Propofol produces preventive analgesia via GluN2B-containing NMDA Receptor/ERK1/2 Signaling Pathway in the rat model of Inflammatory Pain

Compared to other anesthetics, propofol has showed superior analgesic effect used during surgical procedures on acute post-surgical pain. Whether propofol has preventive analgesic property remain debated. The present study investigated the antinociceptive effect of propofol and underlying molecular and cellular mechanisms via pre-emptive administration in a formalin-induced inflammatory pain model in rats. Male adult Sprague-Dawley rats were randomly allocated into 4 groups: naïve (Group Naïve), formalin injection only (Group Formalin), and formalin injection at 30 min (Group P-30min) or 2 h (Group P-2h) after intravenous infusion of propofol (0.6 mg kg-1 min-1) for 1 h. Nociceptive responses were evaluated by composite pain score-weighted scores. Protein expression of phosphorylated- or pan-GluN2B, ERK1/2, p38 MAPK and JNK in the spinal dorsal horn was assessed by Western blot. Alteration of intracellular Ca2+ concentration induced by NMDA receptor agonists with or without pre-treatment of propofol was measured using fluorometry in SH-SY5Y cells. Neuronal activation was assessed by immunofluorescence. Pre-emptive propofol reduced pain with a delayed response to formalin and a reduction in hypersensitivity that lasted at least for 2 h. The formalin-induced activation of spinal GluN2B and ERK1/2 but not p38 or JNK were also diminished by propofol treatment. Preconditioning treatment with 3 µM and 10 µM of propofol inhibited Ca2+ influx mediated through NMDA receptors in SH-SY5Y cells. Propofol also reduced the neuronal expression of c-Fos and p-ERK induced by formalin. These findings indicate that pre-emptive administration of propofol produces preventive analgesic effects on inflammatory pain through regulating neuronal GluN2B-containing NMDA receptor and ERK1/2 pathway in the spinal dorsal horn.published_or_final_versio

Explicitly searching for useful inventions: dynamic relatedness and the costs of connecting versus synthesizing

Inventions combine technological features. When features are barely related, burdensomely broad knowledge is required to identify the situations that they share. When features are overly related, burdensomely broad knowledge is required to identify the situations that distinguish them. Thus, according to my first hypothesis, when features are moderately related, the costs of connecting and costs of synthesizing are cumulatively minimized, and the most useful inventions emerge. I also hypothesize that continued experimentation with a specific set of features is likely to lead to the discovery of decreasingly useful inventions; the earlier-identified connections reflect the more common consumer situations. Covering data from all industries, the empirical analysis provides broad support for the first hypothesis. Regressions to test the second hypothesis are inconclusive when examining industry types individually. Yet, this study represents an exploratory investigation, and future research should test refined hypotheses with more sophisticated data, such as that found in literature-based discovery research

Analysis of antioxidant activity and antioxidant constituents of Chinese toon

Antioxidant activity of the methanol and water extracts of Chinese toon (Toona sinensis) leaf was evaluated using DPPH radical scavenging and lipid peroxidation assays. Contents of four major types of antioxidants including β-carotene, ascorbate, α-tocopherol and phenolics were also quantified. Open column chromatography followed by semi-preparative HPLC were applied to separate phenolic antioxidants whose contents were subsequently determined by HPLC. The methanol extract demonstrated much higher antioxidant activity than the water extract. Contents of β-carotene, ascorbate, α-tocopherol and phenolics were 1.23 μmol g -1, 34.2 μmol g -1, 2.40 μmol g -1 and 872 μmol gallic acid equivalents g -1, respectively. Six phenols were isolated. Their structures were characterized as 5-O-galloylquinic acid, gallic acid, methyl gallate, β-1,2,6-tri-O-galloyl-d-glucose, quercetin 3-O-β-d-glucopyranoside and quercetin 3-O-(2′′-O-galloyl)-β-d-glucopyranoside, respectively. The results indicate that phenolic compounds are the dominant antioxidants in Chinese toon. The compounds β-1,2,6-tri-O-galloyl-d-glucose and quercetin 3-O-(2′′-O-galloyl)-β-d-glucopyranoside were reported for the first time in Chinese toon. © 2009 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Analysis of antioxidant activity and antioxidant constituents of Chinese toon

