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A tomato saponin, esculeoside A, may be metabolized into various steroidal hormones such as pregnane derivatives that are expected to exhibit various bioactivities in the body, such as anti-osteoporosis, anti-menopausal disorder and anti-tumor actions. Therefore, we attempted to examine the esculeoside A contents of fresh tomatoes, tomatoes boiled in water, tomatoes heated using a microwave oven, freeze-dried tomatoes, and commercially available processed tomato products contained in plastic bottles and cans, in order to develop a health food.

Electrospray characteristics were studied using a pure room-temperature molten salt (i.e., an ionic liquid) at pressures around 10−5 Pa as well as at atmospheric pressure. The ionic liquid N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide was tested, which has negligible vapor pressure and high conductivity. During electrospray, the ionic liquid was introduced at a constant flow rate into a stainless-steel capillary (i.d. 30 μm). It was demonstrated that stable electrosprayed currents exceeding ±1 μΑ were continuously produced in both positive and negative modes. The electrosprayed currents in a high vacuum were twice those at atmospheric pressure. It was found that gas pressure rose slightly with increasing electrosprayed currents. Residual gas analysis revealed that gas component at negative mode was different from that at positive mode. Experimental results indicate that vacuum electrospray of pure ionic liquids is applicable to a massive-cluster beam source for SIMS.

An orthogonal acceleration Time-of-Flight Secondary Ion Mass Spectrometer (TOF-SIMS) system has been developed with a metal-cluster-complex ion source. The ion source can produce ion beams of massive molecules called metal-cluster-complexes such as Ir 4 (CO) 12 , which has a molecular weight higher than 1000 u. Using the system, TOF-SIMS of a contaminated silicon substrate and a room temperature molten salt (i.e. an ionic liquid) was performed. The ionic liquid N,N-diethyl-N-methyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide, which has a molecular weight of 426 u, consists of a polyatomic cation, [C 8 H 20 ON] + , and a polyatomic anion, [C 2 F 6 NO 4 S 2 ] - . During SIMS analysis, an analytical sample was bombarded with a continuous primary ion beam of either Ir 4 (CO) 7 + or Ar + in a beam energy of 10 keV at an incident angle of 45°. It was confirmed that the use of Ir 4 (CO) 7 + ions enhanced secondary ion intensity compared with that of Ar + ions. Also, experimental results showed that the bombardment of Ir 4 (CO) 7 + caused less fragmentation. In the case of the ionic liquid, cation-attached ionic-liquid molecules were observed in addition to the cation of the ionic liquid.

Tumor-associated macrophages (TAMs) of M2 phenotype promote tumor proliferation and relate to poor prognosis in patients with gliobrastoma. We screened natural compounds possessing inhibitory effect on M2 polarization in human monocyte-derived macrophages. Among 130 purified natural compounds, some natural compounds such as glycyrrhizin, medicarpin and solasodine significantly inhibited the expression of CD163, one of the phenotypic markers of M2 macrophages, as well as suppressed the secretion of IL-10, one of the anti-inflammatory cytokine preferentially produced by M2 macrophages, thus suggesting that glycyrrhizin, medicarpin and solasodine suppress macrophage polarization towards M2 phenotype. Therefore, glycyrrhizin, medicarpin and solasodine may be potentially useful new strategy for the prevention and therapy of tumor.

To develop a solution-type ion beam source utilizing a wide variety of metal cluster complexes that are stable only in organic solvents, we have investigated an electrospray method for transferring ions from solutions to gas phase. As initial experiments, we have studied electrospray characteristics of ethanol solutions containing a room-temperature molten salt (i.e., an ionic liquid) and acetic acid as alternatives to solutions of metal cluster complexes. In electrospray experiments, we used a stainless-steel capillary with an inner diameter of 30 μm. Experimental results showed that electrosprayed currents increased with applied voltage in both positive-ion and negative-ion modes. In addition to positive currents, stable negative currents were also confirmed to be produced. Current exceeding 250 nA was produced at 2 kV with a flow rate of 2 μL/min at a concentration of 1 × 10−3 mol/L. It was confirmed that several nA out of electrosprayed currents were delivered through an orifice (120 μm internal diameter) into a vacuum chamber. Experimental results indicate that the electrospray method seems to be applicable to an ion beam source for utilizing massive metal cluster complexes in solutions.

Objective: To investigate the accumulation of advanced glycation end products (AGE) in human bladder. Methods: Human bladder specimens were obtained from nine patients during radical cystectomy. Frozen sections were immunohistochemically analyzed by three different monoclonal anti-AGE antibodies such as anti-Ne-(carboxymethyl)lysine (CML), anti-imidazolone and anti-pentosidine antibodies. Bladder sections were stained with these antibodies by indirect immunoperoxidase methods. Double immunohistochemical staining with one of the anti-AGE antibodies or an anti-human macrophage antibody was also carried out. Results: We demonstrated that CML and pentosidine were accumulated in human bladder extracellularly as well as intracellularly, whereas any accumulation of imidazolone was not observed. Double immunohistochemical staining indicated that AGE-accumulated cells in human bladder were derived from macrophages. Conclusions: The present study demonstrated that AGE-structures such as CML and pentosidine are accumulated extracellularly in human bladder, and were endocytosed by tissue macrophages.

The composition of glycoalkaloids in tomato fruit changes with ripening. However, it has not been clarified whether the accumulation of glycoalkaloids is controlled by the ripening-inducing phytohormone, ethylene. Here, we report the effect of ethylene on the accumulation of tomato fruit glycoalkaloids. We investigated the effect of exogenously applied ethylene. In response to ethylene treatment, the content of alpha-tomatine decreased, whereas the content of esculeoside A increased. Next, we analyzed the fruits of ripening mutants, rin, nor, and Nr. In fruits of these mutant lines, the level of accumulation of esculeoside A decreased, whereas alpha-tomatine accumulated to higher levels than in wild-type fruit. These results demonstrated that the esculeoside A accumulation was associated with production and perception of ethylene. Additionally, the accumulation profiles of the intermediate metabolites of esculeoside A biosynthesis in ripening mutant fruits suggest that a glycosylation step in the putative pathway from alpha-tomatine to esculeoside A depends on ethylene.

Angiopoietin-like protein family 4 (Angptl 4) has been shown to regulate lipoprotein metabolism through the inhibition of lipoprotein lipase (LPL). We generated ApoE(-/-)Angptl 4(-/-) mice to study the effect of Angptl 4 deficiency on lipid metabolism and atherosclerosis. Fasting and postolive oil-loaded triglyceride (TG) levels were largely decreased in ApoE(-/-)Angptl 4(-/-) mice compared with and ApoE(-/-)Angptl 4(+/+) mice. There was a significant (75+/-12%) reduction in atherosclerotic lesion size in ApoE(-/-)Angptl 4(-/-) mice compared with ApoE(-/-) Angptl 4(+/+) mice. Peritoneal macrophages, isolated from Angptl 4(-/-) mice to investigate the foam cell formation, showed a significant decrease in newly synthesized cholesteryl ester (CE) accumulation induced by acetyl low-density lipoprotein (acLDL) compared with those from Angptl 4(+/+) mice. Thus, genetic knockout of Angptl 4 protects ApoE(-/-) mice against development and progression of atherosclerosis and strongly suppresses the ability of the macrophages to become foam cells in vitro.

A ruby capillary which is available as an industrial product for the wire bonding machines for the microelectronics has been adopted to focus ion beams passively for the first time. An Ar+ ion beam with a beam current density of 3×10-6 A•cm-2 at an energy of 4 keV has been found to penetrate steadily the ruby capillary and the behavior of the beam through the capillary has been investigated in details. It has been also found that a large amount of secondary electrons are generated when the ion beam hits the capillary and a negative bias should be applied to the Faraday cup to measure the ion beam current through the capillary though the positive ion beam is to be measured.

A new ion source using massive molecules called metal cluster complexes has been developed. Metal cluster complexes are chemically-synthesized organometallic compounds, which have a wide range of chemical compositions with high molecular weight. The ion source is compact enough to be installed in commonly used secondary ion mass spectrometry (SIMS) systems. Using the ion source, sputtering characteristics of silicon bombarded with normally incident Ir4(CO)7+ ions were investigated. Experimental results showed that the sputtering yield at 10 keV was 36, which is higher than that with Ar+ ions by a factor of 24. In addition, SIMS analyses of boron-delta-doped silicon samples and organic films of poly(methyl methacrylate) (PMMA) were performed. Compared with conventional O2+ ion beams, Ir4(CO)7+ ion beams improved depth resolution by a factor of 2.5 at the same irradiation conditions; the highest depth resolution of 0.9 nm was obtained at 5 keV, 45° with oxygen flooding of 1.3×10-4 Pa. Furthermore, experimental results confirmed that Ir4(CO)7+ ion beams significantly enhanced secondary ion intensity in high-mass region.

Metal cluster complexes are chemically synthesized organometallic compounds, which have a wide range of chemical compositions with high molecular weight. Using a metal cluster complex ion source, sputtering characteristics of silicon bombarded with normally incident Ir4(CO)7+ ions were investigated. Experimental results showed that the sputtering yield at 10 keV was 36, which is higher than that with Ar+ ions by a factor of 24. In addition, secondary ion mass spectrometry (SIMS) of boron-delta-doped silicon samples and organic films of poly(methyl methacrylate) (PMMA) was performed. Compared with conventional O2+ ion beams, Ir4(CO)7+ ion beams improved depth resolution by a factor of 2.5 at the same irradiation conditions; the highest depth resolution of 0.9 nm was obtained at 5 keV, 45° with oxygen flooding of 1.3 × 10−4 Pa. Furthermore, it was confirmed that Ir4(CO)7+ ion beams significantly enhanced secondary ion intensity in high-mass region.

