and was related to a lower overall survival rate.PCR array results showed that FOXQ1 is related to the HB-EGF and EGFR pathways.Knockdown of FOXQ1 suppressed the expression of HB-EGF,and led to a decrease in EGFR and its downstream genes AKT,RAF,KRAS expression levels.After knockdown of FOXQ1 in CRC cell lines,cell proliferation,migration and invasion were attenuated.Adding HB-EGF restored the migration and invasion ability of CRC,but not the cell proliferation ability.Kaplan–Meier survival analysis results showed that the combination of FOXQ1 and HB-EGF may serve to predict CRC survival.CONCLUSION Based on these collective data,we propose that FOXQ1 promotes the invasion and metastasis of CRC via the HB-EGF/EGFR pathway.

摘要： Triple-negative breast cancer(TNBC)cell line MDA-MB-231 is known for Warburg metabolism and defects in mitochondria.On the other hand,dipeptidyl peptidase-IV(DPP-IV)inhibitors such as sitagliptin and vildagliptin and GLP-1 agonist exendin-4 are known to improve mitochondrial functions as well as biogenesis,but no study has evaluated the influence of these drugs on mitochondrial biogenesis on metastatic breast cancer cell line.We have recently reported anticancer effects of 5-aminoimidazole-4-carboxamide riboside on MDA-MB-231 cells via activation of AMP-dependent kinase(AMPK),which activates the downstream transcription factors PGC-1α,PGC-1β,or FOXO1 for mitochondrial biogenesis;above-mentioned incretin-based therapies are also known to activate AMPK.This study evaluated the effects of sitagliptin,vildagliptin,and exendin-4 on MDA-MB-231 cells and the underlying changes in mitochondrial biogenesis,were examined.Treatment with sitagliptin(100μM),vildagliptin(100μM),and exendin-4(10 nM)for 72 h to MDA-MB-231 cells led to a decrease in viability indicated by MTT assay,cell migration by scratch,and transwell migration assays,accompanied with marginal reduction in cell numbers along with the apoptotic appearance,the rate of apoptosis,and decreased lactate content in conditioned medium.These changes in the cancer phenotype were accompanied by an increase in the mitochondrial DNA to nuclear DNA ratio,increased MitoTracker green and red staining,and increased expression of transcription factors PGC-1α,NRF-1,NRF-2,TFAM,and HO-1.Pre-treatment of cells with these incretin-based drugs followed by 48 h treatment with 1μM doxorubicin increased doxorubicin sensitivity as observed by a decrease in viability by MTT assay.Thus,sitagliptin,vildagliptin,and exendin-4 exert their beneficial effects on TNBC cells via an increase in mitochondrial biogenesis that helps to switch Warburg metabolism into anti-Warburg effect.Therapeutic response was in the order of:sitagliptin>vildagliptin>exendin-4.

摘要： Objective: To investigate the effect of Caveolin-1on the proliferation and migration ability in gastric carcinoma cells MGC-803 and its mechanism. Methods: Plasmid DNA pcDNA3.1-Cav1 was extracted by extracted kits, and transfected Cav-1 gene sequences were found. The expression levels of Cav-1 protein were detected by Western blot. And the proliferation was analyzed by CCK8 assay. The effect of Cav-1 on migration was detected by wound healing. The expression levels of BMI-1 protein were detected by western blot. Results: 1) Western Blot showed that the expression levels of Cav-1 were higher in MGC-803/Cav-1 than control group, P 0.05. Wound healing showed, that the migration ability of MGC-803/Cav-1 fell off, P Conclusion: Caveolin-1 can inhibit the proliferation and migration ability of gastric carcinoma cells and its mechanism may relate to BMI-1.

摘要： Mesenchymal stem cells(MSCs)have gained wide-ranging reputation in the medical research community due to their promising regenerative abilities.MSCs can be isolated from various resources mostly bone marrow,Adipose tissues and Umbilical cord.Huge advances have been achieved in comprehending the possible mechanisms underlying the therapeutic functions of MSCs.Despite the proven role of MSCs in repairing and healing of many disease modalities,many hurdles hinder the transferring of these cells in the clinical settings.Among the most reported problems encountering MSCs therapy in vivo are loss of tracking signal post-transplantation,insufficient migration,homing and engraftment postinfusion,and undesirable differentiation at the site of injury.Magnetic nanoparticles(MNPs)have been used widely for various biomedical applications.MNPs have a metallic core stabilized by an outer coating material and their magnetic properties can be modulated by an external magnetic field.These magnetic properties of MNPs were found to enhance the quality of diagnostic imaging procedures and can be used to create a carrying system for targeted delivery of therapeutic substances mainly drug,genes and stem cells.Several studies highlighted the advantageous outcomes of combining MSCs with MNPs in potentiating their tracking,monitoring,homing,engraftment and differentiation.In this review,we will discuss the role of MNPs in promoting the therapeutic profile of MSCs which may improve the success rate of MSCs transplantation and solve many challenges that delay their clinical applicability.

摘要： Breast cancer is a highly aggressive cancer in females. Metastasis is a major obstacle to the efficient andsuccessful treatment of breast cancer. Cetyltrimethylammonium bromide (CTAB) has anti-tumor effects on a varietyof tumors. We showed that CTAB inhibits the metastasis of breast cancer to the lungs both in vitro and in vivo.Epithelial-mesenchymal transition (EMT) is thought to be one of the major processes mediating breast cancermetastasis. We found that CTAB suppressed EMT and regulated the levels of the classical EMT markers E-cadherin,N-cadherin, vimentin, Snail and Twist1. Moreover, as a candidate anti-tumor agent, CTAB showed primary safety invivo. Taken together, our results suggest that CTAB inhibits the migration of primary breast cancer to the lungs. Ourfindings confirm the clinical potential of CTAB for the treatment of breast cancer by targeting EMT. CTAB may thusbe a promising novel anti-tumor drug for the treatment of breast cancer metastasis.