Antioxidant activity of the methanol and water extracts of Chinese toon (Toona sinensis) leaf was evaluated using DPPH radical scavenging and lipid peroxidation assays. Contents of four major types of antioxidants including β-carotene, ascorbate, α-tocopherol and phenolics were also quantified. Open column chromatography followed by semi-preparative HPLC were applied to separate phenolic antioxidants whose contents were subsequently determined by HPLC. The methanol extract demonstrated much higher antioxidant activity than the water extract. Contents of β-carotene, ascorbate, α-tocopherol and phenolics were 1.23 μmol g -1, 34.2 μmol g -1, 2.40 μmol g -1 and 872 μmol gallic acid equivalents g -1, respectively. Six phenols were isolated. Their structures were characterized as 5-O-galloylquinic acid, gallic acid, methyl gallate, β-1,2,6-tri-O-galloyl-d-glucose, quercetin 3-O-β-d-glucopyranoside and quercetin 3-O-(2′′-O-galloyl)-β-d-glucopyranoside, respectively. The results indicate that phenolic compounds are the dominant antioxidants in Chinese toon. The compounds β-1,2,6-tri-O-galloyl-d-glucose and quercetin 3-O-(2′′-O-galloyl)-β-d-glucopyranoside were reported for the first time in Chinese toon. © 2009 Elsevier Ltd. All rights reserved.link_to_subscribed_fulltex

Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma

Purpose: Aberrant promoter methylation, an alternative mechanism for gene silencing, is frequently detected in gastric cancer. We studied the feasibility of detecting aberrant methylation in serum of gastric cancer patients. Experimental Design: Patients (54) with gastric adenocarcinoma were studied. The tumor and the paired serum were examined for aberrant methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR. Serum from 30 age-matched noncancer patients was used as control. Results: Promoter methylation in DAP-kinase, Ecadherin, GSTP1, p15, and p16 were detected in 70.3, 75.9, 18.5, 68.5, and 66.7% of primary tumor. In serum of gastric cancer patients, methylation in DAP-kinase, Ecadherin, GSTP1, p15, and p16 were detected in 48.1, 57.4, 14.8, 55.6, and 51.9%, respectively. None of the control serum showed aberrant methylation. Aberrant methylation in serum DNA was all accompanied with methylation in the corresponding tumor samples. In general, >60% of serum from cancers with aberrant methylation demonstrated these epigenetic alterations. Conclusion: Our findings suggest that aberrant promoter methylation in serum can be detected in a substantial proportion of gastric cancer patients, and this strategy should be evaluated in the screening and surveillance of gastric cancer.link_to_subscribed_fulltex

Detection of gene promoter hypermethylation in the tumor and serum of patients with gastric carcinoma

Purpose: Aberrant promoter methylation, an alternative mechanism for gene silencing, is frequently detected in gastric cancer. We studied the feasibility of detecting aberrant methylation in serum of gastric cancer patients. Experimental Design: Patients (54) with gastric adenocarcinoma were studied. The tumor and the paired serum were examined for aberrant methylation in DAP-kinase, E-cadherin, GSTP1, p15, and p16 by methylation-specific PCR. Serum from 30 age-matched noncancer patients was used as control. Results: Promoter methylation in DAP-kinase, Ecadherin, GSTP1, p15, and p16 were detected in 70.3, 75.9, 18.5, 68.5, and 66.7% of primary tumor. In serum of gastric cancer patients, methylation in DAP-kinase, Ecadherin, GSTP1, p15, and p16 were detected in 48.1, 57.4, 14.8, 55.6, and 51.9%, respectively. None of the control serum showed aberrant methylation. Aberrant methylation in serum DNA was all accompanied with methylation in the corresponding tumor samples. In general, >60% of serum from cancers with aberrant methylation demonstrated these epigenetic alterations. Conclusion: Our findings suggest that aberrant promoter methylation in serum can be detected in a substantial proportion of gastric cancer patients, and this strategy should be evaluated in the screening and surveillance of gastric cancer.link_to_subscribed_fulltex

