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Abstract: Aims: The (2′S,7′S)-O-(2-methylbutanoyl)-columbianetin (OMC) is a novel secondary metabolite extracted from Corydalis heterocarpa, which has long been used as a folk medicine for various inflammatory diseases in Korea. We examined the effect of OMC on allergic rhinitis (AR). Main methods: We assessed the therapeutic effects and regulatory mechanisms of OMC on the phorbol 12-myristate 13-acetate plus A23187-stimulated mast cell line, HMC-1 cells and ovalbumin (OVA)-induced AR models. Key findings: OMC significantly decreased the releases of histamine and tryptase from stimulated HMC-1 cells. The degranulation process, characterized by morphological extension of the filopodia on the surface and membrane ruffling, was strongly induced in the stimulated-HMC-1 cell, however OMC suppressed the morphological changes in stimulated-HMC-1 cells. OMC reduced the production and mRNA expression of inflammatory cytokines. These inhibitory actions by OMC were dependent on the regulation of mitogen-activated protein kinases, nuclear factor-κB, and caspapase-1 signaling pathways. In the AR animal model, the increased rub scores and AR biomarkers (histamine and IgE) in ovalbumin (OVA)-sensitized mice were significantly reduced by the administration of OMC. Furthermore, eosinophils and mast cell infiltrations in nasal mucosa tissue were also blocked through the regulation of macrophage-inflammatory protein and intercellular adhesion molecule-1 levels. Significance: OMC showed the possibility to regulate AR in activated mast cells and OVA-induced AR models. Hence, we suggest that OMC is a powerful and feasible new agent to suppress AR. [Copyright &y& Elsevier]

Abstract: PDGFRB is located on chromosome 5q31–q32, a chromosomal region identified by linkage analyses to contain a susceptibility gene for schizophrenia (SCZ). Recent research has focused on the role of the N-methyl-d-aspartate (NMDA) receptor in the pathogenesis of SCZ. D4 dopamine receptor-mediated transactivation of the gene encoding platelet-derived growth factor receptor beta (PDGFRB) has immediate effects on synaptic neurotransmission via calcium-dependent inactivation of NMDA receptors. In this study, we investigate the association between the PDGFRB gene and SCZ in a Korean population. We screened 6 single-nucleotide polymorphisms (SNPs) in the 5′-upstream region of PDGFRB and conducted a case–control study of 381 SCZ patients and 752 controls. The genotype and haplotype frequencies of 3 of the 6 SNPs [SNP1 (g.−1924T>C, rs3756314), SNP3 (g.−1772A>G, rs3756312) and SNP4 (rs3756311, g.−1658G>A)] were significantly associated with SCZ [SNP1, corrected p =0.012 (co-dominant model), 0.002 (Dominant model), and 0.506 (Recessive model); SNP3 and 4, corrected p =0.003, 0.009, and 0.049]. Haplotype analysis also revealed that ht1 (CGG) and ht2 (TAA) were significantly associated with SCZ (ht1, corrected p =0.018, 0.340, and 0.010; ht2, corrected p =0.002, 0.009, and 0.016). Transient transfection in neuronal cells revealed that ht1 had higher luciferase activity than the vector alone. Furthermore, Pdgfrb expression was increased in the frontal cortex and hippocampus in a mouse model of SCZ induced by MK801. We conclude that SNPs of the 5′-upstream region of PDGFRB are associated with SCZ in a Korean population. These are weak positives that require future studies to confirm these results. [Copyright &y& Elsevier]

Ginseng (the root of Panax ginseng C.A. Meyer, family Araliaceae) possesses various biological activities, including anti-inflammatory and anti-tumor actions. However, their topical effect on atopic dermatitis (AD) has not been studied yet. The aim of this study was to examine the therapeutic effects of topical Korean red ginseng saponin fraction (KRGS) and its genuine constituents on AD-like skin lesions in an AD mouse model. The therapeutic effect of topical KRGS and ginsenosides in 2-chloro-1,3,5-trinitrobenzene (TNCB)-treated NC/Nga mice was assessed by measuring the skin severity scores, ear thickness, histological changes of lesional skin including mast cell count, tissue tumor necrosis factor (TNF)-α, interleukin (IL)-4, and interferon (IFN)-γ mRNA expression, and total serum IgE. Topical administration of 0.1% KRGS, 0.1% Rh2 and 0.1% Rh2+0.1% Rg3 significantly reduced the clinical skin severity scores, ear thickness and mast cell infiltration in the TNCB-induced AD-like skin lesions. Topical application of KRGS and its constituents significantly reduced TNCB-induced increase in ear TNF-α and IL-4 mRNA expression, but not IFN-γ mRNA expression. There was little change of serum total IgE level by topical KRGS and its constituents. In this study, topical KRGS and ginsenosides Rh2 and Rg3 were found to exert an anti-inflammatory effect in vivo and proved to be beneficial in an animal model of AD. Our results suggest that KRGS and its ginsenosides Rh2 and Rg3 have potential as a topical agent for the treatment of AD., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Background/aims: Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin alpha(V) (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV-infected hepatocellular carcinoma (HCC)., Patients and Methods: Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV-infected HCC and 107 cases of acute self-limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip., Results: The ITGAV intron SNPs rs9333289 and rs11685758, the 3'-untranslated region SNP rs1839123 and haplotype 3 (T-T-A) were associated with enhanced susceptibility to HBV-infected HCC (OR=1.75-2.42; P=0.02-0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV-infected HCC (OR=1.73-2.01; P=0.01-0.04). In addition, both rs2290083 and ht1 (C-C-G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39-1.62, P=0.04-0.01), Conclusion: ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV-infected HCC.

Recovery from hepatitis B virus (HBV) infection depends on the cellular immune responses. Chemokines and their receptors play significant roles in immune defense. This study was undertaken to investigate the association between HBV infection and single nucleotide polymorphisms (SNPs) of genes for the chemokines and their receptors. Between March 2002 and February 2004, a total of 957 single ethnic Korean patients were enrolled into two different groups; "HBV clearance group" (n=350), who have recovered from HBV infection, and "HBV persistence group" (n=607), who were repeatedly HBsAg-positive. The HBV persistence group was subdivided into "inactive carrier" and "HBV progression group (chronic hepatitis and cirrhosis)". We assessed polymorphisms in regulated and normal T-cell expressed and secreted (RANTES) at position -403, monocyte chemoattractant protein-1 (MCP-1) at position -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T and CXCR4 I138I using single primer extension assay. Genotype distributions of the "HBV clearance versus persistence group" and "inactive carrier versus HBV progression group" were compared. On the basis of unconditional logistic regression analysis with adjustment for age and sex, no statistically significant association with susceptibility to persistent HBV infection was observed with RANTES -403, MCP-1 -2518, CCR2 V64I, CCR5 -2459, CXCR1 S276T, and CXCR4 I138I polymorphisms. In addition, no association of analyzed SNPs with HBV disease progression was found.