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Background/aim Extracellular acidity, a characteristic of solid tumors, has been proposed to be a critical factor for aggravating tumor malignancy and conferring resistance to therapeutics. Recently, acidity has been implicated in inflammatory responses, which are mediated through active lipid metabolites in various human tissues. In the present study, we investigated whether acidity can affect lipid-mediated signaling, and found that phospholipase A2 (PLA2) activity increased at acidic pH in SNU601 and AGS gastric carcinoma cell lines. Materials and methods To identify the PLA2 isoform that is responsible for the acidity-induced activity, we assessed mRNA levels of cPLA2 isotypes through real-time qPCR, and protein levels through immunoblot assay in cells cultured in acidic medium. Results It was found that acidic pH conditions markedly elevated the PLA2γ expression. A gene interference study using specific siRNA of cPLA2γ suggested that expression of cPLA2γ in acidic culture conditions may be associated with protection of cancer cells in acidic environment, as shown by cell viability and clonogenic assays. In addition, expression of cPLA2γ appeared to confer cell resistance to anticancer drugs under acidic pH conditions. Conclusion Acidity-induced cPLA2γ expression may exert protective effects by imparting resistance to the gastric cancer cells under acidic environment.

Background: We investigated the antioxidant, anti-wrinkles, whitening, and moisturizing properties and amounts of phenolic compounds of ethanol extracts from flowers of 10 resource plants from Namwon and Mt. Jiri., Korea. Methods and Results: We measured antioxidant efficacy based on the total polyphenol, and total flavonoid content, and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. We evaluated the inhibitory effect on melanin synthesis and tyrosinase activity for the whitening effect. Furthermore, we analyzed the elastase and matrix metalloproteinase-1 (MMP-1) inhibition activity for anti-wrinkle capacity. To evaluate the moisturizing effect, we examined hyaluronan synthase (HAS) mRNA expression. In addition, the 19 phenolic compounds were detected using high performace liquid chromatography (HPLC). Among the 10 flowers, the antioxidant effect was high in the order of Rosa multiflora, Nelumbo nucifera, and Elsholtzia splendens. Whitening effect was high in the order of N. nucifera, R. multiflora, and Dendranthema zawadskii. As for the anti-wrinkle property, N. nucifera was the most effective followed by R. multiflora. Taraxacum coreanum was the best for moisturizing effect, followed by D. zawadskii, and E. splendens. Seven phenolic compounds were detected in the extracts of the 10 flowers. Conclusions: Overall, the extracts of five flowers extracts showed strong potential as antioxidant, whitening, anti-wrinkle, and moisturizing functional cosmetic agents.

A combination of ab initio calculations and classical molecular dynamics simulations was used to calculate the free energy of reacting an aprotic heterocyclic anion ionic liquid with CO2. The overall reaction was broken into a series of steps using a thermodynamic cycle to calculate the free energy of the gas phase reaction and the free energy contributions of solvation environment effects, which make comparable contributions to the total free energy of reaction. CO2 absorption isotherms that agree reasonably well with experimental data were calculated using a derived expression for the free energy of reaction as a function of temperature, pressure, and the extent of reaction.

Metabolic syndrome is characterized by a combination of several metabolic disorders, including obesity, hyperglycemia, and hyperlipidemia. A simultaneous occurrence is one of the most crucial features of metabolic syndrome, therefore, we selected an animal model in which this would be reflected. We fed C57BL/6N mice a high-fat diet for 23 weeks to develop metabolic syndrome and examined the efficacy of Rubus occidentalis (RO) for hyperglycemia and hypercholesterolemia. Oral administration of RO for 16 weeks improved hyperglycemia as indicated by significantly decreased fasting glucose levels and a glucose tolerance test. Improvements were also observed in hypercholesterolemia, in which significant decreases in serum total cholesterol, non-high-density lipoprotein (non-HDL) cholesterol, apolipoprotein A-1, and apolipoprotein B levels were observed. The time comparison of major biomarkers, observed at the initiation and termination of the experimental period, consistently supported the beneficial effects of RO on each metabolic phenotype. In addition, RO treatment attenuated the excessive fat accumulation in hepatic and adipose tissue by decreasing the size and number of lipid droplets. These results suggested that RO simultaneously exerted antihyperglycemic and antihyperlipidemic effects in mice with diet-induced metabolic syndrome.

