bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of formulation factors on PpIX production and photodynamic action of novel ALA‐loaded microparticles
Authors: Donnelly Ryan F. , McCarron Paul A. , Al‐Kassas Rasil , Juzeniene Asta , Juzenas Petras , Iani Vladimir , Woolfson A. David , Moan Johan 
Published: February 2009

AbstractA novel 5‐aminolevulinic acid (ALA)‐containing microparticulate system was produced recently, based on incorporation of ALA into particles prepared from a suppository base that maintains drug stability during storage and melts at skin temperature to release its drug payload. The novel particulate system was applied to the skin of living animals, followed by study of protoporphyrin IX (PpIX) production. The effect of formulating the microparticles in different vehicles was investigated and also the phototoxicity of the PpIX produced using a model tumour.Particles formulated in propylene glycol gels (10% w/w ALA loading) generated the highest peak PpIX fluorescence levels in normal mouse skin. Peak PpIX levels induced in skin overlying subcutaneously implanted WiDr tumours were significantly lower than in normal skin for both the 10% w/w ALA microparticles alone and the 10% w/w ALA microparticles in propylene glycol gels during continuous 12 h applications. Tumours not treated with photodynamic therapy continued to grow over the 17 days of the anti‐tumour study. However, those treated with 12 h applications of either the 10% w/w ALA microparticles alone or the 10% w/w ALA microparticles in propylene glycol gel followed by a single laser irradiation showed no growth. The gel formulation performed slightly better once again, reducing the tumour growth rate by approximately 105%, compared with the 89% reduction achieved using particles alone. Following the promising results obtained in this study, work is now going on to prepare particle‐loaded gels under GMP conditions with the aim of initiating an exploratory clinical trial. Copyright © 2009 John Wiley & Sons, Ltd.
Gene and microRNA expression in p53‐deficient day 8.5 mouse embryos
Authors: Hosako Hiromi , Martin Gail S. , Barrier Marianne , Chen Yian A. , Ivanov Ivan V. , Mirkes Philip E. 
Published: February 2009

AbstractBACKGROUND: Neural tube defects (NTDs) are one of the most common human birth defects, with a prevalence of approximately 1 in 1000 live births in the United States. In animal studies, deletion of p53 leads to a significant increase in embryos that exhibit exencephaly. Whereas several studies have closely investigated the morphologic changes of p53‐deficient embryos, no study has reported the molecular‐level alteration in p53‐deficient embryos. Here we attempt to identify genes and microRNAs (miRNAs) modified by deletion of p53 in day 8.5 mouse embryos. METHODS: Mouse embryos from p53 heterozygous crosses were collected, genotyped, and embryos of similar genotype (+/+; +/−; −/−) were pooled. RNA from the pooled samples was isolated to determine mRNA and miRNA expression levels using Whole Genome Bioarrays and Low Density Arrays, respectively. RESULTS: In p53 −/− embryos, 388 genes showed statistically significant alteration in gene expression of more than twofold compared to p53 +/+ embryos. Expression of p53 and well known p53 target genes, such as p21 and cyclin G1, were significantly down‐regulated in p53 −/− embryos. In contrast, expression of other p53 target genes, such as Mdm2, Noxa, and Puma, were unchanged. We also identified six genes (Csk, Itga3, Jarid2, Prkaca, Rarg, and Sall4), known to cause NTDs when deleted, that are also down‐regulated in p53 −/− embryos. Finally, five miRNAs (mir‐1, mir‐30e‐3p, mir‐142‐3p, mir‐301, and mir‐331) also showed statistically significant alterations in expression levels in p53 −/− embryos compared to p53 +/+ embryos. Combined analysis of the experimental data using stepwise regression model and two publicly available algorithms identified putative target genes of these miRNAs. CONCLUSIONS: Our data have identified genes and miRNAs that may be involved in the mechanisms underlining NTDs and begin to define the developmental role of p53 in the etiology of NTDs. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.
Endocrine fibroblast growth factors as regulators of metabolic homeostasis
Authors: Kurosu Hiroshi , Kuro‐o Makoto 
Published: February 2009