Multiphoton ionization and the subsequent dissociation process of metal cluster complexes Os 3 (CO) 12 and Ir 4 (CO) 12 , prepared in a supersonic jet, were studied by means of multiphoton ionization with time-of-flight (TOF) mass detection. The ionization energies of Os 3 (CO) 12 and Ir 4 (CO) 12 were determined to be 7.95 and 8.3 eV, respectively, from the laser wavelength at the ionization threshold. The coordination energies of Os 3 (CO) 12 + and Ir 4 (CO) 12 + ions were also determined to be 1.6 and 1.2 eV, respectively, from the excitation energy needed to cause the appearance of fragment ions. The observed values agreed reasonably well with the ones calculated by using the density functional theory method.

Polyclonal and monoclonal antibodies have been widely applied to demonstrate the presence of advanced glycation end products (AGEs) in vivo. However, our previous study showed that monoclonal anti-AGE antibody (6D12) and polyclonal anti-N epsilon-(carboxymethyl)lysine (CML) antibody recognize not only CML but also N epsilon-(carboxyethyl)lysine (CEL), thus indicating that we should pay attention to the specificity of the antibodies. As a result, we prepared specific monoclonal antibodies against CML, CEL, N omega-(carboxymethyl)arginine (CMA), and S-(carboxymethyl)cysteine (CMC). Our immunochemical study using anti-CMA antibody demonstrated that the CMA content increased in a time-dependent manner when collagen was incubated with glucose, indicating that immunological quantification using the specific antibody is especially useful for measuring an acid-labile AGE structure, such as CMA. Monoclonal antibody is also applied to identify a novel biological marker in pathological lesions. We prepared antibody libraries against proteins modified with aldehydes, such as glyoxal, methylglyoxal, and glycolaldehyde (GA), and one antibody, GA5, which specifically reacts with the GA-modified protein that is recognized in human atherosclerotic lesions. Following successive high-performance liquid chromatography purification, the GA5-reactive compound was isolated and its chemical structure was found to be 3-hydroxy-4-hydroxymethyl-1-(5-amino-5-carboxypentyl) pyridinium cation, which was named GA-pyridine. Taken together, these results demonstrate that a specific antibody is a powerful tool for analyzing novel biomarkers, formation pathways, and the efficacy of AGE inhibitors.

The surface sputtering of Si using a proto-type ion gun to utilize metal cluster complexes as ion source has been investigated in detail mainly using Auger spectroscopy and atomic force microscope. The Si surface previously was found to be successfully sputtered with a high sputtering yield and yet resulting in a reasonably smooth surface. However cluster ion beams was not irradiated except Si. Here we report the result of surface irradiated of high orientated pyrolytic graphite (HOPG) using a proto-type compact cluster ion source which has been developed using Os3(CO)12. The irradiated HOPG surface was observed by using atomic force microscope (AFM) and scanning electron microscope (SEM) and AES.

Conversion of the spirosolane-type glycoside, esculeoside A, a major component contained in the ripe tomato Lycopersicon esculentum fruits, into a solanocapsine-type sapogenol, esculeogenin B-2, (5alpha,22S,23R,25S)-22,26-epimino-16beta,23-epoxy-3beta,23,27-trihydroxycholestane, and esculeogenin B-1, (5alpha,22R,23S,25S)-22,26-epimino-16beta,23-epoxy-3beta,23,27-trihydroxycholestane, which are rare naturally occurring compounds was attained by acid hydrolysis with 2 N HCl in dioxane and water (1 : 1).

Three new Lycopodium alkaloids, serralongamines B-D (1-3), have been isolated from the club moss Lycopodium serratum var. longipetiolatum, and the structures were elucidated on the basis of spectroscopic data and chemical transformation. 1 and 3 significantly exhibited the inhibitory activity against foam cell formation in human macrophages, one of characteristic features of early atherosclerotic lesions.

