Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion

<p>Abstract</p> <p>Background</p> <p>Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of <it>Lamiophlomis rotata (Benth.) Kudo</it>. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo.</p> <p>Methods</p> <p>For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h.</p> <p>Results</p> <p>ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation.</p> <p>Conclusion</p> <p>These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway.</p

Combustion synthesis of Ce2LuO5.5:Eu phosphor nanopowders: structure, surface and luminescence investigations

The spherical shape, uniform size and small degree of agglomeration of the particles play crucial roles in promoting the practical applications of the phosphor powders. In this paper, the novel Eu3+ -doped cerium lutetium Ce2LuO5.5 composite nanopowders with a cubic fluorite structure were prepared via a typical solution combustion route, and their internal structure, surface morphology as well as luminescence properties were investigated. The Eu3+ could substitute in either Lu3+ or Ce4+ sites and the existence of oxygen vacancy was confirmed in the composite by X-ray diffraction and Raman spectra techniques. Without the addition of surfactant, most of the as-prepared particles were bound together, and the luminescence was very weak even after a sintering process. Assisted with appropriate polyvinyl alcohol (PVA) surfactant in the combustion reaction and a subsequent heat-treatment process, the bound-particles were evidently separated and seemed to be nearly spherical shape. The particle size could be controlled to 30–120 nm and the luminescence was enhanced by adjusting the subsequent sintering temperature. Excited with 466 nm blue light, the nanopowders exhibited characteristic 5D0 → 7FJ (J  =  0–4) emission transition of Eu3+ and showed enhanced red luminescence as Eu3+ occupied Ce4+ site rather than Lu3+ site. The maximum emission was obtained as 40 mol% Eu substitutes Ce in the composite. Due to the coincidence of 466 nm excitation light with the emission of InGaN chips in white light-emitting diodes, the surface-morphology improved Eu-doped Ce2LuO5.5 phosphor nanopowders have a potential application in solid state lighting fields.publishe

Ln3+ (Ln = Eu, Dy) - doped Sr2CeO4 fine phosphor particles: wet chemical preparation, energy transfer and tunable luminescence

The Sr2CeO4:Ln3+ (Ln = Eu, Dy) fine phosphor particles were prepared by a facile wet chemical approach, in which the consecutive hydrothermal-combustion reaction was performed. The doping of Ln3+ into Sr2CeO4 has little influence on the structure of host, and the as-prepared samples display well-crystallized spherical or elliptical shape with an average particle size at about 100–200 nm. For Eu3+ ions-doped Sr2CeO4, with the increase of Eu3+-doping concentration, the blue light emission band with the maximum at 468 nm originating from a Ce4+ → O2− charge transfer of the host decreases obviously and the characteristic red light emission of Eu3+ (5D0→7F2 transition at 618 nm) is enhanced gradually. Simultaneously, the fluorescent lifetime of the broadband emission of Sr2CeO4 decreases with the doping of Eu3+, indicating an efficient energy transfer from the host to the doping Eu3+ ions. The energy transfer efficiency from the host to Eu3+ was investigated in detail, and the emitting color of Sr2CeO4:Eu3+ can be easily tuned from blue to red by varying the doping concentration of Eu3+ ions. Moreover, the luminescence of Dy3+-doped Sr2CeO4 was also studied. Similar energy transfer phenomenon can be observed, and the incorporation of Dy3+ into Sr2CeO4 host leads to the characteristic emission of 4F9/2 → 6H15/2 (488 nm, blue light) and 4F9/2 → 6H13/2 (574 nm, yellow light) of Dy3+. The Sr2CeO4:Ln3+ fine particles with tunable luminescence are quite beneficial for its potential applications in the optoelectronic fields.publishe

Quantitative DNA Methylation Analysis of DLGAP2 Gene Using Pyrosequencing in Schizophrenia With Tardive Dyskinesia: A Linear Mixed Model Approach