Somatic β-catenin mutation in gastric carcinoma - An infrequent event that is not specific for microsatellite instability

We screened 90 cases of gastric carcinoma (GCA) samples for β-catenin exon 3 mutation and assessed its possible relationship with microsatellite instability (MSI). Three mutations were detected in two samples, including a single mutation in an intestinal type and double mutations in a diffuse type GCA. One of the mutations found in the diffuse type GCA sample was a non-sense mutation at codon 68 (CAG→ TAG). This novel mutation was predicted to disrupt the binding of β-catenin to α-catenin and may be related to the diffuse type morphology. The other two mutations were missense mutations involved or related to the GSK-3β phosphorylation site, which have been reported previously. No MSI can be demonstrated in the two cases with β-catenin mutation. Our results suggested that β-catenin mutation was infrequent in GCA and appeared not specific for MSI. © 2001 Elsevier Science Ireland Ltd.link_to_subscribed_fulltex

Coronaviral hypothetical and structural proteins were found in the intestinal surface enterocytes and pneumocytes of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease that haunted the world from November 2002 to July 2003. Little is known about the biology and pathophysiology of the novel coronavirus that causes SARS. The tissue and cellular distributions of coronaviral hypothetical and structural proteins in SARS were investigated. Antibodies against the hypothetical (SARS 3a, 3b, 6, 7a and 9b) and structural proteins (envelope, membrane, nucleocapsid and spike) of the coronavirus were generated from predicted antigenic epitopes of each protein. The presence of these proteins were first verified in coronavirus-infected Vero E6 tissue culture model. Immunohistochemical studies on different human tissues, including a cohort of nine autopsies, two liver biopsies and intestinal biopsies of SARS patients, further confirmed the existence of coronaviral hypothetical and structural proteins in the cytoplasm of pneumocytes and small intestinal surface enterocytes in SARS patients. With this vast array of antibodies, no signal was observed in other cell types including those organs in which reverse transcriptase-polymerase chain reactions were reported to be positive. Structural proteins and the functionally undefined hypothetical proteins were expressed in coronavirus-infected cells with distinct expression pattern in different organs in SARS patients. These antipeptide antibodies can be useful for the diagnosis of SARS at the tissue level. © 2005 USCAP, Inc All rights reserved.link_to_subscribed_fulltex

Genome-wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray

An analysis of gene expression profiles obtained from cervical cancers was performed to find those genes most aberrantly expressed. Total RNA was prepared from 29 samples of cervical squamous cell carcinoma and 18 control samples, and hybridized to Affymetrix oligonucleotide microarrays with probe sets complementary to over 20,000 transcripts. Unsupervised hierarchical clustering of the expression data readily distinguished normal cervix from cancer. Supervised analysis of gene expression data identified 98 and 139 genes that exhibited >2-fold upregulation and >2-fold down-regulation, respectively, in cervical cancer compared to normal cervix. Several of the genes that were differentially regulated included SPP1 (Osteopontin), CDKN2A (p16), RPL39L, Clorf1, MAL, p11, ARS and NICE-1, These were validated by quantitative RT-PCR on an independent set of cancer and control specimens. Gene Ontology analysis showed that the list of differentially expressed genes included ones that were involved in multiple biological processes, including cell proliferation, cell cycle and protein catabolism. Immunohistochemical staining of cancer specimens further confirmed differential expression of SPP1 in cervical cancer cells vs. nontumor cells. In addition, 2 genes, CTGF and RGS1 were found to be upregulated in late stage cancer compared to early stage cancer, suggesting that they might be involved in cancer progression. The pathway analysis of expression data showed that the SPP1, VEGF, CDC2 and CKS2 genes were coordinately differentially regulated between cancer and normal. The present study is promising and provides potential new insights into the extent of expression differences underlying the development and progression of cervical squamous cell cancer. This study has also revealed several genes that may be highly attractive candidate molecular markers/targets for cervical cancer diagnosis, prognosis and therapy. © 2005 Wiley-Liss, Inc.link_to_subscribed_fulltex