Bioactividad de los extractos y aislamiento de los lignanos de las semillas de Centaurea dealbata

Centaurea dealbata Willd. (Family: Asteraceae) belongs to the big genus Centaurea that comprises ca. 500 species. Then-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the seeds of C. dealbata have been assessed forantioxidant activity and general toxicity using, respectively, the DPPH assay, and the brine shrimp lethality assay. Boththe DCM and the MeOH extract showed signifi cant levels of antioxidant activities with an RC50 value 6.8 x 10-2 and4.7 x 10-2 mg/mL, respectively. None of the extracts exhibited any signifi cant general toxicity (LD50 = >1000 mg/mL).Three major bioactive components of the MeOH extract were found to be the lignans, arctigenin, arctiin and matairesinoside.The structures of these lignans were elucidated by comprehensive spectroscopic analyses, and also by directcomparison with the respective published data. This is the fi rst report on the occurrence of arctiin and matairesionl inC. dealbata. The distribution of these lignans within the genus Centaurea has also been presented.La Centaurea dealbata Willd. (familia: Asteraceae) pertenece al género Centaurea, que comprende unas 500 especies.Para evaluar la actividad antioxidante y la toxicidad general de los extractos de n-hexano, diclorometano (DCM)y metanol (MeOH) de las semillas de C. dealbata se han utilizado, respectivamente, el ensayo DPPH y el ensayo deletalidad de gambas en salmuera. Tanto el extracto de DCM como el de MeOH presentaron niveles signifi cativosde actividad antioxidante, con valores de RC50 de 6,8 x 10-2 y 4,7 x 10-2 mg/mL, respectivamente. Ninguno de losextractos presentó una toxicidad general signifi cativa (LD50 = >1000 mg/mL). Se observó que los tres principalescomponentes bioactivos del extracto de MeOH fueron los lignanos arctigenina, arctiina y matairesinosida. Lasestructuras de estos lignanos se dilucidaron mediante análisis espectroscópicos exhaustivos y comparación directacon los datos respectivos publicados. Éste es el primer informe sobre la ocurrencia de arctiina y matairesinol en C.dealbata. También se presenta la distribución de estos lignanos dentro del género Centaurea

Inhibition of constitutive and cxc-chemokine-induced NF-κB activity potentiates ansamycin-based HSP90-inhibitor cytotoxicity in castrate-resistant prostate cancer cells

Background: We determined how CXC-chemokine signalling and necrosis factor-B (NF-B) activity affected heat-shock protein 90 (Hsp90) inhibitor (geldanamycin (GA) and 17-allylamino-demethoxygeldanamycin (17-AAG)) cytotoxicity in castrate-resistant prostate cancer (CRPC).Methods:Geldanamycin and 17-AAG toxicity, together with the CXCR2 antagonist AZ10397767 or NF-B inhibitor BAY11-7082, was assessed by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay in two CRPC lines, DU145 and PC3. Flow cytometry quantified apoptotic or necrosis profiles. Necrosis factor-B activity was determined by luciferase readouts or indirectly by quantitative PCR and ELISA-based determination of CXCL8 expression.Results:Geldanamycin and 17-AAG reduced PC3 and DU145 cell viability, although PC3 cells were less sensitive. Addition of AZ10397767 increased GA (e.g., PC3 IC 20: from 1.670.4 to 0.180.2 nM) and 17-AAG (PC3 IC 20: 43.77.8 to 0.641.8 nM) potency in PC3 but not DU145 cells. Similarly, BAY11-7082 increased the potency of 17-AAG in PC3 but not in DU145 cells, correlating with the elevated constitutive NF-B activity in PC3 cells. AZ10397767 increased 17-AAG-induced apoptosis and necrosis and decreased NF-B activity/CXCL8 expression in 17-AAG-treated PC3 cells.Conclusion:Ansamycin cytotoxicity is enhanced by inhibiting NF-B activity and/or CXC-chemokine signalling in CRPC cells. Detecting and/or inhibiting NF-B activity may aid the selection and treatment response of CRPC patients to Hsp90 inhibitors.</p

A H-1 magnetic resonance spectroscopy study of aging in parietal white matter: implications for trials in multiple sclerosis

H-1 magnetic resonance spectroscopy (MRS) provides a unique tool to detect and quantify brain metabolites. In multiple sclerosis it can be used to investigate axonal loss or dysfunction through measurement of N-acetyl aspartate (NAA), a neuronal marker. Previous studies in adults have reported variable effects of aging on metabolite concentrations but have predominantly focused on changes in the elderly. This study has examined a younger adult age group to provide a reference database more applicable to the multiple sclerosis population. Single voxel H-1 MRS was carried out in 44 subjects between 22 and 62 years of age. Sixteen subjects underwent repeat examination after one year. Absolute concentrations of NA (the sum of NAA and N-acetyl aspartate glutamate), NAA, creatine/phosphocreatine (Cr), choline containing compounds (Cho) and myo-inositol (mI) were measured. NA, NAA and mI concentrations did not correlate with age but there were significant correlations between age and Cr (r = 0.43, p = 0.004) and Cho (r = 0.38, p = 0.011) concentrations. No significant differences in metabolite concentrations were seen over one year. This study provides evidence that age-related changes of metabolite concentrations occur even in a young to middle aged adult population. This emphasizes the need to perform absolute quantification of metabolite concentrations rather than ratios and the importance of age-matching in H-1 MRS studies of multiple sclerosis. (C) 2000 Elsevier Science Inc. All rights reserved

Microscopic role of carbon on MgB2 wire for critical current density comparable to NbTi

Increasing dissipation-free supercurrent has been the primary issue for practical application of superconducting wires. For magnesium diboride, MgB2, carbon is known to be the most effective dopant to enhance high-field properties. However, the critical role of carbon remains elusive, and also low-field critical current density has not been improved. Here, we have undertaken malic acid doping of MgB2 and find that the microscopic origin for the enhancement of high-field properties is due to boron vacancies and associated stacking faults, as observed by high-resolution transmission electron microscopy and electron energy loss spectroscopy. The carbon from the malic acid almost uniformly encapsulates boron, preventing boron agglomeration and reducing porosity, as observed by three-dimensional X-ray tomography. The critical current density either exceeds or matches that of niobium titanium at 4.2 K. Our findings provide atomic-level insights, which could pave the way to further enhancement of the critical current density of MgB2 up to the theoretical limit

Adenovirus Entry From the Apical Surface of Polarized Epithelia Is Facilitated by the Host Innate Immune Response

Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3β. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apicalepithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection