Downregulation of CLDN6 inhibits cell proliferation, migration, and invasion via regulating EGFR/AKT/mTOR signalling pathway in hepatocellular carcinoma.

Accumulating evidence showed that the claudin-6 (CLDN6) expression was abnormal in many cancers, while its expression and biological functions in hepatocellular carcinoma (HCC) is still unclear. The present study demonstrated that CLDN6 was upregulated in HCC tissues compared with tumour-adjacent tissues. CLDN6 silencing was significantly inhibited proliferation, migration, and invasion of HepG2 cells. Meanwhile, downregulation of CLDN6 remarkably inhibited the activation of EGFR/AKT/mTOR signalling pathway. Interestingly, the effect of CLDN6 overexpression on HepG2 cell proliferation and invasion could be inhibited by EGFR/AKT/mTOR signalling pathway inhibitor (AG1478). SIGNIFICANCE OF THE STUDY: These findings suggested that CLDN6 may act as an oncogene in HCC and improve HepG2 cell proliferation, migration, and invasion may via EGFR/AKT/mTOR signalling pathway.

Effects of swimming on pain and inflammatory factors in rats with lumbar disc herniation.

The aim of the present study was to identify the effect of swimming on nerve root pain in rats with lumbar disc herniation (LDH). A total of 72 male Sprague Dawley rats (215±15 g) were randomly divided into three groups (n=24/group): The sham operation, model and exercise intervention groups, with the latter undergoing 4 weeks of swimming training. On days 0, 7, 14 and 28 following surgery, the changes in the post-limb mechanical claw threshold, the phospholipase A2 (PLA2), interleukin (IL)-6 and tumor necrosis factor (TNF)-α mRNA expression levels, the secretory PLA2 (sPLA2) expression, the IL-6 and TNF-α content, the nuclear factor (NF)-κBp65 protein expression level in the nucleus pulposus, and the apoptotic rate of the nucleus pulposus cells were detected. The results demonstrated that, in the model group, the threshold of hind paw withdrawal was decreased, and that the sPLA2 expression, IL-6 and TNF-α content, PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels in the nucleus pulposus were increased. The apoptotic rate of the nucleus pulposus cells was increased from day 7 following surgery, as compared with the sham operation group. In the exercise intervention group, the hind paw withdrawal threshold increased and the TNF-α and IL-6 content, sPLA2 expression and PLA2, IL-6 and TNF-α mRNA and NF-κBp65 protein expression levels were decreased from day 14 following surgery, and the apoptotic nucleus pulposus cells were decreased from day 7 following surgery, as compared with the model group. Collectively, the present data suggest that swimming can significantly reduce nerve root pain and inhibit inflammatory reaction in LDH, which can have positive effects on the treatment of LDH.

Electrochemical activation of persulfates at BDD anode: Radical or nonradical oxidation?

The combination of persulfates (peroxydisulfate (PDS) and peroxymonosulfate (PMS)) and electrolysis using boron-doped diamond (BDD) anode is a promising green advanced oxidation process. In comparison with electrolysis alone, electrochemical activation of persulfates at BDD anode considerably enhanced the degradation of carbamazepine (CBZ). The experimental results indicate that the surface-adsorbed hydroxyl radical (HO) played the dominant role. The generally proposed nonradical oxidation mechanism ignored hydroxyl radical (HO) oxidation because low concentration of radical scavenger (<10 M methanol or 5 M tertbutanol) could not effectively scavenge the surface-adsorbed HO. The quasi steady-state concentration of HO was estimated to be about 5.0-9.1 × 10-12 M for electrolysis with BDD anode, and it was increased to 1.1-1.6 × 10-11 M and 3.2-5.0 × 10-11 M for addition of 5 mM PDS and PMS, respectively. The results of cyclic voltammetry (CV) and chronoamperometry as well as evolution of dissolved oxygen (DO) reveal that the electrochemically activated persulfates molecule (PDS∗/PMS∗) promoted the production of HO via water dissociation at BDD anode and enhanced the direct electron transfer (DET) reaction, which otherwise inhibited the oxygen evolution side reaction. Therefore, higher current efficiency was achieved in electrochemical activation of persulfates process compared with electrolysis process. Additionally, the transformation products of CBZ were also investigated and their formation pathways were proposed.

Lycorine Induces Apoptosis of A549 Cells via AMPK-Mammalian Target of Rapamycin (mTOR)-S6K Signaling Pathway.

BACKGROUND This study was designed to investigate the effect of lycorine (LY) on the AMPK-mTOR-S6K signaling pathway and to clarify its role in autophagy and apoptosis. MATERIAL AND METHODS Various concentrations of LY were used to treat non-small cell lung carcinoma A549 cells. The MTT assay was used to measure cell viability and acridine orange staining was used to detect cell morphology changes. Western blot analysis was used to test the effect of LY on the expression levels of LC3, caspase 3, and other proteins involved in the AMPK-mTOR-S6K signaling pathway. RESULTS The half maximal inhibitory concentration (IC50) of LY after 24-h treatment was 8.5 µM, with stronger inhibitory effect of 24-h LY treatment over 12-h LY treatment. Morphological observation showed that lower doses (4 µM and 8 µM) of LY treatment induced A549 cell death mainly caused by autophagy, whereas the higher dose (16 µM) of LY treatment induced A549 cell death, mainly caused by apoptosis. Furthermore, 8 µM LY caused the highest conversion of LC3-II from LC3-I. All LY treatments activated caspase-3. LY treatment also promoted AMPK phosphorylation (Thr172) and inhibited the phosphorylation of mTOR and S6K. CONCLUSIONS LY induced apoptosis of A549 cells by regulating the AMPK-mTOR-S6K signaling pathway. Lower levels (4~8 µM) of LY-induced autophagy contributed to LY-induced apoptosis.