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p

Administration of black raspberry (Rubus occidentalis) is known to improve vascular endothelial function in patients at a high risk for cardiovascular (CV) disease. We investigated short-term effects of black raspberry on circulating endothelial progenitor cells (EPCs) and arterial stiffness in patients with metabolic syndrome. Patients with metabolic syndrome (n = 51) were prospectively randomized into the black raspberry group (n = 26, 750 mg/day) and placebo group (n = 25) during the 12-week follow-up. Central blood pressure, augmentation index, and EPCs, such as CD34/KDR(+), CD34/CD117(+), and CD34/CD133(+), were measured at baseline and at 12-week follow-up. Radial augmentation indexes were significantly decreased in the black raspberry group compared to the placebo group (-5% ± 10% vs. 3% ± 14%, P

Objective Black raspberry (Rubus occidentalis) is known for improving vascular function. However, there has been no study evaluating its effects on 24-h systolic and diastolic blood pressure in prehypertensive patients. The aim of this study was to examine those effects. Methods Patients with prehypertension (N = 45) were prospectively randomized into a moderate-dose black raspberry group (n = 15, 1500 mg/d), a high-dose black raspberry group (n = 15, 2500 mg/d), or a placebo group (n = 15) during an 8-wk follow-up period. Raspberries were consumed in the form of a dried powder extract that was fashioned into capsules. The capsules contained 187.5 and 312.5 mg of raspberry powder, which was equivalent to 1500 and 2500 mg raspberries. Ambulatory 24-h blood pressure (BP); central BP; pulse-wave velocity; abdominal visceral fat; serum renin; angiotensin-converting enzyme; and inflammatory cytokines such as interleukin-6, tumor necrosis factor-α, C-reactive protein, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and plasminogen activator inhibitor-1 were measured at baseline and at 8-wk follow-up. Results High-dose black raspberry significantly reduced 24-h systolic blood pressure (SBP; 3.3 ± 10 mm Hg versus –6.7 ± 11.8 mm Hg; P

We show that phosphonium azolide ionic liquids of interest for CO2 capture applications react with CO2 both through the normal anion channel and, at elevated temperatures, through a previously unrecognized cation channel. The reaction is caused by an interaction between the anion and cation that allows proton transfer, and involves a phosphonium ylide intermediate. The cation reaction can be mitigated by using ammonium rather than phosphonium cations. Thus, phosphonium and ammonium cations paired with aprotic heterocyclic anions (AHAs) react with CO2 through different mechanisms at elevated temperatures. This work shows that careful consideration of both physical properties and chemical reactivity of ILs based on AHA anions is needed when designing ionic liquids for CO2 separations.

Benign prostatic hyperplasia (BPH), which is commonly found in aging men, is characterized by hyper- plasia of prostatic stromal and epithelial cells beginning in the periurethral zone of the prostate. The prevalence of BPH increases in an age-dependent manner. Here, we investigated the protective effects of unripe Rubus occidentalis extracts (UROE) on BPH development using a prostate cancer cell line and testosterone-induced BPH rat model. Experiments using an established hormone-dependent prostate cancer cell line (LNCaP) showed that UROE treatment significantly decreased expression of androgen-related genes, including androgen receptor (AR), prostate specific antigen (PSA), and 5-alpha reductase 2, but not 5-alpha reductase 1, which was also observed in flutamide-treated cells. Further, AR and PSA gene expression was reduced by UROE treatment under androgen-stimulated conditions using dihy- drotestosterone (DHT). BPH animals displayed elevated prostate weights. However, UROE as well as finasteride treat- ment significantly reduced prostate weights and DHT levels compared to testosterone-induced BPH animals. Histopathological analysis also showed that UROE treatment suppressed testosterone-induced prostatic hyperplasia. Taken together, the results suggest that UROE may effectively inhibit the development of BPH and thus may be a useful agent in BPH treatment.

Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p

Introduction Therapeutic plasma exchange (TPE) is used for temporary support of liver function in patients presenting with early graft dysfunction after liver transplantation (LT) or liver surgery. We analyzed the effect of therapeutic apheresis on patients with liver disease. Methods Between January 2011 and August 2016, 93 apheresis procedures were performed for 26 patients at our institution. Anti-ABO isoagglutination immunoglobulin (Ig) M titer was checked using a type A and type B 3% red blood cell (RBC) suspension in saline with two-fold serial dilutions of patient serum. Anti-ABO isoagglutination IgG titer was checked by a type A and B 0.8% RBC suspension using a low-ionic strength/Coombs card. Results ABO-incompatible (ABOi) LT was the most common ( n = 10, 38.5%) indication for apheresis; early graft dysfunction after LT ( n = 8, 30.7%) was the second most common. Median initial IgM and IgG anti-ABO titers for ABOi LT recipients were 1:16 (range, 1:8–1:128) and 1:48 (range, 1:8–1:2048). We performed preoperative TPE in 10 recipients (median number of sessions, 1.5; range, 1–11). Among patients with early graft dysfunction, those who underwent living donor LT had better survival (4/4; 100%) than those who underwent nonliving donor LT (0/3; 0%). Patients who underwent living donor LT first and then additional LT also survived after three TPE sessions. Conclusion Therapeutic apheresis is associated with a good survival rate and is essential for liver support in patients with early graft dysfunction after LT or posthepatectomy liver failure and during preparation for ABOi LT.

