Effects of Electroacupuncture on N-Methyl-D-aspartate Receptor-Related Signaling Pathway in the Spinal Cord of Normal Rats

This study examined the influence of the N-methyl-D-aspartate receptor (NMDAR) on the modulation of related spinal signaling after electroacupuncture (EA) treatment in normal rats. Bilateral 2 Hz EA stimulations (1-2-3.0 mA) were delivered at acupoints corresponding to Zusanli (ST36) and Sanyinjiao (SP6) in men for 30 min. Thermal sensitization was strongly inhibited by EA, but this analgesia was reduced by preintrathecal injection of the NMDAR antagonist, MK801. Phosphorylation of the NMDAR NR2B subunit, cAMP response element-binding protein (CREB), and especially phosphatidylinositol 3-kinase (PI3K) were significantly induced by EA. However, these marked phosphorylations were not observed in MK801-pretreated rats. EA analgesia was reduced by preintrathecal injection with the calcium chelators Quin2 and TMB8, similar to the results evident using MK801. Phosphorylation of PI3K and CREB induced by EA was also inhibited by TMB8. Calcium influx by NMDAR activation may play an important role in EA analgesia of normal rats through the modulation of the phosphorylation of spinal PI3K and CREB

Beneficial Effects of Gagam-Palmultang on Scopolamine-Induced Memory Deficits in Mice

From text mining of Dongeuibogam, the 7 herbs in Palmultang can be considered effective candidates for memory enhancement. We sought to determine whether Gagam-Palmultang, comprising these 7 herbs, ameliorates scopolamine-induced memory impairment in mice, by focusing on the central cholinergic system and memory-related signaling molecules. Behavioral tests were performed after inducing memory impairment by scopolamine administration. The cholinergic system activity and memory-related molecules were examined in the hippocampus by enzyme-linked immunosorbent, western blot, and immunofluorescence assays. Gagam-Palmultang ameliorated scopolamine-induced memory impairment in the Morris water maze test, producing a significant improvement in the mean time required to find the hidden platform. Treatment with Gagam-Palmultang reduced acetylcholinesterase activity and expression in the hippocampus induced by scopolamine. The diminished phosphorylated phosphatidylinositide 3-kinase (PI3K), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB), and mature brain-derived neurotrophic factor (mBDNF) expressions caused by scopolamine administration were attenuated by treatment with Gagam-Palmultang. This treatment also promoted neuronal cell proliferation in the hippocampus. Gagam-Palmultang has beneficial effects against scopolamine-induced memory impairments, which are exerted via modulation of the cholinergic system as well as the PI3K and ERK/CREB/BDNF signaling pathway. Therefore, this multiherb formula may be a useful therapeutic agent for diseases associated with memory impairments

The secondary prophylactic efficacy of beta-blocker after endoscopic gastric variceal obturation for first acute episode of gastric variceal bleeding

Background/AimsThe most appropriate treatment for acute gastric variceal bleeding (GVB) is currently endoscopic gastric variceal obturation (GVO) using Histoacryl®. However, the secondary prophylactic efficacy of beta-blocker (BB) after GVO for the first acute episode of GVB has not yet been established. The secondary prophylactic efficacy of BB after GVO for the first acute episode of GVB was evaluated in this study.MethodsNinety-three patients at Soonchunhyang University Hospital with acute GVB who received GVO using Histoacryl® were enrolled between June 2001 and March 2010. Among these, 42 patients underwent GVO alone (GVO group) and 51 patients underwent GVO with adjuvant BB therapy (GVO+BB group). This study was intended for patients in whom a desired heart rate was reached. The rates of rebleeding-free survival and overall survival were calculated for the two study groups using Kaplan-Meyer analysis and Cox's proportional-hazards model.ResultsThe follow-up period after the initial eradication of gastric varices was 18.14±25.22 months (mean±SD). During the follow-up period, rebleeding occurred in 10 (23.8%) and 21 (41.2%) GVO and GVO+BB patients, respectively, and 39 patients died [23 (54.8%) in the GVO group and 16 (31.4%) in the GVO+BB group]. The mean rebleeding-free survival time did not differ significantly between the GVO and GVO+BB groups (65.40 and 37.40 months, respectively; P=0.774), whereas the mean overall survival time did differ (52.54 and 72.65 months, respectively; P=0.036).Conclusions Adjuvant BB therapy after GVO using Histoacryl® for the first acute episode of GVB could decrease the mortality rate relative to GVO alone. However, adjuvant BB therapy afforded no benefit for the secondary prevention of rebleeding in GV

Revealing the nature of morphological changes in carbon nanotube-polymer saturable absorber under high-power laser irradiation

