Lysophosphatidic acid receptor 2 and Gi/Src pathway mediate cell motility through cyclooxygenase 2 expression in CAOV-3 ovarian cancer cells

Lysophosphatidic acid (LPA) is a bioactive phospholipids and involves in various cellular events, including tumor cell migration. In the present study, we investigated LPA receptor and its transactivation to EGFR for cyclooxygenase-2 (COX-2) expression and cell migration in CAOV-3 ovarian cancer cells. LPA induced COX-2 expression in a dose-dependent manner, and pretreatment of the cells with pharmacological inhibitors of Gi (pertussis toxin), Src (PP2), EGF receptor (EGFR) (AG1478), ERK (PD98059) significantly inhibited LPA-induced COX-2 expression. Consistent to these results, transfection of the cells with selective Src siRNA attenuated COX-2 expression by LPA. LPA stimulated CAOV-3 cell migration that was abrogated by pharmacological inhibitors and antibody of EP2. Higher expression of LPA2 mRNA was observed in CAOV-3 cells, and transfection of the cells with a selective LPA2 siRNA significantly inhibited LPA-induced activation of EGFR and ERK, as well as COX-2 expression. Importantly, LPA2 siRNA also blocked LPA-induced ovarian cancer cell migration. Collectively, our results clearly show the significance of LPA2 and Gi/Src pathway for LPA-induced COX-2 expression and cell migration that could be a promising drug target for ovarian cancer cell metastasis.     

A systematic study of stereochemical effects in homologous poly(alkenamer)s: Dewar benzene versus norbornene

Two diastereomeric derivatives of norbornene, dimethyl (1R,2R,3S,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate and dimethyl (1R,2S,3S,4S)-bicyclo[2.2.1]hept-5-ene-2,3-dicarboxylate, were synthesized and polymerized using ring-opening metathesis polymerization (ROMP). For comparative purposes, diastereomeric derivatives of Dewar benzene, dimethyl (1R,2S,3R,4S)-bicyclo[2.2.0]hex-5-ene-2,3-dicarboxylate and dimethyl (1R,2S,3S,4S)-bicyclo[2.2.0]hex-5-ene-2,3-dicarboxylate, were also synthesized and polymerized using ROMP. The polymerization reactions proceeded in a controlled manner as evidenced in part by linear relationships between the monomer-to-catalyst feed ratios and the molecular weights of the polymer products. Chain extension experiments were also conducted which facilitated the formation of block copolymers. Although the poly(norbornene) derivatives exhibited glass transition temperatures that were dependent on their monomer stereochemistry (cis: 115°C vs. trans: 125°C), more pronounced differences were observed upon analysis of the polymers derived from Dewar benzene (cis: 70°C vs. trans: 95°C). Likewise, microphase separation was observed in block copolymers that were prepared using the diastereomeric monomers derived from Dewar benzene but not in block copolymers of the norbornene-based diastereomers. The differential thermal properties were attributed to the relative monomer sizes as reducing the distances between the polymer backbones and the pendant stereocenters appeared to enhance the thermal effects.     

The impact of endotrophin on the progression of chronic liver disease

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and can lead to multiple complications, including non-alcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma. The fibrotic liver is characterized by the pathological accumulation of extracellular matrix (ECM) proteins. Type VI collagen alpha3 (Col6a3) is a biomarker of hepatic fibrosis, and its cleaved form, endotrophin (ETP), plays a critical role in adipose tissue dysfunction, insulin resistance, and breast cancer development. Here, we studied the effects of the Col6a3-derived peptide ETP on the progression of chronic liver diseases, such as NASH and liver cancer. We used a doxycycline (Dox)-inducible liver-specific ETP-overexpressing mouse model on a NAFLD-prone (liver-specific SREBP1a transgenic) background. For this, we evaluated the consequences of local ETP expression in the liver and its effect on hepatic inflammation, fibrosis, and insulin resistance. Accumulation of ETP in the liver induced hepatic inflammation and the development of fibrosis with associated insulin resistance. Surprisingly, ETP overexpression also led to the emergence of liver cancer within 10 months in the SREBP1a transgenic background. Our data revealed that ETP can act as a “second hit” during the progression of NAFLD and can play an important role in the development of NASH and hepatocellular carcinoma (HCC). These observations firmly link elevated levels of ETP to chronic liver disease.Subject terms: Metabolic syndrome, Biological techniques     