Cervical dentinal hypersensitivity (CDH) affects 8-30% of adults and nearly 85% of perio-treated patients. Various treatment schemes have been applied for treating CDH, among them being fluoride application, laser irradiation, and, recently, bioglass. The purpose of this study was to investigate the influence of bioglass, copper-bromide (Cu-Br) laser irradiation and their combination on dentinal tubule occlusion as a potential dentinal hypersensitivity treatment for CDH. 45 human dentin surfaces were organized into three equal groups: group A received Cu-Br laser only; group B received bioglass only; group C received bioglass followed by Cu-Br laser irradiation. Specimens were evaluated with regard to dentinal tubule occlusion under environmental scanning electron microscope. Treatment modality significantly affected dentinal tubule occlusion (p, {"references":["Gillam DG, Mordan NJ, Newman HN. 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J Prosthet Dent. 2002 Mar;87(3):311-8.\n[27]\tChiang YC, Chen HJ, Liu HC, Kang SH, Lee BS, Lin FH, Lin HP, Lin CP. A novel mesoporous biomaterial for treating dentin hypersensitivity. J Dent Res. 2010 Mar;89(3):236-40.\n[28]\tYu Xq, An Yb, Luan Qx. Effects of bio-glass in subgingival scaling and root planing. Beijing Da Xue Xue Bao. 2011 Feb 18;43(1):40-3.\n[29]\tCurtis AR, West NX, Su B. Synthesis of nanobioglass and formation of apatite rods to occlude exposed dentine tubules and eliminate hypersensitivity. Acta Biomater. 2010 Sep;6(9):3740-6.\n[30]\tLee BS, Kang SH, Wang YL, Lin FH, Lin CP. In vitro study of dentinal tubule occlusion with sol-gel DP-bioglass for treatment of dentin hypersensitivity. Dent Mater J. 2007 Jan;26(1):52-61.\n[31]\tFarmakis ET, Beer F, Kozyrakis K, Pantazis N, Moritz A. The influence of different power settings of Nd:YAG laser irradiation, bioglass and combination to the occlusion of dentinal tubules. 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The reduction potentials (E°(Red) versus SHE) of hypercloso boron hydrides B(n)H(n) (n = 6-13) and B(12)X(12) (X = F, Cl, OH, and CH(3)) in water have been computed using the Conductor-like Polarizable Continuum Model (CPCM) and the Solvation Model Density (SMD) method for solvation modeling. The B3LYP/aug-cc-pvtz and M06-2X/aug-cc-pvtz as well as G4 level of theory were applied to determine the free energies of the first and second electron attachment (ΔG(E.A.)) to boron clusters. The solvation free energies (ΔG(solv)) greatly depend on the choice of the cavity set (UAKS, Pauling, or SMD) while the dependence on the choice of exchange/correlation functional is modest. The SMD cavity set gives the largest ΔΔG(solv) for B(n)H(n)(0/-) and B(n)H(n)(-/2-) while the UAKS cavity set gives the smallest ΔΔG(solv) value. The E°(Red) of B(n)H(n)(-/2-) (n = 6-12) with the G4/M06-2X(Pauling) (energy/solvation(cavity)) combination agrees within 0.2 V of experimental values. The experimental oxidative stability (E(1/2)) of B(n)X(n)(2-) (X = F, Cl, OH, and CH(3)) is usually located between the values predicted using the B3LYP and M06-2X functionals. The disproportionation free energies (ΔG(dpro)) of 2B(n)H(n)(-) → B(n)H(n) + B(n)H(n)(2-) reveal that the stabilities of B(n)H(n)(-) (n = 6-13) to disproportionation decrease in the order B(8)H(8)(-)B(9)H(9)(-)B(11)H(11)(-)B(10)H(10)(-). The spin densities in B(12)X(12)(-) (X = F, Cl, OH, and CH(3)) tend to delocalize on the boron atoms rather than on the exterior functional groups. The partitioning of ΔG(solv)(B(n)H(n)(2-)) over spheres allows a rationalization of the nonlinear correlation between ΔG(E.A.) and E°(Red) for B(6)H(6)(-/2-), B(11)H(11)(-/2-), and B(13)H(13)(-/2-).

Rubus occidentalis (RO) has beneficial effects on glucose and lipid profiles in vitro. The aim of the study was to investigate RO extract effect on metabolic parameters in prediabetic patients, adopting a 12-week, randomized, double-blind, placebo-controlled trial. Forty-four patients (age 59.0 ± 8.2 years, 70.5% females, HbA1c 5.8 ± 0.4%) were divided into placebo (n = 13), low-dose RO extract (LRE; n = 14), or high-dose RO extract (HRE; n = 17) groups. Either 900 or 1800 mg per day of RO extract was administered orally. Area under the curve for glucose obtained 2 h after a 75-g oral glucose tolerance test was significantly decreased in the HRE group, compared with the placebo group (-28.1 ± 42.4 vs. +13.4 ± 52.6 mg/dL, p 0.05). Homoeostasis model assessment-B was increased (+17.11 ± 10.69, +5.24 ± 4.10, and +0.86 ± 6.01 in HRE, LRE, and placebo, respectively, p 0.05). Serum levels of monocyte chemoattractant protein-1 and oxidized low-density lipoprotein were significantly decreased by treatment in a dose-dependent manner (monocyte chemoattractant protein-1: -35.0 ± 21.2, +8.4 ± 18.1, and +24.2 ± 14.5; oxidized low-density lipoprotein: -19.7 ± 8.5, -13.1 ± 7.2, and -2.2 ± 11.0 in the HRE, LRE, and placebo, respectively, p 0.05). The results support the beneficial effects of RO extract on the control of glycemia and vascular inflammation in prediabetic patients. (ClinicalTrials.gov: NCT01964703). Copyright © 2016 John WileySons, Ltd.