AbstractEndocrine fibroblast growth factors (FGFs) function as hormones that maintain specific metabolic states by controlling homeostasis of bile acid, glucose, fatty acid, phosphate, and vitamin D. Endocrine FGFs exert their biological activity through a common design of coreceptor system consisting of the Klotho gene family of transmembrane proteins and cognate FGF receptors. Moreover, expression of endocrine FGFs is regulated by nuclear receptors whose lipophilic ligands are generated under the control of these hormones in the target organs. Thus, novel endocrine axes have emerged that regulate diverse metabolic processes through feedback loops composed of the FGF, Klotho, FGF receptor, and nuclear receptor gene families. This review summarizes the role of Klotho family proteins in the regulation of metabolic activity and expression of the endocrine FGFs. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Paraoxonases role in the prevention of cardiovascular diseases
Authors: Rosenblat Mira , Aviram Michael 
Published: February 2009

AbstractIncreased oxidative stress is a characteristic of patients with high risk for atherosclerosis development (hypercholesterolemic, hypertensive, diabetic), and the above phenomenon was shown to be associated with attenuated antioxidative status. The increased oxidative stress in atherosclerotic patients is present in their blood, as well as in their arterial wall cells, including macrophages, the hallmark of foam cells formation during early atherogenesis. Serum high density lipoprotein (HDL)‐associated paraoxonase 1 (PON1) reduces oxidative stress in lipoproteins, in macrophages, and in the atherosclerotic lesion, whereas paraoxonase 2 (PON2, which is present in tissues, but not in serum) acts as an antioxidant at the cellular and not humoral level. Both PON1 and PON2 protect against atherosclerosis development, and this phenomenon could be related to their antioxidative properties. The use of nutritional antioxidants such as vitamin E, carotenoids (lycopene and β‐carotene), and mainly polyphenols (such as those present in red wine, licorice root ethanolic extract, or in pomegranate) by atherosclerotic animals and also by cardiovascular patients, leads to a reduction in oxidative stress and to the attenuation of atherosclerosis development. These latter phenomena could be related to the nutritional antioxidants‐induced increase in HDL PON1 activity (effects on gene expression, on preventing enzyme inactivation, and on increasing PON1 stability through its binding to HDL), as well as an increase in macrophage PON2 activation (at the gene expression level). © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Contributions of hyperhomocysteinemia to atherosclerosis: Causal relationship and potential mechanisms
Authors: Zhou Ji , Austin Richard C. 
Published: February 2009

AbstractHyperhomocysteinemia (HHcy) is considered an independent risk factor for cardiovascular disease, including ischemic heart disease, stroke, and peripheral vascular disease. Mutations in the enzymes and/or nutritional deficiencies in B vitamins required for homocysteine metabolism can induce HHcy. Studies using genetic‐ or diet‐induced animal models of HHcy have demonstrated a causal relationship between HHcy and accelerated atherosclerosis. Oxidative stress and activation of proinflammatory factors have been proposed to explain the atherogenic effects of HHcy. Recently, HHcy‐induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been found to play a role in HHcy‐induced atherogenesis. This review will focus on the cellular mechanisms of HHcy in atherosclerosis from both in vivo and in vitro studies. The contributions of ER stress and the UPR in atherogenesis will be emphasized. Results from recent clinical trials assessing the cardiovascular risk of lowering total plasma homocysteine levels and new findings examining the atherogenic role of HHcy in wild‐type C57BL/6J mice will also be discussed. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Physiological roles of 2‐arachidonoylglycerol, an endogenous cannabinoid receptor ligand
Authors: Sugiura Takayuki 
Published: February 2009

Abstract2‐Arachidonoylglycerol is an arachidonic acid‐containing monoacylglycerol isolated from the rat brain and canine gut as an endogenous ligand for the cannabinoid receptors (CB1 and CB2). 2‐Arachidonoylglycerol binds to both the CB1 receptor, abundantly expressed in the nervous system, and the CB2 receptor, mainly expressed in the immune system, with high affinity, and exhibits a variety of cannabimimetic activities. Notably, anandamide, another endogenous ligand for the cannabinoid receptors, acts as a partial agonist at these cannabinoid receptors, whereas 2‐arachidonoylglycerol acts as a full agonist. The results of structure‐activity relationship experiments strongly suggested that 2‐arachidonoylglycerol rather than anandamide is the true natural ligand for both the CB1 and the CB2 receptors. Evidence is gradually accumulating which shows that 2‐arachidonoylglycerol plays physiologically and pathophysiologically essential roles in various mammalian tissues and cells. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Nitric oxide and vascular insulin resistance
Authors: Wu Guoyao , Meininger Cynthia J. 
Published: February 2009

