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41.
Ana G. Crisostomo Raphael B. Moreno Suppiah Navaratnam James A. Wilkinson 《Free radical research》2013,47(6):730-737
Three potential routes to generation of reactive oxygen species (ROS) from α-tocopherolquinone (α-TQ) have been identified. The quinone of the water-soluble vitamin E analogue Trolox C (Trol-Q) is reduced by hydrated electron and isopropanol α-hydroxyalkyl radical, and the resulting semiquinone reacts with molecular oxygen to form superoxide with a second order rate constant of 1.3 × 108 dm3/mol/s, illustrating the potential for redox cycling. Illumination (UV-A, 355 nm) of the quinone of 2,2,5,7,8-pentamethyl-6-hydroxychromanol (PMHC-Q) leads to a reactive short-lived (ca. 10? 6 s) triplet state, able to oxidise tryptophan with a second order rate constant greater than 109 dm3/mol/s. The triplet states of these quinones sensitize singlet oxygen formation with quantum yields of about 0.8. Such potentially damaging reactions of α-TQ may in part account for the recent findings that high levels of dietary vitamin E supplementation lack any beneficial effect and may lead to slightly enhanced levels of overall mortality. 相似文献
42.
Alice Simon Vinícius Raphael de Almeida Borges Lucio Mendes Cabral Valéria Pereira de Sousa 《AAPS PharmSciTech》2013,14(1):425-434
The intramuscular administration of the injectable suspension betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD) has immediate therapeutic activity due to solubilized BSP and prolonged activity resulting from the slow release of BD micro-crystals. The purpose of this study was to develop and validate a dissolution method for BD in intramuscular injectable suspensions with detection by high-performance liquid chromatography (HPLC) method. Five commercial products presented a distribution of particle sizes, ranging between 7.43 and 40.25 μm as measured by laser diffraction. It was also found that particle sizes differed between batches of the same product. The different products were tested using the paddle apparatus, with stirring speeds of 25 and 50 rpm in 300 mL of phosphate buffer; simulated body fluid, muscle fluid, and synovial fluid were used as biorelevant dissolution media at 37 ± 0.5°C. It was verified that not only does average particle size affect the dissolution rate, but also the mode and the polydispersity index of the particles. Discriminatory power was obtained using the in vitro dissolution method with 0.1 M sodium phosphate buffer pH 7.4 containing 0.1% sodium lauryl sulfate and a stirring speed of 50 rpm. The HPLC-method is linear, precise, selective, and accurate for the quantification of BSP and BD in dissolution profile testing. This dissolution method can be utilized as a method to control the quality of these injectable suspensions.Key words: dipropionate betamethasone, dissolution test, intramuscular injectable suspensions, simulated muscular fluid, sodium phosphate betamethasone 相似文献
43.
The spatial scaling of beta diversity 总被引:1,自引:0,他引:1
Philip S. Barton Saul A. Cunningham Adrian D. Manning Heloise Gibb David B. Lindenmayer Raphael K. Didham 《Global Ecology and Biogeography》2013,22(6):639-647
Beta diversity is an important concept used to describe turnover in species composition across a wide range of spatial and temporal scales, and it underpins much of conservation theory and practice. Although substantial progress has been made in the mathematical and terminological treatment of different measures of beta diversity, there has been little conceptual synthesis of potential scale dependence of beta diversity with increasing spatial grain and geographic extent of sampling. Here, we evaluate different conceptual approaches to the spatial scaling of beta diversity, interpreted from ‘fixed’ and ‘varying’ perspectives of spatial grain and extent. We argue that a ‘sliding window’ perspective, in which spatial grain and extent covary, is an informative way to conceptualize community differentiation across scales. This concept more realistically reflects the varying empirical approaches that researchers adopt in field sampling and the varying scales of landscape perception by different organisms. Scale dependence in beta diversity has broad implications for emerging fields in ecology and biogeography, such as the integration of fine‐resolution ecogenomic data with large‐scale macroecological studies, as well as for guiding appropriate management responses to threats to biodiversity operating at different spatial scales. 相似文献
44.
