Cyclooxygenase Inhibition Limits Blood-Brain Barrier Disruption following Intracerebral Injection of Tumor Necrosis Factor-alpha in the Rat

Increased permeability of the blood-brain barrier (BBB) is important in neurological disorders. Neuroinflammation is associated with increased BBB breakdown and brain injury. Tumor necrosis factor-alpha (TNF-a) is involved in BBB injury and edema formation through a mechanism involving matrix metalloproteinase (MMP) upregulation. There is emerging evidence indicating that cyclooxygenase (COX) inhibition limits BBB disruption following ischemic stroke and bacterial meningitis, but the mechanisms involved are not known. We used intracerebral injection of TNF-a to study the effect of COX inhibition on TNF-a-induced BBB breakdown, MMP expression/activity and oxidative stress. BBB disruption was evaluated by the uptake of 14C-sucrose into the brain and by magnetic resonance imaging (MRI) utilizing Gd-DTPA as a paramagnetic contrast agent. Using selective inhibitors of each COX isoform, we found that COX-1 activity is more important than COX-2 in BBB opening. TNF-a induced a significant upregulation of gelatinase B (MMP-9), stromelysin-1 (MMP-3) and COX-2. In addition, TNF-a significantly depleted glutathione as compared to saline. Indomethacin (10 mg/kg; i.p.), an inhibitor of COX-1 and COX-2, reduced BBB damage at 24 h. Indomethacin significantly attenuated MMP-9 and MMP-3 expression and activation, and prevented the loss of endogenous radical scavenging capacity following intracerebral injection of TNF-a. Our results show for the first time that BBB disruption during neuroinflammation can be significantly reduced by administration of COX inhibitors. Modulation of COX in brain injury by COX inhibitors or agents modulating prostaglandin E2 formation/signaling may be useful in clinical settings associated with BBB disruption

Identification, Characterization, and Expression of a Novel P450 Gene Encoding CYP6AE25 from the Asian Corn Borer, Ostrinia furnacalis

An allele of the cytochrome P450 gene, CYP6AE14, named CYP6AE25 (GenBank accession no. EU807990) was isolated from the Asian com borer, Ostrinia fumacalis (Guenée) (Lepidoptera: Pyralidae) by RT-PCR. The cDNA sequence of CYP6AE25 is 2315 bp in length and contains a 1569 nucleotides open reading frame encoding a putative protein with 523 amino acid residues and a predicted molecular weight of 59.95 kDa and a theoretical pI of 8.31. The putative protein contains the classic heme-binding sequence motif F××G×××C×G (residues 451–460) conserved among all P450 enzymes as well as other characteristic motifs of all cytochrome P450s. It shares 52% identity with the previously published sequence of CYP6AE14 (GenBank accession no. DQ986461) from Helicoverpa armigera. Phylogenetic analysis of amino acid sequences from members of various P450 families indicated that CYP6AE25 has a closer phylogenetic relationship with CYP6AE14 and CYP6B1 that are related to metabolism of plant allelochemicals, CYP6D1 which is related to pyrethroid resistance and has a more distant relationship to CYP302A1 and CYP307A1 which are related to synthesis of the insect molting hormones. The expression level of the gene in the adults and immature stages of O. furnacalis by quantitative real-time PCR revealed that CYP6AE25 was expressed in all life stages investigated. The mRNA expression level in 3rd instar larvae was 12.8- and 2.97-fold higher than those in pupae and adults, respectively. The tissue specific expression level of CYP6AE25 was in the order of midgut, malpighian tube and fatty body from high to low but was absent in ovary and brain. The analysis of the CYP6AB25 gene using bioinformatic software is discussed

Eco-friendly one-pot synthesis of Prussian blue-embedded magnetic hydrogel beads for the removal of cesium from water

A simple one-step approach to fabricating Prussian blue-embedded magnetic hydrogel beads (PBMHBs) was fabricated for the effective magnetic removal of radioactive cesium (Cs-137) from water. Through the simple dropwise addition of a mixed aqueous solution of iron salts, commercial PB and polyvinyl alcohol (PVA) to an ammonium hydroxide (NH4OH) solution, the formation of hydrogel beads and the encapsulation of PB in beads were achieved in one pot through the gelation of PVA with in situ-formed iron oxide nanoparticles as the cross-linker. The obtained PB-MHBs, with 43.77 weight %of PB, were stable without releasing PB for up to 2 weeks and could be effectively separated from aqueous solutions by an external magnetic field, which is convenient for the large-scale treatment of Cs-contaminated water. Detailed Cs adsorption studies revealed that the adsorption isotherms and kinetics could be effectively described by the Langmuir isotherm model and the pseudo-second-order model, respectively. Most importantly, the PB-MHBs exhibited excellent selectivity for Cs-137 in (137)Cscontaminated simulated groundwater (55 Bq/g) with a high removal efficiency (>99.5%), and the effective removal of Cs-137 from real seawater by these PB-MHBs demonstrated the excellent potential of this material for practical application in the decontamination of Cs-137-contaminated seawate

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC

Generation of Reactive Oxygen Species by Polyenylpyrroles Derivatives Causes DNA Damage Leading to G2/M Arrest and Apoptosis in Human Oral Squamous Cell Carcinoma Cells

