Differential effect of NF-κB activity on β-catenin/Tcf pathway in various cancer cells

Abstractβ-Catenin/Tcf and NF-κB pathways play an important role in biological functions. We determined the underlying mechanisms of differential interaction between two pathways in various human cancer cell lines. NF-κB positively regulated β-catenin/Tcf pathways in human glioblastoma, whereas it has an opposite effect on β-catenin/Tcf pathways in colon, liver, and breast cancer cells. Expression of lucine zipper tumor suppressor 2 (lzts2) was positively regulated by NF-κB activity in colon, liver, and breast cancer cells, whereas negatively regulated in glioma cells. Downregulation of lzts2 increased the β-catenin/Tcf promoter activity and inhibited NF-κB-induced modulation of the nuclear translocation of β-catenin. These data indicate that the differential crosstalk between β-catenin/Tcf and NF-κB pathway in various cancer cells is resulted from the differences in the regulation of NF-κB-induced lzts2 expression

JNK pathway is involved in the inhibition of inflammatory target gene expression and NF-kappaB activation by melittin

<p>Abstract</p> <p>Background</p> <p>Bee venom therapy has been used to treat inflammatory diseases including rheumatoid arthritis in humans and in experimental animals. We previously found that bee venom and melittin (a major component of bee venom) have anti-inflammatory effect by reacting with the sulfhydryl group of p50 of nuclear factor-kappa B (NF-κB) and IκB kinases (IKKs). Since mitogen activated protein (MAP) kinase family is implicated in the NF-κB activation and inflammatory reaction, we further investigated whether activation of MAP kinase may be also involved in the anti-inflammatory effect of melittin and bee venom.</p> <p>Methods</p> <p>The anti-inflammatory effects of melittin and bee venom were investigated in cultured Raw 264.7 cells, THP-1 human monocytic cells and Synoviocytes. The activation of NF-κB was investigated by electrophoretic mobility shift assay. Nitric oxide (NO) and prostaglandin E₂(PGE₂) were determined either by Enzyme Linked Immuno Sorbent Assay or by biochemical assay. Expression of IκB, p50, p65, inducible nitric oxide synthetase (iNOS), cyclooxygenase-2 (COX-2) as well as phosphorylation of MAP kinase family was determined by Western blot.</p> <p>Results</p> <p>Melittin (0.5–5 μg/ml) and bee venom (5 and 10 μg/ml) inhibited lipopolysaccharide (LPS, 1 μg/ml) and sodium nitroprusside (SNP, 200 μM)-induced activation of c-Jun NH2-terminal kinase (JNK) in RAW 264.7 cells in a dose dependent manner. However, JNK inhibitor, anthra [1,9-cd]pyrazole-6 (2H)-one (SP600215, 10–50 μM) dose dependently suppressed the inhibitory effects of melittin and bee venom on NF-κB dependent luciferase and DNA binding activity via suppression of the inhibitory effect of melittin and bee venom on the LPS and SNP-induced translocation of p65 and p50 into nucleus as well as cytosolic release of IκB. Moreover, JNK inhibitor suppressed the inhibitory effects of melittin and bee venom on iNOS and COX-2 expression, and on NO and PGE₂generation.</p> <p>Conclusion</p> <p>These data show that melittin and bee venom prevent LPS and SNP-induced NO and PGE₂production via JNK pathway dependent inactivation of NF-κB, and suggest that inactivation of JNK pathways may also contribute to the anti-inflammatory and anti-arthritis effects of melittin and bee venom.</p

Novel Antidepressant-Like Activity of Caffeic Acid Phenethyl Ester Is Mediated by Enhanced Glucocorticoid Receptor Function in the Hippocampus

Caffeic acid phenethyl ester (CAPE) is an active component of propolis that has a variety of potential pharmacological effects. Although we previously demonstrated that propolis has antidepressant-like activity, the effect of CAPE on this activity remains unknown. The present study assessed whether treatment with CAPE (5, 10, and 20 µmol/kg for 21 days) has an antidepressant-like effect in mice subjected to chronic unpredictable stress via tail suspension (TST) and forced swim (FST) tests. CAPE administration induced behaviors consistent with an antidepressant effect, evidenced by decreased immobility in the TST and FST independent of any effect on serum corticosterone secretion. Western blots, conducted subsequent to behavioral assessment, revealed that CAPE significantly decreased glucocorticoid receptor phosphorylation at S234 (pGR(S234)), resulting in an increased pGR(S220/S234) ratio. We also observed negative correlations between pGR(S220)/(S234) and p38 mitogen-activated protein kinase (p38MAPK) phosphorylation, which was decreased by CAPE treatment. These findings suggest that CAPE treatment exerts an antidepressant-like effect via downregulation of p38MAPK phosphorylation, thereby contributing to enhanced GR function

