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Abstract Methanogens are used as catalysts for cathodes in microbial fuel cells, to reduce CO2 to CH4. However, the attachment of microbes to the electrodes via culturing is time‐consuming, and inadequate biofilm formation can lead to lesser surface area coverage, resulting in reduced methane formation. This study aims to improve the production efficiency and performance of methanogen cathodes developed using 3D printing of bioink containing live methanogens. A progressive cavity pump is used for the 3D gel‐printing of methanogens and micro‐sized white charcoal particles into the desired structure. Despite the absence of anaerobic conditions during printing, the 3D‐printed cathodes with higher concentrations of microbial inoculum in the bioink produce more methane gas. Even with an unconcentrated inoculum, the methanogens multiply 800‐fold during incubation, resulting in increased methane gas production. The predominant methanogens in the electrodes included the hydrogenotrophic Methanobacterium spp. Therefore, the technique used in this study can be used to successfully develop 3D‐printed biocathodes catalyzed by methanogenic microbes with verifiable practical applicability. This study is the first to report the growth of methanogens and their methanogenic activity in 3D‐printed cathodes.

Background: It is still unclear whether optimal medical therapy (OMT) after percutaneous coronary intervention (PCI) has beneficial effects on long-term clinical outcomes in patients aged ≥80 years with coronary artery disease (CAD). Methods: This study analyzed the time to the first major adverse clinical event including death or nonfatal myocardial infarction (MI), for up to 3 years after PCI using multicenter registry data. Data for 1056 patients aged > 80 years successfully treated with PCI were included in the analysis. OMT was defined as a combination of antiplatelet drug, statin, beta-blocker, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker. Results: In total, 204 (19%) patients in this study received OMT and 852 (81%) received sub-OMT. During a median follow-up of 725 days, adverse clinical events occurred in 183 patients (death, n=177; nonfatal MI, n=6). Kaplan-Meier analysis showed that patients who received OMT had a lower probability of adverse clinical events than those who received sub-OMT (p

In 4D printing, structures with gradients in physical properties are 3D printed in order to dramatically increase deformation. For example, printing bilayer structures with passive and active layers has been proposed, however, these methods have the disadvantages that the material of each layer is mixed, and the modeling process is complicated. Herein, we present a method of creating gradient gels with different degrees of polymerization on the UV-exposed side and the other side using a single material by simply increasing the amount of initiator. This gel is the first example in which the differential swelling ratio between two sides causes the gradient to curl inward toward the UV-exposed side. The mechanical properties (swelling ratio and Young’s modulus) were measured at different material concentrations and structures, and the effects of each on deformation were analyzed and simulated. The results show that adding an initiator concentration of 0.2 (mol/L) or more causes deformation, that increasing the crosslinker concentration by a factor of three or more increases deformation, and that adding a hinge structure limits the gradient gel to deformation up to 90°. Thus, it was found that the maximum deformation can be predicted to some extent by simulation. In the future, we will be able to create complex structures while utilizing simulation.

In the tribology of mechanical elements using lubricating oil, verification of the dynamic surface pressure distribution during sliding operation is necessary in order to elucidate the sliding condition. The same also applies to the piston rings which are the sliding part of compression reciprocating device. Although some verification case in static condition or limited sliding area has been studied, there are many unknown aspects in this field. The thin-film sensor, since it has small influence on the shape of the sliding surface, is widely used as a measurement method of the sliding surface pressure between two different surfaces, however this method has never been applied to the piston ring in the past. In this study, various film deposition methods on the piston ring of the thin-film sensor were examined, and the thin-film pressure sensor with a total thickness of 4.6 μm was successfully formed on the sliding surface by sputtering. The surface pressure distribution of the sliding part was measured using the reciprocating sliding tester by this thin-film pressure sensor, and the measurement values were in good agreement with the mixed lubrication model between the piston ring and the cylinder liner.

