Shikonin Inhibits the Migration and Invasion of Human Glioblastoma Cells by Targeting Phosphorylated β-Catenin and Phosphorylated PI3K/Akt: A Potential Mechanism for the Anti-Glioma Efficacy of a Traditional Chinese Herbal Medicine

Shikonin is an anthraquinone derivative extracted from the root of lithospermum. Shikonin is traditionally used in the treatment of inflammatory and infectious diseases such as hepatitis. Shikonin also inhibits proliferation and induces apoptosis in various tumors. However, the effect of shikonin on gliomas has not been fully elucidated. In the present study, we aimed to investigate the effects of shikonin on the migration and invasion of human glioblastoma cells as well as the underlying mechanisms. U87 and U251 human glioblastoma cells were treated with shikonin at 2.5, 5, and 7.5 μmol/L and cell viability, migration and invasiveness were assessed with CCK8, scratch wound healing, in vitro Transwell migration, and invasion assays. The expression and activity of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) and the expression of phosphorylated β-catenin (p-β-catenin) and phosphorylated PI3K/Akt were also checked. Results showed that shikonin significantly inhibited the cell proliferation, migration, invasion, and expression of MMP-2 and MMP-9 in U87 and U251 cells. The expression of p-β-catenin showed contrary trends in two cell lines. It was significantly inhibited in U87 cells and promoted in U251 cells. Results in this work indicated that shikonin displayed an inhibitory effect on the migration and invasion of glioma cells by inhibiting the expression and activity of MMP-2 and -9. In addition, shikonin also inhibited the expression of p-PI3K and p-Akt to attenuate cell migration and invasion and MMP-2 and MMP-9 expression in both cell lines, which could be reversed by the PI3K/Akt pathway agonist, insulin-like growth factor-1 (IGF-1).     

BMP3 Alone and Together with TGF-β Promote the Differentiation of Human Mesenchymal Stem Cells into a Nucleus Pulposus-Like Phenotype

Human mesenchymal stem cells (MSCs) have the potential to differentiate into nucleus pulposus (NP)-like cells under specific stimulatory conditions. Thus far, the effects of bone morphogenetic protein 3 (BMP3) and the cocktail effects of BMP3 and transforming growth factor (TGF)-β on MSC proliferation and differentiation remain obscure. Therefore, this study was designed to clarify these unknowns. MSCs were cultured with various gradients of BMP3 and BMP3/TGF-β, and compared with cultures in basal and TGF-β media. Cell proliferation, glycosaminoglycan (GAG) content, gene expression, and signaling proteins were measured to assess the effects of BMP3 and BMP3/TGF-β on MSCs. Cell number and GAG content increased upon the addition of BMP3 in a dose-dependent manner. The expression of COL2A1, ACAN, SOX9, and KRT19 increased following induction with BMP3 and TGF-β, in contrast to that of COL1A1, ALP, OPN, and COMP. Smad3 phosphorylation was upregulated by BMP3 and TGF-β, but BMP3 did not affect the phosphorylation of extracellular-signal regulated kinase (ERK) 1/2 or c-Jun N-terminal kinase (JNK). Our results reveal that BMP3 enhances MSC proliferation and differentiation into NP-like cells, as indicated by increased cell numbers and specific gene expressions, and may also cooperate with TGF-β induced positive effects. These actions are likely related to the activation of TGF-β signaling pathway.     

A Study of Thermodynamic Characteristics of the Zn2P2O7–M4P2O7(M= Li and Na) Systems by Differential Scanning Calorimetry

Glasses, crystals, and melts in the Zn₂P₂O₇–M ₄P₂O₇(M= Li and Na) systems are studied by differential scanning calorimetry (DSC). Temperature dependences of the heat capacity and the enthalpies of melting of Zn₂P₂O₇and Na₂ZnP₂O₇crystals are determined. The thermodynamic characteristics obtained are used for calculating the liquidus curve for the Zn₂P₂O₇–Na₂ZnP₂O₇subsystem on the basis of the Schröder relationship with due regard for the temperature dependences of the enthalpy of melting for components and the nonideal behavior of melts. Reasoning from the Hruby empirical formula, the inference is drawn that the crystallization ability of lithium–zinc phosphate glasses is higher than that of sodium–zinc phosphate glasses. The radius of cooperative motion in the glass transition range for glasses in the Zn₂P₂O₇–Na₄P₂O₇system is estimated in the framework of the phenomenological thermokinetic fluctuation theory. It is assumed that an increase in the radius with an increase in the alkali oxide content is associated with an increase in the ionicity of bonds.     