Nonradical oxidation from electrochemical activation of peroxydisulfate at Ti/Pt anode: Efficiency, mechanism and influencing factors.

Electrochemical activation of peroxydisulfate (PDS) at Ti/Pt anode was systematically investigated for the first time in this work. The synergistic effect produced from the combination of electrolysis and the addition of PDS demonstrates that PDS can be activated at Ti/Pt anode. The selective oxidation towards carbamazepine (CBZ), sulfamethoxazole (SMX), propranolol (PPL), benzoic acid (BA) rather than atrazine (ATZ) and nitrobenzene (NB) was observed in electrochemical activation of PDS process. Moreover, addition of excess methanol or tert-butanol had negligible impact on CBZ (model compound) degradation, demonstrating that neither sulfate radical (SO4-) nor hydroxyl radical (HO) was produced in electrochemical activation of PDS process. Direct oxidation (PDS oxidation alone and electrolysis) and nonradical oxidation were responsible for the degradation of contaminants. The results of linear sweep voltammetry (LSV) and chronoamperometry suggest that electric discharge may integrate PDS molecule with anode surface into a unique transition state structure, which is responsible for the nonradical oxidation in electrochemical activation of PDS process. Adjustment of the solution pH from 1.0 to 7.0 had negligible effect on CBZ degradation. Increase of either PDS concentration or current density facilitated the degradation of CBZ. The presence of chloride ion (Cl-) significantly enhanced CBZ degradation, while addition of bicarbonate (HCO3-), phosphate (PO43-) and humic acid (HA) all inhibited CBZ degradation with the order of HA >> HCO3- > PO43-. The degradation products of CBZ and chlorinated products were also identified. Electrochemical activation of PDS at Ti/Pt anode may serve as a novel technology for selective oxidation of organic contaminants in water and soil.

Effect of pterostilbene on glioma cells and related mechanisms.

Neuroglioma is the most common primary malignant tumor in neurosurgery. Due to unfavorable life quality of patients, the treatment of glioma is a major challenge in clinics. The search for effect treatment drugs thus benefits patient prognosis. As one derivative of resveratrol, pterostilbene has a wide spectrum of pharmaceutical functions, especially with the anti-tumor effects. This study thus investigated the effect of pterostilbene on neuroglioma and related mechanisms. U87 glioma cell line was divided into control, normal culture and different dosages of pterostilbene groups, which received 5 mM or 10 mM pterostilbene for 48 h. MTT assay was used to detect U87 cell proliferation, while invasion assay was employed to test the effect of pterostilbene on cell invasion, followed by flow cytometry assay for analyzing U87 cell apoptosis. Real-time PCR was used to test mRNA expression of Bcl-2 and Bax in glioma cells under the effect of pterostilbene, while Western blotting was used to detect alternation of Bcl-2 and Bax protein levels. Pterostilbene significantly inhibited proliferation and invasion abilities of glioma cells compared to those in control group (P<0.05). It can also enhance cell apoptosis, decrease mRNA and protein of Bcl-2 expression, and increase mRNA and protein expressions of Bax (P<0.05 compared to control group) in a dose-dependent manner. Pterostilbene can facilitate apoptosis of glioma cells, and inhibit their proliferation and invasion via mediating apoptotic/anti-apoptotic homeostasis.

Novel HCN sorbents based on layered double hydroxides: sorption mechanism and performance.

Layered double hydroxides (LDHs) and layered double oxides (LDOs) have been prepared and used as sorbents for hydrogen cyanide (HCN). Based on results from sorbent optimization experiments, the optimal performance for HCN removal was found in Ni-Al LDH. As evidenced by fixed-bed sorption studies, the Ni-Al LDO with the greatest surface area showed better performance and outperformed products calcined at 200, 400, or 500 °C, whereas, the Ni-Al LDH showed a more twofold higher sorption capacity than the Ni-Al LDO. Investigation of the mechanisms between HCN and sorbents reveals that the HCN removal by the Ni-Al LDH and Ni-Al LDO leads to the formation of the complex anion, [Ni(CN)4](2-). Nevertheless, the [Ni(CN)4](2-) can enter interlayer region of the Ni-Al LDH due to its anion exchangeability, which endows this LDH with more binding sites, not only on its external surfaces, but also on its internal surfaces located in the interlayer region. In contrast, [Ni(CN)4](2-) were only adsorbed on the external surface of the Ni-Al LDO. As a result, the sorption capacity of the Ni-Al LDH for HCN is twice as high as that of the Ni-Al LDO, which is at 21.55 mg/g.