Salvianolic acid B inhibits hydrogen peroxide-induced endothelial cell apoptosis through regulating PI3K/Akt signaling

Background. Salvianolic acid B (Sal B) is one of the most bioactive components of Salvia miltiorrhiza, a traditional Chinese herbal medicine that has been commonly used for prevention and treatment of cerebrovascular disorders. However, the mechanism responsible for such protective effects remains largely unknown. It has been considered that cerebral endothelium apoptosis caused by reactive oxygen species including hydrogen peroxide (H2O2) is implicated in the pathogenesis of cerebrovascular disorders. Methodology and Principal Findings. By examining the effect of Sal B on H2O2-induced apoptosis in rat cerebral microvascular endothelial cells (rCMECs), we found that Sal B pretreatment significantly attenuated H2O2-induced apoptosis in rCMECs. We next examined the signaling cascade(s) involved in Sal B-mediated anti-apoptotic effects. We showed that H2O2 induces rCMECs apoptosis mainly through the PI3K/ERK pathway, since a PI3K inhibitor (LY294002) blocked ERK activation caused by H2O2 and a specific inhibitor of MEK (U0126) protected cells from apoptosis. On the other hand, blockage of the PI3K/Akt pathway abrogated the protective effect conferred by Sal B and potentated H2O2-induced apoptosis, suggesting that Sal B prevents H2O2-induced apoptosis predominantly through the PI3K/Akt (upstream of ERK) pathway. Significance. Our findings provide the first evidence that H2 O2 induces rCMECs apoptosis via the PI3K/MEK/ERK pathway and that Sal B protects rCMECs against H2O2-induced apoptosis through the PI3K/Akt/Raf/MEK/ERK pathway. © 2007 Liu et al.published_or_final_versio

Molecular-beam epitaxy of monolayer and bilayer WSe2: a scanning tunneling microscopy/spectroscopy study and deduction of exciton binding energy

Interest in two-dimensional (2D) transition-metal dichalcogenides (TMDs) has prompted some recent efforts to grow ultrathin layers of these materials epitaxially using molecular-beam epitaxy (MBE). However, growths of monolayer (ML) and bilayer (BL) WSe2—an important member of the TMD family—by the MBE method remain uncharted, probably because of the difficulty in generating tungsten fluxes from the elemental source. In this work, we present a scanning tunneling microscopy and spectroscopy (STM/S) study of MBE-grown WSe2 ML and BL, showing atomically flat epifilm with no domain boundary (DB) defect. This contrasts epitaxial MoSe2 films grown by the same method, where a dense network of the DB defects is present. The STS measurements of ML and BL WSe2 domains of the same sample reveal not only the bandgap narrowing upon increasing the film thickness from ML to BL, but also a band-bending effect across the boundary (step) between ML and BL domains. This band-bending appears to be dictated by the edge states at steps of the BL islands. Finally, comparison is made between the STS-measured electronic bandgaps with the exciton emission energies measured by photoluminescence, and the exciton binding energies in ML and BL WSe2 (and MoSe2) are thus estimated.postprin

Impact of Phenanthrene on Organic Acids Secretion and Accumulation by Perennial Ryegrass, Lolium perenne L., Root

A solution culture experiment was performed to investigate the impact of phenanthrene (PHE) on organic acids secretion and accumulation by Lolium perenne L. root. Data showed that, oxalic acid was the dominant composition of organic acids in root and root exudates. In root exudates, increased levels of PHE resulted in higher oxalic acid and its secrete proportion; oxalic acid arranged from 3.00 to 4.72 mg/g FW under spiked PHE treatments, in control, it was 2.33 mg/g FW. In root, oxalic acid rose to 25.61 mg/g FW at 1 mg/L PHE treatment, while the PHE concentration was continuously increasing, organic acids in root decreased

Scalp acupuncture for acute ischemic stroke: a meta-analysis of randomized controlled trials

Scalp acupuncture (SA) is a commonly used therapeutic approach for stroke throughout China and elsewhere in the world. The objective of this study was to assess clinical efficacy and safety of SA for acute ischemic stroke. A systematical literature search of 6 databases was conducted to identify randomized controlled trials (RCTs) of SA for acute ischemic stroke compared with western conventional medicines (WCMs). All statistical analyses were performed by the Rev Man Version 5.0. Eight studies with 538 participants were included in the studies. The studies were deemed to have an unclear risk of bias based on the Cochrane Back Review Group. Compared with the WCM, 6 RCTs showed significant effects of SA for improving neurological deficit scores (P < 0.01); 4 RCTs showed significant effects of SA for favoring the clinical effective rate (P < 0.01) However, the adverse events have not been documented. In conclusion, SA appears to be able to improve neurological deficit score and the clinical effective rate when compared with WCM, though the beneficial effect from SA is possibly overvalued because of generally low methodology of the included trials. No evidence is available for adverse effects. Rigorous well-designed clinical trials are needed.published_or_final_versio

On the selection and design of proteins and peptide derivatives for the production of photoluminescent, red-emitting gold quantum clusters

Novel pathways of the synthesis of photoluminescent gold quantum clusters (AuQCs) using biomolecules as reactants provide biocompatible products for biological imaging techniques. In order to rationalize the rules for the preparation of red-emitting AuQCs in aqueous phase using proteins or peptides, the role of different organic structural units was investigated. Three systems were studied: proteins, peptides, and amino acid mixtures, respectively. We have found that cysteine and tyrosine are indispensable residues. The SH/S-S ratio in a single molecule is not a critical factor in the synthesis, but on the other hand, the stoichiometry of cysteine residues and the gold precursor is crucial. These observations indicate the importance of proper chemical behavior of all species in a wide size range extending from the atomic distances (in the AuI-S semi ring) to nanometer distances covering the larger sizes of proteins assuring the hierarchical structure of the whole self-assembled system