Objectives: The present study investigated the expression of acyl-coenzyme A: cholesterol acyltransferase-1 (ACAT-1) and -2 in clear cell type renal cell carcinoma (RCC). Methods: Clear cell type RCC and corresponding normal kidney tissue samples were obtained from 19 surgical cases (28–85 years of age). Tissue extracts were assayed for ACAT activity and protein expression by immunoblotting with anti-ACAT-1 and anti-ACAT-2 antibodies. Frozen sections were subjected to Oil red O staining for lipids, and were immunostained with ACAT-specific antibodies. Results: Acyl-coenzyme A cholesterol acyltransferase activity was 5.7-fold higher (P

Osteopontin (OPN) has been implicated in various helper T cell type 1 immunity-mediated diseases including rheumatoid arthritis (RA), multiple sclerosis (MS), Crohn's disease, and fulminant hepatitis. Increased expression of OPN has been detected in pathological foci of these diseases. RA and fulminant hepatitis have been successfully treated by administration of neutralizing anti-OPN antibody in mice. Antibody treatment may elicit side effects including allergic reactions against heterologous antibody proteins, thus necessitating humanization of antibody. To provide alternative means to neutralize OPN function, in this study we explored the possibility of using OPN small interfering RNA (siRNA) to silence OPN gene expression. In vitro, OPN siRNA efficiently silenced the expression of both exogenous and endogenous OPN gene. After hydrodynamic intravenous injection of OPN siRNA, OPN siRNA was efficiently delivered to the liver, which resulted in the efficient silencing of OPN gene expression in liver. In a murine model of concanavalin A (ConA)-induced fulminant hepatitis, OPN expression was elevated in liver and severe hepatic necrosis was induced. Importantly, after OPN siRNA treatment, the OPN expression level in liver was significantly reduced and liver tissue injury was ameliorated, as reflected by the significant reduction of serum alanine aminotransferase levels and almost normal liver histology. Thus, this study indicates that OPN siRNA delivery has therapeutic potential in various inflammatory diseases in which OPN play a critical role by silencing OPN gene expression in vivo.

The surface topography of Si(100) bombarded with 2.5–10 keV Ir4(CO)7+ at an incident angle of 45° was investigated by atomic force microscopy. Experimental results showed that self-organized ripple structures with a wavelength below 30 nm were produced at a beam energy of 5 keV. It was found that the wavelength of the ripples increased with decreasing beam energy, which is different from results obtained using conventional ion beams. In addition, surface roughness proved to increase with decreasing beam energy. The phenomena were explained by considering a substantial decrease in sputtering yield and the subsequent compositional change in the target at lower-beam-energy Ir4(CO)7+ bombardment. Furthermore, the surface roughness was also confirmed to increase with increasing oxygen partial pressure.

A prototype compact cluster ion source has been developed using a metal cluster complex as a low damage-sputtering source, since clusters are said to be effective for so-called "lateral sputtering". Using a metal cluster complex ion gun the Si surface was successfully sputtered with high sputtering yield, and yet resulting in reasonably smooth surface for a sputtered depth of 10 nm. Using the prototype compact cluster ion source, an ion beam containing metal cluster complexes of Os 3 (CO) 12 was generated with an acceleration energy of 10 keVand total fluence, N CB , of 5.2 × 10 12 ions (I ave = 0.050 nA, time=278 min). From the results of AFM and SEM measurements, the sputtered Si surface was found to be reasonably smooth for a sputtering depth of ∼ 10 nm. The sputtered Si portion was found to be a truncated (elliptical) cone. The volume was estimated to be 3.2 × 10 -9 cm 3 , i.e., N Si, the number of removed Si atoms was about 1.6 × 10 14 . Thus the sputtering yield, N Si ,/N CB , was estimated to be as large as 30. Surface state characterization and contamination were investigated using XPS (X-ray photoelectron spectroscopy) and AES (Auger electron spectroscopy), showing there was no Os on the sputtered Si surface. These results show that this ion irradiation system using a prototype compact cluster ion source is capable of high rate sputtering resulting in a smooth sputtered surface without deposition, showing the possibility for small penetration depth leading to low damage sputtering, in other words, lateral sputtering due to simultaneous multi-atom bombardment.

SIMS depth profiles using a metal cluster complex ion of Ir 4 ( CO ) 7 + were studied. An unusual increase of the sputtering yield under the condition of small incident angle may be attributed to the suppression of taking oxygen from flooding O2 by the formation of a carbon cover-layer derived from Ir 4 ( CO ) 7 + ion. Even though the roughness of the sputtered surface is small, the depth resolution was not improved by decreasing the cluster ion energy to less than 5 keV, because the carbon cover-layer prevents the formation of surface oxide that buffers atomic mixing. To overcome this issue, it will be necessary to eliminate carbon from the cluster ion.