The dissolution Gibbs free energies (ΔG°diss) of salts (M2X1) have been calculated by density functional theory (DFT) with Conductor-like Polarizable Continuum Model (CPCM) solvation modeling. The ...

We developed three-dimensional quantitative structure activity relationship (3D-QASR) models for 17 adamantyl derivatives as P-glycoprotein (P-gp) inhibitors. Eighteen different partial charge calculation methods were tested to check the feasibility of the 3D-QSAR models. Best predictive comparative molecular field analysis (CoMFA) model was obtained with the Austin Model 1-Bond Charge Correction (AM1-BCC) atomic charge. The 3D-QSAR models were derived with CoMFA and comparative molecular similarity indices analysis (CoMSIA). The final CoMFA model ( = 0.764, = 0.988) was calculated with an AM1-BCC charge and electrostatic parameter, whereas the CoMSIA model ( = 0.655, = 0.964) was derived with an AM1-BCC charge and combined steric, electrostatic, hydrophobic and HB-acceptor parameters. Leave-five-out (LFO) cross-validation was also performed, which yielded good correlation coefficient for both CoMFA (0.801) and CoMSIA (0.656) models. Robustness of the developed models was checked further with 1000 run bootstrapping analyses, which gave an acceptable correlation coefficient for CoMFA (BS- = 0.997, BS-SD = 0.003) and CoMSIA (BS- = 0.996, BS-SD = 0.018).

Ursodeoxycholic acid (UDCA) is known as a suppressor of cholestatic liver diseases and colorectal cancer development. Here, we demonstrate that UDCA induces apoptosis without necrotic features in SNU601, SNU638, SNU1 and SNU216 human gastric cancer cells, implying its possible use as an effective chemotherapeutic agent in treatment of gastric cancer. UDCA-induced apoptosis was dominantly mediated by an extrinsic pathway dependent on caspase-8, -6 and -3. UDCA increased expression of death receptor 5 [(DR5), also known as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor 2], and this DR appeared to be responsible for UDCA-induced apoptosis, as evidenced by DR5 knockdown. UDCA triggered formation of lipid rafts that played crucial roles in UDCA-induced apoptotic actions. Lipid rafts were required not only for provision of a proper site for DR5 action but also for mediation of DR5 expression. In addition, reactive oxygen species (ROS) and protein kinase C (PKC) δ appeared to be implicated in UDCA-induced raft-dependent DR5 expression. Our results indicate that UDCA-induced apoptosis is mediated by DR5 expression, which is regulated by the raft formation/ROS production/PKCδ activation pathway and DR5 localization into lipid rafts in gastric cancer cells. Tumor-suppressive activity of UDCA was confirmed in an in vivo system: UDCA (120 mg/kg/day) significantly decreased tumor growth in gastric cancer xenograft mice. Taken together, our results demonstrate that UDCA can be used as a potent chemotherapeutic agent for treatment of gastric cancer.

An allylic oxidation method for Delta(5)-steroids using TBHP as oxidant with a 2-quinoxalinol salen Cu(II) complex as catalyst is reported. A variety of Delta(5)-steroidal substrates are selectively oxidized to the corresponding enones. Excellent yields are achieved (up to 99% under optimized conditions) while significantly reducing reaction times required as compared to other current methods.

We performed molecular dynamics simulations at 77 K on the non-interpenetrating isoreticular (having the same underlying topology) metal-organic frameworks (IRMOFs) and the interpenetrating IRMOFs to investigate the adsorption behavior of hydrogen on the surface of MOFs, catenation effect on the density of adsorbed hydrogen, and dynamic behavior of adsorbed hydrogen molecules. We tested two classical force fields, universal force field (UFF) and DREIDING force field for the simulations and found out that the UFF describes the adsorption of hydrogen more reliably than DREIDING force field. The simulations showed the density values of adsorbed hydrogen in the small pores of the interpenetrating IRMOFs are higher than those in the larger pores of the non-interpenetrating IRMOFs, and the diffusion of the hydrogen molecules in the interpenetrating IRMOFs is highly restricted compared to the non-interpenetrating IRMOFs. From the simulation results, we concluded that the small pores created by the catenation might contribute the increase of the adsorption capacity of the interpenetrating IRMOFs.

