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Strontium (Sr) ions were added to porous magnesium (Mg) oxide with silicon and fluorine by microarc oxidation (MAO) to improve its osteogenic and pro-angiogenic properties. First, pure Mg was oxidized by MAO, and Sr was added by electrolysis. The surface of the resulting Sr coating was characterized by SEM, EDS, and EDS mapping. The release of Sr ions was monitored by ICP-OES. The antibacterial property of the coating was assessed against Staphylococcus aureus. The effect of Sr coating on osteogenesis was tested in MC3T3-E1 cell line by performing cell adhesion and proliferation tests, alkaline phosphatase (ALP) activity detection, cell morphology characterization, alizarin red staining, and osteogenic-related gene expression analysis. Finally, HUVECs cells were used to test the effect of Sr coating on angiogenesis through cell migration and tube formation assays, VEGF quantification, chicken embryo chorioallantoic membranes (CAM) test, and angiogenic-related gene expression analysis. The results showed that Sr coating had a hierarchical microstructure with a microporous structure evenly covered with nano-grains and that the Sr elements from the coating were released slowly and continuously. Sr coating had effective antibacterial properties and promoted cell adhesion, proliferation, ALP release, calcium nodule formation, and upregulated osteogenic gene expression. Moreover, the coating could promote migration, tube formation, VEGF expression, and angiogenic gene upregulation in endothelial cells. Sr coating also enhanced angiogenesis of CAM. This study supports that Sr coating on Mg- MAO enhances osteogenesis and angiogenesis.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1β and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Micro-arc oxidation (MAO) was used to improve the resistance of pure magnesium (Mg). Copper (Cu), a good antibacterial, angiogenic, and osteogenic element, was added by reaction in a Cu-containing electrolyte to improve the osteogenic and pro-angiogenic activities of Mg. The surface microstructures of the resulting MAO were evaluated by a scanning electron microscope (SEM) and energy-dispersive X-ray spectroscopy (EDS) mapping. The release of Cu ions was detected by ICP-OES. The antibacterial activity of films with different concentrations of Cu ions was assessed against Staphylococcus aureus (S. aureus). The osteogenesis of films was confirmed by cell morphology and proliferation, ALP activity, alizarin red staining, and osteogenic-related gene expression in the MC3T3-E1 cell line. The angiogenesis of the films was tested in human umbilical vein endothelial cells (HUVECs) by cell migration, tube formation, and VEGF quantification in vitro, and by a chicken embryo chorioallantoic membrane (CAM) assay in vivo. The results showed that the microporous structure was shaped by MAO, and the Cu group was denser and more uniform. The Cu coating showed effective antibacterial activity against S. aureus while also enhancing osteogenesis and angiogenesis in vitro. According to the CAM assay, the Cu group showed not only biocompatibility but also a significant angiogenic response, which was consistent with in vitro studies. The findings indicate that a Cu coating on Mg-MAO enhances osteogenesis and angiogenesis.

Background PEST-containing nuclear protein (PCNP), a novel nuclear protein, is involved in cell proliferation and tumorigenesis. However, the precise mechanism of action of PCNP in the process of tumor growth has not yet been fully elucidated. Methods ShRNA knockdown and overexpression of PCNP were performed in human neuroblastoma cells. Tumorigenic and metastatic effects of PCNP were examined by tumor growth, migration, and invasion assays in vitro, as well as xenograft tumor assay in vivo. Results PCNP over-expression decreased the proliferation, migration, and invasion of human neuroblastoma cells and down-regulation of PCNP showed reverse effects. PCNP over-expression increased protein expressions of cleaved caspase-3, cleaved caspase-8, cleaved caspase-9, and cleaved poly adenosine diphosphate-ribose polymerase, as well as ratios of B-cell lymphoma-2 (Bcl-2)-associated X protein/Bcl-2 and Bcl-2-associated death promoter/B-cell lymphoma-extra large in human neuroblastoma cells, however PCNP knockdown exhibited reverse trends. PCNP over-expression increased phosphorylations of extracellular signal-regulated protein kinase 1/2, p38, c-Jun N-terminal kinase, as well as decreased phosphorylations of phosphatidylinositol 3-kinase (PI3K), Akt, and mammalian target of rapamycin (mTOR), nevertheless PCNP knockdown exhibited opposite effects. Furthermore, PCNP over-expression significantly reduced the growth of human neuroblastoma xenograft tumors by down-regulating angiogenesis, whereas PCNP knockdown markedly promoted the growth of human neuroblastoma xenograft tumors through up-regulation of angiogenesis. Conclusions PCNP mediates the proliferation, migration, and invasion of human neuroblastoma cells through mitogen-activated protein kinase and PI3K/AKT/mTOR signaling pathways, implying that PCNP is a therapeutic target for patients with neuroblastoma.

