Expression of the chemokine receptor CXCR4 in human hepatocellular carcinoma and its role in portal vein tumor thrombus

<p>Abstract</p> <p>Background</p> <p>This study was conducted to investigate the expression of CXCR4 in portal vein tumor thrombus (PVTT) tissue and its possible role in the invasiveness of tumor thrombus cells.</p> <p>Methods</p> <p>We detected differential expression of CXCR4 between PVTT and hepatocellular carcinoma (HCC) by an immunohistochemical assay. Lentivirus-mediated RNA interference and a migration assay were performed on human primary cells derived from PVTT to study the impact of CXCR4 on the invasiveness of HCC.</p> <p>Results</p> <p>The expression of CXCR4 in tumor thrombus tissue was higher than that in HCC tissue. The invasion ratio of PVTT cells was significantly decreased (P < 0.05) after being infected with a CXCR4-targeting siRNA lentivirus, indicating that downregulation of CXCR4 by lentivirus-mediated RNA interference significantly impaired the invasive potential of PVTT.</p> <p>Conclusions</p> <p>These results indicate that CXCR4 is an effective curative target for hepatocellular carcinomas with PVTT.</p

Coupled down-regulation of mTOR and telomerase activity during fluorouracil-induced apoptosis of hepatocarcinoma Cells

<p>Abstract</p> <p>Background</p> <p>Hepatocellular carcinoma (HCC) is the most invasive and frequently diagnosed malignancy and the second leading cause of cancer death in many regions of Asia. The PI3K/Akt/mTOR signal pathway is involved in multiple cellular functions including proliferation, differentiation, tumorigenesis, and apoptosis. Up-regulation of telomerase activity is thought to be a critical step leading to cell transformation.</p> <p>Methods</p> <p>This study investigated changes in mTOR pathway and telomerase activity in hepatocarcinoma cell line SMMC-7721 treated with chemotherapeutic agent 5-fluorouracil (5-Fu). We detected apoptosis of hepatocarcinoma cells by TUNEL assay. Telomerase activity, hTERT transcription level and p- p70 S6k was demonstrated by the telomeric repeat amplification protocol and silver staining assay, Dual-Luciferase Reporter Assay and Western blot analysis respectively.</p> <p>Results</p> <p>Treating SMMC-7721 cells with 5-Fu leads to apoptosis of the cells, and reduction in telomerase activity, as well as a dramatic reduction in the activated form of p70 S6 kinase, a mTOR substrate. The 5-Fu treatment nearly abolishes transcription of hTERT (the major component of telomerase) mRNA. Treating SMMC-7721 cells with Rapamycin, a specific mTOR inhibitor, significantly reduce hTERT protein level but did not affect hTERT transcription. 5-Fu and rapamycin were synergistic in regards to down-regulation of telomerase activity in hepatocarcinoma cells.</p> <p>Conclusion</p> <p>These results suggest that chemotherapeutic agent 5-Fu may down-regulate telomerase activity at both transcriptional level and PI3K/Akt/mTOR pathway-dependent post-transcriptional level to facilitate hepatocellular carcinoma cell apoptosis.</p

GWAS Identifies Novel Susceptibility Loci on 6p21.32 and 21q21.3 for Hepatocellular Carcinoma in Chronic Hepatitis B Virus Carriers

Genome-wide association studies (GWAS) have recently identified KIF1B as susceptibility locus for hepatitis B virus (HBV)–related hepatocellular carcinoma (HCC). To further identify novel susceptibility loci associated with HBV–related HCC and replicate the previously reported association, we performed a large three-stage GWAS in the Han Chinese population. 523,663 autosomal SNPs in 1,538 HBV–positive HCC patients and 1,465 chronic HBV carriers were genotyped for the discovery stage. Top candidate SNPs were genotyped in the initial validation samples of 2,112 HBV–positive HCC cases and 2,208 HBV carriers and then in the second validation samples of 1,021 cases and 1,491 HBV carriers. We discovered two novel associations at rs9272105 (HLA-DQA1/DRB1) on 6p21.32 (OR = 1.30, P = 1.13×$10^{−19}$) and rs455804 (GRIK1) on 21q21.3 (OR = 0.84, P = 1.86×$10^{−8}$), which were further replicated in the fourth independent sample of 1,298 cases and 1,026 controls (rs9272105: OR = 1.25, P = 1.71×$10^{−4}$; rs455804: OR = 0.84, P = 6.92×$10^{−3}$). We also revealed the associations of HLA-DRB1*0405 and 0901*0602, which could partially account for the association at rs9272105. The association at rs455804 implicates GRIK1 as a novel susceptibility gene for HBV–related HCC, suggesting the involvement of glutamate signaling in the development of HBV–related HCC