Background A hallmark of heart failure is cardiac fibrosis, which results from the injury‐induced differentiation response of resident fibroblasts to myofibroblasts that deposit extracellular matrix. During myofibroblast differentiation, fibroblasts progress through polarization stages of early proinflammation, intermediate proliferation, and late maturation, but the regulators of this progression are poorly understood. Planar cell polarity receptors, receptor tyrosine kinase–like orphan receptor 1 and 2 (Ror1/2), can function to promote cell differentiation and transformation. In this study, we investigated the role of the Ror1/2 in a model of heart failure with emphasis on myofibroblast differentiation. Methods and Results The role of Ror1/2 during cardiac myofibroblast differentiation was studied in cell culture models of primary murine cardiac fibroblast activation and in knockout mouse models that underwent transverse aortic constriction surgery to induce cardiac injury by pressure overload. Expression of Ror1 and Ror2 were robustly and exclusively induced in fibroblasts in hearts after transverse aortic constriction surgery, and both were rapidly upregulated after early activation of primary murine cardiac fibroblasts in culture. Cultured fibroblasts isolated from Ror1/2 knockout mice displayed a proinflammatory phenotype indicative of impaired myofibroblast differentiation. Although the combined ablation of Ror1/2 in mice did not result in a detectable baseline phenotype, transverse aortic constriction surgery led to the death of all mice by day 6 that was associated with myocardial hyperinflammation and vascular leakage. Conclusions Together, these results show that Ror1/2 are essential for the progression of myofibroblast differentiation and for the adaptive remodeling of the heart in response to pressure overload.

A large quantity of imported unripe green banana of low quality is discarded, resulting in substantial waste of cropped resources. A novel banana powder (Banafine®) from unripe Cavendish bananas was formulated by α-amylase and protease treatments followed by yeast fermentation. Banafine® has a substantially improved taste as the bitter and astringent taste of unripe green banana was eliminated. Pertinently, Banafine® stimulated production of IFN-ɣ and TNF-α in cultured macrophages and improved phagocytosis. An in vivo study in a murine model showed that Banafine® stimulates cytokine production in splenocytes. Moreover, Banafine® fed mice were less affected by influenza A virus infection and exhibited better recovery rates compared to control mice. Further, an active fraction of Banafine® was partially purified followed by size-exclusion chromatography, obtain a 70 kDa macromolecule. This study unveiled the potential usage of unripe green banana as a functional food ingredient, which is valuable for sustainable agriculture.

Mouse hindlimb ischemia has been widely used as a model to study peripheral artery disease. Genetic modulation of the enzymatic source of oxidants or components of the antioxidant system reveal that physiological levels of oxidants are essential to promote the process of arteriogenesis and angiogenesis after femoral artery occlusion, although mice with diabetes or atherosclerosis may have higher deleterious levels of oxidants. Therefore, fine control of oxidants is required to stimulate vascularization in the limb muscle. Oxidants transduce cellular signaling through oxidative modifications of redox sensitive cysteine thiols. Of particular importance, the reversible modification with abundant glutathione, called S-glutathionylation (or GSH adducts), is relatively stable and alters protein function including signaling, transcription, and cytoskeletal arrangement. Glutaredoxin-1 (Glrx) is an enzyme which catalyzes reversal of GSH adducts, and does not scavenge oxidants itself. Glrx may control redox signaling under fluctuation of oxidants levels. In ischemic muscle increased GSH adducts through Glrx deletion improves in vivo limb revascularization, indicating endogenous Glrx has anti-angiogenic roles. In accordance, Glrx overexpression attenuates VEGF signaling in vitro and ischemic vascularization in vivo. There are several Glrx targets including HIF-1α which may contribute to inhibition of vascularization by reducing GSH adducts. These animal studies provide a caution that excess antioxidants may be counter-productive for treatment of ischemic limbs, and highlights Glrx as a potential therapeutic target to improve ischemic limb vascularization. Keywords: Ischemic limb, Angiogenesis, Oxidants, GSH adducts, Glutaredoxin

