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Rationale: The neurosteroid 3α,5β-THP (3α-OH-5β-pregnan-20-one, pregnanolone) is a modulator of the GABAA receptor (GABAR), with α4β2δ GABARs the most sensitive. However, the effects of 3α,5β-THP at α4β2δ are polarity-dependent: 3α,5β-THP potentiates depolarizing current, as has been widely reported, but decreases hyperpolarizing current by accelerating desensitization., Objectives: The present study further characterized 3α,5β-THP inhibition of hyperpolarizing current at this receptor and compared effects of other related steroids at α4β2δ GABARs., Methods: α4β2δ GABARs were expressed in HEK-293 cells, and agonist-gated current recorded with whole cell voltage-clamp techniques using a theta tube to rapidly apply agonist before and after application of neurosteroids., Results: The GABA-modulatory steroids (30 nM) 3α,5α-THP (3α-OH-5α-pregnan-20-one, allopregnanolone) and THDOC (3α,21-dihydroxy-5α-pregnan-20-one) inhibited hyperpolarizing GABA (10 μM)-gated current at α4β2δ GABARs similar to 3α,5β-THP, while the inactive 3β,5β-THP isomer had no effect. Greater inhibition was seen for current gated by the high efficacy agonist gaboxadol (THIP, 100 μM) than for GABA (0.1-1000 μM), consistent with an effect of 3α,5β-THP on desensitization. Inhibitory effects of the steroid were not seen under low [Cl(-)] conditions or in the presence of calphostin C (500 nM), an inhibitor of protein kinase C. Chimeras swapping the IL (intracellular loop) of α4 with α1, when expressed with β2 and δ, produced receptors (α[414]β2δ) which were not inhibited by 3α,5β-THP when GABA-gated current was hyperpolarizing, while α[141]β2δ exhibited steroid-induced polarity-dependent modulation., Conclusions: These findings suggest that numerous neurosteroids exhibit polarity-dependent effects at α4β2δ GABARs, which are dependent upon protein kinase C and the IL of α4.

Objective: To evaluate the effects and possible mechanisms of rutaecarpine on angiotensin II (Ang II)-induced proliferation in cultured rat vascular smooth muscle cells (VSMCs)., Methods: VSMCs were isolated from Male Sprague-Dawley rat aorta, and cultured by enzymic dispersion method. Experiments were performed with cells from passages 3-8. The cultured VSMCs were randomly divided into control, model (Ang II 0.1 μmol/L), and rutaecarpine (0.3-3.0 μmol/L) groups. VMSC proliferation was induced by Ang II, and was evaluated by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and cell counting. To examine the mechanisms involved in anti-proliferative effects of rutaecarpine, nitric oxide (NO) levels and NO synthetase (NOS) activity were determined. Expressions of VSMC proliferation-related genes including endothelial nitric oxide synthase (eNOS), and c-myc hypertension related gene-1 (HRG-1) were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR)., Results: Rutaecarpine (0.3-3.0 μmol/L) inhibited Ang II-induced VSMC proliferation and the best effects were achieved at 3.0 μmol/L. The Ang II-induced decreases in cellular NO contents and NOS activities were antagonized by rutaecarpine (P <0.05). Ang II administration suppressed the expressions of eNOS and HRG-1, while increased c-myc expression (P <0.05). All these effects were attenuated by 3.0 μmol/L rutaecarpine (P <0.05)., Conclusion: Rutaecarpine is effective against Ang II-induced rat VSMC proliferation, and this effect is due, at least in part, to NO production and the modulation of VMSC proliferation-related gene expressions.

Post-operative cognitive dysfunction (POCD) is a severe complication characterized by cognitive decline in patients following anesthesia and surgery. Previous studies have suggested that volatile anesthetics, for example isoflurane, may contribute to such impairment. In the present study, the effects of emulsified isoflurane (EI) exposure on cognitive function, as well as the potential mechanisms, were investigated in animal models. Eight-month-old male rats were administered a single intravenous injection of 8% EI. The rats were then subjected to the Morris water maze test to assess their cognitive functions at different time-points following drug administration. Samples were taken in order to detect the plasma corticosterone concentration and the levels of hippocampal brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), as well as the expression of BDNF and NGF in the hippocampal region. The results showed that a single injection of EI caused reversible learning and memory dysfunction in adult rats. It was found that downregulation of BDNF expression may contribute to the isoflurane-induced cognitive impairment of these rats. Increased expression of NGF may be associated with the protection mechanism subsequent to learning and memory function decline, and therefore may accelerate the recovery of cognitive function.

Phosphodiesterase-5 (PDE5) inhibitors are predominantly used in the treatment of erectile dysfunction, and have been recently shown to have a potential therapeutic effect for the treatment of Alzheimer's disease (AD) through stimulation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling by elevating cGMP, which is a secondary messenger involved in processes of neuroplasticity. In the present study, the effects of a PDE5 inhibitor, icarrin (ICA), on learning and memory as well as the pathological features in APP/PS1 transgenic AD mice were investigated. Ten-month-old APP/PS1 transgenic mice overexpressing human amyloid precursor protein (APP695swe) and presenilin 1 (PS1-dE9) were given ICA (30 and 60 mg/kg) or sildenafil (SIL) (2 mg/kg), age-matched wild-type (WT) mice were given ICA (60 mg/kg), and APP/PS1 and WT control groups were given an isovolumic vehicle orally twice a day for four months. Results demonstrated that ICA treatments significantly improved learning and memory of APP/PS1 transgenic mice in Y-maze tasks. The amyloid precursor protein (APP), amyloid-beta (Aβ1-40/42) and PDE5 mRNA and/or protein levels were increased in the hippocampus and cortex of APP/PS1 mice, and ICA treatments decreased these physiopathological changes. Furthermore, ICA-treated mice showed an increased expression of three nitric oxide synthase (NOS) isoforms at both mRNA and protein levels, together with increased NO and cGMP levels in the hippocampus and cortex of mice. These findings demonstrate that ICA improves learning and memory functions in APP/PS1 transgenic mice possibly through the stimulation of NO/cGMP signalling and co-ordinated induction of NOS isoforms.

Background: Heme oxygenase-1 (HO-1) has potential anti-apoptotic properties. A novel compound [4-(2-acetoxy-3-((R)-3-(benzylthio)-1-methoxy-1-oxopropan-2- ylamino)-3-oxopropyl)-1,2-phenylene diacetate (DSC)] was synthesized by joining danshensu and cysteine through an appropriate linker. This study investigated if the cytoprotective properties of DSC involved the induction of HO-1., Methods: We evaluated the cytoprotective effects of DSC on H2O2-induced cell damage, apoptosis, intracellular and mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential (ΔΨm) loss, and apoptosis-related proteins expression and its underlying mechanisms., Results: DSC concentration-dependently attenuated cell death, lactate dehydrogenase release, intracellular and mitochondrial ROS production, and ΔΨm collapse, modulated apoptosis-related proteins (Bcl-2, Bax, caspase-3, p53, and cleaved PARP) expression, and inhibited phosphorylation of extracellular signal-regulated kinase 1/2 in SH-SY5Y cells induced by H2O2. In addition, DSC concentration-dependently induced HO-1 expression associated with nuclear translocation of nuclear factor-erythroid 2 related factor 2 (Nrf-2), while the effect of DSC was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Furthermore, the protective effect of DSC on H2O2-induced cell death was abolished by HO-1 inhibitor ZnPP, but was mimicked by carbon monoxide-releasing moiety CORM-3 or HO-1 by-product bilirubin. Finally, DSC inhibited H2O2-induced changes of Bcl-2, Bax, and caspase-3 expression, and all of these effects were reversed by HO-1 silencing., Conclusions: Induction of HO-1 may be, at least in part, responsible for the anti-apoptotic property of DSC, an effect that involved the activation of PI3K/Akt/Nrf-2 axis., General Significance: DSC might have the potential for beneficial therapeutic interventions for neurodegenerative diseases., (Copyright © 2013. Published by Elsevier B.V.)

