Analysis of diagnostic decision in acupuncture from the actual functional dyspepsia patient's clinical information.

BACKGROUND: Clinical research in acupuncture has been criticized for not reflecting real-world practice in terms of diagnosis and intervention. This study aimed to collect data on the principles of diagnosis and selection of acupoints from Korean medicine doctors (KMDs) and analyze the patterns and priorities in decision-making. METHODS: The study design was based on the data of an actual patient with functional dyspepsia (FD) (according to Rome III criteria) to create simulated patients, and a KMD specialized in gastrointestinal disorders was allocated to collect the clinical information as objectively as possible. Sixty-nine KMDs were recruited to diagnose a simulated patient based on the actual patient's clinical information, in a manner similar to that performed in their clinics. RESULTS: After the diagnostic procedures were completed, the pattern identification, selected acupoints, reasons for choosing them, and importance of symptoms for deciding their diagnoses were documented. The information needed was clearly distinguishable from those routinely asked in western medicine, and information regarding fecal status, abdominal examination, appetite status, pulse diagnosis, and tongue diagnosis were listed as vital. The doctors identified the patient's pattern as "spleen-stomach weakness", "liver qi depression", or "food accumulation or phlegm-fluid retention". The most frequently selected acupoints were CV12, LI4, LR3, ST36, and PC6. CONCLUSION: There are common acupoints across different patterns, but pattern-specific acupoints were also recommended. These results can provide useful information to design clinical research and education for better clinical performance in acupuncture that reflects real-world practice.

Predicting risk of type 2 diabetes mellitus in Korean adults aged 40-69 by integrating clinical and genetic factors.

AIMS: The purpose of our investigation was to identify the genetic and clinical risk factors of type 2 diabetes mellitus (T2DM) and to predict the incidence of T2DM in Korean adults aged 40-69 at follow-up intervals of 5, 7, and 10years. METHODS: Korean Genome and Epidemiology Study (KoGES) cohort data (n=10,030) were used to develop T2DM prediction models. Both clinical-only and integrated (clinical factors+genetic factors) models were derived using the Cox proportional hazards model. Internal validation was performed to evaluate the prediction capabilities of the clinical and integrated models. RESULTS: The clinical model included 10 selected clinical risk factors. The selected SNPs for the integrated model were rs9311835 in PTPRG, rs10975266 in RIC1, rs11057302 in TMED2, rs17154562 in ADAM12, and rs8038172 in CGNL1. For the clinical model, validated c-indices with time points of 5, 7, and 10 years were 0.744, 0.732, and 0.732, respectively. Slightly higher validated c-indices were observed for the integrated model at 0.747, 0.736, and 0.738, respectively. The p-values of the survival net reclassification improvement (NRI) for the SNP point-based score were statistically significant. CONCLUSIONS: Clinical and integrated models can be effectively used to predict the incidence of T2DM in Koreans.

Biological age as a useful index to predict seventeen-year survival and mortality in Koreans.

BACKGROUND: Many studies have been conducted to quantitatively estimate biological age using measurable biomarkers. Biological age should function as a valid proxy for aging, which is closely related with future work ability, frailty, physical fitness, and/or mortality. A validation study using cohort data found biological age to be a superior index for disease-related mortality than chronological age. The purpose of this study is to demonstrate the validity of biological age as a useful index to predict a person's risk of death in the future. METHODS: The data consists of 13,106 cases of death from 557,940 Koreans at 20-93 years old, surveyed from 1994 to 2011. Biological ages were computed using 15 biomarkers measured in general health check-ups using an algorithm based on principal component analysis. The influence of biological age on future mortality was analyzed using Cox proportional hazards regression considering gender, chronological age, and event type. RESULTS: In the living subjects, the average biological age was almost the same as the average chronological age. In the deceased, the biological age was larger than the chronological age: largest increment of biological age over chronological age was observed when their baseline chronological age was within 50-59 years. The death rate significantly increased as biological age became larger than chronological age (linear trend test, p value < 0.0001). The largest hazard ratio was observed in subjects whose baseline chronological age was within 50-59 years when the cause was death from non-cancerous diseases (HR = 1.30, 95% confidence intervals = 1.26 - 1.34). The survival probability, over the 17 year term of the study, was significantly decreased in the people whose biological age was larger than chronological age (log rank test, p value < 0.001). CONCLUSIONS: Biological age could be used to predict future risk of death, and its effect size varied according to gender, chronological age, and cause of death.

