The Pro-Apoptotic Role of the Regulatory Feedback Loop between miR-124 and PKM1/HNF4α in Colorectal Cancer Cells

Accumulating evidence indicates that miRNA regulatory circuits play important roles in tumorigenesis. We previously reported that miR-124 is correlated with prognosis of colorectal cancer due to PKM-dependent regulation of glycolysis. However, the mechanism by which miR-124 regulates apoptosis in colorectal cancer remains largely elusive. Here, we show that miR-124 induced significant apoptosis in a panel of colorectal cancer cell lines. The mitochondrial apoptosis pathway was activated by miR-124. Furthermore, the pro-apoptotic role of miR-124 was dependent on the status of PKM1/2 level. PKM1 was required for miR-124-induced apoptosis. Via direct protein-protein interaction, PKM1 promoted HNF4α binding to the promoter region of miR-124 and transcribing miR-124. Moreover, HNF4α or PKM1 had a more dramatic effect on colorectal cancer cell apoptosis in the presence of miR-124. However, inhibition of miR-124 blocked cell apoptosis induced by HNF4α or PKM1. These data indicate that miR-124 not only alters the expression of genes involved in glucose metabolism but also stimulates cancer cell apoptosis. In addition, the positive feedback loop between miR-124 and PKM1/HNF4α plays an important role in colorectal cancer cell apoptosis; it suggests that disrupting this regulatory circuit might be a potential therapeutic tool for colorectal cancer treatment.     

Hypoxic Conditioned Medium from Human Amniotic Fluid-Derived Mesenchymal Stem Cells Accelerates Skin Wound Healing through TGF-β/SMAD2 and PI3K/Akt Pathways

In a previous study, we isolated human amniotic fluid (AF)-derived mesenchymal stem cells (AF-MSCs) and utilized normoxic conditioned medium (AF-MSC-norCM) which has been shown to accelerate cutaneous wound healing. Because hypoxia enhances the wound healing function of mesenchymal stem cell-conditioned medium (MSC-CM), it is interesting to explore the mechanism responsible for the enhancement of wound healing function. In this work, hypoxia not only increased the proliferation of AF-MSCs but also maintained their constitutive characteristics (surface marker expression and differentiation potentials). Notably, more paracrine factors, VEGF and TGF-β1, were secreted into hypoxic conditioned medium from AF-MSCs (AF-MSC-hypoCM) compared to AF-MSC-norCM. Moreover, AF-MSC-hypoCM enhanced the proliferation and migration of human dermal fibroblasts in vitro, and wound closure in a skin injury model, as compared to AF-MSC-norCM. However, the enhancement of migration of fibroblasts accelerated by AF-MSC-hypoCM was inhibited by SB505124 and {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, inhibitors of TGF-β/SMAD2 and PI3K/AKT, suggesting that AF-MSC-hypoCM-enhanced wound healing is mediated by the activation of TGF-β/SMAD2 and PI3K/AKT. Therefore, AF-MSC-hypoCM enhances wound healing through the increase of hypoxia-induced paracrine factors via activation of TGF-β/SMAD2 and PI3K/AKT pathways.     

The role of K2O on sintering and crystallization of glass powder compacts in the Li2O–K2O–Al2O3–SiO2 system

The effects of K₂O content on sintering and crystallization of glass powder compacts in the Li₂O–K₂O–Al₂O₃–SiO₂ system were investigated. Glasses featuring SiO₂/Li₂O molar ratios of 2.69–3.13, far beyond the lithium disilicate (LD-Li₂Si₂O₅) stoichiometry, were produced by conventional melt-quenching technique. The sintering and crystallization behaviour of glass powders was explored using hot stage microscopy (HSM), scanning electron microscopy (SEM), differential thermal (DTA) and X-ray diffraction (XRD) analyses. Increasing K₂O content at the expense of SiO₂ was shown to lower the temperature of maximum shrinkage, eventually resulting in early densification of the glass-powder compacts. Lithium metasilicate was the main crystalline phase formed upon heat treating the glass powders with higher amounts of K₂O. In contrast, lithium disilicate predominantly crystallized from the compositions with lower K₂O contents resulting in strong glass–ceramics with high chemical and electrical resistance. The total content of K₂O should be kept below 4.63 mol% for obtaining LD-based glass–ceramics.     