The interface modification between the organic active layer and the inorganic electrode affects the performance of organic solar cell (OSC). A buffer layer of alkylthiol (ethanethiol, hexanethiol, dodecanethiol)/Au self-assembly layer was introduced into OSC to substitute Poly(3,4-ethylenedioxythiophene) : poly(styrene sulfonate) (PEDOT : PSS) layer, in order to improve the organic/inorganic interface. We fabricated devices with structure of "ITO/Au (annealed Au film of 2 nm)-thiol self assembly layer/poly(3-hexylthiophene) : 1-(3-methoxycarbonyl) -propyl-1-phenyl-(6,6)C61(P3HT : PCBM) /LiF/Al". After alkanethiol self-assembling, the alkanethiol prevented exciton quenching owe to direct contact between the Au NPs and the active layer. We studied the impact of alkanethiol with different chain length on device performance. With? the? growth? of? the? alkyl chain, the coverage of the thiol on Au NPs got better, and the device performance become better. In the OSC with dodecane-thiol/Au (2 nm Au film annealed) self-assembly film, the short-circuit current increases from 5.19 mA x cm(-2) to 6.24 mA x cm(-2).

In our previous studies, we have reported that leonurine, a plant phenolic alkaloid in Herba leonuri, exerted cardioprotective properties in a number of preclinical experiments. Herein, we investigated the roles and the possible mechanisms of leonurine for reducing fibrotic responses in angiotensin II (Ang II)-stimulated primary neonatal rat cardiac fibroblasts and post-myocardial infarction (MI) rats. In in vitro experiments performed in neonatal rat cardiac fibroblasts, leonurine (10-20 μM) pretreatment attenuated Ang II-induced activation of extracellular signal-regulated kinase 1/2, production of intracellular reactive oxygen species (ROS), expression and activity of matrix metalloproteinase (MMP)-2/9, and expression of α-smooth muscle actin and types I and III collagen. A small interfering RNA-mediated knockdown strategy for NADPH oxidase 4 (Nox4) revealed that Nox4 was required for Ang II-induced activation of cardiac fibroblasts. In vivo studies using a post-MI model in rats indicated that administration of leonurine inhibited myocardial fibrosis while reducing cardiac Nox4 expression, ROS production, NF-κB activation, and plasma MMP-2 activity. In conclusion, our results provide the first evidence that leonurine could prevent cardiac fibrosis and the activation of cardiac fibroblasts partly through modulation of a Nox4-ROS pathway., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Electrospinning is a simple and effect technology which can produce continuous nanofibers. We get aligned electrospun nanofibers successfully by using parallel electrodes. We report our studies on transient fluorescence of aligned electrospun fibers. The fibers are excited and their fluorescences are observed both at axial and radial polarization. Steady-state PL spectra shows radial emission blue-shift more than axial! emission, due to weakened aggregation of molecular chains in radial direction. At all emission wavelength, radial emission excitons migrate faster than axial emission excitons.

We report an experimental and theoretical study of very low-energy photoelectrons in tunneling ionization process from noble gas atoms interacting with ultrashort intense infrared laser pulses. A universal peak structure with electron energy well below 1 eV in the photoelectron spectrum, corresponding to the double-hump structure in the longitudinal momentum distribution, is identified experimentally for all atomic species. Our quantum and semiclassical analysis reveal the role of long-range Coulomb potential in the production of this very low-energy peak structure.

Significance: Hydrogen sulfide (H(2)S) has traditionally been considered a toxic environmental pollutant. In the late 1990s, the presumed solely harmful role of H(2)S has been challenged because H(2)S may also be involved in the maintenance and preservation of cardiovascular homeostasis., Recent Advances: The production of endogenous H(2)S has been attributed to three key enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase, and 3-mercaptopyruvate sulfurtransferase. The recognition of H(2)S as the third gaseous signaling molecule has stimulated research on a multitude of pathophysiologic events in the cardiovascular system. In particular, important roles in cardiovascular disorder processes are ascribed to the CSE/H(2)S pathway, such as atherosclerosis, myocardial infarction, hypertension, and shock., Critical Issues: Many biological activities and molecular mechanisms of H(2)S in the cardiovascular system have been demonstrated in studies using different tools, such as the genetic overexpression of CSE, the direct administration of H(2)S donors, or the use of H(2)S-releasing pro-drugs. Unfortunately, the role of the CSE/H(2)S pathway in cardiovascular disease remains controversial in numerous areas, and many questions regarding the gaseous molecule still remain unanswered., Future Directions: Advances in basic research indicate that the CSE/H(2)S pathway may provide potential therapeutic targets for treating cardiovascular disorders. But the molecular targets of H(2)S still need to be identified.