Advanced glycation end-products (AGE) play a role in the pathogenesis of several diseases, including diabetic complications and atherosclerosis. In atherosclerotic lesions of human aortas, AGE are localized in the extracellular matrix and intracellularly in foam cells. Two interpretations are possible for AGE accumulation inside macrophages, one is endocytic uptake of extracellular AGE-proteins by scavenger receptors; the other is intracellular AGE formation inside the macrophages. In the present study, we determined the pathways involved in AGE accumulation inside macrophages. RAW 264.7 cells, a murine macrophage cell line, incubated with BSA and 1600 mM glucose for 40 weeks, recognized heavily modified AGE- BSA. In contrast, the cells showed no ligand activity for mildly modified AGE-BSA, prepared by incubating BSA with 50 mM glucose for 24 weeks. Nepsilon-(carboxymethyl)lysine (CML)-modified proteins of about 65 kDa were detected in human monocyte-derived macrophages incubated for 7 days with 30 mM glucose and phorbol myristate acetate. Furthermore, CML was generated when glycated protein was incubated with hypochloric acid. Taken together, our results indicate that AGE detected inside foam cells in atherosclerotic lesions are generated intracellularly rather than representing endocytic uptake of extracellular AGE-proteins by scavenger receptors.

The surface sputtering of Si using a proto-type ion gun to utilize metal cluster complexes as ion source has been investigated in detail mainly using Auger spectroscopy and atomic force microscope. The Si surface was found to be successfully sputtered with a high sputtering yield and yet resulting in a reasonably smooth surface. However, the sputtered surface roughness behavior against the incident angle of the ion beam show strong dependence to the accelerating energy of the cluster ions, which could be explained by the balance between the sputtering effect and deposition of ions themselves.

Tetrairidium dodecacarbonyl, Ir4(CO)12, is a metal cluster complex which has a molecular weight of 1104.9. Using a metal-cluster-complex ion source, the interaction between Ir 4 ( CO ) n + ions (n = 0–12) and silicon substrates was studied at a beam energy ranging from 2 keV to 10 keV at normal incidence. By adjusting Wien-filter voltage, the influence of CO ligands was investigated. Experimental results showed that sputtering yield of silicon bombarded with Ir 4 ( CO ) n + ions at 10 keV decreased with the number of CO ligands. In the case of 2 keV, deposition tended to be suppressed by removing CO ligands from the impinging cluster ions. The influence of CO ligands was explained by considering changes in surface properties caused by the irradiation of Ir 4 ( CO ) n + ions. It was also found that the bombardment with Ir 4 ( CO ) 7 + ions at 2.5 keV caused deposition on silicon target.

Since the accumulation of N(epsilon)-(carboxymethyl)lysine (CML), a major antigenic advanced glycation end product, is implicated in tissue disorders in hyperglycemia and inflammation, the identification of the pathway of CML formation will provide important information regarding the development of potential therapeutic strategies for these complications. The present study was designed to measure the effect of hypochlorous acid (HOCl) on CML formation from Amadori products. The incubation of glycated human serum albumin (glycated-HSA), a model of Amadori products, with HOCl led to CML formation, and an increasing HOCl concentration and decreasing pH, which mimics the formation of these products in inflammatory lesions. CML formation was also observed when glycated-HSA was incubated with activated neutrophils, and was completely inhibited in the presence of an HOCl scavenger. These data demonstrated that HOCl-mediated CML formation from Amadori products plays a role in CML formation and tissue damage at sites of inflammation.

Because inhibitors of advanced glycation end-products (AGEs), for example pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of lifestyle-related diseases such as diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N (e) -(carboxymethyl)lysine (CML) and N (ω) -(carboxymethyl)arginine (CMA) during incubation of collagen-derived gelatin with ribose. Furthermore, compounds with inhibitory effects against CML and CMA formation were isolated from EH. Two new prenylflavonoids (compounds 1 and 2) and two known compounds (3 and 4) were found to significantly inhibit the formation of both CML and CMA; compound 4 (epimedokoreanin B) had the strongest inhibitory effect of the isolated compounds. These data suggest that epimedokoreanin B could prevent clinical complications of diabetes by inhibiting AGEs.

The macrophage is known to be a multifunctional antigen presenting cells and playing a central role in inflammation. Macrophages infiltrate into malignant tumor tissues in high numbers (the so-called tumor-associated macrophages [TAMs]) and many studies over the past decade have demonstrated that macrophages have protumor functions and are closely related to tumor progression. It has been shown that protumor macrophages that have differentiated through interaction with tumor cells are involved in stem cell niches, immunosuppression, invasion, and metastasis. Consistent with these functions, studies using human tumor samples have demonstrated that a higher density of macrophages, especially macrophages with the M2 phenotype, is closely associated with worse clinical prognosis in many kinds of malignant tumors. Infiltrating TAMs themselves or polarization pathway of TAMs are considered as new therapeutic targets for the therapy of malignant tumors.

