Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain

The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered

Functional role of NF-IL6β and its sumoylation and acetylation modifications in promoter activation of cyclooxygenase 2 gene

NF-IL6β regulates gene expression and plays function roles in many tissues. The EGF-regulated cyclooxygenase-2 (cox-2) expression is mediated through p38(MAPK) signaling pathway and positively correlates with NF-IL6β expression in A431 cells. NF-IL6β coordinated with c-Jun on cox-2 transcriptional activation by reporter and small interfering RNA assays. NF-IL6β could directly bind to CCAAT/enhancer-binding protein (C/EBP) and cyclic AMP-response element (CRE) sites of the cox-2 promoter by in vitro-DNA binding assay. The C/EBP site was important for basal and, to a lesser extent, for EGF-regulated cox-2 transcription, while the CRE site was a more specific response to EGF inducibility of cox-2 gene. SUMO1 expression attenuated EGF- and NF-IL6β-induced cox-2 promoter activities. NF-IL6β was found to be sumoylated by in vivo- and in vitro-sumoylation assays, and the SUMO1-NF-IL6β (suNF-IL6β) lost its ability to interact with p300 in in vitro-binding assay. NF-IL6β was also acetylated by p300, and acetylation of NF-IL6β enhanced the cox-2 promoter activity stimulated by NF-IL6β itself. In vivo-DNA binding assay demonstrated that EGF stimulated the recruitment of p300 and NF-IL6β to the cox-2 promoter, yet promoted the dissociation of SUMO1-modificated proteins from the promoter. These results indicated that NF-IL6β plays a pivotal role in the regulation of basal and EGF-induced cox-2 transcription

ATIVS: analytical tool for influenza virus surveillance

The WHO Global Influenza Surveillance Network has routinely performed genetic and antigenic analyses of human influenza viruses to monitor influenza activity. Although these analyses provide supporting data for the selection of vaccine strains, it seems desirable to have user-friendly tools to visualize the antigenic evolution of influenza viruses for the purpose of surveillance. To meet this need, we have developed a web server, ATIVS (Analytical Tool for Influenza Virus Surveillance), for analyzing serological data of all influenza viruses and hemagglutinin sequence data of human influenza A/H3N2 viruses so as to generate antigenic maps for influenza surveillance and vaccine strain selection. Functionalities are described and examples are provided to illustrate its usefulness and performance. The ATIVS web server is available at http://influenza.nhri.org.tw/ATIVS/

Antidepressant-Like Activity of the Ethanolic Extract from Uncaria lanosa Wallich var. appendiculata Ridsd in the Forced Swimming Test and in the Tail Suspension Test in Mice

This study investigated the antidepressant activity of ethanolic extract of U. lanosa Wallich var. appendiculata Ridsd (ULEtOH) for two-weeks administrations by using FST and TST on mice. In order to understand the probable mechanism of antidepressant-like activity of ULEtOH in FST and TST, the researchers measured the levels of monoamines and monoamine oxidase activities in mice brain, and combined the antidepressant drugs (fluoxetine, imipramine, maprotiline, clorgyline, bupropion and ketanserin). Lastly, the researchers analyzed the content of RHY in the ULEtOH. The results showed that ULEtOH exhibited antidepressant-like activity in FST and TST in mice. ULEtOH increased the levels of 5-HT and 5-HIAA in cortex, striatum, hippocampus, and hypothalamus, the levels of NE and MHPG in cortex and hippocampus, the level of NE in striatum, and the level of DOPAC in striatum. Two-week injection of IMI, CLO, FLU and KET enhanced the antidepressant-like activity of ULEtOH. ULEtOH inhibited the activity of MAO-A. The amount of RHY in ULEtOH was 17.12 mg/g extract. Our findings support the view that ULEtOH exerts antidepressant-like activity. The antidepressant-like mechanism of ULEtOH may be related to the increase in monoamines levels in the hippocampus, cortex, striatum, and hypothalamus of mice

The Influence of Functional Fitness and Cognitive Training of Physical Disabilities of Institutions