This study aims to investigate the effects of ginsenoside Rb(1) on vascular intimal hyperplasia in rats and explore the mechanisms. The rat vascular neointimal hyperplasia model was made by rubbing the endothelia of carotid artery with a balloon and Rb(1) (10 and 30 mg/kg/day) was given the day after surgery for 14 consecutive days. The neointimal hyperplasia level and the degree of vascular smooth muscle cells (VSMCs) proliferation were evaluated by histopathology and by calculating the proliferating cell nuclear antigen (PCNA) positive expression percentage; protein expressions of PCNA, phosphorylation extracellular signal-regulated kinase 1/2 (pERK1/2), smooth muscle α-actin (SM α-actin), and the mRNA expressions of proto-oncogene c-myc, SM α-actin, SM-emb (embryonic smooth muscle myosin heavy chain) and p38 MAPK were detected by immunohistochemistry and Real Time RT-PCR, respectively. Compared with the endothelia rubbing model group, Rb(1) 10 and 30 mg/kg/day medication significantly ameliorated the neointimal hyperplasia (P<0.05), and decreased the positive expression percentage of PCNA(P<0.05). Rb(1) medication also significantly decreased the elevated protein expression of pERK1/2 and the mRNA expression of c-myc(P<0.05), and tended to reduce the expression of p38 MAPK mRNA. Endothelial rubbing increased the SM-emb mRNA expression, but decreased the expression of SM α-actin mRNA which was reversed by Rb(1) (P<0.05). The results indicate that Rb(1) inhibits the vascular neointimal hyperplasia induced by balloon-injury in rats via suppressing the VSMC proliferation, which may be involved in part the inhibition of pERK1/2 protein and related to its inhibition on VSMC phenotype modulation., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Objectives: Peroxisome proliferator-activated receptor gamma (PPARγ) plays a critical role in regulation of diverse biological processes, including lipid metabolism and adipogenesis, cell division and apoptosis, and is involved in variety of disease conditions, such as obesity, atherosclerosis, inflammation and tumour. Developing a cell-based reporter gene model targeting PPARγ would be useful to screen human PPARγ agonists that could be beneficial to patients with these diseases., Methods: We stably co-transfected human embryonic kidney (HEK) cell line 293T cells with phPPARγ-IRES2-EGFP vector to express human PPARγ (hPPARγ), a reporter vector pPPRE×3-TK-LUC, and control vector pRL-CMV. The efficiency of the co-transfection was evaluated with flow cytometry of hPPARγ expressing cells. Specificity of hPPARγ activity was determined by dual luciferase reporter assay of co-transfected cells exposed to PPARγ agonist rosiglitazone, PPARα agonist WY14643 and retinoic acid receptor alpha (RARα) agonist all-trans-retinoic acid (ATRA)., Key Findings: The phPPARγ-IRES2-EGFP co-transfected HEK293T cells showed concentration- and time-dependent luciferase induction upon exposure to the rosiglitazone, while WY14643 and ATRA were unable to activate the co-transfected HEK293T cells., Conclusions: These data indicated that the HEK293T cells could be stably transfected with hPPARγ. This cell-based drug screening platform could be used targeting specific nuclear receptor of hPPARγ with effectiveness and specificity for hPPARγ agonists discovery., (© 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.)

Leonurine, an active alkaloid of Traditional Chinese Medicine Herba leonuri, displayed cardioprotective effects by anti-oxidative and anti-apoptotic activities in vitro and in vivo. Herein, we explored the effects and possible mechanisms of leonurine on lipopolysaccharide (LPS)-induced inflammatory responses in human umbilical vein endothelial cells (HUVEC). We found that leonurine pretreatment concentration-dependently attenuated LPS-induced mRNA expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and monocyte chemoattractant protein-1. Meanwhile, LPS-mediated expression/release of ICAM-1, VCAM-1, and cyclooxygenase-2, and tumor necrosis factor-α was also reduced by leonurine. In addition, we confirmed that leonurine suppressed degradation of IκBα and phosphorylation of nuclear factor-κB (NF-κB) p65 as well as production of intracellular reactive oxygen species in a concentration dependent manner. Furthermore, the cytoprotective enzyme heme oxygenase-1 could be upregulated in leonurine-treated HUVEC. Our present results indicated leonurine exerted beneficial effects in inflammatory conditions partly through inhibition of reactive oxygen species and NF-κB signaling pathways., (Copyright © 2012. Published by Elsevier B.V.)

Ginsenoside Rg1 (Rg1) has been reported to suppress the proliferation of vascular smooth muscle cells (VSMCs). This study aimed to observe the role of nitric oxide (NO) in Rg1-antiproliferative effect. VSMCs from the thoracic aorta of SD rats were cultured by tissue explant method, and the effect of Rg1 (20 mg·L(-1), 60 mg·L(-1), and 180 mg·L(-1)) on platelet-derived growth factor-BB (PDGF-BB)-induced proliferation was evaluated by MTT assay. The cell cycle was analyzed by flow cytometry. For probing the mechanisms, the content of NO in supernatant and cGMP level in VSMCs was measured by nitric oxide kit and cGMP radio-immunity kit, respectively; the expressions of protooncogene c-fos and endothelial NO synthase (eNOS) mRNA in the VSMCs were detected by real-time RT-PCR; the intracellular free calcium concentration ([Ca2(+)](i)) was detected with Fura-2/AM-loaded VSMCs. Comparing with that in normal group, Rg1 180 mg·L(-1) did not change the absorbance of MTT and cell percent of G(0)/G(1), G(2)/M, and S phase in normal cells (P > 0.05). Contrarily, PDGF-BB could increase the absorbance of MTT (P < 0.01) and the percent of the S phase cells but decrease the G(0)/G(1) phase cell percent in the cell cycle, accompanied with an upregulating c-fos mRNA expression (P < 0.01), which was reversed by additions of Rg1(20 mg·L(-1), 60 mg·L(-1), and 180 mg·L(-1)). Rg1 administration could also significantly increase the NO content in supernatant and the cGMP level in VSMCs, as well as the eNOS mRNA expression in the cells, in comparison of that in the group treated with PDGF-BB alone (P < 0.01). Furthermore, Rg1 caused a further increase in the elevated [Ca(2+)](i) induced by PDGF-BB. It was concluded that Rg1 could inhibit the VSMC proliferation induced by PDGF-BB through restricting the G(0)/G(1) phase to S-phase progression in cell cycle. The mechanisms may be related to the upregulation of eNOS mRNA and the increase of the formation of NO and cGMP.

The blend morphology and vertical arrangement are critical to the performance of organic bulk-heterojunction photovoltaic devices. In the present paper, the authors proposed a new annealing method that controls the blend morphology and vertical arrangement of two materials by means of simultaneously applying external electrical field and violet irradiation on the active layer of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl C61-butyric acid methyl ester (PCBM) during annealing process. By using this annealing method, the power conversion efficiency increased by 36%, which was caused by vertical phased-separated blend of crystalline P3HT and PCBM and better charge extraction of electrodes. X-ray photoelectron spectroscopy (XPS) was measured to prove more fullerene derivatives at the organic/cathode interfaces by using this annealing method. The X-ray diffraction (XRD) analysis and UV-Vis absorption spectrum analysis also revealed more ordered polymer crystallization.

Ethnopharmacological Relevance: Ginsenoside Rg1 (Rg1) is one of the main active components of Panax ginseng a well-known herbal medicine. It has been demonstrated to inhibit proliferation of vascular smooth muscle cells (VSMCs) induced by tumor necrosis factor-αin vitro. The present study is aimed to examine the possible effects of Rg1 on vascular neointimal hyperplasia in balloon-injured carotid artery of rats in vivo., Materials and Methods: The animal model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of male Sprague Dawley rats. Then the rats were intraperitoneally injected with distilled water in model group and sham operation control, or with Rg1 4, 8 and 16mg/kg/d in other balloon injured groups. After consecutive 14 days, the vascular intimal hyperplasia was evidenced by histopathological alterations of the CCA and by changes observed in the marker of the proliferation of VSMCs-the proliferating cell nuclear antigen (PCNA). The protein expressions of PCNA and the phosphorylated extracellular signal-regulated kinase2 (p-ERK2) as well as mitogen-ativated protein kinase phosphatase-1 (MKP-1) were examined by immunohistochemistry; while the expressions of proto-oncogene (c-fos), ERK2 and smooth muscle α-actin (SM α-actin) mRNA were analyzed by Real-Time RT-PCR., Results: Rg1 administration could significantly ameliorate the histopathology of CCA and decrease the protein expression of PCNA induced by endothelia rubbing; and Rg1 medication also significantly decreased the expressions of p-ERK2 protein, ERK2 and c-fos mRNA in vessel wall, but up-regulated the MKP-1 expression, which was reported to inactivate mitogen-ativated protein kinase pathway. Furthermore, Rg1 could elevate the decreased SM α-actin mRNA expression induced by balloon injury., Conclusions: Rg1 can suppress the vascular neointimal hyperplasia induced by balloon injury, the mechanism may be involved in the inhibition on ERK2 signaling, and related, at least partly, to the increase in MKP-1 expression., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