AbstractObesity and type‐II diabetes are growing major health issues worldwide. They are the leading risk factors for vascular insulin resistance, which plays an important role in the pathogenesis of cardiovascular disease, the leading cause of death in developed nations. Recent studies have shown that reduced synthesis of nitric oxide (NO; a major vasodilator) from L‐arginine in endothelial cells is a major factor contributing to the impaired action of insulin in the vasculature of obese and diabetic subjects. The decreased NO generation results from a deficiency of (6R)‐5,6,7,8‐tetrahydrobiopterin [BH4; an essential cofactor for NO synthase (NOS)], as well as increased generation of glucosamine (an inhibitor of the pentose cycle for the production of NADPH, another cofactor for NOS) from glucose and L‐glutamine. Accordingly, endothelial dysfunction can be prevented by (1) enhancement of BH4 synthesis through supplementation of its precursor (sepiapterin) via the salvage pathway; (2) transfer of the gene for GTP cyclohydrolase‐I (the first and key regulatory enzyme for de novo synthesis of BH4); or (3) dietary supplementation of L‐arginine (which stimulates GTP cyclohydrolase‐I expression and inhibits hexosamine production). Modulation of the arginine–NO pathway by BH4 and arginine is beneficial for ameliorating vascular insulin resistance in obesity and diabetes. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Interferons and viral infections
Authors: Fensterl Volker , Sen Ganes C. 
Published: February 2009

AbstractInterferons represent a family of cytokines, which is of central importance in the innate immune response to virus infections. All interferons act as secreted ligands of specific cell surface receptors, eliciting the transcription of hundreds of interferon‐stimulated genes whose protein products have antiviral activity, as well as antimicrobial, antiproliferative/antitumor, and immunomodulatory effects. Expression of type I and III interferons is induced in virtually all cell types upon recognition of viral molecular patterns, especially nucleic acids, by cytoplasmic and endosomal receptors, whereas type II interferon is induced by cytokines such as IL‐12, and its expression is restricted to immune cells such as T cells and NK cells. The effectiveness of the interferon system in counteracting viral infections is reflected by the multitude of inhibitors of interferon induction or interferon action that are encoded by many viruses, preventing their eradication and resulting in the continued coexistence of viruses and vertebrates. The unique biological functions of interferons have led to their therapeutic use in the treatment of diseases such as hepatitis, multiple sclerosis, and certain leukemias. © 2009 International Union of Biochemistry and Molecular Biology, Inc.
Model for Continual Depolymerization of Biomass Catalyzed by Dilute Sulfuric Acid
Authors: Qi W. , Zhang S. , Xu Q. , Li H. , Ren Z. , Li T. , Yan Y. 
Published: February 2009

AbstractEthanol fuel from biomass is conventionally produced via the hydrolysis of biomass catalyzed by acid. In this paper, it is understood that the degree of polymerization of cellulose is randomly distributed and that the rupture of β‐1,4‐glucosidic bonds during acidic hydrolysis of cellulose is a process of continual depolymerization. From this perception, a model is established for the continual depolymerization of cellulose catalyzed by acid. Meanwhile, analog computation resulted in the activation energy and the reaction rate constant related to the rupture of β‐1,4‐glucosidic bonds. The established model is highly validated by test runs and thus assumed as a model that can be used to describe the depolymerization route taken in acidic hydrolysis of cellulose. The calculated activation energy and rate constant for the rupture of β‐1,4‐glucosidic bonds correspond to the rule of acidic hydrolysis of cellulose. Investigation of the model is of great significance in further studies on the hydrolysis mechanism of cellulose.
Enhancement of Ca‐Based Sorbent Multicyclic Behavior in Ca Looping Process for CO2 Separation
Authors: Li Y. , Zhao C. , Chen H. , Liu Y. 
Published: February 2009

AbstractThe Ca‐based sorbent looping cycle represents an innovative way of CO2 capture for power plants. However, the CO2 capture capacity of the Ca‐based sorbent decays sharply with calcination/carbonation cycle number increasing. In order to improve the CO2 capture capacity of the sorbent in the Ca looping cycle, limestone was modified with acetic acid solution. The cyclic carbonation behaviors of the modified and original limestones were investigated in a twin fixed‐bed reactor system. The modified limestone possesses better cyclic carbonation kinetics than the original limestone at each cycle. The modified limestone carbonated at 640–660 °C achieves the optimum carbonation conversion. The acetic acid modification improves the long‐term performance of limestone, resulting in directly measured conversion as high as 0.4 after 100 cycles, while the original limestone remains at a conversion of less than 0.1 at the same reaction conditions. Both the pore volume and pore area distributions of the calcines derived from the modified limestone are better than those derived from the original limestone. The CO2 partial pressure for carbonation has greater effect on conversion of the original limestone than on that of the modified sorbent because of the difference in their pore structure characteristics. The carbonation conversion of the original limestone decreases with the increase in particle size, while the change in particle size of the modified sorbent has no clear effect on cyclic carbonation behavior.
Electron‐Deficient Alkynes as Cleavable Reagents for the Modification of Cysteine‐Containing Peptides in Aqueous Medium
Authors: Shiu Hoi‐Yan , Chan Tak‐Chung , Ho Chi‐Ming , Liu Yungen , Wong Man‐Kin , Che Chi‐Ming 
Published: February 2009