Effects of B2O3 and P2O5 doping on the microstructure evolution and mechanical strength in a lithium aluminosilicate glass–ceramic material with TiO2 and ZrO2

During the devitrification process, the coordination number of Ti changes from 4 and 5 to 6; and the coordination number of Zr changes from 6 to 8 in a lithium aluminosilicate glass–ceramic material. The flexural strength of the glass–ceramics strongly depends on the composition of additives. The strength of a well-crystallized sample increases 45% by doping with B₂O₃ and decreases 56% by doping with P₂O₅. Thermal expansion mismatch and microstructure non-uniformity are the proposed mechanisms responsible for the changes in strength. The effects of doping concentration of B₂O₃ and P₂O₅ and thermal treatment conditions on the microstructure and mechanical strength of a lithium aluminosilicate glass–ceramic material with TiO₂ and ZrO₂ were studied. The local environment around Ti and Zr correlated to the secondary phase development, such as TiZrO₄ and ZrSiO₄, during the crystallization process was observed by X-ray absorption near edge structure. The electronic structure of each peak in the X-ray absorption near edge spectra was also assigned in terms of phase evolutions. The phase transformation temperature of β-quartz solid solutions to β-spodumene solid solutions is decreased for about 100 °C by adding B₂O₃ and P₂O₅.     

Hydroxyapatite forming ability,ion release and antibacterial activity of the melt-derived SiO2–P2O5–Na2O–CaO–F glasses modified by replacing CaO with SrO and ZnO

Since the discovery of 1970s, bioactive glass has been a hot topic of research because of its excellent biological activity, which makes it a material that can repair and replace human bone tissue organs. In this work, the bioactive glasses in the system SiO₂–P₂O₅–Na₂O–CaO–F with different amounts of strontium oxide (SrO) and zinc oxide (ZnO) were prepared by the conventional melt quenching technology. The hydroxyapatite (HA) forming ability, ion release and antibacterial activity of these prepared glasses were investigated and the obtained results illustrated that SrO-doped samples had a better ability to form HA in modified simulated body fluid (MSBF) than ZnO-doped samples. As the immersion time of the sample in MSBF increased, the content of HA phase gradually increased. In the same immersion time, the formation ability of HA and the variation of SrO substitution amount showed a non-linear trend, which is mainly related to the influence of SrO content on the glass network structure. The results of ion concentration showed that the formation of HA was the result of the comprehensive action of various ions in the solution, especially the release rate of Si⁴⁺ ions, which had a direct impact on the formation ability of HA. The antibacterial test illustrated that the difference in antibacterial activity of bacteria solution at different sample concentrations may be related to the high pH environment and the osmotic effects caused by the non-physiological concentration of ions in the solution. The glass sample contained 4 wt% SrO showed the minimum bactericidal concentration at 64 mg/mL. The glass samples prepared in this experiment had good biological activity and antibacterial effect, making them suitable for using in dentistry and orthopedic applications, as well as providing a valuable composition reference for the preparation of bioactive glass with excellent comprehensive properties.     

Comparative study on the tribological properties of laser post-treated and untreated AISI304 stainless steel matrix composite reinforced with hard ceramic particles (TiB2–TiN–SiC) and prepared by ex-situ P/M route

This work highlights evaluation of suitable process parameters to result significantly higher hardness, fracture toughness and wear resistance in metal matrix composites (MMC) developed with different proportions of reinforcements, namely, TiB₂, TiN, and SiC in steel (AISI 304). The composites are developed through powder metallurgical route and are subsequently laser surface glazed. Thorough characterizations of composites’ mechanical and tribological behaviors before and after laser surface treatment and application of response surface methodology (RSM) for modeling and analysis of its behavioral responses towards variations in process parameters are performed.     