Audrey Schlernitzauer Catherine Oiry Raphael Hamad Simon Galas Fabienne Cortade Béatrice Chabi Fran?ois Casas Laurence Pessemesse Gilles Fouret Christine Feillet-Coudray Gérard Cros Gérard Cabello Richard Magous Chantal Wrutniak-Cabello 《PloS one》2013,8(11)
Chicoric acid (CA) is a caffeoyl derivative previously described as having potential anti-diabetic properties. As similarities in cellular mechanism similarities between diabetes and aging have been shown, we explored on L6 myotubes the effect of CA on the modulation of intracellular pathways involved in diabetes and aging. We also determined its influence on lifespan of Caenorhabditis elegans worm (C. elegans). In L6 myotubes, CA was a potent reactive oxygen species (ROS) scavenger, reducing ROS accumulation under basal as well as oxidative stress conditions. CA also stimulated the AMP-activated kinase (AMPK) pathway and displayed various features associated with AMPK activation: CA (a) enhanced oxidative enzymatic defences through increase in glutathion peroxidase (GPx) and superoxide dismutase (SOD) activities, (b) favoured mitochondria protection against oxidative damage through up-regulation of MnSOD protein expression, (c) increased mitochondrial biogenesis as suggested by increases in complex II and citrate synthase activities, along with up-regulation of PGC-1α mRNA expression and (d) inhibited the insulin/Akt/mTOR pathway. As AMPK stimulators (e.g. the anti-diabetic agent meformin or polyphenols such as epigallocatechingallate or quercetin) were shown to extend lifespan in C. elegans, we also determined the effect of CA on the same model. A concentration-dependant lifespan extension was observed with CA (5–100 μM). These data indicate that CA is a potent antioxidant compound activating the AMPK pathway in L6 myotubes. Similarly to other AMPK stimulators, CA is able to extend C. elegans lifespan, an effect measurable even at the micromolar range. Future studies will explore CA molecular targets and give new insights about its possible effects on metabolic and aging-related diseases. 相似文献
45.
Emmanuel S. Buys Yu-Chieh Ko Clemens Alt Sarah R. Hayton Alexander Jones Laurel T. Tainsh Ruiyi Ren Andrea Giani Maeva Clerté Emma Abernathy Robert E. T. Tainsh Dong-Jin Oh Rajeev Malhotra Pankaj Arora Nadine de Waard Binglan Yu Raphael Turcotte Daniel Nathan Marielle Scherrer-Crosbie Stephanie J. Loomis Jae H. Kang Charles P. Lin Haiyan Gong Douglas J. Rhee Peter Brouckaert Janey L. Wiggs Meredith S. Gregory Louis R. Pasquale Kenneth D. Bloch Bruce R. Ksander 《PloS one》2013,8(3)
Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. The molecular signaling involved in the pathogenesis of POAG remains unknown. Here, we report that mice lacking the α1 subunit of the nitric oxide receptor soluble guanylate cyclase represent a novel and translatable animal model of POAG, characterized by thinning of the retinal nerve fiber layer and loss of optic nerve axons in the context of an open iridocorneal angle. The optic neuropathy associated with soluble guanylate cyclase α1–deficiency was accompanied by modestly increased intraocular pressure and retinal vascular dysfunction. Moreover, data from a candidate gene association study suggests that a variant in the locus containing the genes encoding for the α1 and β1 subunits of soluble guanylate cyclase is associated with POAG in patients presenting with initial paracentral vision loss, a disease subtype thought to be associated with vascular dysregulation. These findings provide new insights into the pathogenesis and genetics of POAG and suggest new therapeutic strategies for POAG. 相似文献
46.
47.
Mieczyslaw Torchala Tereza Gerguri Raphael A. G. Chaleil Patrick Gordon Francis Russell Miriam Keshani Paul A. Bates 《Proteins》2020,88(8):962-972
The formation of specific protein-protein interactions is often a key to a protein's function. During complex formation, each protein component will undergo a change in the conformational state, for some these changes are relatively small and reside primarily at the sidechain level; however, others may display notable backbone adjustments. One of the classic problems in the protein-docking field is to be able to a priori predict the extent of such conformational changes. In this work, we investigated three protocols to find the most suitable input structure conformations for cross-docking, including a robust sampling approach in normal mode space. Counterintuitively, knowledge of the theoretically best combination of normal modes for unbound-bound transitions does not always lead to the best results. We used a novel spatial partitioning library, Aether Engine (see Supplementary Materials ), to efficiently search the conformational states of 56 receptor/ligand pairs, including a recent CAPRI target, in a systematic manner and selected diverse conformations as input to our automated docking server, SwarmDock, a server that allows moderate conformational adjustments during the docking process. In essence, here we present a dynamic cross-docking protocol, which when benchmarked against the simpler approach of just docking the unbound components shows a 10% uplift in the quality of the top docking pose. 相似文献
48.