Determination of acetylsalicylic acid and its major metabolite, salicylic acid, in human plasma using liquid chromatography-tandem mass spectrometry: application to pharmacokinetic study of Astrix in Korean healthy volunteers

The first liquid chromatography-tandem mass spectrometry (LC/MS/MS) method for determination of acetylsalicylic acid (aspirin, ASA) and one of its major metabolites, salicylic acid (SA), in human plasma using simvastatin as an internal standard has been developed and validated. For ASA analysis, a plasma sample containing potassium fluoride was extracted using a mixture of ethyl acetate and diethyl ether in the presence of 0.5% formic acid. SA, a major metabolite of ASA, was extracted from plasma using protein precipitation with acetonitrile. The compounds were separated on a reversed-phase column with an isocratic mobile phase consisting of acetonitrile and water containing 0.1% formic acid (8:2, v/v). The ion transitions recorded in multiple reaction monitoring mode were m/z 179 --> 137, 137 --> 93 and 435 --> 319 for ASA, SA and IS, respectively. The coefficient of variation of the assay precision was less than 9.3%, and the accuracy exceeded 86.5%. The lower limits of quantification for ASA and SA were 5 and 50 ng/mL, respectively. The developed assay method was successfully applied for the evaluation of pharmacokinetics of ASA and SA after single oral administration of Astrix (entero-coated pellet, 100 mg of aspirin) to 10 Korean healthy male volunteers.     

Coordination power adjustment of surface-regulating polymers for shaping gold polyhedral nanocrystals

PVP (poly(vinyl pyrrolidone)) is a common polymer that behaves as a surface-regulating agent that shapes metal nanocrystals in the polyol process. We have used different polymers containing tertiary amide groups, namely PVCL (poly(vinyl caprolactam)) and PDMAm (poly(N,N-dimethyl acrylamide)), for the synthesis of gold polyhedrons, including octahedrons, cuboctahedrons, cubes, and higher polygons, under the present polyol reaction conditions. The basicity and surface coordination power of the polymers are in the order of PVCL, PVP, and PDMAm. A correlation is observed between the coordination power of the polymers and the resulting gold nanocrystal size. Strong coordination and electron donation from the polymer functional groups to the gold surface restrict particle growth rates, which leads to small nanocrystals. The use of PVCL can yield gold polyhedral structures with small sizes, which cannot be achieved in the reactions with PVP. Simultaneous hydrolysis of the amide group in PDMAm leads to carboxylate functionality, which is very useful for generating chemical and bioconjugates through the formation of ester and amide bonds.     

Roles of gangliosides in mouse embryogenesis and embryonic stem cell differentiation

Gangliosides have been suggested to play important roles in various functions such as adhesion, cell differentiation, growth control, and signaling. Mouse follicular development, ovulation, and luteinization during the estrous cycle are regulated by several hormones and cell-cell interactions. In addition, spermatogenesis in seminiferous tubules of adult testes is also regulated by several hormones, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and cell-cell interactions. The regulation of these processes by hormones and cell-cell interactions provides evidence for the importance of surface membrane components, including gangliosides. During preimplantation embryo development, a mammalian embryo undergoes a series of cleavage divisions whereby a zygote is converted into a blastocyst that is sufficiently competent to be implanted in the ma ternal uterus and continue its development. Mouse embryonic stem (mES) cells are pluripotent cells derived from mouse embryo, specifically, from the inner cell mass of blastocysts. Differentiated neuronal cells are derived from mES cells through the formation of embryonic bodies (EBs). EBs recapitulate many aspects of lineage-specific differentiation and temporal and spatial gene expression patterns during early embryogenesis. Previous studies on ganglioside expression during mouse embryonic development (including during in vitro fertilization, ovulation, spermatogenesis, and embryogenesis) reported that gangliosides were expressed in both undifferentiated and differentiated (or differentiating) mES cells. In this review, we summarize some of the advances in our understanding of the functional roles of gangliosides during the stages of mouse embryonic development, including ovulation, spermatogenesis, and embryogenesis, focusing on undifferentiated and differentiated mES cells (neuronal cells).     