In recent years, antibiotic resistance of bacteria has become a global health crisis. Especially, the new class of "superbug" was found in South Asia, which is resistant to almost known antibiotics and causes worldwide alarm. Through the underlying mechanisms of bacterial pathogenecity, the expression of many pathogen virulence factors is regulated by the process of quorum sensing. Screening efficient quorum sensing inhibitors is an especially compelling approach to the future treatment of bacterial infections and antibiotic resistance. This article focuses on bacterial quorum sensing system, quorum sensing screening model for in vitro and evaluation of animal models in vivo, recent research of quorum sensing inhibitors and so on.

The present study attempts to investigate the effects of S-propargyl-cysteine (SPRC), a sulfur-containing amino acid, on lipopolysaccharide (LPS)-induced inflammatory response in H9c2 cardiac myocytes. We found that SPRC prevented nuclear factor-κB (NF-κB) activation assessed by NF-κB p65 phosphorylation and IκBα degradation, suppressed LPS-induced extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and intracellular reactive oxygen species (ROS) production. Furthermore, incubation of H9c2 cells with SPRC induced phosphorylation of Akt in a time- and concentration-dependent manner. In addition, SPRC attenuated LPS-induced mRNA and protein expression of tumor necrosis factor-α (TNF-α), and mRNA expression of intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS). The effects of SPRC were abolished by cystathionine γ-lyase [CSE-an enzyme that synthesizes hydrogen sulfide (H(2)S)] inhibitor, DL: -propargylglycine (PAG), SPRC-induced Akt phosphorylation and TNF-α release was also abolished by the phosphoinositide 3-kinase (PI3K) inhibitor LY294002. Furthermore, SPRC also increased LPS-induced down-regulation expression of CSE and H(2)S level in H9c2 cells. PAG abolished SPRC-induced up-regulation of H(2)S level. Therefore, we concluded that SPRC produced an anti-inflammatory effect in LPS-stimulated H9c2 cells partly through the CSE/H(2)S pathway by impairing IκBα/NF-κB signaling and by activating PI3K/Akt signaling pathway.

Background: Hydrogen sulfide (H(2)S), the third physiologically relevant gaseous molecule, is recognized increasingly as an anti-inflammatory mediator in various inflammatory conditions. Herein, we explored the effects and mechanisms of sodium hydrosulfide (NaHS, a H(2)S donor) on tumor necrosis factor (TNF)-α-induced human umbilical vein endothelial cells (HUVEC) dysfunction., Methodology and Principal Findings: Application of NaHS concentration-dependently suppressed TNF-α-induced mRNA and proteins expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), mRNA expression of P-selectin and E-selectin as well as U937 monocytes adhesion to HUVEC. Western blot analysis revealed that the expression of the cytoprotective enzyme, heme oxygenase-1 (HO-1), was induced and coincident with the anti-inflammatory action of NaHS. Furthermore, TNF-α-induced NF-κB activation assessed by IκBα degradation and p65 phosphorylation and nuclear translocation and ROS production were diminished in cells subjected to treatment with NaHS., Significance: H(2)S can exert an anti-inflammatory effect in endothelial cells through a mechanism that involves the up-regulation of HO-1.

Femtosecond time-resolved fluorescence spectra technique based on non-collinear optical parametric amplification is a new method for ultrafast spectroscopy research In the present report, the authors discuss the dynamic range for amplifying fluorescence. The supercontinuum seed can be amplified linearly to its transient intensity. Due to large amplification ratio up to 10(7), small instability in pump pulse energy produces large fluctuation in final output amplitude. Here the authors introduce a method using cone emission as reference to overcome this difficulty. The results show significant improvement in fluorescence dynamics curve.

Energy is most important issue in the world now because the chemical energy (oil, natural gas, coal et al) is on the edge of depleting. Many Countries are now paying attention to the use of sun power. Photovoltaic device is the most important way to make use of sun energy. Organic solar cell is one promising kind of photovoltaic device, though it's low power conversion efficiency hampers its commercialization. This paper briefly reviewed two ways to improve the power conversion efficiency of organic solar cells and pointed out the unsolved problems.

Beta-amyloid (Aβ) is considered to be responsible for the pathogenesis of Alzheimer's disease (AD), and accumulation and aggregation of Aβ peptide in the brains of AD patients result in activation of glial cells which, in turn, initiates neuroinflammatory responses that involve reactive oxygen intermediates and release of inflammatory cytokines. In the present study, the protective effects of S-propargyl-cysteine (SPRC), also named as ZYZ-802, a sulphur-containing amino acid, on cognitive impairment and neuronal ultrastructure damage induced by Aβ were examined in rats, and the possible mechanisms were explored. These data showed that SPRC administration at the doses of 40, 80 mg/kg by intraperitoneal injection (i.p.) may inhibit cognitive impairment and neuronal ultrastructure damage induced by intracerebroventricular (i.c.v.) injection of 10 μg of Aβ(25-35) in rats. Subsequently, SPRC inhibited the expressions of tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) mRNA, and protein in rat hippocampus. SPRC afforded a beneficial action on inhibitions of extracellular signal-regulated kinase (ERK1/2), as well as inhibitions of IκB-α degradation and activation of transcription factors of the nuclear factor κB (NF-κB) produced by Aβ. These findings suggested that SPRC might be a potential agent for treatment of AD.

For hundreds of years, hydrogen sulfide (H2S) has been known solely as a toxic gas with the smell of rotten eggs. Nevertheless, the notoriety of H2S as a toxic gas is experiencing a transformation, with an increasing amount of research showing that it regulates a range of physiological and pathological processes in mammals. Hence H2S is a physiologically important molecule and has been referred to as the third gaseous mediator alongside nitric oxide and carbon monoxide. This past decade has seen an exponential growth of scientific interest in the physiological and pathological significance of H2S. In particular, in the central nervous system, H2S facilitates long-term potentiation and regulates intracellular calcium concentration and pH level in brain cells. Interestingly, H2S may exert antioxidant, anti-apoptotic, and anti-inflammatory effects which are related to neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia. Meanwhile, abnormal generation and metabolism of H2S are involved in most of these neurodegenerative disorders. This review presents current knowledge of H2S and its neuroprotective effects in neurodegenerative disorders, with a special emphasis on AD and PD. It is concluded that a H2S-modulated agent will be a new hope for neurodegenerative disorders including AD and PD.