The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion. The shRNA was utilized for RNA interference. The target gene and protein expression levels were assessed using reverse transcription-PCR and western blot assay. The DNA-binding activity of nuclear factor κB (NF-κB) was examined using electrophoretic mobility shift assays. Luciferase reporter assay was used to detect the binding of NF-κB to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317 inhibited the invasion and migration of A549 cells in a dose-dependent manner. Meanwhile, we further indicated that activation of LXRβ, one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXRβ triggered by T0901317 inhibited the invasion and metastasis of A549 cells by repressing NF-κB/MMP-9 signaling pathway. Taken together, our study shows that activation of LXRs triggered by T0901317 inhibits the invasion and metastasis of human non-small-cell lung cancer by repressing the NF-κB/MMP-9 signaling pathway.

A simple transition-metal-free protocol for the synthesis of indoles has been developed using aryne cycloaddition. The in situ-generated arynes couple with α-amino ketones through a one-step N-arylation–nucleophilic addition process under mild conditions and efficiently produce multisubstituted N-arylindoles.

Green liquor, a process liquor of alkali recovery in pulp and papermaking industry, pretreatment used in poplar kraft pulping process and the influences of pretreatment conditions on pentosan extraction have been studied. The results show that the influence of green liquor dosage on pentosan extraction is the most remarkable, with temperature taking the second place and time the third. Under the conditions of liquor ratio 1:4, green liquor dosage 1.5 L/kg (based on oven dried material), temperature 100 °C, time 90 min, higher pentosan extraction ratio of 13.81% (based on the pentosan content of raw material) is achieved. The wood was pulped under normal KP conditions after pretreated by the optimal pentosan extraction conditions. Comparing two kinds of pulp with and without pretreatment at similar stock yield level, the results show that the former has a little lower viscosity, significantly decreased Kappa number and excellent paper physical properties.

The multidrug resistance 1 (MDR1) gene product P-glycoprotein is an ATP-dependent efflux pump associated with chemotherapy failure in breast cancer. In the present study, we show that paclitaxel induces MDR1 expression in the MCF-7 breast cancer cell line in a MAPK/Egr-1-dependent manner. Paclitaxel exposure activated the Erk1/2/MAPK pathway and promoted the accumulation of the early response transcription factor Egr-1 in MCF-7 cells. Egr-1 binds to the GC element on the proximal MDR1 promoter to enhance MDR1 transcription. Loss of Egr-1 function in paclitaxel-resistant MCF-7 cells decreased MDR1 expression, whereas inhibiting Erk1/2 activity reduced both Egr-1 accumulation and MDR1 expression. These findings suggest that Erk1/2-induced Egr-1 accumulation activates MDR1 transcription and thereby induces the drug resistance observed in paclitaxel-resistant MCF-7 cells. Further mechanistic studies indicate that Egr-1 most likely does not induce the constitutive activation of Erk1/2 through its target gene geranylgeranyl diphosphate synthase (GGPPS), which regulates Ras prenylation. Indeed, our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.

