Protective Effect of Ferulic Acid against Hydrogen Peroxide Induced Apoptosis in PC12 Cells

Ferulic Acid (FA) is a highly abundant phenolic phytochemical which is present in plant tissues. FA has biological effects on physiological and pathological processes due to its anti-apoptotic and anti-oxidative properties, however, the detailed mechanism(s) of function is poorly understood. We have identified FA as a molecule that inhibits apoptosis induced by hydrogen peroxide (H₂O₂) or actinomycin D (ActD) in rat pheochromocytoma, PC12 cell. We also found that FA reduces H₂O₂-induced reactive oxygen species (ROS) production in PC12 cell, thereby acting as an anti-oxidant. Then, we analyzed FA-mediated signaling responses in rat pheochromocytoma, PC12 cells using antibody arrays for phosphokinase and apoptosis related proteins. This FA signaling pathway in PC12 cells includes inactivation of pro-apoptotic proteins, SMAC/Diablo and Bad. In addition, FA attenuates the cell injury by H₂O₂ through the inhibition of phosphorylation of the extracellular signal-regulated kinase (ERK). Importantly, we find that FA restores expression levels of brain-derived neurotrophic factor (BDNF), a key neuroprotective effector, in H₂O₂-treated PC12 cells. As a possible mechanism, FA increases BDNF by regulating microRNA-10b expression following H₂O₂ stimulation. Taken together, FA has broad biological effects as a neuroprotective modulator to regulate the expression of phosphokinases, apoptosis-related proteins and microRNAs against oxidative stress in PC12 cells.     

A Novel Synthesis of 4‐Pyridazineacetic Acids via Ring Expansion of N‐Cyanomethylated 3‐Pyrazoline‐4‐acetic Acids

A novel synthetic route to 4‐pyridazineacetic acids 10 – 12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 – 9 . 1H‐Pyrazole‐4‐acetic acids 1 – 3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4 – 6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7 – 9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10 – 12 .     

Non-destructive elemental analysis of large meteorite samples by prompt gamma-ray neutron activation analysis with the internal mono-standard method

Prompt gamma-ray neutron activation analysis (PGNAA) using the internal mono-standard method was tested for its applicability to analyzing large solid samples including irregularly shaped meteorite samples. For evaluating the accuracy and precision of the method, large quantities of the Geological Survey of Japan standardized rock powders (JB-1a, JG-1a, and JP-1) were analyzed and 12 elements (B, Na, Mg, Al, Cl, K, Ca, Ti, Mn, Fe, Sm, and Gd) were determined by using Si as an internal standard element. Analytical results were mostly in agreement with literature values within 10 %. The precision of the method was also shown to be within 10 % (1σ) for most of these elements. The analytical procedure was then applied to four stony meteorites (Allende, Kimble County, Leedey, Lake Labyrinth) and four iron meteorites (Canyon Diablo, Toluca (Mexico), Toluca (Xiquipilco), Squaw Creek) consisting of large chunks or single slabs. For stony meteorites, major elements (Mg, Al, Si, S, Ca, and Ni), minor elements (Na and Mn) and trace element (B, Cl, K, Ti, Co, and Sm) were determined with adequate accuracy. For iron meteorites, results for the Co and Ni mass fractions determined are all consistent with corresponding literature values. After the analysis, it was confirmed that the residual radioactivity remaining in the sample after PGNAA was very low and decreased down to the background level. This study shows that PGNAA with the internal mono-standard method is highly practical for determining the elemental composition of large, irregularly shaped solid samples including meteorites.     

Noncatalytic kinetic study on site-selective H/D exchange reaction of phenol in sub- and supercritical water

The site-selective H/D exchange reaction of phenol in sub- and supercritical water is studied without added catalysts. In subcritical water in equilibrium with steam at 210-240 degrees C, the H/D exchange proceeds both at the ortho and para sites in the phenyl ring, with no exchange observed at the meta site. The pseudo-first-order rate constants are of the order of 10(-4) s(-1); 50% larger for the ortho than for the para site. In supercritical water, the exchange is observed also at the meta site with the rate constant in the range of 10(-6)-10(-4) s(-1). As the bulk density decreases, the exchange slows down and the site selectivity toward the ortho is enhanced. The enhancement is due to the phenol-water interaction preference at the atomic resolution. The site selectivity toward the ortho is further enhanced when the reaction is carried out in benzene/water solution. Using such selectivity control and the reversible nature of the hydrothermal deuteration/protonation process, it is feasible to synthesize phenyl compounds that are deuterated at any topological combination of ortho, meta, and para sites.     