According to an investigation done by Taiwan Ministry of the Interior in 2013, there was more than 90% of the disability care institutions mainly based on life care. Previous studies have shown that individuals can effectively improve physical and cognitive training, improved in independent living and everyday competence. The purpose of the study was to investigate influence of the intervention program applying functional fitness and cognitive training to disabled residents in the institution. The subjects were disabled persons of a care institution in southern Taiwan and were randomly divided into training and control groups, both having 17 subjects. The age of the subjects was between 56 and 98 years with a mean age of 79.08 ± 10.04 years; the subjects of training group implemented 12 weeks of training on physical and cognitive training, while the control group subjects did not have any training program. The results revealed that subjects of the training group have significantly improved their functional shoulder rotation flexibility of left and right anterior hip muscle group flexibility of right, sitting functional balance of left and right, naming, attention, delayed recall, orientation, and Montreal cognitive assessment (MOCA). The study suggested developing physical fitness programs and physical and cognitive prescriptions for the disabled people of the institutions

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC. METHODS: Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis. RESULTS: Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3. CONCLUSIONS: Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis

Identification of low-abundance proteins via fractionation of the urine proteome with weak anion exchange chromatography

<p>Abstract</p> <p>Background</p> <p>Low-abundance proteins are difficultly observed on the two-dimensional gel electrophoresis (2-DE) maps of urine proteome, because they are usually obscured by high-abundance proteins such as albumin and immunoglobulin. In this study, a novel fractionation method was developed for enriching low-abundance proteins by removing high-abundance proteins and progressive elution with salts of various concentrations.</p> <p>Results</p> <p>Stepwise weak anion exchange (WAX) chromatography, which applied DEAE-Sephacel resin with non-fixed volume elution, was used to fractionate urine proteome prior to performing 2-DE. Urine proteome was separated into four fractions by progressively eluting the column with 0 M, 50 mM, 100 mM, and 1 M NaCl solutions. Most of the heavy and light immunoglobulin chains appeared in the eluent. After the high-abundance proteins were removed, various low-abundance proteins were enriched and could be easily identified. The potential of this method for obtaining diversified fractionations was demonstrated by eluting the column separately with Na₂SO₄and MgCl₂solutions. The 2-DE maps of the fractions eluted with these different salt solutions of identical ionic strength revealed markedly different stain patterns.</p> <p>Conclusion</p> <p>The present study demonstrated that this fractionation method could be applied for purposes of enriching low-abundance proteins and obtaining diversified fractionations of urine, and potentially other proteomes.</p

Hubba: hub objects analyzer—a framework of interactome hubs identification for network biology

One major task in the post-genome era is to reconstruct proteomic and genomic interacting networks using high-throughput experiment data. To identify essential nodes/hubs in these interactomes is a way to decipher the critical keys inside biochemical pathways or complex networks. These essential nodes/hubs may serve as potential drug-targets for developing novel therapy of human diseases, such as cancer or infectious disease caused by emerging pathogens. Hub Objects Analyzer (Hubba) is a web-based service for exploring important nodes in an interactome network generated from specific small- or large-scale experimental methods based on graph theory. Two characteristic analysis algorithms, Maximum Neighborhood Component (MNC) and Density of Maximum Neighborhood Component (DMNC) are developed for exploring and identifying hubs/essential nodes from interactome networks. Users can submit their own interaction data in PSI format (Proteomics Standards Initiative, version 2.5 and 1.0), tab format and tab with weight values. User will get an email notification of the calculation complete in minutes or hours, depending on the size of submitted dataset. Hubba result includes a rank given by a composite index, a manifest graph of network to show the relationship amid these hubs, and links for retrieving output files. This proposed method (DMNC || MNC) can be applied to discover some unrecognized hubs from previous dataset. For example, most of the Hubba high-ranked hubs (80% in top 10 hub list, and >70% in top 40 hub list) from the yeast protein interactome data (Y2H experiment) are reported as essential proteins. Since the analysis methods of Hubba are based on topology, it can also be used on other kinds of networks to explore the essential nodes, like networks in yeast, rat, mouse and human. The website of Hubba is freely available at http://hub.iis.sinica.edu.tw/Hubba