Sinomenine Derivatives: Synthesis,Antitumor Activity,and Apoptotic Induction in MCF-7 Cells via IL-6/PI3K/Akt/NF-κB Signaling Pathway

Natural products have been widely considered as an important resource for new drugs or lead compounds. Sinomenine (SIN) and its derivatives exert antitumor activity via regulation of inflammatory mediators. For these reasons we synthesized three series of SIN derivatives (compounds 4 a – i , 7 a – c and 11 a – c ) as antitumor agents from this natural product. All compounds were prepared by modification at the C1 and C4 positions of the A ring, the C4 position of the A ring, and the C6 and C7 positions of the C ring, respectively. All the derivatives were subjected to in vitro antitumor activity against HeLa, A549, HepG-2, MCF-7 and HT-29 cell lines. To observe the apoptotic induction of SIN derivatives and its mechanism, fluorescent staining and western blot assays were carried out for active compound against MCF-7. Based on the screening results, most of the SIN derivatives showed better antitumor activity than SIN. Some of them were found to possess broad-spectrum antitumor activity. Most notably, 11 c exhibited obvious antitumor activity in both cell lines with IC₅₀ values less than 11 μM. Besides, 11 c induced apoptosis of MCF-7 in a dose-dependent manner. Western blot assay demonstrated that 11 c inhibited IL-6-mediated activation of PI3K/Akt pathway. A docking study revealed that 11 c had stronger binding interaction with the residues of IL-6 than SIN. All these results indicate that 11 c may be a potential anti-breast cancer agent by directly targeting IL-6.     

The impact of nano-quartz on the structure of glass-ceramic glazes from the SiO2–Al2O3–CaO–MgO–Na2O–K2O system

The present study reports the impact of the introduction of nano-grained quartz (SA = 325 m²/g) into the composition on the structure and properties of the ceramic glaze of the CMAS-Na₂O–K₂O system. The results were compared to the glaze which had an identical oxide composition, with a difference that quartz was introduced in the form of quartz powder with a much smaller specific surface area SA = 1.41 m²/g. Both glazes are characterized by a large part of the glassy phase, above 90% by volume. The results obtained show a higher arrangement of the continuous glassy phase structure in the glaze with the addition of nano-quartz. This glaze also shows significantly higher values for all measured mechanical properties. It seems that if, in the near future, new cheaper methods for the production of nano-quartz are developed, it will be a new interesting direction of research aimed at improving the parameters of glazes and glass-ceramic materials of CMAS type.     

Preparation and properties of KH550-Al2O3/PI–EP nanocomposite material

First, polyimide (PI)–epoxy resin (EP) polymer matrix was prepared from 3,3′-diethyl-4,4′-diamino diphenyl methane (DEDADPM), benzophenone tetracarboxylic acid dianhydride (BTDA) and epoxy resin (E-51), through thermal imide process. Then, the nanometer alumina (Al₂O₃) modified by the coupling agent, (3-aminopropyl)triethoxysilane (KH550), was doped into the PI–EP polymer matrix, using an in situ sol–gel method to prepare a series of KH550-Al₂O₃/PI–EP nanocomposite materials based on different KH550-Al₂O₃ contents. Fourier transform infrared spectroscopy (FTIR) indicated that in the presence of chemical reaction between poly(amic acid) and epoxy resin, an imide ring was formed, the thermal imidization reaction of the materials was completed and the KH550-Al₂O₃ had doped into the PI–EP polymer matrix. The heat-resistance, dielectric specification and mechanical properties of KH550-Al₂O₃/PI–EP nanocomposite materials were evaluated. The results showed that the decomposition temperatures were ranged between 438 and 450 °C, dielectric constant and dielectric loss were in the range of 3.32–3.71 and 1.5 × 10^?3–2.5 × 10^?2, respectively, and they all increased with the increase of KH550-Al₂O₃ content (0–10 wt%), but the shear strength first increased and then decreased, attained its maximum value of 10.64 MPa at 8 wt%, which was about 119 % higher than that of undoped material. The adhesive forces of nanocomposite materials were all at higher level (one or two levels). Thus, the overall performance of KH550-Al₂O₃/PI–EP nanocomposites was the best when the doping amount of KH550-Al₂O₃ was 8 wt%. The properties such as high heat-resistance, dielectric properties and ready attachment of impregnating varnish to steel plate with very high strength fully met the necessary requirement.     