Tardive dyskinesia (TD) is a side effect of antipsychotic medications used to treat schizophrenia (SCZ) and other mental health disorders. No study has previously used pyrosequencing to quantify DNA methylation levels of the DLGAP2 gene; while the quantitative methylation levels among CpG sites within a gene may be correlated. To deal with the correlated measures among three CpG sites within the DLGAP2 gene, this study analyzed DNA methylation levels of the DLGAP2 gene using a linear mixed model (LMM) in a Chinese sample consisting of 35 SCZ patients with TD, 35 SCZ without TD (NTD) and 34 healthy controls (HCs) collected in Beijing, China. The initial analysis using the non-parametric Kruskal-Wallis test revealed that three groups (TD, NTD and HC) had significant differences in DNA methylation level for CpG site 2 (p = 0.0119). Furthermore, the average methylation levels among the three CpG sites showed strong correlations (all p values \u3c 0.0001). In addition, using the LMM, three groups had significant differences in methylation level (p = 0.0027); while TD, NTD and TD + NTD groups showed higher average methylation levels than the HC group (p = 0.0024, 0.0151, and 0.0007, respectively). In conclusion, the LMM can accommodate a covariance structure. The findings of this study provide first evidence of DNA methylation levels in DLGAP2 associated with SCZ with TD in Chinese population. However, TD just showed borderline significant differences to NTD in this study

Silencing SARS-CoV Spike protein expression in cultured cells by RNA interference

AbstractThe severe acute respiratory syndrome (SARS) has been one of the most epidemic diseases threatening human health all over the world. Based on clinical studies, SARS-CoV (the SARS-associated coronavirus), a novel coronavirus, is reported as the pathogen responsible for the disease. To date, no effective and specific therapeutic method can be used to treat patients suffering from SARS-CoV infection. RNA interference (RNAi) is a process by which the introduced small interfering RNA (siRNA) could cause the degradation of mRNA with identical sequence specificity. The RNAi methodology has been used as a tool to silence genes in cultured cells and in animals. Recently, this technique was employed in anti-virus infections in human immunodeficiency virus and hepatitis C/B virus. In this study, RNAi technology has been applied to explore the possibility for prevention of SARS-CoV infection. We constructed specific siRNAs targeting the S gene in SARS-CoV. We demonstrated that the siRNAs could effectively and specifically inhibit gene expression of Spike protein in SARS-CoV-infected cells. Our study provided evidence that RNAi could be a tool for inhibition of SARS-CoV

Active YAP promotes pancreatic cancer cell motility, invasion and tumorigenesis in a mitotic phosphorylation-dependent manner through LPAR3.

The transcriptional co-activator Yes-associated protein, YAP, is a main effector in the Hippo tumor suppressor pathway. We recently defined a mechanism for positive regulation of YAP through CDK1-mediated mitotic phosphorylation. Here, we show that active YAP promotes pancreatic cancer cell migration, invasion and anchorage-independent growth in a mitotic phosphorylation-dependent manner. Mitotic phosphorylation is essential for YAP-driven tumorigenesis in animals. YAP reduction significantly impairs cell migration and invasion. Immunohistochemistry shows significant upregulation and nuclear localization of YAP in metastases when compared with primary tumors and normal tissue in human. Mitotic phosphorylation of YAP controls a unique transcriptional program in pancreatic cells. Expression profiles reveal LPAR3 (lysophosphatidic acid receptor 3) as a mediator for mitotic phosphorylation-driven pancreatic cell motility and invasion. Together, this work identifies YAP as a novel regulator of pancreatic cancer cell motility, invasion and metastasis, and as a potential therapeutic target for invasive pancreatic cancer

Hydrothermal catalytic production of fuels and chemicals from aquatic biomass

One of the promising avenues for biomass processing is the use of water as a reaction medium for wet or aquatic biomass. This review focuses on the hydrothermal catalytic production of fuels and chemicals from aquatic biomass. Two different regimes for conversion of aquatic biomass in hydrothermal conditions are discussed in detail. The first is hydrothermal liquefaction, and the second is hydrothermal gasification. The goals of these processes are to produce liquid‐fuel‐range hydrocarbons and methane or hydrogen, respectively. The catalytic upgrading of biocrude resulting from noncatalytic liquefaction and the stability and degradation of catalysts in high temperature water are also discussed. The review concludes with a brief discussion of the outlook for and opportunities within the field of hydrothermal catalytic valorization of biomass. Copyright © 2012 Society of Chemical IndustryPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94889/1/jctb3933.pd

The Relationship Between Cognitive Dysfunction and Symptom Dimensions Across Schizophrenia, Bipolar Disorder, and Major Depressive Disorder