10.1371/journal.pone.0067603PLoS ONE86-POLN

Automatic Detection and Classification of Breast Tumors in Ultrasonic Images Using Texture and Morphological Features

Due to severe presence of speckle noise, poor image contrast and irregular lesion shape, it is challenging to build a fully automatic detection and classification system for breast ultrasonic images. In this paper, a novel and effective computer-aided method including generation of a region of interest (ROI), segmentation and classification of breast tumor is proposed without any manual intervention. By incorporating local features of texture and position, a ROI is firstly detected using a self-organizing map neural network. Then a modified Normalized Cut approach considering the weighted neighborhood gray values is proposed to partition the ROI into clusters and get the initial boundary. In addition, a regional-fitting active contour model is used to adjust the few inaccurate initial boundaries for the final segmentation. Finally, three textures and five morphologic features are extracted from each breast tumor; whereby a highly efficient Affinity Propagation clustering is used to fulfill the malignancy and benign classification for an existing database without any training process. The proposed system is validated by 132 cases (67 benignancies and 65 malignancies) with its performance compared to traditional methods such as level set segmentation, artificial neural network classifiers, and so forth. Experiment results show that the proposed system, which needs no training procedure or manual interference, performs best in detection and classification of ultrasonic breast tumors, while having the lowest computation complexity

Star forming dwarf galaxies

Star forming dwarf galaxies (SFDGs) have a high gas content and low metallicities, reminiscent of the basic entities in hierarchical galaxy formation scenarios. In the young universe they probably also played a major role in the cosmic reionization. Their abundant presence in the local volume and their youthful character make them ideal objects for detailed studies of the initial stellar mass function (IMF), fundamental star formation processes and its feedback to the interstellar medium. Occasionally we witness SFDGs involved in extreme starbursts, giving rise to strongly elevated production of super star clusters and global superwinds, mechanisms yet to be explored in more detail. SFDGs is the initial state of all dwarf galaxies and the relation to the environment provides us with a key to how different types of dwarf galaxies are emerging. In this review we will put the emphasis on the exotic starburst phase, as it seems less important for present day galaxy evolution but perhaps fundamental in the initial phase of galaxy formation.Comment: To appear in JENAM Symposium "Dwarf Galaxies: Keys to Galaxy Formation and Evolution", P. Papaderos, G. Hensler, S. Recchi (eds.). Lisbon, September 2010, Springer Verlag, in pres

A Spatial Analysis of County-level Variation in Syphilis and Gonorrhea in Guangdong Province, China

Sexually transmitted infections (STI) have made a resurgence in many rapidly developing regions of southern China, but there is little understanding of the social changes that contribute to this spatial distribution of STI. This study examines county-level socio-demographic characteristics associated with syphilis and gonorrhea in Guangdong Province.This study uses linear regression and spatial lag regression to determine county-level (n = 97) socio-demographic characteristics associated with a greater burden of syphilis, gonorrhea, and a combined syphilis/gonorrhea index. Data were obtained from the 2005 China Population Census and published public health data. A range of socio-demographic variables including gross domestic product, the Gender Empowerment Measure, standard of living, education level, migrant population and employment are examined. Reported syphilis and gonorrhea cases are disproportionately clustered in the Pearl River Delta, the central region of Guangdong Province. A higher fraction of employed men among the adult population, higher fraction of divorced men among the adult population, and higher standard of living (based on water availability and people per room) are significantly associated with higher STI cases across all three models. Gross domestic product and gender inequality measures are not significant predictors of reported STI in these models.Although many ecological studies of STIs have found poverty to be associated with higher reported STI, this analysis found a greater number of reported syphilis cases in counties with a higher standard of living. Spatially targeted syphilis screening measures in regions with a higher standard of living may facilitate successful control efforts. This analysis also reinforces the importance of changing male sexual behaviors as part of a comprehensive response to syphilis control in China

Long-Term Mortality of Patients with Septic Ocular or Central Nervous System Complications from Pyogenic Liver Abscess: A Population-Based Study

Background: Taiwan is endemic for pyogenic liver abscess (PLA). Septic ocular or central nervous system (CNS) complications derived from PLA can result in catastrophic disability. We investigated the epidemiology and long-term prognosis of PLA patients with septic ocular or CNS complications over an 8-year period. Methodology/Principal Findings: We extracted 21,307 patients with newly diagnosed PLA from a nationwide health registry in Taiwan between 2000 and 2007. The frequency of and risk factors for PLA with septic ocular or CNS complications were determined. The 2-year survival of these patients was compared between those with and without septic ocular or CNS complications. Septic ocular or CNS complications accounted for 2.1 % of all PLA patients. Age and the Charlson comorbidity index were significantly lower in PLA patients with ocular or CNS complications than those without. Diabetes and age,65 years were independent predictors of septic ocular or CNS complications. The 2-year mortality of patients with septic ocular or CNS complications was similar to those without complications (24.8 % vs. 27.5%, p = 0.502). However, among patients,65 years old and a Charlson index #1, the 2-year mortality was significantly higher in those with than without complications (18.6 % vs. 11.8%, p = 0.001). Conclusions/Significance: Physicians should recognize that catastrophic disability due to ocular or neurologica

Hydrogen Sulfide Protects HUVECs against Hydrogen Peroxide Induced Mitochondrial Dysfunction and Oxidative Stress

10.1371/journal.pone.0053147PLoS ONE82