Modulation of the PI3K/Akt Pathway and Bcl-2 Family Proteins Involved in Chicken’s Tubular Apoptosis Induced by Nickel Chloride (NiCl2)

Exposure of people and animals to environments highly polluted with nickel (Ni) can cause pathologic effects. Ni compounds can induce apoptosis, but the mechanism and the pathway of Ni compounds-induced apoptosis are unclear. We evaluated the alterations of apoptosis, mitochondrial membrane potential (MMP), phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway, and Bcl-2 family proteins induced by nickel chloride (NiCl₂) in the kidneys of broiler chickens, using flow cytometry, terminal deoxynucleotidyl transferase 2ʹ-deoxyuridine 5ʹ-triphosphate dUTP nick end-labeling (TUNEL), immunohistochemstry and quantitative real-time polymerase chain reaction (qRT-PCR). We found that dietary NiCl₂ in excess of 300 mg/kg resulted in a significant increase in apoptosis, which was associated with decrease in MMP, and increase in apoptosis inducing factor (AIF) and endonuclease G (EndoG) protein and mRNA expression. Concurrently, NiCl₂ inhibited the PI3K/Akt pathway, which was characterized by decreasing PI3K, Akt1 and Akt2 mRNA expression levels. NiCl₂ also reduced the protein and mRNA expression of anti-apoptotic Bcl-2 and Bcl-xL and increased the protein and mRNA expression of pro-apoptotic Bax and Bak. These results show that NiCl₂ causes mitochondrial-mediated apoptosis by disruption of MMP and increased expression of AIF and EndoG mRNA and protein, and that the underlying mechanism of MMP loss involves the Bcl-2 family proteins modulation and PI3K/Akt pathway inhibition.     

Effect of Soot During Operation of a Pt–K/Al2O3 LNT Catalyst

The effect of soot on the NO _x storage-reduction performances of a Pt–K/Al₂O₃ catalyst is analysed in this work by performing lean-rich cycles at constant temperature. The interaction between soot and the stored NO _x has been also investigated by temperature programmed methods. It has been found that the presence of soot reduces the NO _x storage capacity of the catalyst; besides the presence of soot favours the decomposition of the stored nitrates. A direct reaction between the stored nitrates and soot is suggested, that has been explained on the basis of the surface mobility of the adsorbed nitrates.     

The catalytic conversion of CO2 to hydrocarbons over Fe–K supported on Al2O3–MgO mixed oxides

Al₂O₃–MgO mixed oxides prepared by a co-precipitation method have been used as supports for potassium-promoted iron catalysts for CO₂ hydrogenation to hydrocarbons. The catalysts have been characterized by XRD, BET surface area, CO₂ chemisorption, TPR and TPDC techniques. The CO₂ conversion, the total hydrocarbon selectivity, the selectivities of C₂–C₄ olefins and C₅₊ hydrocarbons are found to increase with increase in MgO content upto 20 wt% in Fe–K/Al₂O₃–MgO catalysts and to decrease above this MgO content. The TPR profiles of the catalysts containing pure Al₂O₃ and higher (above 20 wt%) MgO content are observed to contain only two peaks, corresponding to the reduction of Fe₂O₃ to Fe⁰ through Fe₃O₄. However, the TPR profile of 20 wt% MgO catalyst exhibits three peaks, which indicate the formation of iron phase through FeO phase. The TPDC profiles show the formation of three types of carbide species on the catalysts during the reaction. These profiles are shifted towards high temperatures with increasing MgO content in the catalyst. The activities of the catalysts are correlated with physico-chemical characteristics of the catalysts. This revised version was published online in July 2006 with corrections to the Cover Date.     