Background: Oxidative stress is implicated in increased vascular permeability associated with metabolic disorders, but the underlying redox mechanism is poorly defined. S-glutathionylation, a stable adduct of glutathione with protein sulfhydryl, is a reversible oxidative modification of protein and is emerging as an important redox signaling paradigm in cardiovascular physiopathology. The present study determines the role of protein S-glutathionylation in metabolic stress-induced endothelial cell permeability. Methods and results: In endothelial cells isolated from patients with type-2 diabetes mellitus, protein S-glutathionylation level was increased. This change was also observed in aortic endothelium in ApoE deficient (ApoE-/-) mice fed on Western diet. Metabolic stress-induced protein S-glutathionylation in human aortic endothelial cells (HAEC) was positively correlated with elevated endothelial cell permeability, as reflected by disassembly of cell-cell adherens junctions and cortical actin structures. These impairments were reversed by adenoviral overexpression of a specific de-glutathionylation enzyme, glutaredoxin-1 in cultured HAECs. Consistently, transgenic overexpression of human Glrx-1 in ApoE-/- mice fed the Western diet attenuated endothelial protein S-glutathionylation, actin cytoskeletal disorganization, and vascular permeability in the aorta. Mechanistically, glutathionylation and inactivation of Rac1, a small RhoGPase, were associated with endothelial hyperpermeability caused by metabolic stress. Glutathionylation of Rac1 on cysteine 81 and 157 located adjacent to guanine nucleotide binding site was required for the metabolic stress to inhibit Rac1 activity and promote endothelial hyperpermeability. Conclusions: Glutathionylation and inactivation of Rac1 in endothelial cells represent a novel redox mechanism of vascular barrier dysfunction associated with metabolic disorders.

Wavelength division multiplexing (WDM) technology transmits multiple optical communication channels in an optical fiber. Routing and wavelength assignment (RWA) problems on WDM network have widely attracted interest of many researchers. Recently, so called sub-wavelength paths which are smaller granular paths than the wavelength-paths are discussed. In this paper, we deal with the RWA problem with considering sub-wavelength assignment on optical networks. One of the purpose of our study is to investigate active rates for optical networks. We formulate a sub-wavelength path assignment problem maximizing accommodated traffic demands by integer programming and solve it by a cutting plane algorithm. Since, in actuality, RWA is done individually for each demand on the time when the demand occurs, we consider a greedy type on-line algorithm. Numerical experiments show the efficiency of our algorithms and give some observation for active rates. Moreover, we verify the efficiency of our greedy-type algorithm on realistic situations which follow 10/40/100 Gbps system used for the current communication on optical networks. Our experimental results conclude that the active rates are depending on the configurations of the underlying graphs, and that our greedy-type algorithm is efficient for several kinds of instances.

We report on the synergic effect of surfactants and chelating agents on the mechanism to remove stubborn keratin grime (keratin-Ca), which is bound with calcium ions and one of the most difficult grimes to remove, in order to make it easier to clean bathtubs in less time and with less scrubbing. Our approach was to focus on keratin swelling, which we achieved by applying aqueous solutions with chelating agents and anionic surfactants, the combination of which greatly improved the swelling ratio, resulting in quick, easy removal of keratin-Ca with water rinsing and little scrubbing. For the swelling process, we added chelating agents and anionic surfactants to swell the keratin-Ca by both capturing calcium ions and improving solution permeation. Furthermore, we measured the structural change of the keratin-Ca during swelling by TD-NMR and confirmed that a certain combination of chelating agent and anionic surfactant improved swelling by affecting not only the amorphous part such as the keratin matrix, but also the crystalline part such as the intermediate filaments (IFs). [ABSTRACT FROM AUTHOR]

In this study, we synthesized hierarchical CuO nanoleaves in large-quantity via the hydrothermal method. We employed different techniques to characterize the morphological, structural, optical properties of the as-prepared hierarchical CuO nanoleaves sample. An electrochemical based nonenzymatic glucose biosensor was fabricated using engineered hierarchical CuO nanoleaves. The electrochemical behavior of fabricated biosensor towards glucose was analyzed with cyclic voltammetry (CV) and amperometry (i-t) techniques. Owing to the high electroactive surface area, hierarchical CuO nanoleaves based nonenzymatic biosensor electrode shows enhanced electrochemical catalytic behavior for glucose electro-oxidation in 100 mM sodium hydroxide (NaOH) electrolyte. The nonenzymatic biosensor displays a high sensitivity (1467.32 µA/(mM cm²)), linear range (0.005-5.89 mM), and detection limit of 12 nM (S/N = 3). Moreover, biosensor displayed good selectivity, reproducibility, repeatability, and stability at room temperature over three-week storage period. Further, as-fabricated nonenzymatic glucose biosensors were employed for practical applications in human serum sample measurements. The obtained data were compared to the commercial biosensor, which demonstrates the practical usability of nonenzymatic glucose biosensors in real sample analysis. [ABSTRACT FROM AUTHOR]