Methodological Considerations of Electron Spin Resonance Spin Trapping Techniques for Measuring Reactive Oxygen Species generated from metal oxide nanomaterials

Qualitative and quantitative analyses of reactive oxygen species (ROS) generated on the surfaces of nanomaterials are important for understanding their toxicity and toxic mechanisms, which are in turn beneficial for manufacturing more biocompatible nanomaterials in many industrial fields. Electron spin resonance (ESR) is a useful tool for detecting ROS formation. However, using this technique without first considering the physicochemical properties of nanomaterials and proper conditions of the spin trapping agent (such as incubation time) may lead to misinterpretation of the resulting data. In this report, we suggest methodological considerations for ESR as pertains to magnetism, sample preparation and proper incubation time with spin trapping agents. Based on our results, each spin trapping agent should be given the proper incubation time. For nanomaterials having magnetic properties, it is useful to remove these nanomaterials via centrifugation after reacting with spin trapping agents. Sonication for the purpose of sample dispersion and sample light exposure should be controlled during ESR in order to enhance the obtained ROS signal. This report will allow researchers to better design ESR spin trapping applications involving nanomaterials

Variability of Response Time as a Predictor of Methylphenidate Treatment Response in Korean Children with Attention Deficit Hyperactivity Disorder

PURPOSE: Methylphenidate (MPH) is an effective medication for the treatment of attention deficit hyperactivity disorder (ADHD). However, about 30% of patients do not respond to or are unable to tolerate MPH. Based on previous findings, we hypothesized that great variability in response time (RT) among Korean children with ADHD on a computerized continuous performance attention test would be related to poor MPH treatment response. MATERIALS AND METHODS: Children (ages 6-18 years) with ADHD were recruited for a prospective 12-week, open-labeled, multicenter study to examine optimal dosage of OROS methylphenidate. Of the 144 subjects selected, 28 dropped out due to adverse events, medication noncompliance, or follow-up loss, and an additional 26 subjects with comorbid disorders were excluded from statistical analyses. We defined 'responders' as subjects who received a score of less than 18 on the attention deficit hyperactivity disorder rating scale (ARS; Korean version, K-ARS) and a score of 1 or 2 on the Clinical Global Impression-Improvement scale (CGI-I). RT variability was assessed with the ADHD diagnostic system (ADS). RESULTS: Fifty-nine (67%) subjects responded to MPH treatment. The non-responders showed greater RT variability at baseline (Mann Whitney U = 577.0, p < 0.01). Baseline RT variability was a significant predictor of MPH response (Nagelkerke R(2) = 0.136, p < 0.01). It predicted 94.9% of responder, 17.2% of non-responder and 69.3% of overall group. CONCLUSION: High RT variability may predict poor response to MPH treatment in children with ADHDope

Immunogenicity and Safety of Trivalent Inactivated Influenza Vaccine: A Randomized, Double-Blind, Multi-Center, Phase 3 Clinical Trial in a Vaccine-Limited Country

Influenza vaccines are the primary method for controlling influenza and its complications. This study was conducted as a phase 3, randomized, double-blind, controlled, multi-center trial at seven university hospitals to evaluate the immunogenicity and safety of an inactivated, split, trivalent influenza vaccine (GC501, Green Cross Corporation, Yongin, Korea), which was newly manufactured in Korea in 2008. Between September 21 and 26, a total of 329 healthy subjects were recruited for the immunogenicity analysis, while 976 subjects were enrolled for the safety analysis. The GC501 vaccine met both FDA and EMEA criteria with ≥ 80% of subjects achieving post-vaccination titers ≥ 40 for all three subtypes, even in the elderly. The vaccine was well tolerated with only mild systemic and local adverse events. In summary, GC501 showed excellent immunogenicity and a good safety profile in both young adults and the elderly. The licensure of GC501 might be an important basis in preparation for the future influenza pandemic

Coinfection of hepatitis A virus genotype IA and IIIA complicated with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive immunoglobulin M anti-hepatitis E virus: a case report

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV

Photodistributed Telangiectasia Induced by Amlodipine

Calcium channel blockers are widely used antihypertensive drugs, which are uncommonly associated with cutaneous reactions, such as pruritus, urticaria, or alopecia. Photosensitivity presenting with telangiectasia has rarely been described. We present here a case of photodistributed telangiectasia induced clinically by amlodipine and histologically by enlarged capillaries in the upper dermis without signs of vasculitis