Epoxidation of Propylene by Molecular Oxygen Over the Ag–Y2O3–K2O/α-Al2O3 Catalyst

Abstract The Ag/α-Al₂O₃ catalyst modified with rare earth metal oxide (Y₂O₃) and alkali metal oxide (K₂O) for the epoxidation of propylene by molecular oxygen were prepared and characterized by TG-DTA, XRD and XPS. The results show that a small quantity of Y₂O₃ added plays a role of electron and structure-type promoters, and can change the binding energies of Ag3d and restrain the sintering of Ag crystallites during catalyst preparation. The effects of promoters loading, Ag loading, reaction temperature, and calcination atmosphere on the performance of Ag catalyst were investigated. The results show that the loadings of K₂O, Y₂O₃ and Ag, and reaction temperature affect obviously the catalytic performance of Ag–Y₂O₃–K₂O/α-Al₂O₃ for the epoxidation of propylene to propylene oxide. Under the reaction conditions of 0.1 MPa, 245 °C, GHSV of 2000 h⁻¹ and the feed gas of 20%C₃H₆/8%O₂/N₂, the conversion of propylene of 4% and the selectivity to propylene oxide of 46.8% were achieved over the 20%Ag–0.1%Y₂O₃–0.1%K₂O/α-Al₂O₃ catalyst. Graphical Abstract Y₂O₃ plays a role of electron and structure-type promoters in the Ag–Y₂O₃–K₂O/α-Al₂O₃ catalyst, which can change the binding energies of Ag3d and restrain the sintering of Ag crystallites, resulting in obvious improvement of the catalytic performance of Ag–Y₂O₃–K₂O/α-Al₂O₃ for the epoxidation of propylene to propylene oxide by molecular oxygen.      

The influence of In2O3 on electrical characteristics of iron mixed Li2O–PbO–B2O3–SiO2–Bi2O3 multi-component glass system

Glasses of the composition 19Li₂O–20PbO–20B₂O₃–30SiO₂–(10−x) Bi₂O₃–1Fe₂O₃: xIn₂O₃ with six values of x (0 to 5.0) were synthesized. Dielectric properties viz., dielectric constant, ε′(ω), loss, tan δ, ac conductivity, σ_ac, electric modulus, M(ω) over wide ranges of frequency and temperature and also dielectric break down strength have been studied as a function of In₂O₃ concentration. The temperature dispersion of real part of dielectric constant, ε′(ω) has been analyzed using space charge polarization model. The dielectric loss (and also the electric moduli) variation with frequency and temperature exhibited relaxation effects and these effects were attributed to the divalent iron ion complexes. The ac conductivity exhibited maximal effect, whereas the activation energy for the conductivity demonstrated minimal magnitude at about 1.0 mol% of In₂O₃. The conductivity mechanism is understood due to the polaronic transfer between Fe²⁺ and Fe³⁺ ions. The low temperature ac conductivity mechanism is explained following the quantum mechanical tunneling model. Spectroscopic studies viz., optical absorption and ESR spectra have revealed that the redox ratio (Fe²⁺/Fe³⁺) is maximal when the concentration of In₂O₃ is ~1.0 mol%. The higher values of dielectric parameters observed at 1.0 mol% of In₂O₃ are attributed to the presence of iron ions largely in divalent state and act as modifiers. The analysis of these results together with spectroscopic studies has indicated that when In₂O₃ is present in the glass matrix in higher concentrations (more than 1.0 mol%) iron ions predominantly exist in trivalent state, occupy substitutional positions and make the glass more rigid. Such enhanced rigidity of the network is causing the decrease of dielectric parameters with the concentration of In₂O₃. Finally it is concluded that In₂O₃ mostly participate in the glass network in octahedral positions and make act as reducing agent (for iron ions) in the studied glass matrix when its concentration is ≤1.0 mol%.     

Simultaneous Removal of NO x and Soot Over Pt–Ba/Al2O3 and Pt–K/Al2O3 DPNR Catalysts

The effect of NO _x storage on the soot combustion activity when alkaline- and alkaline/earth-containing model DPNR catalysts are used is investigated in this work. The influence of different experimental conditions (NO concentration, temperature, and particulate loading) is addressed and discussed in relation to the NO _x storage efficiency and soot oxidation activity as well.     

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).     

The role of the distribution of Ce species on MoO3/CeO2–Al2O3 catalysts in sulfur-resistant methanation

CeO₂–Al₂O₃ supports were prepared by different methods and applied as MoO₃/CeO₂–Al₂O₃ catalysts for sulfur-resistant methanation. All characterization analyses of the catalysts indicated that when the Ce species are distributed in the bulk of the catalysts, they are favorable for the stability of the catalyst whereas when the Ce species are distributed on the surface of the catalyst, they are beneficial for the initial activity. Stepwise sulfidation is applied on MoO₃/CeO₂–Al₂O₃ catalyst to eliminate surface Ce species and migrate them to the inside of the catalyst, this also demonstrates that the Ce species distributed in the bulk of the catalysts are favorable for the stability.     