Water by Pre-oxidation with Membrane Separation Technique

The purpose of this study is to establish a model to analyze and compare different types of pre-oxidation technologies in shale gas backflow, so as to guide actual production. With the progress of membrane-based processes, membrane separation technique shows great potential in shale gas flowback and produced water (SGFPW) reuse. But membrane fouling due to high concentration of organic matter is still a big problem. Therefore, using integrated process, which combines pre-oxidation with membrane separation, is a good way to deal with membrane fouling. However, there are various kinds of oxidation technologies that can be used into shale gas wastewater treatment, meaning that there needs to be a scheme to guide which technology can do best in different situations. In this paper, the output-output model is used to analyze the pre-oxidation technology. The current pre-oxidation technology is divided into two types, among which the most representative ozonation and Fenton oxidation are selected as examples, and the capital investment in this link is taken as the index for analysis. It is concluded that Fenton oxidation method can be used when the amount of waste water is small, but when the amount of waste water is large, the economic benefit of ozonation is higher. Similarly, this model can be widely applied to the analysis and comparison of a large number of pre-oxidation technologies in shale gas wastewater, and can also be modified as the technology advances

A Computer Vision-Based Real-Time Load Perception Method for Belt Conveyors

Real-time load detection method for belt conveyors based on computer vision is the research topic of this paper. A belt conveyor system equipped with cameras and a laser generator is used as the test apparatus. As the basis for conveyor intelligent speed regulation, two methods from different angles to perceive the load of conveyor belt were proposed, applied, and compared in this paper. Method 1 is based on the area proportion and method 2 is the detection based on laser-based computer vision technology. Laboratory experiments show that both methods can well detect the load on the conveyor belt. Method 2 is more economical and practical under the background of existing technology, also compared to the method 1, which provides a new idea and theoretical basis for the energy-saving control and intelligent development of the conveyor

A Computer Vision Based Conveyor Deviation Detection System

The monitoring of conveyor belt deviation based on computer vision is the research topic of this paper. A belt conveyor system equipped with cameras and a laser generator is used as the test apparatus. Two kinds of conveyor condition monitoring algorithms are developed, applied and compared in this paper. Method 1 is to extract the edges of the conveyor belt based on the methods of edge detection and line fitting, and an analysis method is proposed to quickly determine whether the conveyor belt is off course. This method simplifies the information processing process after edge line extraction and realizes the fast and effective state detection of the conveyor belt. A conveyor belt deviation detection system was built in Method 2 with the aid of laser technology and the Labview platform. The result of deviation detection was more accurate and reliable with the addition of the laser line. It is observed that both methods can perform well for belt deviation detection, especially Method 2 that resulted in higher reliability and accuracy with faster processing speed. It provides new ideas for ensuring the safe and efficient operation of the conveyor

Electrical-field-induced magnetic Skyrmion ground state in a two-dimensional chromium tri-iodide ferromagnetic monolayer

Using fully first-principles non-collinear self-consistent field density functional theory (DFT) calculations with relativistic spin-orbital coupling effects, we show that, by applying an out-of-plane electrical field on a free-standing two-dimensional chromium tri-iodide (CrI3) ferromagnetic monolayer, the Néel-type magnetic Skyrmion spin configurations become more energetically-favorable than the ferromagnetic spin configurations. It is revealed that the topologically-protected Skyrmion ground state is caused by the breaking of inversion symmetry, which induces the non-trivial Dzyaloshinskii-Moriya interaction (DMI) and the energetically-favorable spin-canting configuration. Combining the ferromagnetic and the magnetic Skyrmion ground states, it is shown that 4-level data can be stored in a single monolayer-based spintronic device, which is of practical interests to realize the next-generation energy-efficient quaternary logic devices and multilevel memory devices

Nanosized Mesoporous Bioactive Glass/Poly(lactic-co-glycolic Acid) Composite-Coated CaSiO3 Scaffolds with Multifunctional Properties for Bone Tissue Engineering

It is of great importance to prepare multifunctional scaffolds combining good mechanical strength, bioactivity, and drug delivery ability for bone tissue engineering. In this study, nanosized mesoporous bioglass/poly(lactic-co-glycolic acid) composite-coated calcium silicate scaffolds, named NMBG-PLGA/CS, were successfully prepared. The morphology and structure of the prepared scaffolds were characterized by scanning electron microscopy and X-ray diffraction. The effects of NMBG on the apatite mineralization activity and mechanical strength of the scaffolds and the attachment, proliferation, and alkaline phosphatase activity of MC3T3 cells as well as drug ibuprofen delivery properties were systematically studied. Compared to pure CS scaffolds and PLGA/CS scaffolds, the prepared NMBG-PLGA/CS scaffolds had greatly improved apatite mineralization activity in simulated body fluids, much higher mechanical property, and supported the attachment of MC3T3 cells and enhanced the cell proliferation and ALP activity. Furthermore, the prepared NMBG-PLGA/CS scaffolds could be used for delivering ibuprofen with a sustained release profile. Our study suggests that the prepared NMBG-PLGA/CS scaffolds have improved physicochemical, biological, and drug-delivery property as compared to conventional CS scaffolds, indicating that the multifunctional property of the prepared scaffolds for the potential application of bone tissue engineering