The formation of foam cells in macrophages has been suggested to play an essential role in the progression of early atherosclerotic lesions in vivo and, thus, its suppression is considered to be one of the major approaches for the treatment of atherosclerosis. We isolated eight brominated-tyrosine derivatives, bastadins, from the EtOH extract of the marine sponge Ianthella vasta as inhibitors of the formation of foam cells induced by acetylated low-density lipoproteins in human monocyte-derived macrophages. Bastadin 6 was the strongest inhibitor of foam cell formation due to its suppression of acyl-coenzyme A:cholesterol acyltransferase.

Newly identified cyclic sulfoxides-garlicnins K1 (1), K2 (2), and H1 (3)-were isolated from the acetone extracts of the bulbs of garlic, Allium sativum. Garlicnin H1 (3) demonstrated potential to suppress tumor cell proliferation by regulating macrophage activation. The structures of garlicnins K1 and K2, 3,4-dimethyl-5-allyl-tetrahydrothiophen-2-one-S-oxides, and the structure of garlicnin H1, 3-carboxy-3-hydroxy-4-methyl-5-allylsulfoxide-tetrahydrothiophen-2-(ethane-1,2-diol)-S-oxide were characterized by spectroscopic analysis.

Tetrairidium dodecacarbonyl, Ir4(CO)12, is a metal cluster complex that has a molecular weight of 1104.9. Using a metal-cluster-complex ion source, secondary ion mass spectrometry (SIMS) of poly(methyl methacrylate) (PMMA) thin films on silicon substrates was performed with a quadrupole mass spectrometer. The secondary ion intensity of PMMA bombarded with Ir4(CO)7+ ions was investigated in the beam energy ranging from 3 to 10 keV at an incident angle of 45°. For comparison, bombardment with oxygen ions, O2+, was also tested. It was confirmed that the use of Ir4(CO)7+ ions enhanced secondary ion intensity by at least one order of magnitude compared with that of O2+ ions. Experimental results also showed that secondary ion intensity increased with beam energy; particularly, high-mass secondary ion intensity markedly increased.

Emission of oxygen negative ions O− from a bare surface of yttria-stabilized zirconia (YSZ) was studied at 925°C with a quadrupole mass spectrometer capable of detecting negative ions. The use of the mass spectrometer allowed one to identify O− ions, thereby enabling the investigation of emission stability of O− ions. Experimental results demonstrated that O− ions were emitted from the surface of YSZ continuously over 120h. Although emission rate of O− ions decreased gradually with time, the emission rate of O− ions was confirmed to be temporarily restored after intervals. It was found that time constant of decay curve of O− ions was different from that of emission current. An analysis of the decay curves indicated that the difference in the time constants would be due to emission of electrons. Further, the analysis indicated that the number of emitted electrons would decrease with time more rapidly than O− ions, suggesting that it would be attributed to a variation in surface density of chemisorbed oxyge...

The oxygen ion emission characteristics of CeO 2 were studied under electric field in a vacuum chamber to find a candidate material for a novel ion source, "solid oxide ion source (SOIS)". The emission current was observed from CeO 2 under a pressure of around 10 -3 Pa, at the temperature ranging from 973 K to 1173 K. It was found that the emission current increased with temperature and applied voltage. The ions emitted from CeO 2 were confirmed to be oxygen negative ions (O - ) by the use of quadrupole mass spectrometer. The emission current decreased with time as was observed in the earlier works with other oxide ion conductors such as stabilized zirconia [1,2] or other materials [3]. To enhance the emission current from CeO 2 , an introduction of donor into CeO 2 was tested using Ce 0.992 Nb 0.008 O 2 . For comparison, effect of acceptor doping was also tested using Ce 0.9 Gd 0.1 O 1.95 . The emission current from Ce 0.9 Gd 0.1 O 1.95 was smaller than that from donor-doped and pure CeO 2 . Clear enhancement of the emission current was not observed with Ce 0.992 Nb 0.008 O 2 .

A cluster-ion source has been developed to produce stable ion beams of metal-cluster-complex ions. As a metal cluster complex, triosmium dodecacarbonyl, Os 3 (CO) 12 , was used, which has a molecular weight of 906.7. Using the ion source, energy dependence of beam current and sputtering yield of silicon bombarded with Os 3 (CO) n + (n = 7-8) were investigated at beam energies from 2 to 10 keV under the normal incidence condition. By high-resolution Rutherford backscattering spectrometry (HR-RBS), a silicon target bombarded with the normally incident Os 3 (CO) 7-8 + ions at 10 keV with oxygen flooding at 5 × 10 -4 Pa was analyzed. The experimental results showed that the ion-beam current increased almost linearly with the acceleration voltage. It was found that the sputtering yields of silicon with Os 3 (CO) 7-8 + ions varied substantially with beam energy. The sputtering yield with Os 3 (CO) 7-8 + at 10 keV was higher than that with SF 5 + or Ar + by a factor of 3-20, whereas the yield at 3 keV was lower than that with Ar + . In the case of 2 keV, deposition was found to occur on the silicon surface. The substantial variation in the sputtering yield with beam energy would arise from the lower kinetic energy of each atom constituting the metal-cluster-complex ions. From HR-RBS results, it was confirmed that the constituent atoms of the Os 3 (CO) 7-8 + ions, Os, C, and 0, were implanted into the silicon target. The observed depth profiles of Os and C atoms were in good agreement with results of TRIM simulation, while that of the 0 atom was significantly different from the simulation results. The depth profile of the 0 atom was examined in terms of oxygen diffusion and implantation.