The Suppressive Effects of Cinnamomi Cortex and Its Phytocompound Coumarin on Oxaliplatin-Induced Neuropathic Cold Allodynia in Rats.

Oxaliplatin, a chemotherapy drug, induces acute peripheral neuropathy characterized by cold allodynia, spinal glial activation and increased levels of pro-inflammatory cytokines. Herein, we determined whether Cinnamomi Cortex (C. Cortex), a widely used medicinal herb in East Asia for cold-related diseases, could attenuate oxaliplatin-induced cold allodynia in rats and the mechanisms involved. A single oxaliplatin injection (6 mg/kg, i.p.) induced significant cold allodynia signs based on tail immersion tests using cold water (4 °C). Daily oral administration of water extract of C. Cortex (WECC) (100, 200, and 400 mg/kg) for five consecutive days following an oxaliplatin injection dose-dependently alleviated cold allodynia with only a slight difference in efficacies between the middle dose at 200 mg/kg and the highest dose at 400 mg/kg. WECC at 200 mg/kg significantly suppressed the activation of astrocytes and microglia and decreased the expression levels of IL-1ß and TNF in the spinal cord after injection with oxaliplatin. Furthermore, oral administration of coumarin (10 mg/kg), a major phytocompound of C. Cortex, markedly reduced cold allodynia. These results indicate that C. Cortex has a potent anti-allodynic effect in oxaliplatin-injected rats through inhibiting spinal glial cells and pro-inflammatory cytokines. We also suggest that coumarin might play a role in the anti-allodynic effect of C. Cortex.

Genetic polymorphisms to predict gains in maximal O2 uptake and knee peak torque after a high intensity training program in humans.

PURPOSE: The study aimed to identify single nucleotide polymorphisms (SNPs) that significantly influenced the level of improvement of two kinds of training responses, including maximal O2 uptake (V'O2max) and knee peak torque of healthy adults participating in the high intensity training (HIT) program. The study also aimed to use these SNPs to develop prediction models for individual training responses. METHODS: 79 Healthy volunteers participated in the HIT program. A genome-wide association study, based on 2,391,739 SNPs, was performed to identify SNPs that were significantly associated with gains in V'O2max and knee peak torque, following 9 weeks of the HIT program. To predict two training responses, two independent SNPs sets were determined using linear regression and iterative binary logistic regression analysis. False discovery rate analysis and permutation tests were performed to avoid false-positive findings. RESULTS: To predict gains in V'O2max, 7 SNPs were identified. These SNPs accounted for 26.0 % of the variance in the increment of V'O2max, and discriminated the subjects into three subgroups, non-responders, medium responders, and high responders, with prediction accuracy of 86.1 %. For the knee peak torque, 6 SNPs were identified, and accounted for 27.5 % of the variance in the increment of knee peak torque. The prediction accuracy discriminating the subjects into the three subgroups was estimated as 77.2 %. CONCLUSIONS: Novel SNPs found in this study could explain, and predict inter-individual variability in gains of V'O2max, and knee peak torque. Furthermore, with these genetic markers, a methodology suggested in this study provides a sound approach for the personalized training program.

Constructing a knowledge-based database for dermatological integrative medical information.

Recently, overuse of steroids and immunosuppressive drugs has produced incurable dermatological health problems. Traditional medical approaches have been studied for alternative solutions. However, accessing relevant information is difficult given the differences in information for western medicine (WM) and traditional medicine (TM). Therefore, an integrated medical information infrastructure must be utilized to bridge western and traditional treatments. In this study, WM and TM information was collected based on literature searches and information from internet databases on dermatological issues. Additionally, definitions for unified terminology and disease categorization based on individual cases were generated. Also a searchable database system was established that may be a possible model system for integrating both WM and TM medical information on dermatological conditions. Such a system will yield benefits for researchers and facilitate the best possible medical solutions for patients. The DIMI is freely available online.

Gene expression profile analysis of genes in rat hippocampus from antidepressant treated rats using DNA microarray.