ADOC, Abu Dhabi Oil Co., Ltd. (Japan), marks another historical milestone with the commencement of oil production from a new oil field in November 2017. ADOC was established in 1968, and since then has been conducting stable operations through utilization of the best production technology that fully copes with the environment protection rules and regulations. The new oil field was granted as an additional oil field to its existing three oil fields when ADOC renewed its concession agreement in December 2012. Soon after the renewal of the concession, ADOC launched the new oil field development activities. The development plan of the field consisted of; 3D seismic acquisition, subsurface studies, drilling of appraisal wells and production wells, dredging of a channel and construction of the new artificial island and surface facilities. This paper will summarize the various challenges of field development in an environmentally sensitive area and the measures that were implemented. [ABSTRACT FROM AUTHOR]

ADOC, Abu Dhabi Oil Co., Ltd. (Japan), has been operating three oil fields offshore Abu Dhabi for more than 45 years. Recently, ADOC developed and commenced production from an oil field located in a Marine Protected Area, an area designated as a Biosphere Reserve by the UNESCO Secretariat. Therefore, special environmental measures were considered for the development of the field. The development plan of the field consisted of; 3D seismic acquisition, subsurface studies, zero discharge operations, dredging of a channel and construction of artificial island and surface facilities. This paper will summarize the various challenges of field development in an environmentally sensitive area, the measures that were implemented and the lessons learnt. [ABSTRACT FROM AUTHOR]

Murine membrane-bound phospholipase A2 receptor 1 (PLA2R) is shed and released into plasma in a soluble form that retains all of the extracellular domains. Relatively little is known about human PLA2R. This study examined whether human soluble PLA2R has biological functions and whether soluble PLA2R exists in human plasma. Here, we showed that human recombinant soluble PLA2R (rsPLA2R) bound to collagen-I and inhibited interaction of collagen-I with the extracellular domain of integrin 1 on the cell surface of human embryonic kidney 293 (HEK293) cells. As a result, rsPLA2R suppressed integrin 1-mediated migratory responses of HEK293 cells to collagen-I in Boyden chamber experiments. Inhibition of phosphorylation of FAK Tyr397 was also observed. Similar results were obtained with experiments using soluble PLA2R released from HEK293 cells transfected with a construct encoding human soluble PLA2R. rsPLA2R lacking the fibronectin-like type II (FNII) domain had no inhibitory effects on cell responses to collagen-I, suggesting an important role of the FNII domain in the interaction of rsPLA2R with collagen-I. In addition, rsPLA2R suppressed the migratory response to collagen-IV and binding of collagen-IV to the cell surface of human podocytes that endogenously express membranebound, full-length PLA2R. Immunoprecipitation and Western blotting showed the existence of immunoreactive PLA2R in human plasma. In conclusion, human recombinant soluble PLA2R inhibits integrin 1- mediated cell responses to collagens. Further studies are warranted to elucidate whether immunoreactive PLA2R in human plasma has the same properties as rsPLA2R. [ABSTRACT FROM AUTHOR]

We describe a case of choroid plexus carcinoma arising in the cerebrum of a 7-weekold male Sprague-Dawley rat. The tumor mass occupied the right lateral ventricle of the cerebrum. Histological analyses revealed that the epithelial tumor cells had proliferated in tubular, cribriform, papillary and solid growth patterns in the vicinity of the choroid plexus, with slight invasion into the cerebrum parenchyma. We divided the tumor cells into cuboidal, elongated and intermediate cells. Immunohistochemical studies showed that these tumor cells expressed relatively high levels of cytokeratin AE1/AE3, vimentin and glial fibrillary acidic proteins and low levels of nestin, oligodendrocyte transcription factor and doublecortin proteins. The present case was diagnosed as a choroid plexus carcinoma with neuronal and glial differentiation. [ABSTRACT FROM AUTHOR]