At present the concept of instantaneous equilibrium is often adopted for simulating the wellbore pressure and temperature distribution in heavy oil wells. In this paper, the mathematical model was built and the diffusion of gas in the oil phase was researched. It proves that the non-equilibrium phenomenon is not obvious in convenient oil wells and it could be overlooked, while in heavy oil wells the non-equilibrium phenomenon is too prominent to be overlooked. Basing on the mass conservation principle, the momentum conservation principle and the energy conservation principle, the calculated model for wellbore pressure and temperature in heavy oil wells considering of the non-equilibrium effect was established. One example shows that the model can accurately reflect the flowing laws in heavy oil wells, which has a relative value for engineering.

Small molecular hydrogels hold important potential applications in bioengineering and biomedicine. However, they suffer usually from weak mechanical and water-retention properties. In this work, hydrophilic dextran polysaccharide was used for the first time to modify the properties of the supramolecular hydrogel derived from a low-molecular-mass gelator, 2, 6-di[N-(carboxyethyl carbonyl)amino]pyridine (DAP). When the DAP hydrogel was formed in aqueous dextran solution with a rather low viscosity, we found that it could be significantly reinforced with respect to its viscoelastic moduli, complex viscosity and hydrogel strength. Moreover, the modified DAP hydrogel has a higher bound water content. These property changes could be attributed to the formation of intermolecular hydrogen bonds between DAP and dextran. By relating the dynamic rheological data with a scaling model, it was found that native and modified DAP hydrogels had both a fractal aggregate structure and the incorporation of dextran resulted in an increase of the fractal dimension. Scanning electron microscopy revealed that a more complex network structure was formed in the DAP hydrogel with dextran.

CONTEXT: To systematically evaluate the effects of hepatoprotective agents, when delivered either alone or in combination with other antiviral or non-antiviral drugs in patients with hepatitis B and hepatic fibrosis. OBJECTIVES: The current randomized controlled clinical trials aimed to evaluate the efficacy of combinations of antiviral and non-antiviral hepatoprotective agents on indexes of liver function and liver fibrosis in patients with hepatitis B. DATA SOURCES: Published literatures in Chinese and English on hepatoprotective treatment strategies for chronic hepatitis B and liver fibrosis were searched in three databases and randomized controlled clinical trials were selected. STUDY SELECTION: Data were extracted according to a variety of inclusion and exclusion criteria. Meta-analysis was employed to analyze the data. RESULTS: A total of 22 randomized controlled trials encompassing 1,714 cases were considered in the meta-analysis. The obtained results indicated that the combination of antiviral drug and hepatoprotective agent was better than antiviral drug alone to improve liver function. Similarly, regarding liver fibrosis, using two different hepatoprotective agents was better than using one agent. The normalization rates of Aminotransferase (ALT) and total Bilirubin (TBil) were improved 25.7% by two hepatoprotective agents compared to the single agent. Acetylcysteine was superior to ursodeoxycholic acid or silibinin to reduce ALT. Ursodeoxycholic acid was superior to acetylcysteine or silibinin to reduce TBIL. CONCLUSIONS: Hepatoprotective agents combined with antiviral drugs can significantly improve liver function and liver fibrosis parameters in patients with hepatitis B.

A simple transition-metal-free protocol for the synthesis of indoles has been developed using aryne cycloaddition. The in situ-generated arynes couple with α-amino ketones through a one-step N-arylation–nucleophilic addition process under mild conditions and efficiently produce multisubstituted N-arylindoles.

In situ crosslinkable hydrogel formed from an amphiphilic amylopectin-based hydrogelator in aqueous solution was investigated with respect to its viscoelasticity, structure as well as protein encapsulation and release. Different from the physical hydrogel formed from an aqueous amylopectin system of sufficiently high concentration, such a hydrogel could be formed rapidly at room temperature and exhibit enhanced viscoelastic properties, mechanical strength, and shear thinning behavior. In addition, it has a more complex network structure with a higher fractal dimension due to intermolecular hydrophobic interactions and macromolecular chain entanglements. By circular dichroism analyses and in vitro release experiments, this hydrogel material was found to have a great potential as new matrix for the entrapment and sustained release of bovine serum albumin.