Poly(3-hexylthiophene) (P3HT) thin films were electrochemically deposited directly on indium tin oxide (ITO)/poly (3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT : PSS) substrates. Its optical absorption peak is located at about 410 nm and tailing to 610 nm, corresponding to 2.04 eV of bandgap. Its highest occupied molecular orbital (HOMO) energy is -5.21 eV, while the HOMO energy of the chemically synthesized P3HT is -5.02 eV. The lower HOMO energy of the electrodeposited P3HT may be attributed to the enhancement of regularity. The morphology of the P3HT thin film characterized by atomic force microscopy (AFM) indicates that the molecules contact firmly. The cyclic voltammetry results show that its electrochemical property is stable. The authors prepared photovoltaic cell with the P3HT and [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) as the active layer. Because of the lower HOMO of the electrodeposited P3HT, the open circuit voltage (V(oc)) of the device is up to 0.76 V, indicating a new way to enhance the V(oc) of the organic photovoltaic cells.

Ginsenosides, the active components found in Panax ginseng, have been reported to inhibit the cardiac hypertrophy in rats. This study aims to observe the potential effect of total ginsenosides (TG) on the hypertrophic vascular diseases. The model of vascular neointimal hyperplasia was established by rubbing the endothelia of the common carotid artery with a balloon in male Sprague Dawley rats. TG (15 mg/kg/day, 45 mg/kg/day), L-arginine (L-arg) 200 mg/kg/day, and NG-nitro-L-arginine-methyl ester (L-NAME) 100 mg/kg/day used with the same dose of L-arg or TG 45 mg/kg/day were given for 7 and 14 consecutive days after surgery. TG and L-arg administrations significantly ameliorated the histopathology of injured carotid artery, which was abolished or blunted by L-NAME, an NOS inhibitor; TG and L-arg could also remarkably reduce the expression of proliferating cell nuclear antigen (PCNA), a proliferation marker of vascular smooth muscle cells(VSMCs), in neointima of the injured artery wall. Further study indicated that balloon injury caused a decreased superoxide dismutase (SOD) activity and an elevated malondialdehyde (MDA) content in plasma, and reduced the cGMP level in the artery wall, which were reversed by TG. It was concluded that TG suppress the rat carotid artery neointimal hyperplasia induced by balloon injury, which may be involved in its anti-oxidative action and enhancing the inhibition effects of NO/cGMP on VSMC proliferation., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Neuroinflammation exacerbates hyperphosphorylated tau and amyloid-β (Aβ) generation by generating a plethora of inflammatory mediators and neurotoxic compounds in a transgenic model of Alzheimer's disease (AD), and it was reported that hydrogen sulfide (H₂S) attenuates lipopolysaccharide (LPS)-induced neuroinflammation both in vitro and in vivo. In the present study, the protective effects of S-propargyl-cysteine (SPRC) on spatial learning and memory impairment induced by LPS were examined in vivo, and the possible mechanisms were explored. The data showed that SPRC administration by intraperitoneal (i.p.) injection may attenuate cognitive impairment induced by bilateral intracerebroventricular (b.i.c.v.) injection of 5 μg of LPS in rats. Subsequently, SPRC prevented a decrease of H₂S levels in rat hippocampus subjected to LPS. Furthermore, SPRC afforded beneficial actions in inhibitions tumor necrosis factor (TNF)-α, TNF-α receptor 1 (TNFR1) and Aβ generation, as well as IκB-α degradation and phospho-transcription factors of the nuclear factor κB p65 (p-NF-κB p65) activation induced by LPS. These findings suggested that SPRC, a novel H₂S-modulated agent, might be a potential agent for the treatment of neuroinflammation-related diseases, such as AD., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Apoptosis of cardiomyocytes induced by oxidative stress play a critical role in cardiac dysfunction associated with ventricular remodeling and heart failure. We recently reported that leonurine attenuated hypoxia-induced cardiomyocyte damage. In this study, we investigated the mechanism of leonurine (originally from Herba leonuri but we synthesized it chemically it as also called SCM-198) (H₂O₂)-induced rat embryonic heart-derived H9c2 cells from apoptosis. Exposing H9c2 cells to H₂O₂ significantly decreased cell viability, and this was attenuated by pretreatment with leonurine for 4 h in a concentration-dependent manner. Meanwhile, leonurine was found to reduce intracellular reactive oxygen species (ROS) generation in H₂O₂-stimulated cell. Moreover, H9c2 cells stimulated by H₂O₂ was accompanied with apparent apoptotic characteristics, including fragmentation of DNA, apoptotic body formation, release of cytochrome c, translocation of Bax to mitochondria, loss of mitochondrial membrane potential (ΔΨ(m)) and activation of caspase 3. Furthermore, H₂O₂ also induced rapid and significant phosphorylation of the c-Jun-N-terminal kinase 1/2 (JNK1/2), which was inhibited SP600125 (a JNK1/2 inhibitor). All of these events were attenuated by leonurine pretreatment. Taken together, these results demonstrated that leonurine could protect H9c2 cells from H₂O₂-induced apoptosis via modulation of mitochondrial dysfunction associated with blocking the activation of JNK1/2.

The effects of icariin (ICA), a major constituent of flavonoids from the Chinese medical herb Epimedium brevicornum Maxim, on spatial memory performances and expressions of hippocampus brain-derived neurotrophic factor (BDNF) and tyrosine kinase TrkB (tropomyosin receptor kinase B) were investigated in d-galactose (d-gal)-treated rats. Subcutaneous injection of d-gal (500mg/kg/d) for four months caused memory loss as detected by the Morris water maze, morphologic abnormalities of neurons in hippocampus region and the reduced expression of BDNF and TrkB were observed. ICA (60mg/kg/d) given orally 1h after subcutaneous injection of d-gal daily for 4months markedly attenuated d-gal-induced rats behavioral dysfunction and neurodegeneration, as evidenced by shortened escape latency and searching distance and rescued morphologic abnormalities, and also elevated the mRNA levels and the protein expressions of BDNF and TrkB in hippocampus, as evidenced by quantitative real-time RT-PCR and Western blotting analysis. But ICA had no significant influence on normal rats which were not injected d-gal. These results clearly demonstrated that d-gal produced learning and memory deficits after chronic administration, and ICA can protect neuron from d-gal insults and improve the memory loss., (Copyright 2010 Elsevier Inc. All rights reserved.)

The present study investigated the effect of sodium hydrosulfide (NaHS), a H(2)S donor, on cognitive impairment and neuroinflammatory changes induced by bilateral intracerebroventricular injections of LPS at a dose of 10mug/rat. Rats received 5mg/kg NaHS or volume-matched vehicle administration by intraperitoneal injection 3days before LPS injection then for 9days once daily. Morris water maze was used to detect the cognitive function. Compared to the sham-treated rats, LPS injection significantly prolonged the mean escape latency in the navigation test (P<0.05) and shortened the adjusted escape latency by approximately 30% (P<0.05). Meanwhile, LPS injection decreased H(2)S level but increased pro-inflammatory mediators (i.e., TNF-alpha, TNFR1, degradation of IkappaB-alpha and thereafter activation of NF-kappaB) in hippocampus. However, these effects of LPS were significantly ameliorated with NaHS treatment (P<0.05 vs vehicle-treated group). The present data suggest that H(2)S attenuates LPS-induced cognitive impairment through reducing the overproduction of pro-inflammatory mediators via inhibition of NF-kappaB pathways in rats. This study sets the stage for exploring a novel H(2)S releasing agent for preventing or retarding the development or progression of neurological disorders such as Alzheimer's disease., (Copyright 2010 Elsevier Inc. All rights reserved.)