BACKGROUND: The molecular and biological mechanisms by which many antidepressants function are based on the monoamine depletion hypothesis. However, the entire cascade of mechanisms responsible for the therapeutic effect of antidepressants has not yet been elucidated. RESULTS: We used a genome-wide microarray system containing 30,000 clones to evaluate total RNA that had been isolated from the brains of treated rats to identify the genes involved in the therapeutic mechanisms of various antidepressants, a tricyclic antidepressant (imipramine). a selective serotonin reuptake inhibitor (fluoxetine), a monoamine oxidase inhibitor (phenelzine) and psychoactive herbal extracts of Nelumbinis Semen (NS). To confirm the differential expression of the identified genes, we analyzed the amount of mRNA that was isolated from the hippocampus of rats that had been treated with antidepressants by real-time RT-PCR using primers specific for selected genes of interest. These data demonstrate that antidepressants interfere with the expression of a large array of genes involved in signaling, survival and protein metabolism, suggesting that the therapeutic effect of these antidepressants is very complex. Surprisingly, unlike other antidepressants, we found that the standardized herbal medicine, Nelumbinis Semen, is free of factors that can induce neurodegenerative diseases such as caspase 8, α-synuclein, and amyloid precursor protein. In addition, the production of the inflammatory cytokine, IFNγ, was significantly decreased in rat hippocampus in response to treatment with antidepressants, while the inhibitory cytokine, TGFß, was significantly enhanced. CONCLUSIONS: These results suggest that antidepressants function by regulating neurotransmission as well as suppressing immunoreactivity in the central nervous system.

The modulative effect of Cyperi Rhizoma on Th1/Th2 lineage development.

To evaluate the direct effects of Cyperi Rhizoma (CR), a plant water extract, on Th1/Th2 lineage development in vitro, this study was conducted. Sorted CD4(+) T cells obtained from the splenocytes of BALB/c mice were activated with anti-CD3/anti-CD28 and then cultured in medium that contained CR medium under Th1 inducing or Th2 inducing conditions. Subsequently, IFN-gamma or IL-4 secreting cells were quantitated using flow cytometry analysis. In addition, IFN-gamma and IL-4 protein secretions were detected by ELISA analysis, after which, IFN-gamma and T-bet transcripts, key players in the Th1 immune function, and also, IL-4 and GATA-3, which are primary components in the Th2 immune mechanism, were quantitated by real-time RT-PCR. CR had no mitogenic effects on un-stimulated CD4(+) T cells, however, it increased the CD4(+) T cell population. Th1/Th2 polarization experiments revealed that CR enhanced IFN-gamma secretion in Th1 cells, but reduced the IL-4 in Th2 cells, and this occurred in a dose-dependent manner and showed significances. In addition, under Th1/Th2 skewed conditions, the transcription levels of IFN-gamma and T-bet were considerably increased, while the expressions of IL-4 and GATA-3 were relatively decreased with CR treatment. These findings suggest that CR enhances Th1 lineage development by increasing Th1 specific cytokine expression and secretion and reduces Th2 lineage development by repressing Th2 specific cytokine productions. Therefore, CR extract may be useful for preventing the onset of allergies or improving allergic symptoms.

Effects of protostane-type triterpenoids on the 5-HT3A receptor-mediated ion current in Xenopus oocytes.

Alisol derivatives are unique protostane-type triterpenoid compounds that are isolated from Alismatis rhizoma, which is a well-known traditional medicine in East Asia. In the present study, we investigated the effects of protostane-type triterpenoids (AA, Alisol A; AB, Alisol B; AB-ac, Alisol B 23-acetate; AC-ac, Alisol C 23-aceteate) on 5-HT-induced currents mediated by the human 5-HT(3)A receptor expressed in Xenopus laevis oocytes. Co-treatment with triterpenoids regulated the 5-HT-induced inward peak current in a concentration-dependent and reversible manner. In addition, regulation of I(5-HT) by triterpenoids occurred in a non-competitive manner. Taken together, these results indicate that triterpenoids may regulate the 5-HT(3)A receptors that are expressed in Xenopus oocytes. Furthermore, this regulation of the ligand-gated ion channel activity by triterpenoids may be one of the pharmacological actions of Alismatis rhizoma.