This study investigated radioresistance mechanisms in the doxorubicin-resistant acute myelogenous leukemia (AML)-2/DX100. AML-2/DX100 also showed resistance to radiation. AML-2/DX100 characterized by down-regulated catalase expression was supersensitive to exogenous hydrogen peroxide whereas they increased defense mechanisms against endogenous reactive oxygen species (ROS) as compared with AML-2/WT. In AML-2/WT, radiation increased Bax expression and its translocation to mitochondria but had little effect on translocation of Bcl-2 and consequently induced the release of cytochrome c from the mitochondria with the subsequent caspase-3 activation. On the contrary, in AML-2/DX100, radiation neither increased Bax expression nor its translocation to mitochondria while it increased Bcl-2 translocation to mitochondria. A specific p38 MAPK inhibitor SB203580 increased radioresistance in AML-2/WT but little in AML-2/DX100. It inhibited radiation-induced Bax translocation in AML-2/WT but not in AML-2/DX100, indicating that p38 MAPK is working after irradiation in AML-2/WT but not in AML-2/DX100. Electrophoretic mobility shift assay and Western blot analysis revealed that NF-kappaB in AML-2/DX100 was more activated with degradation of cytosolic IkappaBalpha than was that of AML-2/WT. cDNA microarray showed that Bfl-1/A1 and granzyme H in AML-2/DX100 were highly up-regulated (6.21-fold) and down-regulated (6.49-fold), respectively, as compared with each of AML-2/WT, which were confirmed by RT-PCR assay. Taken together, these results indicate that radioresistance mechanisms of AML-2/DX100 could be related to alterations in ROS-scavenging activity, in mitochondrial translocation of Bax and Bcl-2, and in expression of pro-apoptotic (granzyme H) and anti-apoptotic (Bfl-1/A1) genes. It has been shown that balance of p38 MAPK and NF-kappaB signals is a determinant in radiosensitivity of AML-2/WT and AML-2/DX100.

We performed grand canonical Monte Carlo simulations on the series of MOFs, that are Metal-Organic Frameworks having various organic linkers and nanocube frameworks, to find out rational design and synthetic strategies toward efficient hydrogen storage materials. The adsorption amounts of hydrogen molecules showed diverse range according to the variation of parameter values. This indicated that the hydrogen adsorption was sensitive to the values of parameters corresponding to the non-bonding interactions. The optimization of the parameters was done to fit the experimental results at 77 K. After the parameterization of the potential function, we adopted this condition to predict the adsorption amount of hydrogen molecules on IRMOF-3, which has NH2 group as the substituent of hydrogen bonded to benzene ring. The calculation results showed good agreement with experimental adsorptions and we analyzed the adsorption sites of each MOF and the relationship between the adsorption characteristics and the hydrogen uptake capacity.

A new mixed-valent iron MOF, formulated as Fe3O(F4BDC)3(H2O)3·(DMF)3.5 (1), has been synthesized by using a perfluorinated linear dicarboxylate to link trigonal prismatic Fe3(μ3-O)(O2C–)6 clusters. The structure refinement based on single crystal X-ray diffraction data collected from 1 reveals the material exhibits the acs topology with large channels along the crystallographic c-axis. Due to the presence of fluorine atoms the organic link, 2,3,5,6-tetrafluorobenzene-1,4-dicarboxylate (F4BDC), has a 63° torsion angle between the carboxylate and aromatic planes, resulting in larger channels compared to those in the isoreticular material MOF-235. While few iron-based MOFs have demonstrated porosity, nitrogen and hydrogen sorption experiments carried out at 77 K proved the porosity of outgassed 1, which has a Langmuir surface are of 635 m2/g and a gravimetric capacity of 0.9 wt% of hydrogen at 1 bar.

We have investigated the relationship between the molecular structures of metal-organic frameworks (MOFs) and their hydrogen uptake capabilities. Quantitative structure–property analysis was used to find out MOF structural factors important for hydrogen adsorption. To determine the quantitative interaction strength between hydrogen molecules and MOFs, the iso-value surface area of electrostatic potential was developed as a new descriptor. Quantitative analysis of structurally similar MOFs showed that the functionalization of aromatic organic linkers could induce noticeable polarization effect on the framework surface. We also found that the topology of MOFs plays an important role in determining the amount of ultimate hydrogen uptake. Through this quantitative structure–uptake relationship analysis, structural descriptors for the prediction of MOF hydrogen sorption capacity have been identified.

Hydrogen adsorption mechanism into MOF-5, a porous metal-organic framework (MOF) has been studied by density functional theory calculation. The selected functionals for the prediction of interaction energies between hydrogen and potential adsorption sites of MOF-5 were utilized after the evaluation with the various functionals for interaction energy of H 2 ⋯C 6 H 6 model system. The adsorption energy of hydrogen molecule into MOF-5 was investigated with the consideration of the favorable adsorption sites and the orientations. We also calculated the second favorable adsorption sites by geometry optimization using every combination of two first adsorbed hydrogen molecules. Based on the calculation of the first and the second adsorption sites and energies, it has been suggested that the hydrogen adsorption into MOF-5 follows a cooperative mechanism in which the metal sites initiate the propagation of the hydrogen adsorption on the whole frameworks. In addition, the interaction mode between the simple benzene ring with hydrogen is significantly changed when the benzene ring has been incorporated into the framework of MOF-5.