Resolving the polymorphism-in-probe problem is critical for correct interpretation of expression QTL studies 总被引:1,自引:0,他引:1
Adaikalavan Ramasamy Daniah Trabzuni J. Raphael Gibbs Allissa Dillman Dena G. Hernandez Sampath Arepalli Robert Walker Colin Smith Gigaloluwa Peter Ilori Andrey A. Shabalin Yun Li Andrew B. Singleton Mark R. Cookson for NABEC John Hardy for UKBEC Mina Ryten Michael E. Weale 《Nucleic acids research》2013,41(7):e88
49.
Jessica E. Lisle Inga Mertens-Walker Raphael Rutkowski Adrian C. Herington Sally-Anne Stephenson 《生物化学与生物物理学报:癌评论》2013
Although at present, there is a high incidence of prostate cancer, particularly in the Western world, mortality from this disease is declining and occurs primarily only from clinically significant late stage tumors with a poor prognosis. A major current focus of this field is the identification of new biomarkers which can detect earlier, and more effectively, clinically significant tumors from those deemed “low risk”, as well as predict the prognostic course of a particular cancer. This strategy can in turn offer novel avenues for targeted therapies. The large family of Receptor Tyrosine Kinases, the Ephs, and their binding partners, the ephrins, has been implicated in many cancers of epithelial origin through stimulation of oncogenic transformation, tumor angiogenesis, and promotion of increased cell survival, invasion and migration. They also show promise as both biomarkers of diagnostic and prognostic value and as targeted therapies in cancer. This review will briefly discuss the complex roles and biological mechanisms of action of these receptors and ligands and, with regard to prostate cancer, highlight their potential as biomarkers for both diagnosis and prognosis, their application as imaging agents, and current approaches to assessing them as therapeutic targets. This review demonstrates the need for future studies into those particular family members that will prove helpful in understanding the biology and potential as targets for treatment of prostate cancer. 相似文献
50.
Joachin D. Gbenou Judith F. Ahounou Huguette B. Akakpo Anatole Laleye Eléonore Yayi Fernand Gbaguidi Lamine Baba-Moussa Raphael Darboux Pierre Dansou Mansourou Moudachirou Simeon O. Kotchoni 《Molecular biology reports》2013,40(2):1127-1134
Cymbopogon citratus and Eucalyptus citriodora are widely used herbs/plants as a source of ethnomedicines in tropical regions of the world. In this work, we studied the anti-inflammatory and gastroprotective effects of C. citratus and E. citriodora essential oils on formol-induced edema, and acetic acid induced abdominal cramps in Wistar rats. To fully understand the chemically induced anti-inflammatory properties of these plants, we first analyzed the chemical composition of the essential oils. A total of 16 chemical constituents accounting for 93.69 % of the oil, were identified in C. citratus among which, Geranial (27.04 %), neral (19.93 %) and myrcene (27.04 %) were the major constituents. For E. citriodora, 19 compounds representing 97.2 % of the extracted oil were identified. The dominant compound of E. citriodora essential oil was citronellal (83.50 %). In vivo analysis and histological assay showed that the two essential oils displayed significant dose dependent edema inhibition effect over time. They displayed strong analgesic and antipyretic properties similar to that induced by 50 mg/kg of acetylsalicylate of lysine. However, the E. citriodora essential oil was more effective than that of C. citratus. We identified significant numbers of aldehyde molecules in both essential oils mediating antioxidant activity that may contribute to the anti-inflammatory effects observed on the rats. Altogether, this work demonstrates the anti-inflammatory property of C. citratus and E. citriodora suggesting their potential role as adjuvant therapeutic alternatives in dealing with inflammatory-related diseases. 相似文献