Theoretical investigation on the IR spectra of four‐membered silicon oxide ring

To test the mass effect on the ring vibrational frequencies (SiO₂) shift of the four‐membered silicon oxide ring, the deuterium and the tritium substituted cyclodisiloxanes on the hydrogen positions are examined at the CCSD(T)/cc‐pVTZ level of theory. The SiO₂ ring vibrations for a silicon oxide surface model compound, substituted cyclodisiloxane (Si₃O₅? O₂? Si₃O₅) with two six‐membered ring, are also calculated at the B3LYP/cc‐pVTZ level of theory. Our results of 909 and 920 cm^?1 are in good agreement with the experimental result. © 2010 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Changes in the surface structure of Pd/Ta2O5 by oxygen and CO studied using X‐ray Photoelectron Spectroscopy (XPS)

Behaviors of Pd structures with different thicknesses supported by Ta₂O₅/Ta in the reaction with oxygen and CO were studied by XPS and SEM. For the samples with a Pd thickness of 3 nm, a new low‐binding‐energy component appeared in the Pd 3d level upon O₂ exposure at ～200 °C and was reduced in intensity after a subsequent CO exposure at 150 and 200 °C. The change in the Ta 4f state could also be found upon oxygen and CO exposure, indicating that both Pd and the Ta‐oxide substrate participate in the chemical reactions. For the sample with a higher Pd thickness, a positive shift in the Pd 3d level due to the oxidation of Pd was observed after exposure to O₂ at a higher temperature (280 °C). A subsequent CO exposure at ～150 °C could not reduce Pd‐oxide layers, as confirmed by the unchanged Pd 3d spectra after CO treatment, i.e. Pd‐oxide was not reactive for CO oxidation. Copyright © 2010 John Wiley & Sons, Ltd.     

Propane combustion over supported Pt catalysts

We prepared Pt catalysts supported on various metal oxides, viz., ZrO₂, CeO₂, TiO₂, yttria-stabilized zirconia (YSZ), SiO₂, SiO₂–Al₂O₃, and γ-Al₂O₃, using an incipient wetness method and applied them to propane combustion. In the cases of ZrO₂-, CeO₂-, and TiO₂-supported Pt catalysts, supports with different surface areas were also used. The Pt dispersion in Pt catalysts supported on metal oxides increased with increasing surface area of the support for the same metal oxide. Pt catalysts on supports with lower surface areas (ZrO₂, CeO₂, and TiO₂) showed higher catalytic activities for propane combustion than did Pt catalysts on supports with higher surface areas. The catalytic activity decreased in the following order: Pt/ZrO₂ (2) > Pt/CeO₂ (9) > Pt/TiO₂ (1) = Pt/SiO₂ (350) > Pt/ZrO₂ (18) = Pt/YSZ > Pt/TiO₂ (330) > Pt/SiO₂–Al₂O₃ (350) > Pt/ZrO₂ (73) > Pt/γ-Al₂O₃ (180) > Pt/CeO₂ (160). The catalytic activity is inversely proportional to the amount of O₂ chemisorbed up to the reaction temperature. It can be concluded that metallic Pt is essential for propane combustion and is maintained for the Pt catalysts with large Pt metal particles, which can be prepared by using a support with a low surface area.     

Dye-sensitized solar cells employing amphiphilic poly(ethylene glycol) electrolytes

Poly(ethylene glycol) (PEG) was modified with a long alkyl acid to produce a self-organized amphiphilic polymer (amPEG). FT-IR and NMR spectroscopies confirmed the amPEG synthesis. This polymer was complexed with lithium iodide (LiI) and 1-methyl-3-propylimidazolium iodide (MPII) to prepare polymer electrolytes to be applied to dye-sensitized solar cells (DSSC). FT-IR studies showed that upon the addition of litium salt the free ether and ester carbonyl bands shifted towards lower wavenumbers, indicating the complexation of Li ions with oxygens on the amPEG. Alkylation and salt introduction reduced PEG crystallinity, as characterized by wide angle X-ray scattering (WAXS) and differential scanning calorimetry (DSC). The ionic conductivities of the polymer electrolytes increased with increasing salt concentrations, and the energy conversion efficiency of DSSC reached 2.6% at 100 mW cm^?2 for amPEG/MPII system which is higher than amPEG/LiI. This may be due to the higher mobility of MPII ion than the lithium ion in the polymer electrolyte. The interfacial properties between electrolytes and electrodes were investigated using field-emission scanning electron microscopy (FE-SEM) and electrochemical impedance spectroscopy (EIS).