Knockdown of Notch1 inhibits nasopharyngeal carcinoma cell growth and metastasis via downregulation of CCL2, CXCL16, and uPA

Notch pathway is a highly conserved cell signaling system that plays very important roles in controlling multiple cell differentiation processes during embryonic and adult life. Multiple lines of evidence support the oncogenic role of Notch signaling in several human solid cancers; however, the pleiotropic effects and molecular mechanisms of Notch signaling inhibition on nasopharyngeal carcinoma (NPC) remain unclear. In this study, we evaluated Notch1 expression in NPC cell lines (CNE1, CNE2, SUNE1, HONE1, and HK1) by real-time quantitative PCR and Western blot analysis, and we found that CNE1 and CNE2 cells expressed a higher level of Notch1 compared with HONE1, SUNE1, and HK1 cells. Then Notch1 expression was specifically knocked down in CNE1 and CNE2 cells by Notch1 short hairpin RNA (shRNA). In Notch1 knockdown cells, cell proliferation, migration, and invasion were significantly inhibited. The epithelial-mesenchymal transition of tumor cells was reversed in Notch1-shRNA-transfected cells, accompanied by epithelioid-like morphology changes, increased protein levels of E-cadherin, and decreased expression of vimentin. In addition, knockdown of Notch1 markedly inhibited the expression of urokinase plasminogen activator (uPA) and its receptor uPAR, and chemokines C-C motif chemokine ligand 2 and C-X-C motif chemokine ligand 16, indicating that these factors are downstream targets of Notch1. Furthermore, deleting uPA expression had similar effects as Notch1. Finally, knockdown of Notch1 significantly diminished CNE1 cell growth in a murine model concomitant with inhibition of cell proliferation and induction of apoptosis. These results suggest that Notch1 may become a novel therapeutic target for the clinical treatment of NPC.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151248/1/mc23082_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151248/2/mc23082.pd

Proliferative Activity and Neuroprotective Effect of Ligustrazene Derivative by Irritation of Vascular Endothelial Growth Factor Expression in Middle Cerebral Artery Occlusion Rats

Purpose: To investigate the proliferative activity and neuroprotective effect of a newly identified ligustrazine derivative (4-((3,5,6-trimethylpyrazine-2 yl)methoxyl)-3-methox-ybenzoic acid-3,5,6- trimethylpyrazin- 2-methyl ester, T VA) and the possible mechanism related to vascular endothelial growth factor (VEGF) in cerebral ischemic injury.Methods: The pharmacological activity of T-VA was evaluated using MTT ((3 (4,5-dimethylthiazolyl2- yl)-2,5-diphenyltetrazolium bromide)) assay, while cellular morphology was observed with hematoxylin and eosin (HE) staining. Chick chorioallantoic membrane (CAM) model, immuno-histochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to determine the expression of VEGF. Middle cerebral artery occlusion (MCAO) model was used to investigate both VEGF expression and the survival rate after treatment with T-VA.Results: T-VA promoted neuron activity, and the doses of 15 and 30 μM showed more significant effect (p < 0.05). The viability of PC12 cells increased significantly in T-VA (30 and 60 μM) groups (p < 0.05) and increased in a dose dependent manner. Immunohistochemical analysis showed stimulated VEGF expression, and CAM model results showed that T-VA (20 mg/egg) significantly promoted microangiogenesis (p < 0.01). Moreover, in MCAO model, the survival rate of T-VA (60 mg/kg) group reached 86.7 % while for the ischemia group it was 60.0 %. In addition, ELISA results showed that T-VA promoted the expression of VEGF (p < 0.05).Conclusion: These findings indicate that T-VA helps to prevent ischemic injury by increasing VEGF expression.Keywords: Ligustrazine, Neuron, PC12 cell, Chick Chorioallantoic Membrane, Middle Cerebral Artery Occlusion, Vascular Endothelial Growth Facto

In-situ Construction of Superhydrophilic g-C3N4 Film by Vapor-Assisted Confined Deposition for Photocatalysis

Herein, we report an improved strategy for the synthesis of superhydrophilic g-C3N4 film by vapor-assisted confined deposition method. With minimum amount of precursor, the vapor could be confined in the microenvironment for facilitating the film growth on both sides of the substrates. The obtained films showed similar physiochemical properties with the bulk counterpart and could be peeled off from the substrates by soaking in hot water. The free-standing film is flexible and superhydrophilic, featuring many microfibers atop. The g-C3N4 film from both sides of the substrates could be used in the photocatalytic dye degradation in a repeated manner and showed excellent performance and stability. The current work should shed light on the optimized growth of the g-C3N4 film and could find more application in future device field

