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

Increased p38-MAPK is responsible for chemotherapy resistance in human gastric cancer cells

<p>Abstract</p> <p>Background</p> <p>Chemoresistance is one of the main obstacles to successful cancer therapy and is frequently associated with Multidrug resistance (MDR). Many different mechanisms have been suggested to explain the development of an MDR phenotype in cancer cells. One of the most studied mechanisms is the overexpression of P-glycoprotein (P-gp), which is a product of the <it>MDR1 </it>gene. Tumor cells often acquire the drug-resistance phenotype due to upregulation of the <it>MDR1 </it>gene. Overexpression of <it>MDR1 </it>gene has often been reported in primary gastric adenocarcinoma.</p> <p>Methods</p> <p>This study investigated the role of p38-MAPK signal pathway in vincristine-resistant SGC7901/VCR cells. P-gp and MDR1 RNA were detected by Western blot analysis and RT-PCR amplification. Mitgen-activated protein kinases and function of P-gp were demonstrated by Western blot and FACS Aria cytometer analysis. Ap-1 activity and cell apoptosis were detected by Dual-Luciferase Reporter Assay and annexin V-PI dual staining.</p> <p>Results</p> <p>The vincristine-resistant SGC7901/VCR cells with increased expression of the multidrug-resistance 1 (<it>MDR1</it>) gene were resistant to P-gp-related drug and P-gp-unrelated drugs. Constitutive increases of phosphorylated p38-MAPK and AP-1 activities were also found in the drug-resistant cells. Inhibition of p38-MAPK by SB202190 reduced activator protein-1 (AP-1) activity and <it>MDR1 </it>expression levels and increased the sensitivity of SGC7901/VCR cells to chemotherapy.</p> <p>Conclusion</p> <p>Activation of the p38-MAPK pathway might be responsible for the modulation of P-glycoprotein-mediated and P-glycoprotein-unmediated multidrug resistance in the SGC7901/VCR cell line.</p

Record thermopower found in an IrMn-based spintronic stack

The Seebeck effect converts thermal gradients into electricity. As an approach to power technologies in the current Internet-of-Things era, on-chip energy harvesting is highly attractive, and to be effective, demands thin film materials with large Seebeck coefficients. In spintronics, the antiferromagnetic metal IrMn has been used as the pinning layer in magnetic tunnel junctions that form building blocks for magnetic random access memories and magnetic sensors. Spin pumping experiments revealed that IrMn Néel temperature is thickness-dependent and approaches room temperature when the layer is thin. Here, we report that the Seebeck coefficient is maximum at the Néel temperature of IrMn of 0.6 to 4.0 nm in thickness in IrMn-based half magnetic tunnel junctions. We obtain a record Seebeck coefficient 390 (±10) μV K-1 at room temperature. Our results demonstrate that IrMn-based magnetic devices could harvest the heat dissipation for magnetic sensors, thus contributing to the Power-of-Things paradigm

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

Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells

Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3′ untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011let7T to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011let7T in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011let7T may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated

Pricing decision and channel selection of fresh agricultural products dual-channel supply chain based on blockchain.

The application of blockchain can effectively improve the efficiency of fresh agricultural product circulation and consumer trust, but it can also increase investment costs. In this context, this paper introduces parameters such as blockchain unit variable cost, the level of blockchain technology investment, and consumer channel preference in two dual-channel supply chain systems dominated by fresh agricultural product manufacturers: online direct sales and distribution. It compares and analyzes pricing and channel selection strategies in both cases of not using and using blockchain. The research shows that when blockchain is used, manufacturer profits are higher in the direct sales model than in the distribution model. Traditional retailers' profits are lower in the direct sales model than in the distribution model. Total supply chain profits are higher in the direct sales model than in the distribution model, and they exhibit an inverted "U" shape as the level of blockchain investment increases. In the online direct sales model, if the blockchain technology unit variable cost is within a certain threshold range, manufacturer profits, traditional retailer profits, and total supply chain profits are all higher than when blockchain technology is not used. In the online distribution model, when the blockchain variable cost and blockchain usage level meet certain conditions, manufacturers, traditional retailers, and online distributors all have higher profits when using blockchain technology than when not using it. This study provides theoretical guidance for the practical application of blockchain technology in dual-channel fresh agricultural product supply chains

A theoretical study on toluene oxidization by OH radical

Abstract Toluene, a prominent member of volatile organic compounds (VOCs), exerts a substantial adverse influence on both human life and the environment. In the context of advanced oxidation processes, the ·OH radical emerges as a highly efficient oxidant, pivotal in the elimination of VOCs. This study employs computational quantum chemistry methods (G4MP2//B3LYP/6-311++G(d,p)) to systematically investigate the degradation of toluene by ·OH radicals in an implicit solvent model, and validates the rationale of choosing a single-reference method using T1 diagnostics. Our results suggest three possible reaction mechanisms for the oxidation of toluene by ·OH: firstly, the phenyl ring undergoes a hydrogen abstraction reaction followed by direct combination with ·OH to form cresol; secondly, ·OH directly adds to the phenyl ring, leading to ring opening; thirdly, oxidation of sidechain to benzoic acid followed by further addition and ring opening. The last two oxidation pathways involve the ring opening of toluene via the addition of ·OH, significantly facilitating the process. Therefore, both pathways are considered feasible for the degradation of toluene. Subsequently, the UV-H2O2 system was designed to induce the formation of ·OH for toluene degradation and to identify the optimal reaction conditions. It was demonstrated that ·OH and 1O2 are the primary active species for degrading toluene, with their contribution ranking as ·OH > 1O2. The intermediates in the mixture solution after reactions were characterized using GC–MS, demonstrating the validity of theoretical predictions. A comparative study of the toluene consumption rate revealed an experimental comprehensive activation energy of 10.33 kJ/mol, which is consistent with the preliminary activation energies obtained via theoretical analysis of these three mechanisms (0.56 kJ/mol to 13.66 kJ/mol), indicating that this theoretical method can provide a theoretical basis for experimental studies on the oxidation of toluene by ·OH