AbstractEnriched cleavage: An efficient chemoselective cysteine modification of unprotected peptides and proteins has been developed by using electron‐deficient alkynes in aqueous media. Interestingly, terminal alkynone‐modified peptides could be converted back into the unmodified peptides by cleavage by adding thiols under mild conditions (see scheme).magnified imageAn efficient method has been developed for the chemoselective cysteine modification of unprotected peptides and proteins in aqueous media through the formation of a vinyl sulfide linkage by using electron‐deficient alkynes, including alkynoic amides, esters and alkynones. The terminal alkynone‐modified peptides could be converted back into the unmodified peptides (81 % isolated yield) by adding thiols under mild conditions. The usefulness of this thiol‐assisted cleavage of the vinyl sulfide linkage in peptides has been exemplified by the enrichment of a cysteine‐containing peptide (71 % recovery) from a mixture of cysteine‐containing and non‐cysteine‐containing peptides.
A Highly Efficient Macrolactonization Method via Ethoxyvinyl Ester
Authors: Ohba Yusuke , Takatsuji Mayuko , Nakahara Kenji , Fujioka Hiromichi , Kita Yasuyuki 
Published: February 2009

AbstractFacile and efficient macrolactonization of hydroxycarboxylic acid via ethoxyvinyl esters (EVEs), which can give 9‐ to 14‐membered macrolactones in good yields, has been developed (see scheme; DCE = 1,2‐dichloroethane). The method is useful for acid‐/base‐sensitive substrates and applicable to the compound with many functional groups.magnified imageWe present the highly efficient reaction procedure of the macrolactonization method via ethoxyvinyl esters (EVEs). The following procedure was performed: 1) The EVE was prepared from hydroxycarboxylic acid and ethoxyacetylene in the presence of the Ru catalyst [RuCl2(p‐cymene)]2 in acetone; 2) after filtration of the Ru catalyst through a short‐neutral SiO2 pad and evaporation of acetone, the EVE formed was diluted in 1,2‐dichloroethane (DCE) and the solution was slowly added by a syringe pump to the highly diluted DCE solution of pTsOH (10 mol %) at 80 °C. Various‐sized lactones could be produced by the method described here. It is noteworthy that the method can give 9‐ to 14‐membered macrolactones in good yields. This macrolactonization method via EVEs is useful for acid‐/base‐sensitive substrates. Furthermore, it was found that EVE formation was possible without loosing activity of the Ru catalyst even for the compounds with nucleophilic amine functions. The characteristic feature of the method was exemplified by the reaction of the compound 14 with many functional groups.
Selective Formic Acid Decomposition for High‐Pressure Hydrogen Generation: A Mechanistic Study
Authors: Fellay Céline , Yan Ning , Dyson Paul J. , Laurenczy Gábor 
Published: February 2009

AbstractA viable storage systemfor hydrogen based on selective formic acid decomposition into H2and CO2has been developed (see scheme). Continuous generation of H2of very high purity, over a wide range of pressures and under mild conditions was achieved.magnified imageA homogenous catalytic system has been developed that efficiently and selectively decomposes formic acid into hydrogen and carbon dioxide. [Ru(H2O)6]2+, [Ru(H2O)6]3+and RuCl3⋅x H2O are all excellent pre‐catalysts in presence of TPPTS (TPPTS=meta‐trisulfonated triphenylphosphine), the formic acid decomposition taking place in the aqueous phase, under mild conditions and over a large range of pressures. Optimisation of the reaction conditions is described together with a detailed mechanistic study leading to a tentative catalytic cycle. The performance of the catalytic system for continuous hydrogen generation is presented. Overall, the method proposed overcomes the limitations of other catalysts for the decomposition of formic acid making it a viable hydrogen‐storage material.
Carbon Nanotube–Acridine Nanohybrids: Spectroscopic Characterization of Photoinduced Electron Transfer
Authors: Mackiewicz Nicolas , Delaire Jacques A. , Rutherford A. William , Doris Eric , Mioskowski Charles 
Published: February 2009