Composites of single-walled carbon nanotubes (SWNTs) and water-soluble polymers (WSP) are the focus of significant worldwide research due to a number of applications in biotechnology and photonics, particularly for ultrashort pulse generation. Despite the unique possibility of constructing non-linear optical SWNT-WSP composites with controlled optical properties, their thermal degradation threshold and limit of operational power remain unexplored. In this study, we discover the nature of the SWNT-polyvinyl alcohol (PVA) film thermal degradation and evaluate the modification of the composite properties under continuous high-power ultrashort pulse laser operation. Using high-precision optical microscopy and micro-Raman spectroscopy, we have examined SWNT-PVA films before and after continuous laser radiation exposure (up to 40 hours) with a maximum optical fluence of 2.3 mJ·cm−2. We demonstrate that high-intensity laser radiation results in measurable changes in the composition and morphology of the SWNT-PVA film due to efficient heat transfer from SWNTs to the polymer matrix. The saturable absorber modification does not affect the laser operational performance. We anticipate our work to be a starting point for more sophisticated research aimed at the enhancement of SWNT-PVA films fabrication for their operation as reliable saturable absorbers in high-power ultrafast lasers

Genome Sequence of Striga asiatica Provides Insight into the Evolution of Plant Parasitism

Parasitic plants in the genus Striga, commonly known as witchweeds, cause major crop losses in sub-Saharan Africa and pose a threat to agriculture worldwide. An understanding of Striga parasite biology, which could lead to agricultural solutions, has been hampered by the lack of genome information. Here, we report the draft genome sequence of Striga asiatica with 34,577 predicted protein-coding genes, which reflects gene family contractions and expansions that are consistent with a three-phase model of parasitic plant genome evolution. Striga seeds germinate in response to host-derived strigolactones (SLs) and then develop a specialized penetration structure, the haustorium, to invade the host root. A family of SL receptors has undergone a striking expansion, suggesting a molecular basis for the evolution of broad host range among Striga spp. We found that genes involved in lateral root development in non-parasitic model species are coordinately induced during haustorium development in Striga, suggesting a pathway that was partly co-opted during the evolution of the haustorium. In addition, we found evidence for horizontal transfer of host genes as well as retrotransposons, indicating gene flow to S. asiatica from hosts. Our results provide valuable insights into the evolution of parasitism and a key resource for the future development of Striga control strategies.Peer reviewe

Hypomethylation of Intragenic LINE-1 Represses Transcription in Cancer Cells through AGO2

In human cancers, the methylation of long interspersed nuclear element -1 (LINE-1 or L1) retrotransposons is reduced. This occurs within the context of genome wide hypomethylation, and although it is common, its role is poorly understood. L1s are widely distributed both inside and outside of genes, intragenic and intergenic, respectively. Interestingly, the insertion of active full-length L1 sequences into host gene introns disrupts gene expression. Here, we evaluated if intragenic L1 hypomethylation influences their host gene expression in cancer. First, we extracted data from L1base (http://l1base.molgen.mpg.de), a database containing putatively active L1 insertions, and compared intragenic and intergenic L1 characters. We found that intragenic L1 sequences have been conserved across evolutionary time with respect to transcriptional activity and CpG dinucleotide sites for mammalian DNA methylation. Then, we compared regulated mRNA levels of cells from two different experiments available from Gene Expression Omnibus (GEO), a database repository of high throughput gene expression data, (http://www.ncbi.nlm.nih.gov/geo) by chi-square. The odds ratio of down-regulated genes between demethylated normal bronchial epithelium and lung cancer was high (p<1E−27; OR = 3.14; 95% CI = 2.54–3.88), suggesting cancer genome wide hypomethylation down-regulating gene expression. Comprehensive analysis between L1 locations and gene expression showed that expression of genes containing L1s had a significantly higher likelihood to be repressed in cancer and hypomethylated normal cells. In contrast, many mRNAs derived from genes containing L1s are elevated in Argonaute 2 (AGO2 or EIF2C2)-depleted cells. Hypomethylated L1s increase L1 mRNA levels. Finally, we found that AGO2 targets intronic L1 pre-mRNA complexes and represses cancer genes. These findings represent one of the mechanisms of cancer genome wide hypomethylation altering gene expression. Hypomethylated intragenic L1s are a nuclear siRNA mediated cis-regulatory element that can repress genes. This epigenetic regulation of retrotransposons likely influences many aspects of genomic biology

Cathelicidin-like Helminth Defence Molecules (HDMs) Absence of Cytotoxic, Anti-microbial and Anti-protozoan Activities Imply a Specific Adaptation to Immune Modulation

Host defence peptides (HDPs) are expressed throughout the animal and plant kingdoms. They have multifunctional roles in the defence against infectious agents of mammals, possessing both bactericidal and immune-modulatory activities. We have identified a novel family of molecules secreted by helminth parasites (helminth defence molecules; HDMs) that exhibit similar structural and biochemical characteristics to the HDPs. Here, we have analyzed the functional activities of four HDMs derived from Schistosoma mansoni and Fasciola hepatica and compared them to human, mouse, bovine and sheep HDPs. Unlike the mammalian HDPs the helminth-derived HDMs show no antimicrobial activity and are non-cytotoxic to mammalian cells (macrophages and red blood cells). However, both the mammalian- and helminth-derived peptides suppress the activation of macrophages by microbial stimuli and alter the response of B cells to cytokine stimulation. Therefore, we hypothesise that HDMs represent a novel family of HDPs that evolved to regulate the immune responses of their mammalian hosts by retaining potent immune modulatory properties without causing deleterious cytotoxic effects. © 2013 Thivierge et al