Background Cyclooxygenase (COX)-2 is believed to be an important enzyme related to the pathogenesis of colorectal cancer (CRC). p53 has been reported to be a negative regulator of COX-2 expression in in vitro studies. The aim of this study was to investigate COX-2 expression and its relationship with nuclear p53 accumulation and their prognostic significance in CRC. Methods COX-2 expression and nuclear p53 accumulation were examined by immunohistochemistry in 231 sporadic CRCs. Their prognostic significance and interrelationship were statistically evaluated. Results We found 42.4% of the 231 cases of CRCs with positive COX-2 expression. Nuclear p53 accumulation was observed in 46.8% of cases. There was no significant correlation between COX-2 expression and nuclear p53 accumulation. COX-2 expression had no correlation with patient survival, whereas nuclear p53 accumulation was significantly correlated with poor patient survival on univariate and multivariate analysis. Conclusions These results suggest that COX-2 expression does not play a role in the prognosis of CRC and COX-2 expression is not affected by the status of nuclear p53 accumulation in CRC. In addition, our findings support that nuclear p53 accumulation may be a useful prognostic marker for patients with CRC. J. Surg. Oncol. 2008;97:51–56. © 2007 Wiley-Liss, Inc.

Among recently synthesized isoreticular metal-organic frameworks (IRMOFs), interpenetrating IRMOFs show high hydrogen adsorption capacities at low temperature and under ambient pressure. However, little is known about the molecular basis of their hydrogen binding properties. In this work, we performed grand canonical Monte Carlo (GCMC) simulations to investigate the effect of catenation on the interactions between hydrogen molecules and IRMOFs. We identified the adsorption sites and analyzed the adsorption energy distributions. The simulation results show that the small pores generated by catenation can play a role to confine the hydrogen molecules more densely, so that the capacity of the interpenetrating IRMOFs could be higher than that of the non-interpenetrating IRMOFs.

To develop synthetic strategies toward efficient hydrogen storage materials, density functional theory calculations were performed on a series of isoreticular metal-organic frameworks (IRMOFs) containing functionalized organic linkers. Based on the shape of the frontier orbitals and the electrostatic potential maps of a various IRMOFs, it was predicted that the electronic structure of the organic linker plays an important role in the hydrogen storage capacity of these materials. This is supported by hydrogen adsorption measurements, which reveal greater hydrogen storage capacity in the amine-substituted framework.

The purpose of this study was to investigate the adaptive mechanisms of hydrogen peroxide-supersensitive AML cells against the reactive oxygen species (ROS). Their scavenging capacity against ROS was determined using a fluorometric probe in the doxorubicin-resistant AML-2/DX100 cell characterized by the down-regulation of catalase. AML-2/DX100 cells had more scavenging capacity against endogenous pro-oxidants than did the parental cells AML-2/WT, suggesting that an anti-oxidant adaptation against ROS occurred. cDNA microarrays for 8000 human genes revealed that among 21 anti-oxidant genes, each four gene was up- and down-regulated more than 1.5-fold in AML-2/DX100 compared with AML-2/WT. The mRNA expression of glutathione S-transferase Pi, peroxiredoxin 2, thioredoxin 2, and glutaredoxin was elevated whereas that of peroxiredoxin 3, metallothionein-1F, superoxide dismutase 2, and thioredoxin reductase 1 was depressed. The result indicates that the down-regulation of certain anti-oxidant mechanisms can be compensated for by the up- and down-regulation of the other anti-oxidant mechanisms.

The electronic structures and the structural deformations of silicon containing poly(p-phenylenevinylene) (PPV) polymers have been studied theoretically. The results of the calculations indicate that the regular π conjugated system is effectively interrupted by the organosilicon units yielding a blue emission. It has also been observed that substitution of methoxy on vinylene group caused significant structural deformation of the PPV lumophore, and subsequently, decreased the ionization potential (IP) and increased the electron affinity of the SiBu PPV. Experimentally, it is known that light emitting diodes made of silicon containing copolymers operate at low voltages, due to the reduction of the LUMO level in the luminescence polymers. The flat deformation of the PPV moiety induced a red shift of the absorption maxima. The substitution of phenyl ring on silicon atoms constrained free rotation around the Si C bond increasing the torsional angles of the lumophore and caused slight blue shift of absorption peak. Substitution of the cyano group on the vinylene moiety increased the ionization potential as well as the electron affinity. On the other hand, the electron donating methoxy group decreased the ionization potential and electron affinity. Those calculated results agree well with the experimental observations. The density functional calculation method, which account for electron correlation, yielded much more accurate values for the HOMO–LUMO gap than the Hartree–Fock method.