Reactive oxygen species (ROS) are increased in ischemic tissues and necessary for revascularization; however, the mechanism remains unclear. Exposure of cysteine residues to ROS in the presence of glutathione (GSH) generates GSH-protein adducts that are specifically reversed by the cytosolic thioltransferase, glutaredoxin-1 (Glrx). Here, we show that a key angiogenic transcriptional factor hypoxiainducible factor (HIF)-1α is stabilized by GSH adducts, and the genetic deletion of Glrx improves ischemic revascularization. In mouse muscle C2C12 cells, HIF-1α protein levels are increased by increasing GSH adducts with cell-permeable oxidized GSH (GSSG-ethyl ester) or 2-acetylamino-3-[4-(2-acetylamino-2-carboxyethylsulfanyl thiocarbonylamino) phenylthiocarbamoylsulfanyl] propionic acid (2-AAPA), an inhibitor of glutathione reductase. A biotin switch assay shows that GSSG-ester-induced HIF-1α contains reversibly modified thiols, and MS confirms GSH adducts on Cys520 (mouse Cys533). In addition, an HIF-1α Cys520 serine mutant is resistant to 2-AAPA-induced HIF-1α stabilization. Furthermore, Glrx overexpression prevents HIF-1α stabilization, whereas Glrx ablation by siRNA increases HIF-1α protein and expression of downstream angiogenic genes. Blood flow recovery after femoral artery ligation is significantly improved in Glrx KO mice, associated with increased levels of GSH-protein adducts, capillary density, vascular endothelial growth factor (VEGF)-A, and HIF- 1α in the ischemic muscles. Therefore, Glrx ablation stabilizes HIF-1α by increasing GSH adducts on Cys520 promoting in vivo HIF-1α stabilization, VEGF-A production, and revascularization in the ischemic muscles. [ABSTRACT FROM AUTHOR]

The role of stromal cell-derived factor-1α (SDF-1α) expressed in infarcted myocardium is unknown in humans. We examined whether SDF-1α produced in an infarcted myocardial lesion may play a role in left ventricle (LV) remodeling and dysfunction in patients with acute myocardial infarction (AMI). We measured SDF-1α levels in plasma obtained from aortic root (AO) and anterior interventricular vein (AIV) in the early phase (2 wk after MI) and the chronic phase (6 mo after MI) in 80 patients with anterior MI. An increment in SDF-1α level from AO to AIV, reflecting SDF-1α release from infarcted myocardium, was more frequent in patients with MI in the early phase of MI [n = 52 (65%), P = 0.03] but not in the chronic phase of MI [n = 46 (58%), P = 0.11] compared with that in control patients [n = 6/17 (35%)]. On linear regression analysis, the transmyocardial gradient in SDF-1α level in the chronic phase of MI was correlated with percentage changes in LV end-diastolic volume index (r = 0.39, P < 0.001), LV end-systolic volume index (r = 0.38, P < 0.001), and LV ejection fraction (r = -0.26, P = 0.01) 6 mo after AMI. By contrast, the transmyocardial gradient of SDF-1α in the early phase of MI had no significant correlations. In conclusion, the production of SDF-1α in infarcted myocardium in the chronic phase of MI was associated with LV adverse remodeling and progressive dysfunction in AMI survivors. [ABSTRACT FROM AUTHOR]

Localized oscillations in finite mass-spring chains, driven sinusoidally at one end with the other fixed, are studied numerically. It is assumed that the restoring force of the spring is given by a piecewise linear function of a relative displacement between neighbouring masses, i.e. a spring constant changes at a threshold of the displacement. Linear damping proportional to the velocity of the mass is taken into account. The mass at one end is forced to be displaced in the direction of the chains at a frequency above the cut-off frequency. It is shown that when the amplitude exceeds the threshold, localized oscillations are excited intermittently at the driving end and propagated down the chain at a constant speed. [ABSTRACT FROM AUTHOR]