The first complex of the pentameric phosphazane macrocycle [{P(μ-NtBu)}2(μ-NH)]5 with a neutral molecular guest: Synthesis and structure of [{P(μ-NtBu)}2(μ-NH)]5(CH2Cl2)2

The reaction of [{P(μ-N^tBu)}₂(μ-NH)}₅I]⁻[Li(thf)₄]⁺([1 · I]⁻[Li(thf)₄]⁺) with NaOMe in CH₂Cl₂ gives the title compound [{P(μ-N^tBu)}₂(μ-NH)]₅(CH₂Cl₂)₂ [1 · (CH₂Cl₂)₂] the first adduct containing this type of macrocyclic phosph(III)azane host and a neutral guest.     

Two new selenidostannates with a [Sn3Se7]n2n− layer from the imidazolium-based ionic liquids: The role of (Bzmim)+ and aggregated cation of [(Emim)3Cl]2+

Herein, we report on the syntheses, crystal structures, and optical properties of two new selenidostannates, namely, [Emim]₅[Sn₃Se₇]₂Cl (1, Emim = 1-ethyl-3-methylimidazolium) and [Bzmim]₂[Sn₃Se₇] (2, Bzmim = 1-benzyl-3-methylimidazolium). The ionic liquids (ILs) of [Emim]Cl with a short ethyl chain and [Bzmim]Cl with a bulky substituent benzyl group were used in the syntheses of compounds 1 and 2, respectively. Although both the structures feature an anionic lamellar [Sn₃Se₇]_n^2n– layer, the packing of the layers are dramatically different; such structural diversity may be ascribed to the difference of structure-directing cations incorporated in between the layers, that is [(Emim)₃Cl]²⁺ aggregates in 1 and bulky [Bzmim]⁺ in 2, respectively.     

Studies on the synthesis of cholane derivatives containing a mercapto group and their dimers with disulfide spacers. Part 2. 3α-Mercapto-5β-cholane-7α,12α,24-triol and its C(3)–C(3′) disulfide dimer

Two new sulfur-containing cholane derivatives were obtained from cholic acid: 3α-mercapto-5β-cholane-7α,12α,24-triol 2 and its C(3)–C(3′) disulfide dimer 3 as a potential supramolecular host.     

Comparative study of lithium ion conductors in the system Li1+xAlxA2−xIV (PO4)3 with AIV=Ti or Ge and 0≤x≤0·7 for use as Li+ sensitive membranes

Preparations and physico-chemical characterizations of NASICON-type compounds in the system Li_1+xAl_xA_2−x^IV(PO₄)₃ (A^IV=Ti or Ge) are described. Ceramics have been fabricated by sol-gel and co-grinding processes for use as ionosensitive membrane for Li⁺ selective electrodes. The structural and electrical characteristics of the pellets have been examined. Solid solutions are obtained with Al/Ti and Al/Ge substitutions in the range 0≤x≤0·6. A minimum of the rhombohedral c parameter appears for x about 0·1 for both solutions. The grain ionic conductivity has been characterized only in the case of Ge-based compounds. It is related to the carrier concentration and the structural properties of the NASICON covalent skeleton. The results confirm that the Ti-based framework is more calibrated to Li⁺ migration than the Ge-based one. A grain conductivity of 10⁻³ S cm⁻¹ is obtained at 25°C in the case of Li_1·3Al_0·3Ti_1·7(PO₄)₃. A total conductivity of about 6×10⁻⁵ S cm⁻¹ is measured on sintered pellets because of grain boundary effects. The use of such ceramics in ISE devices has shown that the most confined unit cell (i.e. in Ge-based materials) is more appropriate for selectivity effect, although it is less conductive.©