Optimizing method of mechanism angle of upper limb rehabilitation robot at glenohumeral joint

At present, there are seventy million stroke patients in China and annual death toll of stroke is 1 million 650 thousand people. The survivors about 75% become disabled persons and lose the ability to move. To address this issue, a kind of rehabilitation exoskeleton robot called YANARM is proposed which for training of shoulder complex. This paper, a kind of method for optimizing the angle parameters of series dynamic axes under given workspace conditions is presented. The forward and inverse kinematics solutions of glenohumeral mechanism are solved based on the exponential product formula (POE) and the Paden-Kahan sub-problem. The range of joint rotation angle can be inversely solved according to the end of the arm position at the borderline of the workspace. A curve between the angle and the CP which equal mean variance of joint rotation range plus sum of all joint rotation ranges is solved. The mechanism angle of glenohumeral joint is optimized by this method

Identifying the Antiproliferative Effect of Astragalus Polysaccharides on Breast Cancer: Coupling Network Pharmacology With Targetable Screening From the Cancer Genome Atlas

Background:Astragalus polysaccharides (APS), natural plant compounds, have recently emerged as a promising strategy for cancer treatment, but little is known concerning their effects on breast cancer (BC) tumorigenesis.Methods: We obtained breast cancer genetic data from The Cancer Genome Atlas (TCGA) database, network pharmacology to further clarify its biological properties. Survival analysis and molecular docking techniques were implemented for the final screening to obtain key target information. Our experiments focused on the detection of intervention effects of APS on BC cells (MCF-7 and MDA-MB-231), and quantitative RT-PCR (qRT-PCR) was used to assess the expression of key targets.Results: A total of 1,439 differentially expressed genes (DEGs) were identified by TCGA and used to build disease networks. Module analysis, gene ontology and pathway analysis revealed characteristic of the DEGs network. Topological properties were used to identify key targets, survival analysis and molecular docking finally found that the targets of APS regulation of BC cells may be CCNB1, CDC6, and p53. Through cell viability, migration and invasion assays, we found that APS interferes with the development of breast cancer in MCF7 and MDA-MB-231 cells in a dose-dependent manner. Furthermore, qRT-PCR verification suggested that the expression of CCNB1 and CDC6 in breast cancer cells was significantly downregulated in response to APS, while expression of the tumor suppressor gene P53 was significantly increased.Conclusion: Results of this study suggest therapeutic potential for APS in BC treatment, possibly through interventions with CCNB1, CDC6, and P53. Furthermore, these findings illustrate the feasibility of using network pharmacology to connect large-scale target data as a way to discover the mechanism of natural products interfering with disease

FECTS: A Facial Emotion Cognition and Training System for Chinese Children with Autism Spectrum Disorder

Traditional training methods such as card teaching, assistive technologies (e.g., augmented reality/virtual reality games and smartphone apps), DVDs, human-computer interactions, and human-robot interactions are widely applied in autistic rehabilitation training in recent years. In this article, we propose a novel framework for human-computer/robot interaction and introduce a preliminary intervention study for improving the emotion recognition of Chinese children with an autism spectrum disorder. The core of the framework is the Facial Emotion Cognition and Training System (FECTS, including six tasks to train children with ASD to match, infer, and imitate the facial expressions of happiness, sadness, fear, and anger) based on Simon Baron-Cohen's E-S (empathizing-systemizing) theory. Our system may be implemented on PCs, smartphones, mobile devices such as PADs, and robots. The training record (e.g., a tracked record of emotion imitation) of the Chinese autistic children interacting with the device implemented using our FECTS will be uploaded and stored in the database of a cloud-based evaluation system. Therapists and parents can access the analysis of the emotion learning progress of these autistic children using the cloud-based evaluation system. Deep-learning algorithms of facial expressions recognition and attention analysis will be deployed in the back end (e.g., devices such as a PC, a robotic system, or a cloud system) implementing our FECTS, which can perform real-time tracking of the imitation quality and attention of the autistic children during the expression imitation phase. In this preliminary clinical study, a total of 10 Chinese autistic children aged 3-8 are recruited, and each of them received a single 20-minute training session every day for four consecutive days. Our preliminary results validated the feasibility of the developed FECTS and the effectiveness of our algorithms based on Chinese children with an autism spectrum disorder. To verify that our FECTS can be further adapted to children from other countries, children with different cultural/sociological/linguistic contexts should be recruited in future studies