The hydrogel with shape memory was synthesized and investigated for possible biomedical science applications. The mechanical and optical properties of the chemically cross-linked shape memory hydrogel prepared from N,N-dimethyl acrylamide (DMAAm) and a crystalline monomer (i.e., stearyl acrylate (SA)) with varying concentrations of DMAAm were studied. The elastic modulus depends on the hydrophobic crystalline components. The refractive index exhibits an inverse relationship with the degree of swelling. Due to the transparency, high refractive index and high mechanical strength, the experimental results indicate the potential for use in biomedical applications. [ABSTRACT FROM AUTHOR]

Background and purpose: Measurement of either flow-mediated endothelium-dependent dilatation (FMD) of the brachial artery, brachial-ankle pulse wave velocity (baPWV), or intima-media thickness (IMT) of the carotid artery is useful for risk assessment of future cardiovascular events. This study examined whether combination of these vascular parameters may have an additive effect on the ability of traditional risk factors to predict coronary events in patients with chronic coronary artery disease (CAD). Methods: Patients (n = 923) with stable CAD had measurements of FMD, baPWV, and maximum IMT (maxIMT), and were prospectively followed up for <8.5 years or until a coronary event - cardiac death, non-fatal myocardial infarction (MI) or unstable angina pectoris (uAP) requiring unplanned coronary revascularization. Results: During the follow-up period, 116 events occurred (29 cardiac deaths, 46 non-fatal MIs and 41 cases of uAP). A multivariate Cox proportional hazards analysis showed that FMD (HR 0.50, 95% CI 0.38-0.66) and baPWV (HR 1.52, 95% CI 1.27-1.82) but not maxIMT were significant predictors of coronary events. Based on the concordance statistics, the predictive value of traditional risk factors [area under the receiver operating characteristic curve (AUC), 0.67] was increased more by the addition of FMD and baPWV combined (AUC, 0.75) compared with the addition of either maxIMT, FMD, or baPWV alone, or the combination of maxIMT and FMD or maxIMT and baPWV (AUC, 0.67, 0.71, 0.71, 0.71 and 0.71, respectively). Conclusions: The combined addition of FMD and baPWV to the risk assessment algorithms may be useful for risk stratification of chronic CAD patients. [ABSTRACT FROM AUTHOR]

Group IV A cytosolic phospholipase A2 (cPLA2α), which preferentially cleaves arachidonic acid from phospholipids, plays a role in apoptosis and tissue injury. Downstream signals in response to tumor necrosis factor (TNF)-α, a mediator of myocardial ischemia-reperfusion (I/R) injury, involve cPLA2α activation. This study examined the potential role of cPLA2α and its mechanistic link with TNF-α in myocardial I/R injury using cPLA2α knockout (cPLA2α-/-) mice. Myocardial I/R was created with 10-wk-old male mice by 1 h ligation of the left anterior descending coronary artery, followed by 24 h of reperfusion. As a result, compared with wild-type (cPLA2α+/+) mice, cPLA2α-/- mice had a 47% decrease in myocardial infarct size, preservation of echocardiographic left ventricle (LV) function (%fractional shortening: 14 vs. 21%, respectively), and lower content of leukotriene B4 and thromboxane B2 (62 and 50% lower, respectively) in the ischemic myocardium after I/R. Treatment with the TNF-α inhibitor (soluble TNF receptor II/IgG1 Fc fusion protein, sTNFR:Fc) decreased myocardial I/R injury and LV dysfunction in cPLA2α+/+ mice but not cPLA2α-/- mice. sTNFR:Fc also suppressed cPLA2α phosphorylation in the ischemic myocardium after I/R of cPLA2α+/+ mice. Similarly, sTNFR:Fc exerted protective effects against hypoxia-reoxygenation (H/R)-induced injury in the cultured cardiomyocytes from cPLA2α+/+ mice but not cPLA2α-/- cardiomyocytes. H/R and TNF-α induced cPLA2α phosphorylation in cPLA2α+/+ cardiomyocytes, which was reversible by sTNFR:Fc. In cPLA2α-/- cardiomyocytes, TNF-α induced apoptosis and release of arachidonic acid to a lesser extent than in cPLA2α+/+ cardiomyocytes. In conclusion, disruption of cPLA2α attenuates myocardial I/R injury partly through inhibition of TNF-α-mediated pathways. [ABSTRACT FROM AUTHOR]

