Anti-Tumor Activity and Mechanism of Silibinin Based on Network Pharmacology and Experimental Verification.

Silibinin is a flavonoid compound extracted from the seeds of Silybum marianum (L.) Gaertn. It has the functions of liver protection, blood-lipid reduction and anti-tumor effects. However, the potential molecular mechanism of silibinin against tumors is still unknown. This study aimed to assess the anti-tumor effects of silibinin in adenoid cystic carcinoma (ACC2) cells and Balb/c nude mice, and explore its potential mechanism based on network pharmacology prediction and experimental verification. A total of 347 targets interacting with silibinin were collected, and 75 targets related to the tumor growth process for silibinin were filtrated. Based on the PPI analysis, CASP3, SRC, ESR1, JAK2, PRKACA, HSPA8 and CAT showed stronger interactions with other factors and may be the key targets of silibinin for treating tumors. The predicted target proteins according to network pharmacology were verified using Western blot analysis in ACC2 cells and Balb/c nude mice. In the pharmacological experiment, silibinin was revealed to significantly inhibit viability, proliferation, migration and induce the apoptosis of ACC2 cells in vitro, as well as inhibit the growth and development of tumor tissue in vivo. Western blot analysis showed that silibinin affected the expression of proteins associated with cell proliferation, migration and apoptosis, such as MMP3, JNK, PPARα and JAK. The possible molecular mechanism involved in cancer pathways, PI3K-Akt signaling pathway and viral carcinogenesis pathway via the inhibition of CASP3, MMP3, SRC, MAPK10 and CDK6 and the activation of PPARα and JAK. Overall, our results provided insight into the pharmacological mechanisms of silibinin in the treatment of tumors. These results offer a support for the anti-tumor uses of silibinin.

Spine Segmentation with Multi-view GCN and Boundary Constraint.

Multi-class segmentation of vertebrae and inter-vertebral discs (IVDs) is crucial for the diagnosis and treatment of spinal diseases. However, it is still a challenge due to similarities between neighboring vertebrae of a subject and differences among the IVDs from different subjects. In this paper, we propose a novel spine segmentation framework to achieve automatic segmentation of vertebrae and IVDs in MR images. The core component of the new framework is a Multi-View GCN (MVGCN), which utilizes multi-view features and graph convolutional network (GCN) to reason about the relations of vertebrae and IVDs. We additionally use a boundary constraint for better segmentation of the boundary between vertebrae and IVDs. We test our method on a public spine dataset of 172 MR volumetric images for the vertebrae and IVDs segmentation. The experimental results demonstrate the efficacy of our method. Code and models of our method will be available in the future.

Design of a High Sensitivity Microwave Sensor for Liquid Dielectric Constant Measurement.

In order to improve the sensitivity of liquid dielectric constant measurements, a liquid dielectric constant sensor based on a cubic container structure is proposed for the first time. The cubic container, which consists of a dielectric substrate with a split resonant ring (SRR) and microstrip lines, can enhance the electric field intensity in the measuring area. High sensitivity can be obtained from measuring the dielectric constant with the characteristics of the structure resonate. The research results show that the resonant frequency of the sensor is shifted from 7.69 GHz to 5.70 GHz, with about a 2 GHz frequency offset, when the dielectric constant of the sample varied from 1 to 10. A resonance frequency offset of 200 MHz for the per unit dielectric constant is achieved, which is excellent regarding performance. The permittivity of oil with a different metal content is measured by using the relation between the fitted permittivity and the resonant frequency. The relative error is less than 1.5% and the sensitivity of measuring is up to 3.45%.

Design of Substrate-Integrated Waveguide Loading Multiple Complementary Open Resonant Rings (CSRRs) for Dielectric Constant Measurement.