The present study was undertaken to investigate the protective effects of icariin on the learning and memory abilities in Alzheimer's disease model rats and explore its protection mechanisms. Beta-amyloid peptide (Abeta) is a key etiology in Alzheimer's disease and targeting on Abeta production and assembly is a new therapeutic strategy. Six-month (400-600 g) Wistar rats were unilaterally injected with amyloid beta-protein fragment 25-35 (Abeta(25-35)) 10 microg (5 g/l, 2 microl) into the right hippocampus. The day following Abeta injection, icariin 30, 60 or 120 mg/kg was administered by gavage for 14 days. The ability of spatial learning and memory of the animals was tested by the Morris water maze. In place navigation test, icariin significantly decreased the mean escape latency and searching distance. In the space probing test, icariin increased remarkably the searching time and searching distance in the quadrant where the platform was originally located. All tests indicated icariin improved the ability of spatial learning and memory in Alzheimer's disease model rats. Furthermore, immunohistochemistry and real time RT-PCR analysis showed that icariin significantly reduced the contents of Abeta(1-40) and the mRNA levels of beta-secretase in the hippocampus and increased the mRNA level of superoxide dismutase-2, but it had no apparent effects on the immunostain and mRNA level of amyloid protein precursor. These results demonstrate that icariin can improve the learning and memory abilities in Abeta(25-35)-induced Alzheimer's disease rats. The mechanisms appear to be due to the decreased production of insoluble fragments of Abeta through suppression of beta-secretase expression.

1. Icariin is a major constituent of flavonoids derived from the Chinese medicinal herb Epimedium revicornum Maxim. The aim of the present study was to investigate whether icariin has protective effects on learning ability and memory in a rat model of chronic cerebral hypoperfusion. 2. Chronic cerebral hypoperfusion was induced by permanent ligation of the common carotid artery in Wistar rats for 4 months. One month after permanent artery occlusion, rats were adminitered icariin at doses of 0, 30, 60 or 120 mg/kg per day, p.o., for 3 months. Neurobehavioural and neurobiochemical parameters were examined to evaluate the effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion. 3. The Morris water maze test revealed that learning ability and memory were severely impaired in untreated rats, but were significantly improved in icariin-treated rats. Icariin treatment also ameliorated chronic cerebral hypoperfusion-induced oxidative stress in the brain, as evidenced by reduced malondialdehyde formation and maintained superoxide dismutase activity. In addition, the decreased hippocampal levels of acetylcholine, acetylcholinesterase and choline acetyltransferase associated with chronic cerebral hypoperfusion were significantly prevented by icariin treatment. 4. In conclusion, icariin protects against cognitive deficits induced by chronic cerebral hypoperfusion in rats. These effects appear to be mediated through its anti-oxidant effects, as well as its effects on the circulatory and cholinergic systems.

The present study was undertaken to investigate the neuroprotective effects of resveratrol on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease in rats. 6-OHDA-induced Parkinson's disease rat model involves chronic inflammation, mitochondrial dysfunction, and oxidative stress, and the loss of the dopaminergic neurons in the substantia nigra is the predominant lesion. Resveratrol has been shown to have anti-inflammatory actions, and thus was tested for its beneficial effects using 6-OHDA-induced Parkinson's disease rat model. Adult Sprague-Dawley (SD) rats were unilaterally injected with 6-OHDA (5 microg/2 microl) into the right striatum, and the striatum damage was assessed by rotational test, ultrahistopathology, and molecular alterations. Resveratrol (10, 20 and 40 mg/kg) was then given orally to Parkinson's disease rats, daily for 10 weeks to examine the protective effects. Rotational test (turns of rats) showed that resveratrol significantly attenuated apomorphine-induced turns of rats in 6-OHDA-injuried Parkinson's disease rat model as early as two weeks of administration. Ultrastructural analysis showed that resveratrol alleviated 6-OHDA-induced chromatin condensation, mitochondrial tumefaction and vacuolization of dopaminergic neurons in rat substantia nigra. Furthermore, resveratrol treatment also significantly decreased the levels of COX-2 and TNF-alpha mRNA in the substantia nigra as detected by real-time RT-PCR. COX-2 protein expression in the substantia nigra was also decreased as evidenced by Western blotting. These results demonstrate that resveratrol exerts a neuroprotective effect on 6-OHDA-induced Parkinson's disease rat model, and this protection is related to the reduced inflammatory reaction.

Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in cardiovascular diseases. Isorhynchophylline, an alkaloid from a traditional Chinese medicine Gambirplant, has been used to treat cardiovascular diseases. The aim of this study was to investigate the effects of isorhynchophylline on angiotensin II (Ang II)-induced proliferation of rat VSMCs. VSMCs were isolated from rat artery and cultured for 14 days before experimentation. The effect of isorhynchophylline on Ang II-induced proliferation was evaluated by cell number, MTT assay and flow cytometry, and nitric oxide (NO) content and activity of NO synthase (NOS) were measured. The expression of proto-oncogene c-fos, osteopontin (OPN) and proliferating cell nuclear antigen (PCNA) mRNAs was measured by real-time RT-PCR. VSMC cultures were verified by morphology and immunostaining with alpha-smooth muscle actin. Isorhynchophylline (0.1-10.0 microM) was not toxic to VSMCs, but markedly decreased Ang II (1.0 microM)-enhanced cell number and MTT intensity, and blocked cell transition from G(0)/G(1) to S phase. Furthermore, isorhynchophylline increased the NO content and NOS activity, and suppressed Ang II-induced over-expression of c-fos, OPN and PCNA. Thus, isorhynchophylline was effective against Ang-II induced cell proliferation, an effect that appears to be due, at least in part, to increased NO production, regulation of the cell cycle, and depressed expression of c-fos, OPN and PCNA related to VMSC proliferation.

Ginsenosides have been reported to release nitric oxide (NO) and decrease intracellular free Ca(2+) in cardiovascular system, which play important roles in antihypertrophic effect. This study investigated the potential inhibitory effect of total ginsenosides (TG) on right ventricular hypertrophy induced by monocrotaline (MCT, 60 mg/kg/d) and examined the possible antihypertrophic mechanism in male Sprague Dawley rats. MCT-intoxicated animals were treated with TG (20, 40, 60 mg/kg/d) for 18 d. TG treatment ameliorated MCT-induced elevations in right ventricular peak systolic pressure, right ventricular hypertrophy and the expression of atrial natriuretic peptide; N(G)-nitro-L-arginine-methyl ester (L-NAME), an NO synthase (NOS) inhibitor, had no influence on these inhibitory effects of TG 40 mg/kg/d, and TG at this dose had no any effect on the eNOS mRNA expression, suggesting the limited rule of NO in TG's effects. To further examine the mechanisms of the protection, the expression of calcineurin and its catalytic subunit CnA, as well as extracellular signal-regulated kinase-1 (ERK-1) and mitogen-activated protein kinase (MAPK) Phosphatase-1 (MKP-1) was examined. TG treatment significantly suppressed MCT-induced elevations of these signaling pathways in a dose-dependent manner. In summary, TG is effective in protecting against MCT-induced right ventricle hypertrophy, possibly through lowering pulmonary hypertension. Multiple molecular mechanisms appeared to be involved in this protection, such as the suppression of MCT-activated calcineurin and ERK signaling pathways.