The effects of Cl-induced alloying in Pt–Sn/Al2O3 catalysts on butane/H2 reactions

The effects of oxidation/reduction regeneration treatments, with and without 1,2-dichloropropane present as a chlorinating agent, on the structure of Pt(3%)–Sn(4.5%)/Al₂O₃ catalysts have been correlated with selectivities for butane/H₂ reactions. Particles of Pt⁰ fin Cl-free catalysts were partly covered by Sn⁰, but retained exposed ensembles of Pt atoms which were active for isomerisation, hydrogenolysis and dehydrogenation reactions, the latter becoming dominant at high reaction temperatures. Coking reduced Pt ensemble size and, hence, also favoured high selectivities for dehydrogenation as hydrogenolysis and isomerisation sites became poisoned. In contrast, the addition of 1,2-dichloropropane in an oxychlorination step before reduction promoted 1:1 Pt⁰–Sn⁰ alloy formation after reduction, the proportion of the total Pt in alloy being enhanced by increasing 1,2-dichloropropane concentration and oxychlorination temperature. The alloy surfaces were inactive for isomerisation and hydrogenolysis reactions, giving dehydrogenation as the sole catalytic reaction.     

DRIFT Studies of Adsorbed CO Over Sulfided K–Rh–Mo/Al2O3 Catalysts: Detection of Rh–Mo–S Phase

Diffuse reflectance infrared Fourier transform (DRIFT) spectroscopy was used to study the nature of active species in K–Rh–Co–MoS₂/Al₂O₃ catalyst by means of probing with CO molecule. The effects of K addition to Rh and interaction between Mo and Rh were studied with varying K and Mo loadings over 1 wt% Rh/Al₂O₃ catalyst. In sulfided Rh–Mo/Al₂O₃, the formation of Rh–Mo–S phase was evidenced first time by a band at 2,095 cm^?1. The introduction of Co to K–Rh–MoS₂/Al₂O₃ catalyst showed the existence of both Rh and Co promoted MoS₂ sites, but the CO absorption frequencies in DRIFT spectra are significantly at lower side compared to Co free Rh–Mo catalyst. The stabilities of CO band from Rh and Co promoted and unpromoted MoS₂ sites are studied at different temperatures. When activated carbon used as support, bands for both promoted and unpromoted MoS₂ sites were appeared, but the intensity of these bands were decreased largely compared to alumina based catalyst, resulted from the coverage of added K not only on the support surface but also on the active metal components due to the neutral nature of activated carbon.     

The effect of Fe-acceptor doping on the electrical properties of Na1/2Bi1/2TiO3 and 0.94 (Na1/2Bi1/2)TiO3–0.06 BaTiO3

Na_1/2Bi_1/2TiO₃ (NBT) based ceramics are amongst the most promising lead-free ferroelectric materials. It was expected that the defect chemistry and the effect of doping of NBT would be similar to that observed for lead based materials, however, acceptor doping does not lead to ferroelectric hardening. Instead, high oxygen ionic conductivity is induced. Nevertheless, for solid solutions with BaTiO₃ (BT), which are more relevant with respect to ferroelectric applications, such a drastic change of electrical properties has not been observed so far. To rationalize the difference in defect chemistry between NBT and its solid solution 94(Na_1/2Bi_1/2TiO₃)–0.06 BaTiO₃ (NBT–6BT) compositions with different concentrations of Fe-dopant were investigated. The study illustrates that the materials exhibit very similar behavior to NBT, and extraordinarily high oxygen ionic conductivity could also be induced in NBT–6BT. The key difference between NBT–6BT and NBT is the range of the dependence of ionic conductivity with dopant concentration. Previous studies of NBT–6BT have not reached sufficiently high dopant concentrations to observe high conductivity. In consequence, the same defect chemical model can be applied to both NBT and its solid solutions. This will help to rationalize the effect of doping on ferroelectric properties of NBT-ceramics and defect chemistry related degradation and fatigue.