Background: Cognitive dysfunction is considered a core feature among schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). Despite abundant literature comparing cognitive dysfunction among these disorders, the relationship between cognitive dysfunction and symptom dimensions remains unclear. The study aims are a) to identify the factor structure of the BPRS-18 and b) to examine the relationship between symptom domains and cognitive function across SZ, BD, and MDD.Methods: A total of 716 participants [262 with SZ, 104 with BD, 101 with MDD, and 249 healthy controls (HC)] were included in the study. One hundred eighty participants (59 with SZ, 23 with BD, 24 with MDD, and 74 HC) completed the MATRICS Consensus Cognitive Battery (MCCB), and 507 participants (85 with SZ, 89 with BD, 90 with MDD, and 243 HC) completed the Wisconsin Card Sorting Test (WCST). All patients completed the Brief Psychiatric Rating Scale (BPRS).Results: We identified five BPRS exploratory factor analysis (EFA) factors (“affective symptoms,” “psychosis,” “negative/disorganized symptoms,” “activation,” and “noncooperation”) and found cognitive dysfunction in all of the participant groups with psychiatric disorders. Negative/disorganized symptoms were the most strongly associated with cognitive dysfunctions across SZ, BD, and MDD.Conclusions: Our findings suggest that cognitive dysfunction severity relates to the negative/disorganized symptom domain across SZ, BD, and MDD, and negative/disorganized symptoms may be an important target for effective cognitive remediation in SZ, BD, and MDD

Caveolin-1 Plays a Crucial Role in Inhibiting Neuronal Differentiation of Neural Stem/Progenitor Cells via VEGF Signaling-Dependent Pathway

In the present study, we aim to elucidate the roles of caveolin-1(Cav-1), a 22 kDa protein in plasma membrane invaginations, in modulating neuronal differentiation of neural progenitor cells (NPCs). In the hippocampal dentate gyrus, we found that Cav-1 knockout mice revealed remarkably higher levels of vascular endothelial growth factor (VEGF) and the more abundant formation of newborn neurons than wild type mice. We then studied the potential mechanisms of Cav-1 in modulating VEGF signaling and neuronal differentiation in isolated cultured NPCs under normoxic and hypoxic conditions. Hypoxic embryonic rat NPCs were exposed to 1% O2 for 24 h and then switched to 21% O2 for 1, 3, 7 and 14 days whereas normoxic NPCs were continuously cultured with 21% O2. Compared with normoxic NPCs, hypoxic NPCs had down-regulated expression of Cav-1 and up-regulated VEGF expression and p44/42MAPK phosphorylation, and enhanced neuronal differentiation. We further studied the roles of Cav-1 in inhibiting neuronal differentiation by using Cav-1 scaffolding domain peptide and Cav-1-specific small interfering RNA. In both normoxic and hypoxic NPCs, Cav-1 peptide markedly down-regulated the expressions of VEGF and flk1, decreased the phosphorylations of p44/42MAPK, Akt and Stat3, and inhibited neuronal differentiation, whereas the knockdown of Cav-1 promoted the expression of VEGF, phosphorylations of p44/42MAPK, Akt and Stat3, and stimulated neuronal differentiation. Moreover, the enhanced phosphorylations of p44/42MAPK, Akt and Stat3, and neuronal differentiation were abolished by co-treatment of VEGF inhibitor V1. These results provide strong evidence to prove that Cav-1 can inhibit neuronal differentiation via down-regulations of VEGF, p44/42MAPK, Akt and Stat3 signaling pathways, and that VEGF signaling is a crucial target of Cav-1. The hypoxia-induced down-regulation of Cav-1 contributes to enhanced neuronal differentiation in NPCs

Regulation of High-Temperature Stress Response by Small RNAs

Temperature extremes constitute one of the most common environmental stresses that adversely affect the growth and development of plants. Transcriptional regulation of temperature stress responses, particularly involving protein-coding gene networks, has been intensively studied in recent years. High-throughput sequencing technologies enabled the detection of a great number of small RNAs that have been found to change during and following temperature stress. The precise molecular action of some of these has been elucidated in detail. In the present chapter, we summarize the current understanding of small RNA-mediated modulation of high- temperature stress-regulatory pathways including basal stress responses, acclimation, and thermo-memory. We gather evidence that suggests that small RNA network changes, involving multiple upregulated and downregulated small RNAs, balance the trade-off between growth/development and stress responses, in order to ensure successful adaptation. We highlight specific characteristics of small RNA-based tem- perature stress regulation in crop plants. Finally, we explore the perspectives of the use of small RNAs in breeding to improve stress tolerance, which may be relevant for agriculture in the near future