We successfully treated a case of a 2-year-old male with aortic coarctation coexisting with severe mitral regurgitation via left posteriolateral thoracotomy at one stage. After a mitral valve replacement under perfused ventricular fibrillation with moderate hypothermia, we repaired the aortic coarctation with coarctation resection and end-to-end anastamosis with the aid of deep hypothermic circulatory arrest and selective low-flow cerebral perfusion. The patient had an uneventful hospital course and remains well.

Purpose: A genetic and clinical study of three unrelated Chinese pedigrees with a variable phenotype of lattice corneal dystrophy type I (LCD I)., Methods: The eyes of the patients were examined by slit lamp microscopy, and other clinical records were also collected. Genomic DNA was extracted from peripheral leukocytes of the affected patients and their family members. Exons of the transforming growth factor beta induced TGFBI gene were amplified by polymerase chain reaction and directly sequenced to verify the mutation. Fifty healthy volunteers were analyzed as normal controls., Results: Variable atypical clinical features of LCD I were found by slit lamp microscopy in these three Chinese pedigrees. A heterozygous single base-pair transition from C to T (C417T), leading to amino acid substitution (R124C) in the encoded TGFBI protein, was detected in all of the affected patients. No mutation was found in unaffected family members and 50 normal controls., Conclusions: Clinical features of Chinese patients with the same R124C mutation are quite variable even within the same family. Molecular genetic analysis of TGFBI can offer a rapid, accurate diagnosis of patients with atypical corneal dystrophies.

The influence of air turbulence on the long-range filamentation of femtosecond laser pulses has been numerically investigated. Simulations are performed for different parameters of air turbulence and laser pulses. Simulation results indicate that the diameter of filaments formed by free propagated fs laser pulse can be widened to mm level under air turbulence. However, the widening effect can be suppressed if the propagating distance before the on-set position of filamentation becomes shorter. The reduction of non-linear focal length can be realized by pre-focusing of the laser pulse or increasing of the laser intensity. The effect of the inner scale of air turbulence on the filamentation has also been studied.

The authors present photoluminescence (PL) and Raman spectra of PPV converted in vacuum by ultraviolet(UV) irradiation which indicate partial conjugation similar to thermally converted poly(p-phenylene vinylene) (PPV). The authors have fabricated OLEDs based on photo-converted PPV. Though the electroluminescence (EL) spectra are poor, doped PPV-based OLED devices are achieved.

Aim: To investigate the influence of resveratrol (Res), a nutritional antioxidant, on the inhibition of apoptosis in rat primary neuron cultures., Methods: The cultured cortical neurons of neonatal Sprague-Dawley rats were pretreated with Res (0.1, 1.0, and 10.0 micromol/L) and oxygen-glucose deprivation/reperfusion (OGD/RP) with oxygen and glucose were initiated at d 10 in vitro. Neuronal apoptosis was determined by flow cytometry, and morphological changes of neurons were observed by an electron microscope. For the mechanism studies, the intracellular free calcium concentration ([Ca2+]i) and the transcription of caspases-3 and -12 in neurons were detected by Fura 2/AM loading and real-time RT-PCR, respectively., Results: OGD/RP insult could induce an increase in the apoptotic rate of neurons (from 11.1% to 49.0%), and elicit an obvious morphological change in neurons; pretreatments with Res (0.1, 1.0, and 10.0 micromol/L, respectively) significantly reduced the elevated rate of apoptosis to 41.7%, 40.8%, and 37.4%, respectively, and ameliorated the neuronal morphological injury. Similarly, the OGD/RP insult obviously elicited the elevated levels of the [Ca2+]i and the expressions of caspases-3 and -12 mRNA in neurons. Res pretreatments markedly depressed the neuronal abnormal elevation of [Ca2+]i and the overexpression of caspases-3 and -12 mRNA in a concentration-dependent manner., Conclusion: Res can attenuate the rat cortical neuronal apoptosis induced by OGD/RP. The mechanisms are, at least partly, due to the inhibition of the calcium overload and the overexpression of caspases-3 and -12 mRNA.

Background: Familial hypercholesterolemia (FH) is a type of dominant autosomal disease that causes high levels of plasma low-density lipoprotein cholesterol (LDL-C). In the past years, molecular data related to FH were limited in China. Now, to gain more information about FH, we analyzed one proband with a severe FH phenotype as well as his relatives., Methods: After the entire coding sequence and the intron-exon junctions of the low-density lipoprotein receptor (LDLR) gene were amplified using PCR, we sequenced the LDLR gene of a Chinese FH family. RT-PCR was used to detect changes in the mRNA., Results: Two novel mutations were identified in the LDLR gene of this family. One, W165X, was a G > A substitution at the third nucleotide of codon 165. The other, IVS5-1G > A, was also a G > A substitution at the acceptor splice site of intron 5. The most striking discovery is that the proband was heterozygous for W165X but homozygous for IVS5-1G > A. The cDNA sequencing showed that the IVS5-1G > A mutation caused the insertion of 10 nucleotides, namely GCTCTCACAA, between exon 5 and exon 6., Conclusions: The two nucleotide variations are thought to be the FH-causing mutations because the co-segregation of the mutant allele with the phenotype of FH has been shown in this Chinese family. These data show an increase in the mutational spectrum of FH in China and verify a scarce mutational form in the LDLR gene.

Neurosteroids, such as the progesterone metabolite 3alpha-OH-5alpha[beta]-pregnan-20-one (THP or [allo]pregnanolone), function as potent positive modulators of the GABA(A) receptor (GABAR) when acutely administered. However, fluctuations in the circulating levels of this steroid at puberty, across endogenous ovarian cycles, during pregnancy or following chronic stress produce periods of prolonged exposure and withdrawal, where changes in GABAR subunit composition may occur as compensatory responses to sustained levels of inhibition. A number of laboratories have demonstrated that both chronic administration of THP as well as its withdrawal transiently increase expression of the alpha4 subunit of the GABAR in several areas of the central nervous system (CNS) as well as in in vitro neuronal systems. Receptors containing this subunit are insensitive to benzodiazepine (BDZ) modulation and display faster deactivation kinetics, which studies suggest underlie hyperexcitability states. Similar increases in alpha4 expression are triggered by withdrawal from other GABA-modulatory compounds, such as ethanol and BDZ, suggesting a common mechanism. Other studies have reported puberty or estrous cycle-associated increases in delta-GABAR, the most sensitive target of these steroids which underlies a tonic inhibitory current. In the studies reported here, the effect of steroids on inhibition, which influence anxiety state and seizure susceptibility, depend not only on the subunit composition of the receptor but also on the direction of Cl(-) current generated by these target receptors. The effect of neurosteroids on GABAR function thus results in behavioral outcomes relevant for pubertal mood swings, premenstrual dysphoric disorder and catamenial epilepsy, which are due to fluctuations in endogenous steroids.