Background and aims: It has been proposed that the expression of Fas ligand (Fas L) in tumors may play an important role in immune escape. This study was undertaken to test a ‘counterattack’ theory as a mechanism of immune escape in gastric carcinoma. Methods: Expression of Fas and Fas L was examined in the human gastric cancer cell lines using reverse transcription–polymerase chain reaction. Cytotoxicity was determined by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Apoptosis of target Jurkat cells was examined after coculture with the effector gastric cancer cells in vitro. Immunohistochemical staining was performed for the detection of Fas and FasL in tumor-infiltrating lymphocytes (TIL) and gastric cancer cells in vivo. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) method in vitro and in vivo. Results: Fas and FasL mRNA were found to be differentially expressed in gastric cancer cell lines. The coculture experiment showed that apoptosis of Jurkat was induced by a FasL-overexpressing effector gastric cell SNU-484. In a Fas-expressing gastric cell SNU-638, Fas expression was upregulated by the treatment of gamma-interferon in a time- and concentration-dependent manner. SNU-638 treated with gamma-interferon was more sensitive to anti-Fas antibody-mediated cytotoxicity than was the control cell line, suggesting an increase of functional Fas in gastric cancer cells. The expression of FasL in gastric cancer cells and of Fas in apoptotic TIL was also detected in vivo. Conclusion: The data indicate that the FasL expression of gastric cancer cells supports a ‘counterattack theory’ in gastric cancer cells and that the upregulation of Fas by IFN-γ in SNU-638 may accelerate the apoptosis pathway through the Fas and FasL interaction between gastric cancer cells and immune cells. This result is supported by the expression of FasL in gastric cancer cells and apoptotic TIL in vivo. It is implicated that the different biological behaviors of gastric cancer cells could be at least in part explained by Fas and FasL interaction with immune cells.

The Cu(II) complex 1, Cu(II)-6-N-3,5-di-tert-butylsalicylidene-6,7-quinoxalinol-diamine, has been developed to address problems with current methods of catalytic oxidation using tert-butyl hydroperoxide (TBHP). Complex 1 demonstrated an increased capability to utilize TBHP while limiting interference from free radical reactions and was demonstrated to be highly effective in the oxidations of a variety of olefins.

Ionic liquids (ILs) with aprotic heterocyclic anions, or AHAs, can bind CO2 with reaction enthalpies that are suitable for gas separations and without suffering large viscosity increases. In the present work, we have synthesized ILs bearing an alkyl-phosphonium cation with indazolide, imidazolide, pyrrolide, pyrazolide and triazolide-based anions that span a wide range of predicted reaction enthalpies with CO2. Each AHA-based IL was characterized by NMR spectroscopy and their physical properties (viscosity, glass transition, and thermal decomposition temperature) determined. In addition, the influence of substituent groups on the reaction enthalpy was investigated by measuring the CO2 solubility in each IL at pressures between 0 and 1 bar at 22 °C using a volumetric method. The isotherm-derived enthalpies range between -37 and -54 kJ mol(-1) of CO2, and these values are in good agreement with computed enthalpies of gas-phase IL-CO2 reaction products from molecular electronic structure calculations. The AHA ILs show no substantial increase in viscosity when fully saturated with CO2 at 1 bar. Phase splitting and compositional analysis of one of the IL/H2O and IL/H2O/CO2 systems conclude that protonation of the 2-cyanopyrrolide anion is improbable, and this result was confirmed by the equimolar CO2 absorption in the presence of water. Taking advantage of the tunable binding energy and absence of viscosity increase after the reaction with CO2, AHA ILs are promising candidates for efficient and environmental-friendly absorbents in postcombustion CO2 capture.

Black raspberry (Rubus occidentalis) has been known for its anti-inflammatory and anti-oxidant effects. However, short-term effects of black raspberry on lipid profiles and vascular endothelial function have not been investigated in patients with metabolic syndrome. Patients with metabolic syndrome (n = 77) were prospectively randomized into a group with black raspberry (n = 39, 750 mg/day) and a placebo group (n = 38) during a 12-week follow-up. Lipid profiles, brachial artery flow-mediated dilatation (baFMD), and inflammatory cytokines such as IL-6, TNF-α, C-reactive protein, adiponectin, sICAM-1, and sVCAM-1 were measured at the baseline and at the 12-week follow-up. Decreases from the baseline in the total cholesterol level (-22.8 ± 30.4 mg/dL vs. -1.9 ± 31.8 mg/dL, p 0.05, respectively) and total cholesterol/HDL ratio (-0.31 ± 0.64 vs. 0.07 ± 0.58, p 0.05, respectively) were significantly greater in the group with black raspberry than in the placebo group. Increases in baFMD at the 12-week follow-up were significantly greater in the group with black raspberry than in the placebo group (0.33 ± 0.44 mm vs. 0.10 ± 0.35 mm, p 0.05, respectively). Decreases from the baseline in IL-6 (-0.4 ± 1.5 pg/mL vs. -0.1 ± 1.0 pg/mL, p 0.05, respectively) and TNF-α (-2.9 ± 4.7 pg/mL vs. 0.1 ± 3.6 pg/mL, p 0.05, respectively) were significantly greater in the group with black raspberry. The use of black raspberry significantly decreased serum total cholesterol level and inflammatory cytokines, thereby improving vascular endothelial function in patients with metabolic syndrome during the 12-week follow-up.