Anisotropic Impurity-States, Quasiparticle Scattering and Nematic Transport in Underdoped Ca(Fe1-xCox)2As2

Iron-based high temperature superconductivity develops when the `parent' antiferromagnetic/orthorhombic phase is suppressed, typically by introduction of dopant atoms. But their impact on atomic-scale electronic structure, while in theory quite complex, is unknown experimentally. What is known is that a strong transport anisotropy with its resistivity maximum along the crystal b-axis, develops with increasing concentration of dopant atoms; this `nematicity' vanishes when the `parent' phase disappears near the maximum superconducting Tc. The interplay between the electronic structure surrounding each dopant atom, quasiparticle scattering therefrom, and the transport nematicity has therefore become a pivotal focus of research into these materials. Here, by directly visualizing the atomic-scale electronic structure, we show that substituting Co for Fe atoms in underdoped Ca(Fe1-xCox)2As2 generates a dense population of identical anisotropic impurity states. Each is ~8 Fe-Fe unit cells in length, and all are distributed randomly but aligned with the antiferromagnetic a-axis. By imaging their surrounding interference patterns, we further demonstrate that these impurity states scatter quasiparticles in a highly anisotropic manner, with the maximum scattering rate concentrated along the b-axis. These data provide direct support for the recent proposals that it is primarily anisotropic scattering by dopant-induced impurity states that generates the transport nematicity; they also yield simple explanations for the enhancement of the nematicity proportional to the dopant density and for the occurrence of the highest resistivity along the b-axis

Extending colonic mucosal microbiome analysis - Assessment of colonic lavage as a proxy for endoscopic colonic biopsies

This study was supported through GI Research funds and MRC Grant Ref: MR/M00533X/1 to GH.Peer reviewedPublisher PD

Modular construction of mammalian gene circuits using TALE transcriptional repressors

An important goal of synthetic biology is the rational design and predictable implementation of synthetic gene circuits using standardized and interchangeable parts. However, engineering of complex circuits in mammalian cells is currently limited by the availability of well-characterized and orthogonal transcriptional repressors. Here, we introduce a library of 26 reversible transcription activator–like effector repressors (TALERs) that bind newly designed hybrid promoters and exert transcriptional repression through steric hindrance of key transcriptional initiation elements. We demonstrate that using the input-output transfer curves of our TALERs enables accurate prediction of the behavior of modularly assembled TALER cascade and switch circuits. We also show that TALER switches using feedback regulation exhibit improved accuracy for microRNA-based HeLa cancer cell classification versus HEK293 cells. Our TALER library is a valuable toolkit for modular engineering of synthetic circuits, enabling programmable manipulation of mammalian cells and helping elucidate design principles of coupled transcriptional and microRNA-mediated post-transcriptional regulation.National Institutes of Health (U.S.) (Grant 5R01CA155320-04)National Institutes of Health (U.S.) (Grant P50GM098792)National Institutes of Health (U.S.) (Grant 1R01CA173712-01

Ventilatory drive and the apnea-hypopnea index in six-to-twelve year old children

BACKGROUND: We tested the hypothesis that ventilatory drive in hypoxia and hypercapnia is inversely correlated with the number of hypopneas and obstructive apneas per hour of sleep (obstructive apnea hypopnea index, OAHI) in children. METHODS: Fifty children, 6 to 12 years of age were studied. Participants had an in-home unattended polysomnogram to compute the OAHI. We subsequently estimated ventilatory drive in normoxia, at two levels of isocapnic hypoxia, and at three levels of hyperoxic hypercapnia in each subject. Experiments were done during wakefulness, and the mouth occlusion pressure measured 0.1 seconds after inspiratory onset (P(0.1)) was measured in all conditions. The slope of the relation between P(0.1 )and the partial pressure of end-tidal O(2 )or CO(2 )(P(ET)O(2 )and P(ET)CO(2)) served as the index of hypoxic or hypercapnic ventilatory drive. RESULTS: Hypoxic ventilatory drive correlated inversely with OAHI (r = -0.31, P = 0.041), but the hypercapnic ventilatory drive did not (r = -0.19, P = 0.27). We also found that the resting P(ET)CO(2 )was significantly and positively correlated with the OAHI, suggesting that high OAHI values were associated with resting CO(2 )retention. CONCLUSIONS: In awake children the OAHI correlates inversely with the hypoxic ventilatory drive and positively with the resting P(ET)CO(2). Whether or not diminished hypoxic drive or resting CO(2 )retention while awake can explain the severity of sleep-disordered breathing in this population is uncertain, but a reduced hypoxic ventilatory drive and resting CO(2 )retention are associated with sleep-disordered breathing in 6–12 year old children

Astrocytic Ion Dynamics: Implications for Potassium Buffering and Liquid Flow

We review modeling of astrocyte ion dynamics with a specific focus on the implications of so-called spatial potassium buffering, where excess potassium in the extracellular space (ECS) is transported away to prevent pathological neural spiking. The recently introduced Kirchoff-Nernst-Planck (KNP) scheme for modeling ion dynamics in astrocytes (and brain tissue in general) is outlined and used to study such spatial buffering. We next describe how the ion dynamics of astrocytes may regulate microscopic liquid flow by osmotic effects and how such microscopic flow can be linked to whole-brain macroscopic flow. We thus include the key elements in a putative multiscale theory with astrocytes linking neural activity on a microscopic scale to macroscopic fluid flow.Comment: 27 pages, 7 figure