Major novel steroidal alkaloid glycosides, named esculeoside A ( 1 ) and esculeoside B ( 2 ), have been isolated from the pink color-type and the red color-type, respectively, of the ripe tomato fruits of Lycopersicon esculentum MILL. for the first time. The structures of 1 and 2 have been characterized as 3-O-β-lycotetraosyl (5S,22S,23S,25S)-23-acetoxy-3β,27-dihydroxyspirosolane 27-O-β- d -glucopyranoside and 3-O-β-lycotetraosyl (5S,22S,23R,25S)-22,26-epimino-16β,23-epoxy-3β,23,27-trihydroxycholestane 27-O-β- d -glucopyranoside, respectively.

Sulfur compounds obtained from onion, Welsh onion, and garlic are reviewed. A major component (onionin A1) depressed tumor progression and metastasis in both osteosarcoma and ovarian cancer-bearing mouse models.

In this study, the new stable sulfur-containing compounds onionins A2 (1) and A3 (2) were isolated from the acetone extracts of the bulbs of Allium cepa L. and identified as the stereoisomers of onionin A1 discovered in our previous study. Their chemical structures, 3,4-dimethyl-5-(1E-propenyl)-tetrahydrothiophene-2-sulfenic acid-S-oxides, were characterized using various spectroscopic techniques. In addition, 1 and 2 together with onionin A1 were successfully isolated from the leaves of the Welsh onion, Allium fistulosum L. The onion-extracted fractions showed good potential to inhibit the polarization of M2 activated macrophages, indicating their possible ability to inhibit tumor cell proliferation.

Six novel acyclic sulfides, named garlicnins L-1 (I), L-2, L-3, L-4 (II), E (III) and F are isolated which are able to suppress M2 macrophage activation.

CD169 (sialoadhesin) is a sialic acid receptor that is specifically expressed on macrophages, including lymph node sinus macrophages. Animal studies suggest that CD169+ macrophages in lymph nodes have properties in preventing cancers. In order to determine the significance of CD169+ macrophages in patients with malignant melanoma, we evaluated tissue samples from 93 patients to investigate CD169 expression in regional lymph nodes (RLN) and determine the relationship of this expression with overall survival and various clinicopathologic factors. Higher densities of CD169+ cells were significantly associated with longer overall survival (P = 0.001). A multivariate analysis showed that the density of CD169+ cells was an independent prognostic factor, with higher densities correlating with higher density of CD8+ cytotoxic T cells within tumor sites. High CD169 expression in macrophages could be stimulated by IFNα in vitro, and in RLNs, IFNα-producing macrophages and CD303+ plasmacytoid dendritic cells were identified surrounding CD169+ macrophages. These data suggest that IFNα-stimulated CD169+ macrophages in RLNs are closely involved in T-cell–mediated antitumor immunity and may be a useful marker for assessing the clinical prognosis and monitoring antitumor immunity in patients with malignant melanoma. Cancer Immunol Res; 3(12); 1356–63. ©2015 AACR.

Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were isolated from the marine sponge Acanthostrongylophora ingens along with manzamine A (1) and neo-kauluamine (2). Acantholactam contains a γ-lactam ring N-substituted with a (Z)-2-hexenoic acid moiety and is proposed to be biosynthetically derived from manzamine A by oxidative cleavage of the eight-membered ring. Compound 4 was converted to the dimer 2 during storage, suggesting nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4 showed proteasome inhibitory activity.

Here reports new conversions methods of tomato saponins, esculeoside A (1) and a mixture of esculeosides B-1 (2) and B-2 (3), (the latter two were obtained from tomato cans) into pregnane derivative (5) by an alkal treatment followed by acid treatment. Compound 1 or a mixture of 2 and 3 were each refluxed with 1 N KOH to afford a characteristic pyridine steroidal glycoside (4), which was then treated with 2 N HCl-MeOH to afford a pregnane derivative, 3β-hydroxy-5α-pregn-16-en-20-one (5). The results of the above two reactions indicated that tomato saponins are chemically closely related to pregnane hormones. We assume that the assimilated tomato saponins via the small intestine are metabolized into pregnane derivatives, demonstrating various bioactivities such as anti-cancer, anti-osteoporosis, and anti-menopausal disorder activities.