In order to solve the low-sensitivity problem of the dielectric constant with the resonant cavity method, a sensor based on a substrate-integrated waveguide structure loaded with a multi-complementary open resonant ring is proposed. With the enhanced resonance characteristics of the sensor, this design realized the measurement of complex dielectric constants in a wide range. The frequency selectivity of the sensor is improved by the high-quality factor of the substrate-integrated waveguide. By loading three complementary resonant rings with different opening directions in the ground plane, a deeper notch and better out-of-band suppression are achieved. The effect of the complex dielectric constant on both resonant frequency and quality factor is discussed by calculating the material under test with a known dielectric constant. Simulation and experimental results show that a resonance frequency offset of 102 MHz for the per unit dielectric constant is achieved. A wide frequency offset is the prerequisite for accurate measurement. The measurement results of four plates match well with the standard values, with a relative error of the real part of the dielectric constant of less than 2% and an error of less than 0.0099 for the imaginary part.

Mechanism study on highly efficient polymer light-emitting diodes utilizing double-layered alkali halide electron injection layer.

Enhancing the injection of electron is an effective strategy to improve the performance of polymer light-emitting diodes (PLEDs). In this work, we reported a 286% improvement in current efficiency (CE) of PLEDs by using double-layered alkali halide electron injection layer (EIL) NaCl/LiF instead of LiF. A significant enhancement of electron injection was observed after inserting the NaCl layer. To understand the mechanism of such improvement, the devices with KBr/LiF and CsF/LiF as EILs were also investigated. Experimental results show that metal cation migrated under the effect of built-in electric field (Vbi), which plays the main role on the improvement of electron injection in PLEDs.

Decreased TOB1 expression and increased phosphorylation of nuclear TOB1 promotes gastric cancer.

TOB1, a member of the BTG/TOB protein family, inhibits tumor cell proliferation. We previously observed down-regulation and phosphorylation of TOB1 in gastric cancer (GC). Here, we examined the subcellular distribution and clinical significance of TOB1 expression and phosphorylation in GC. Immunohistochemical analysis of 341 primary GC and corresponding normal gastric tissue samples demonstrated that nuclear TOB1 expression was lower in GC than normal tissue (80.4% vs. 92.4%), and decreased nuclear TOB1 expression correlated with high TNM stage. By contrast, phosphorylation of nuclear TOB1 was higher in GC than normal gastric tissue (66.0% vs. 36.4%), and was associated with poorly differentiated and high TNM stage tumors. Patients with intestinal type GC and increased nuclear TOB1 phosphorylation had poor overall survival. Multivariate survival analysis indicated the nuclear concentration of phosphorylated TOB1 was an independent prognostic factor for intestinal type GC. Overexpression of TOB1 containing mutations in its nuclear export signal inhibited GC cell proliferation, migration, and invasion compared to cells expressing TOB1 with the nuclear localization signal. Thus, decreased TOB1 expression and increased phosphorylation of nuclear TOB1 is associated with aggressive tumor behavior and poor prognosis in intestinal type GC. Additionally, TOB1 nuclear retention is critical for its anti-proliferative activity.

Aberrant expression of the candidate tumor suppressor gene DAL-1 due to hypermethylation in gastric cancer.

By allelotyping for loss of heterozygosity (LOH), we previously identified a deletion region that harbors the candidate tumor suppressor gene DAL-1 at 18p11.3 in sporadic gastric cancers (GCs). The expression and function of DAL-1 in GCs remained unclear. Here, we demonstrated that the absence of or notable decreases in the expression of DAL-1 mRNA and protein was highly correlated with CpG hypermethylation of the DAL-1 promoter in primary GC tissues and in GC cell lines. Furthermore, abnormal DAL-1 subcellular localization was also observed in GC cells. Exogenous DAL-1 effectively inhibited cancer cell proliferation, migration, invasion and epithelial to mesenchymal transition (EMT); exogenous DAL-1 also promoted apoptosis in GC AGS cells. When endogenous DAL-1 was knocked down in GC HGC-27 cells, the cells appeared highly aggressive. Taken together, these findings provide solid evidence that aberrant expression of DAL-1 by hypermethylation in the promoter region results in tumor suppressor gene behavior that plays important roles in the malignancy of GCs. Understanding the role of it played in the molecular pathogenesis of GC, DAL-1 might be a potential biomarker for molecular diagnosis and evaluation of the GC.