Group X secretory PLA2 (sPLA2-X) is expressed in neutrophils and plays a role in the pathogenesis of neutrophil-mediated tissue inflammation and injury. This study tested the hypothesis that sPLA2-X in neutrophils may contribute to the pathogenesis of abdominal aortic aneurysms (AAA) using sPLA2-X-/- mice. AAA was created by application of CaCl2 to external surface of aorta. As a result, the aortas of sPLA2- X-/- mice had smaller diameters (percent increase from baseline; 24.8 ± 3.5% vs. 49.9 ± 9.1%, respectively; P < 0.01), a reduced grade of elastin degradation, and lower activities of elastase and gelatinase (26% and 19% lower, respectively) after CaCl2 treatment compared with sPLA2-X+/+ mice. In sPLA2-X-/- mice, immunofluorescence microscopic images showed that the immunoreactivity of sPLA2-X was detected only in neutrophils within aortic walls 3 days, 1, 2, and 6 wk after CaCl2 treatment, whereas the immunoreactivity was not detected in macrophages or mast cells in aortic walls. sPLA2-X immunoreactivity also was colocalized in cells expressing matrix metalloproteinase (MMP)-9. Neutrophils isolated from sPLA2- X-/- mice had lower activities of elastase, gelatinase, and MMP-9 in response to stimuli compared with sPLA2-X+/+ mice. The attenuated release of elastase and gelatinase from sPLA2-X-/- neutrophils was reversed by exogenous addition of mouse sPLA2-X protein. The adoptive transfer of sPLA2-X+/+ neutrophils days 0 and 3 after CaCl2 treatment reversed aortic diameters and elastin degradation grades in the lethally irradiated sPLA2-X+/+ mice reconstituted with sPLA2- X-/- bone marrow to an extent similar to that seen in sPLA2-X+/+ mice. In conclusion, sPLA2-X in neutrophils plays a pathogenic role in AAA in a mice model. [ABSTRACT FROM AUTHOR]

Abstract  We report a 48-year-old woman with primary diffuse leptomeningeal gliomatosis (PDLG) histologically diagnosed as gliosarcoma. She was admitted complaining of headache, numbness of the right arm, double vision, and visual field defects. Computerized tomography (CT) scans showed ventricular dilatation consistent with communicating hydrocephalus. Magnetic resonance imaging (MRI) revealed diffuse meningeal thickening and gadolinium enhancement without a definite intraparenchymal lesion. Whole-spine MRI demonstrated across-the-board dural thickening and gadolinium enhancement. Cytological examination showed atypical anaplastic cells. As no diagnosis could be made she underwent biopsy of the leptomeninges. Histological examination of the specimen returned a diagnosis of gliosarcoma. Despite chemotherapy and radiotherapy she died 11 months after admission. Autopsy findings included gliosarcoma in the leptomeninges and spinal cord without an underlying parenchymal tumor. To our knowledge, this is the first report of primary diffuse leptomeningeal gliosarcomatosis. [ABSTRACT FROM AUTHOR]