AbstractChange happens: Acridine–carbon nanotube nanohybrids were built (see figure) and their photoinduced electron‐transfer properties investigated, showing variable behaviour depending on the acridine partner.magnified imageSingle‐walled carbon nanotubes (NT) were covalently functionalized with either 9‐phenyl acridine (PhA) or 10‐methyl‐9‐phenyl acridinium (PhMeA+). Absorption and fluorescence properties of acridine derivatives tethered to the nanotubes were studied in homogeneous dispersions. Exciplex emission was observed for NT functionalized with 9‐phenylacridine. This phenomenon was attributed to an “intramolecular” interaction between excited phenyl acridine and carbon nanotubes. Interestingly, reverse photoinduced electron transfer from the nanotube to 10‐methyl‐9‐phenylacridinium was detected for the NT‐PhMeA+ nanohybrid. This electron transfer led to a strong quenching of the acridinium fluorescence and to the formation of a metastable acridine radical. Evidence for the formation of this radical was obtained by ESR studies.
Synthetic and Structural Insights into the Zincation of Toluene: Direct Synergic Ring Metallation versus Indirect Nonsynergic Lateral Metallation
Authors: Armstrong David R. , García‐Álvarez Joaquín , Graham David V. , Honeyman Gordon W. , Hevia Eva , Kennedy Alan R. , Mulvey Robert E. 
Published: February 2009

AbstractUnprecedented direct zincation of toluene can be achieved by using a bimetallic base that bypasses the acidic methyl group and instead affords a statistical mixture of the meta and para deprotonated regioisomers (see scheme).magnified imageToluene has been directly zincated by reaction with the heteroleptic sodium zincate [(tmeda)Na(tBu)(tmp)Zn(tBu)] (1) to afford a statistical mixture of the meta and para regioisomers of [(tmeda)Na(C6H4Me)(tmp)Zn(tBu)] (2) (TMEDA=N,N,N′,N′‐tetramethylethylenediamine, TMP=2,2,6,6‐tetramethylpiperidide). Interestingly, the methyl group of toluene has been left untouched by the mixed‐metal base. The crystal structures of both regioisomers have been elucidated by using X‐ray crystallography, which revealed a common motif, in which zinc lies in the same plane as the tolyl ring and binds strongly to the carbon that has experienced the deprotonation, leading to a covalent σ bond; whereas sodium adopts a perpendicular disposition, π‐engaging with the aromatic ring. DFT studies of the reaction of 1 with toluene showed that of the four possible regioisomers, the experimentally observed meta and para ones are the most thermodynamically preferred products due to a large extent to the combined (synergic) effect of the zinc and sodium and the different way in which each metal binds to the tolyl anion. In contrast, the more straightforward benzyl‐based zincate [(tmeda)2Na(CH2Ph)Zn(tBu)2] (3) is obtained through an indirect route, in which toluene is first laterally metallated by monometallic butylsodium to afford benzylsodium, which then forms a mixed‐metal compound by co‐complexation with tBu2Zn. Zincate 3 has been characterised by X‐ray crystallography in the solid state and by NMR spectroscopy in deuterated THF solution.
First Example of Highly Stereoselective Synthesis of 1,2,3‐Trisubstituted Cyclopropanes via Chiral Selenonium Ylides
Authors: Wang Hai‐Yang , Yang Fei , Li Xin‐Liang , Yan Xue‐Ming , Huang Zhi‐Zhen 
Published: February 2009

AbstractA new strategy for the highly stereoselective synthesis of three stereoisomers of chiral 1,2,3‐trisubstituted cyclopropanes in good yields with excellent diastereoselectivities and very high enantioselectivities (up to >99 % ee) was developed via selenonium ylides (see scheme). Possible pathways for the asymmetric cyclopropanations were also proposed.magnified imageAs the first example of the application of chiral selenonium ylides in asymmetric cyclopropanation, a new strategy for the highly stereoselective synthesis of chiral 1,2,3‐trisubstituted cyclopropanes via selenonium ylides is described. The reaction afforded three stereoisomers of chiral 1,2,3‐trisubstituted cyclopropanes with good yields, excellent diastereoselectivities, very high enantioselectivities (up to >99 % ee), good generality and recyclability of chiral selenides. The possible pathways and models of the asymmetric cyclopropanation via the chiral selenonium ylides were also proposed to rationalize the excellent enantioselectivities and diastereoselectivities.