1. The present study examined the protective effects of icariin against the learning and memory deficits in aluminium-treated rats and its potential mechanisms of action. 2. Qualified rats were treated with 1600 p.p.m. AlCl(3) in drinking water for 8 months and the ability of spatial learning and memory was tested by the Morris water maze. In the place navigation test, aluminium administration significantly increased the mean escape latency and searching distance. In space probing test, aluminium markedly decreased the searching time and searching distance in the quadrant where the platform was originally located. All tests indicated deficits in rat spatial learning and memory induced by aluminium. Icariin treatment (60 and 120 mg/kg, by gavage for 3 months) dose-dependently protected against the development of aluminium-induced spatial learning and memory deficits. 3. To examine the mechanisms responsible for the protection afforded by icariin, the superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in the hippocampus were assayed biochemically and the level of Abeta(1-40) in the hippocampus was determined immunohistochemically. Icariin treatment significantly increased SOD activity and decreased MDA and Abeta(1-40) content in the hippocampus of aluminium-intoxicated rats. 4. In conclusion, the present study demonstrates that icariin is effective in improving the spatial learning and memory of aluminium-intoxicated rats. The mechanisms responsible appear to be due, at least in part, to an increased anti-oxidant capacity and decreased lipid peroxidation and Abeta(1-40) levels in the rat hippocampus.

A metal-insulator complex film made by co-evaporating metal Pb and transparent insulator LiF was tested as a low-reflecting cathode to realize high contrast organic light-emitting diodes (OLED). The optical reflectivity and electrical characteristic of the high contrast OLED were studied as compared with the device based on Al as the cathode. The reflectivity of the Pb-LiF complex cathode is 18% only, about 5 times lower than that of Al cathode. The experimental result shows that the high contrast and the conventional OLEDs are similar in terms of the electroluminescent property.

Several recent studies have suggested that alphabetadelta subtypes of gamma-aminobutyric acid type A (GABAA) receptors (delta-GABAR) are a target for low dose ethanol (<30 mM). However, there are also conflicting reports suggesting that only high doses of the drug (100 mM) modulate these receptors. In addition, the studies which have demonstrated a clear effect of low dose ethanol on delta-GABAR find different effective concentrations for this effect. Here, we test the hypothesis that the apparent disparity in effective concentration is due to time-course effects when low (1-3 mM) dose ethanol is preapplied. To this end, we tested ethanol effects on native GABAR in CA1 hippocampus in a model of increased alpha4betadelta GABAR expression following 48h administration of the GABA-modulatory steroid THP (3alpha-OH-5beta-pregnan-20-one) to adult, female rats. GABA(EC20)-gated current was recorded with whole-cell patch clamp procedures from acutely isolated pyramidal cells. We assessed ethanol's effect on GABA-gated current using either (1) 2-5 min application of ethanol in increasing concentrations (0.1-30 mM) or (2) coadministration of ethanol with GABA. Two minute application of 1-3 mM ethanol produced optimal potentiation of GABA-gated current following steroid treatment, with higher concentrations less effective. In contrast, 30 mM ethanol produced optimal effects when ethanol was not preapplied. However, following preapplication of 1mM ethanol, 30 mM ethanol decreased the peak GABA-gated current. These findings suggest that ethanol may act at multiple interacting sites to affect GABAR efficacy and desensitization. These data also suggest that ethanol effects on GABA-gated current are affected by the time course of exposure and previous exposure to low concentrations of the drug.

Objective: To analyze the multiple factors affecting the postoperative mechanical ventilation supporting time in infants less than 10 kg with simple congenital heart diseases and to seize time by the forelock of extube and improve the outcome of surgical treatment., Methods: Data of 231 infants less than 10 kg with atrial septal defect(ASD),ventricular septal defect, and combining patent ductus arteriosus were retrospectively analyzed. The multivaricate stepwise logistic regression statistics were done for the predisposing factors affecting the ventilative supporting time., Results: The ventilative supporting time was 3~375 (average 23.5 h) h. The multivaricate stepwise logistic regression analysis indicated that severe pulmonary hyperpressure, cross-cramp aortic time, cardiopulmonary bypass time, preoperational pulmonary infection, membrane oxygenator, modified ultrafiltration, weight, and postoperative complications were significantly correlated to the ventilative supporting time., Conclusion: Severe pulmonary hyperpressure, preoperational pulmonary infection, long cross-cramp aortic time, long cardiopulmonary bypass time, postoperative complications all prolong the ventilation supporting time; the use of membrane oxygenator and modified ultrafiltration during the operation and big weight can diminish the pulmonary complications and shorten the ventilation supporting time.

Puberty is characterized by mood swings and anxiety, which are often produced by stress. Here we show that THP (allopregnanolone), a steroid that is released as a result of stress, increases anxiety in pubertal female mice, in contrast to its anxiety-reducing effect in adults. Anxiety is regulated by GABAergic inhibition in limbic circuits. Although this inhibition is increased by THP administration before puberty and in adults, during puberty THP reduces the tonic inhibition of pyramidal cells in hippocampal region CA1, leading to increased excitability. This paradoxical effect of THP results from inhibition of alpha4betadelta GABAA receptors. These receptors are normally expressed at very low levels, but at puberty, their expression is increased in hippocampal area CA1, where they generate outward currents. THP also decreases the outward current at recombinant alpha4beta2delta receptors, and this effect depends on arginine 353 in the alpha4 subunit, a putative site for modulation by Cl-. Therefore, inhibition of alpha4beta2delta GABAA receptors by THP provides a mechanism for the generation of anxiety at puberty.

Objective: To examine the protective effect of Ginkgo biloba leaf extract (GbE) on learning and memory deficit induced by aluminum chloride (AlCl(3)), and explore its mechanisms., Methods: The rat models with learning and memory deficit were induced by administering via gastrogavage and drinking of AlCl(3) solution. And the model rats were treated with GbE at the dose of 50, 100, 200 mg/kg every day for 2 months accompanied with drinking of AlCl(3) solution, respectively. Their abilities of spatial learning and memory were tested by Morris water maze, and the acetylcholinesterase (AChE) activity in serum was assayed with chemical method, the AChE expression in hippocampus was observed by immunohistochemistry assay, and then quantitative analysis was done by BI 2000 image analysis system., Results: Learning and memory deficit of rats could be induced by AlCl(3) solution (P < 0.01), and AChE expressions in rats hippocampus were increased (P < 0.01); GbE ameliorated learning and memory deficit and reduced AChE expression in rats hippocampus in a dose-dependent manner, while GbE significantly increased serum AChE activity at the dose of 200 mg/kg each day (P < 0.05)., Conclusion: GbE can ameliorate learning and memory deficit induced by AlCl(3), which may be due to its inhibition of the AChE expression in hippocampus.