Secretory phospholipase A2 (sPLA2) plays a critical role in the genesis of lung inflammation through proinflammatory eicosanoids. A previous in vitro experiment showed a possible role of cell surface receptor for sPLA2 (PLA2R) in the clearance of extracellular sPLA2. PLA2R and groups IB and X sPLA2 are expressed in the lung. This study examined a pathogenic role of PLA2R in airway inflammation using PLA2R-deficient (PLA2R-/-) mice. Airway inflammation was induced by immunosensitization with OVA. Compared with wild-type (PLA2R+/+) mice, PLA2R-/- mice had a significantly greater infiltration of inflammatory cells around the airways, higher levels of groups IB and X sPLA2, eicosanoids, and Th2 cytokines, and higher numbers of eosinophils and neutrophils in bronchoalveolar lavage fluid after OVA treatment. In PLA2R-/- mice, intratracheally instilled [125I]-labeled sPLA2-IB was cleared much more slowly from bronchoalveolar lavage fluid compared with PLA2R+/+ mice. The degradation of the instilled [125I]-labeled sPLA2-IB, as assessed by trichloroacetic acid-soluble radioactivity in bronchoalveolar lavage fluid after instillation, was lower in PLA2R-/- mice than in PLA2R+/+ mice. In conclusion, PLA2R deficiency increased sPLA2-IB and -X levels in the lung through their impaired clearance from the lung, leading to exaggeration of lung inflammation induced by OVA treatment in a murine model. [ABSTRACT FROM AUTHOR]

Background Contrast-enhanced ultrasound (CEUS) of the carotid artery is a potential technique for imaging plaque neovascularization, a feature of unstable atherosclerotic plaques. This study examined whether assessment of intra-plaque neovascularization of the carotid artery using CEUS provides prognostic information in patients with coronary artery disease (CAD). Methods A total of 206 patients with stable CAD underwent a CEUS examination of the carotid artery and were followed up prospectively for < 38 months or until a cardiac event (cardiac death, non-fatal myocardial infarction (MI), unstable angina pectoris (uAP) requiring unplanned coronary revascularization, or heart failure requiring hospitalization). The degree of contrast signals measured within the carotid plaque was quantified by calculating the mean gray scale level within the region of interest of the carotid plaque, expressed as plaque enhanced intensity. Results During the follow-up period, 31 events occurred (2 cardiac deaths, 7 non-fatal MIs, 16 uAP, and 6 heart failure). Multivariate Cox proportional hazard analysis showed that plaque enhanced intensity was a significant predictor of cardiac events independent of traditional risk factors (HR, 1.13; 95% CI, 1.05-1.21; p < 0.001). The addition of the plaque enhanced intensity to traditional risk factors resulted in net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.62, p = 0.001; and IDI 0.106, p = 0.002). Conclusions The assessment of carotid plaque neovascularization using quantitative analysis of CEUS may be useful for risk stratification in patients with CAD. [ABSTRACT FROM AUTHOR]

Glutaredoxin-1 (Glrx) is a cytosolic enzyme that regulates diverse cellular function by removal of GSH adducts from S-glutathionylated proteins including signaling molecules and transcription factors. Glrx is up-regulated during inflammation and diabetes, and Glrx overexpression inhibits VEGF-induced EC migration. The aim was to investigate the role of up-regulated Glrx in EC angiogenic capacities and in vivo revascularization in the setting of hind limb ischemia. Glrx-overexpressing EC from Glrx transgenic (TG)mice showed impaired migration and network formation and secreted higher levels of soluble VEGF receptor 1 (sFlt), an antagonizing factor to VEGF. After hind limb ischemia surgery Glrx TG mice demonstrated impaired blood flow recovery, associated with lower capillary density and poorer limb motor function compared with wild type litter-mates. There were also higher levels of anti-angiogenic sFlt expression in the muscle and plasma of Glrx TG mice after surgery. Noncanonical Wnt5a is known to induce sFlt. Wnt5a was highly expressed in ischemic muscles and EC from Glrx TG mice, and exogenous Wnt5a induced sFlt expression and inhibited network formation in human microvascular EC. Adenoviral Glrx-induced sFlt in EC was inhibited by a competitive Wnt5a inhibitor. Furthermore, Glrx overexpression removed GSH adducts on p65 in ischemic muscle and EC and enhanced NF-κB activity, which was responsible for Wnt5a-sFlt induction. Taken together, up-regulated Glrx induces sFlt in EC via NF-κB-dependent Wnt5a, resulting in attenuated revascularization in hind limb ischemia. The Glrx-induced sFlt explains part of the mechanism of redox-regulated VEGF signaling. [ABSTRACT FROM AUTHOR]