Onionin A (1), a new, stable, sulfur-containing compound, was isolated from acetone extracts of bulbs of onion (Allium cepa), and its structure was characterized as 3,4-dimethyl-5-(1E-propenyl)-tetrahydrothiophen-2-sulfoxide-S-oxide, on the basis of the results of spectroscopic analysis. This compound showed the potential to suppress tumor-cell proliferation by inhibiting the polarization of M2 alternatively activated macrophages.

A Ir4(CO)7+ primary ion beam, at energies from 2.5 keV to 10 keV, was used to profile boron-delta layers in Si to investigate the influences of atomic mixing and surface roughness on the degradation of depth resolution. Factorial analyses using the mixing-roughness-information (MRI) model indicated that the influence of the mixing increased as beam energy was reduced below 5 keV in the case of oxygen flooding. It was confirmed that the magnitude of the MRI surface roughness was different from that of the AFM surface roughness. The discrepancy in the magnitude of roughness was examined by considering the difference in sputtering depth as well as the definition of the MRI surface roughness.

Since pyridoxamine, which traps intermediates in the Maillard reaction and lipid peroxidation reaction, significantly inhibits the development of retinopathy and neuropathy in the streptozotocin-induced diabetic rat, treatment with advanced glycation end product inhibitors and antioxidants may be a potential strategy for the prevention of clinical diabetic complications. However, the paradoxical effect of green tea has been reported; although plasma hydroperoxide levels were ameliorated, the level of N epsilon-(carboxyethyl)lysine (CML) in tendon and plasma was increased by the oral administration of green tea to diabetic rats. In the present study, we measured the effect of natural compounds on CML formation by enzyme-linked immunosorbent assay. A significant amount of CML was observed when bovine serum albumin was incubated with ribose for 7 days. Under the same conditions, natural compounds, such as desgalactotigonin, showed inhibitory effects, whereas quercetin and acteoside enhanced CML formation, indicating that natural compounds contain both inhibitors and enhancers for CML formation.

Previously, we reported an interesting reaction by which esculeogenin A [(5alpha,22S,23S,25S)-3beta,23,27-trihydroxyspirosolane], a sapogenol of tomato-saponin, esculeoside A, was easily converted into a pregnane derivative, 5alpha-pregn-16-en-3beta-ol-20-one, merely by refluxing with pyridine and water. Its chemical mechanism including air oxidation is here described.

Tetrairidium dodecacarbonyl, Ir4(CO)12, is a massive compound called metal cluster complex, which has a molecular weight of 1104.9. Using an Ir4(CO)7+ primary ion beam, secondary ion mass spectrometry (SIMS) of boron-delta-doped silicon samples was performed. Depth resolution, defined by 1/e decay length for the trailing edge of the boron delta layer, was investigated in the beam energy ranging from 2.5 to 10 keV at an incident angle of 45°. Experimental results showed that the depth resolution improved with oxygen partial pressure at a beam energy of 5 keV. It was confirmed that the depth resolution without oxygen flooding monotonically improved as beam energy decreased. Furthermore, it was found that the favorable effect of oxygen flooding on depth resolution weakened as beam energy was reduced.

We report the results of surface sputtering of Si using a proto type ion source to utilize a compact cluster ion source which was developed using Os3(CO)12 as a low-damage sputtering source. The surface roughening of Si sputtered with cluster ions with an acceleration energy of 10 keV at incidence angles between 0 and 60° was investigated. The sputtered Si surface was observed using an atomic force microscope and a scanning electron microscope. At incident angles between 0 and 45°, the surface remained smooth while at 60°, roughening was observed.

From the methanol extract of the fruits of the blackberry (Rubus allegheniensis Port.), four triterpenoids – pomolic acid (1), tormentic acid (2), euscaphic acid (3) and 1β-hydroxyeuscaphic acid (4) – were isolated, while six triterpenoids – 2, 3, myrianthic acid (5), ziyu glycoside II (6), sericic acid (7) and 19-hydroxy-2,3-secours-12-ene-2,3,28-trioic acid 3-methyl ester (8) – were obtained from the methanol extract of the leaves of this plant. Their structures were determined on the basis of spectral data. Compounds 1–8 were examined for their inhibitory activities on foam cell formation in human monocyte-derived macrophages induced by acetylated low-density lipoproteins at a 50 μM concentration. Among the tested compounds, 1 showed the strongest activity, with the inhibitory effect being 90%. The inhibitory activities of 2–8 were evaluated to be 30%, 32%, 33%, 4%, 48%, 4% and 24%, respectively. Further, the structure–activity relationship of these compounds was investigated.