Convenient synthesis of alkoxyhalosilanes from hydrosilanes

Selective dehydrogenative coupling of di- and trihydrosilanes with alcohols catalyzed by PdCl₂ or NiCl₂ afforded alkoxyhydro- and dialkoxyhydrosilanes in good yield. Further treatment of the resulting alkoxyhydrosilanes with carbon tetrachloride or allyl bromide in the presence of the same catalyst led to the formation of alkoxychloro- and alkoxybromosilanes, respectively. Similar reactions of dialkoxyhydrosilanes with carbon tetrachloride afforded dialkoxychlorosilanes in good yield, although contamination of small amounts of trialkoxysilanes and alkoxydichlorosilanes was detected in the products. Selective substitution of the alkoxyhalosilanes with nucleophiles is also reported.     

Determination of bithionol, bromophen, nitroxynil, oxyclozanide, and tribromsalan in milk with liquid chromatography coupled with tandem mass spectrometry

LC/MS/MS was developed to determine the residues of bithionol (BTN), bromofen (BMF), nitroxynil (NTX), oxyclozanide (OCZ), and tribromsalan (TBS) in milk. Samples were extracted with ethyl acetate and cleaned up by liquid-liquid separation with acetonitrile and n-hexane. The compounds were determined by RP-LC using a C18 column with 0.1% formic acid-methanol. Mass spectral acquisition was performed in the negative mode by applying selected-reaction monitoring. The method was validated in milk spiked with these compounds at 5-600 microg/kg; average recoveries were in the range 83.8-97.1%, with RSD values of 1.4-8.0%. The interassay RSDs were less than 11%. The LODs of these compounds in milk were 0.1 microg/kg. The method was applied to 24 raw milk samples. The concentration of these compounds in all samples was lower than the Japanese maximum residue limits. The method is rapid, sensitive, and specific for monitoring residues of BTN, BMF, NTX, OCZ, and TBS in milk.     

Reaction of 2,3-diaminomaleonitrile with diones

2,3-Diaminomaleonitrile (DAMN) was allowed to react with 2,6-heptanedione to produce (2Z)-2-amino-3-[(1E)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile and (2Z)-2-amino-3-[(1Z)-3-methylcyclohex-2-enylideneamino]but-2-enedinitrile. The reaction of DAMN with 2,7-octanedione yielded trans-5,8a-dimethyl-1,5a,6,7,8,8a-hexahydrocyclopenta[e]-1,4-diazepine-2,3-dicarbonitrile. DAMN reacted with 2,8-nonanedione to afford trans- and cis-5,9a-dimethyl-5a,6,7,8,9,9a-hexahydro-1H-benzo[e]-1,4-diazepine-2,3-dicarbonitrile. These compounds were characterized by X-ray crystallography, NMR spectroscopy, and DFT calculations.     

Biological activities of phenolic compounds isolated from galls of Terminalia chebula Retz. (Combretaceae)

The aqueous extract of galls from Terminalia chebula Retz. (Combretaceae) was fractionated on Diaion and refractionated on octadecyl silica column. Six phenolic compounds were isolated and identified as gallic acid (1), punicalagin (2), isoterchebulin (3), 1,3,6-tri-O-galloyl-β-D-glucopyranose (4), chebulagic acid (5) and chebulinic acid (6). All of the compounds showed stronger 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and melanin inhibitory activities than ascorbic acid, butylated hydroxytoluene, α-tocopherol, arbutin and kojic acid, the reference compounds. Gallic acid (1) exhibited inhibitory activity against nitric oxide production in lipopolysaccharide-activated macrophages. However, all isolated compounds exhibited less activity than the reference compounds in mushroom tyrosinase inhibition and human tumour cytotoxicity assays. This study has demonstrated that the phenolic compounds isolated from galls of T. chebula might contribute significantly due to their antioxidant and whitening activities.     

Pressure calculation in hybrid particle-field simulations

In the framework of a recently developed scheme for a hybrid particle-field simulation techniques where self-consistent field (SCF) theory and particle models (molecular dynamics) are combined [J. Chem. Phys. 130, 214106 (2009)], we developed a general formulation for the calculation of instantaneous pressure and stress tensor. The expressions have been derived from statistical mechanical definition of the pressure starting from the expression for the free energy functional in the SCF theory. An implementation of the derived formulation suitable for hybrid particle-field molecular dynamics-self-consistent field simulations is described. A series of test simulations on model systems are reported comparing the calculated pressure with those obtained from standard molecular dynamics simulations based on pair potentials.     

Recent progress in the solid-phase synthesis of glycopeptide

The recent understanding of the biological role of glycoproteins has brought about a demand for the highly homogeneous glycopeptides as the functional model for glycoproteins. Thus, much efforts have been made to establish easy and efficient method for glycopeptide synthesis. In this paper, we briefly review the recent advances in the synthesis of O- and N-linked glycopeptide based on the solid-phase method. In O-glycopeptide section, the preparation of glycosylated amino acid units with mucin type and other O-linked carbohydrate chains and their use for solid-phase synthesis are summarized. Other approaches, such as the glycosylation of resin bound peptide are also overviewed. In N-glycopeptide section, the synthesis using glycosylated amino acid units as well as other methods are described.