A major obstacle to successful cancer chemotherapy is the development of multidrug resistance (MDR). The previous study revealed that a doxorubicin-resistant AML subline (AML-2/DX100) overexpressed an MDR-associated protein (MRP) but not P-glycoprotein. The AML-2/DX100 also showed various levels of resistance to daunorubicin and vincristine but was paradoxically sensitive to hydrogen peroxide (5-fold), t-butyl hydroperoxide (3-fold), and paraquat (2-fold) when compared to the drug-sensitive parental AML-2 cells (AML-2/WT). We compared the activities of antioxidant enzymes to detoxify reactive oxygen species (ROS), including superoxide dismutases, glutathione S-transferase, catalase, glutathione reductase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase in both AML-2/WT and AML-2/DX100. Interestingly, of these antioxidant enzymes, catalase activity of AML-2/DX100 decreased significantly to about one-third that of AML-2/WT (P < 0.000005). The decreased activity of catalase was due to reduced expression of the catalase gene; confirmed by Western blot and reverse transcription-polymerase chain reaction (RT-PCR) analyses. The decreased activity of catalase was maintained even in the absence of doxorubicin for 3 months as well as by the treatment of probenecid, an MRP inhibitor. In addition, there was no difference in catalase activity between HL-60 and another MRP-overexpressing subline HL-60/Adr. Taken together, the paradoxical increase in the sensitivity of an MRP-overexpressing AML-2/DX100 in response to peroxides and paraquat is due to the down-regulation of catalase gene expression, which totally independent of overexpression of MRP. It is therefore possible that decreased catalase activity could be exploited as an Achilles' heel in resistant cells such as this.

A nanosphere was formed from a temperature-responsive random copolymer of (N,N-dimethylamino)ethyl methacrylate (DMAEMA) and ethyl acrylamide (EAAm) without a crosslinker. When the copolymerization was performed in a water/ethanol solvent mixture (90/10 v/v %) above the lower critical-solution temperature of poly(DMAEMA-co-EAAm), the nanosphere was formed with the propagation of copolymerization. Atomic force microscopy analysis and dynamic light scattering both showed the formation of nanosphere and the size was decreased as the EAAm content increased in the copolymer. To illuminate this nanosphere formation phenomena, molecular dynamic simulations were performed with model polymer solutions. According to the analysis of the simulation trajectory, the ethyl groups of ethanol bind to the hydrophobic sites of poly(DMAEMA) or poly(DMAEMA-co-EAAm), and water molecules can bind preferentially to CO groups that are abundant on the surface of the core, which is composed of oligomer and ethanol. This may enable the polymerization to proceed within the core, which is transformed into nanosphere. © 2001 John Wiley & Sons, Inc. J Polym Sci B: Polym Phys 39: 594–600, 2001

A new class of silicon-containing poly(cyanoterephthalylidene) copolymers with a uniform π-conjugated segment was synthesized using the Knoevenagel reaction between the dialdehyde monomer and the appropriate diacetonitrile. The incorporation of organosilicon units with the flexible alkyl side group into the polymer rigid backbone would afford processable electroluminescent materials and interrupt the regular π-conjugated chains. The resulting polymers were highly soluble in common organic solvents. The Mn and Mw of the resulting polymers are in the range 3800−4200 and 5400−6000 with a polydispersity index range of 1.38−1.43, respectively. Their glass transition temperature was in the range of 82−87 °C. According to the molecular mechanical calculations for single chain models of SiBuPPV and SiBuCNPPV, trans conformations are more stable than cis conformations. The UV−visible absorbance of present polymers show strong absorption bands around 340−360 nm, since the π-conjugated system is regulated by organos...

The present study aimed to evaluate the role of melanoma antigen family A (MAGEA) in gastric and colorectal cancer cell lines and clinical tissue samples. we used 10 gastric and 9 colorectal cancer cell lines, 20 early-stage and 21 advanced-stage gastric cancer tissues, 20 colon adenomas and 19 colorectal cancer tissues. Real-time RT-PCR assay was used for the determination of MAGEA mRNA levels. Western blot analysis and immunohistochemistry were used for the determination of MAGEA protein levels in cell lines and tissues, respectively. Gastric and colorectal cancer cell lines showed variable mRNA expression levels of MAGEA. The MAGEA protein was detected in 30% of gastric cancer cell lines and in 22.2% of colorectal cancer cell lines. There was a high correlation between mRNA and protein expression. Regarding the clinical samples, MAGEA expression was noted in 25, 28.6 and 31.6%, respectively in early-stage, advanced-stage gastric cancer tissues and colon adenocarcinoma, but was negative in the adjacent normal tissues of the stomach and colon as well as colon adenoma. These results indicate that MAGEA is involved in the carcinogenesis of gastric and colorectal cancer and, therefore, can be used as a diagnostic marker to predict these cancers.