CHESS (CgHExpreSS): a comprehensive analysis tool for the analysis of genomic alterations and their effects on the expression profile of the genome.

BACKGROUND: Genomic alterations frequently occur in many cancer patients and play important mechanistic roles in the pathogenesis of cancer. Furthermore, they can modify the expression level of genes due to altered copy number in the corresponding region of the chromosome. An accumulating body of evidence supports the possibility that strong genome-wide correlation exists between DNA content and gene expression. Therefore, more comprehensive analysis is needed to quantify the relationship between genomic alteration and gene expression. A well-designed bioinformatics tool is essential to perform this kind of integrative analysis. A few programs have already been introduced for integrative analysis. However, there are many limitations in their performance of comprehensive integrated analysis using published software because of limitations in implemented algorithms and visualization modules. RESULTS: To address this issue, we have implemented the Java-based program CHESS to allow integrative analysis of two experimental data sets: genomic alteration and genome-wide expression profile. CHESS is composed of a genomic alteration analysis module and an integrative analysis module. The genomic alteration analysis module detects genomic alteration by applying a threshold based method or SW-ARRAY algorithm and investigates whether the detected alteration is phenotype specific or not. On the other hand, the integrative analysis module measures the genomic alteration's influence on gene expression. It is divided into two separate parts. The first part calculates overall correlation between comparative genomic hybridization ratio and gene expression level by applying following three statistical methods: simple linear regression, Spearman rank correlation and Pearson's correlation. In the second part, CHESS detects the genes that are differentially expressed according to the genomic alteration pattern with three alternative statistical approaches: Student's t-test, Fisher's exact test and Chi square test. By successive operations of two modules, users can clarify how gene expression levels are affected by the phenotype specific genomic alterations. As CHESS was developed in both Java application and web environments, it can be run on a web browser or a local machine. It also supports all experimental platforms if a properly formatted text file is provided to include the chromosomal position of probes and their gene identifiers. CONCLUSIONS: CHESS is a user-friendly tool for investigating disease specific genomic alterations and quantitative relationships between those genomic alterations and genome-wide gene expression profiling.

Inhibition effects of Vitex rotundifolia on inflammatory gene expression in A549 human epithelial cells.

BACKGROUND: Vitex rotundifolia has long been used in traditional medicine to treat asthma and other allergic diseases. OBJECTIVE: To evaluate the anti-inflammatory mechanisms of V rotundifolia in cultured A549 human alveolar epithelial cells. METHODS: In the present study, A549 cells were stimulated with tumor necrosis factor alpha, interleukin 4, and interleukin 1beta to induce expression of chemokines and adhesion molecules involved in eosinophil chemotaxis. The anti-inflammatory effects of V rotundifolia on stimulated A549 cells were then evaluated by analyzing eotaxin secretion and eosinophil migration. In addition, the effects of V rotundifolia on gene expression profiles in stimulated A549 cells were evaluated by oligonucleotide microarray and real-time reverse transcription-polymerase chain reaction (RTRP). RESULTS: The V rotundifolia-treated A549 cells had significantly suppressed eotaxin secretion and eosinophil migration in a dose-dependent manner. In addition, the results of the microarray analysis and RTRP revealed that inflammation-related genes and cell adhesion-related genes were down-regulated in V rotundifolia-treated A549 cells. Furthermore, several genes related to the mitogen-activated protein kinase pathway were down-regulated in V rotundifolia-treated A549 cells. CONCLUSIONS: The mechanism responsible for the effects of V rotundifolia on A549 cells is closely associated with regulation of the mitogen-activated protein kinase pathway. Thus, V rotundifolia may be useful in the treatment of asthma and other allergic diseases.

Panax ginseng C.A. Meyer modulates the levels of MMP3 in S12 murine articular cartilage cell line.

AIM OF THE STUDY: The destruction of cartilage in patients with osteoarthritis occurs due to an imbalance between matrix synthesis and degradation. Cartilage degradation is induced by the activation of matrix metalloproteinases (MMPs). Therefore, this study was conducted to evaluate the cartilage protective effect of Panax ginseng C.A. Meyer (PG). MATERIALS AND METHODS: S12 cells were treated with various concentrations of extract of PG and gensenosides Rd and Rb(3) for 3h, after which 10 ng/ml interleukin-1beta (IL-1beta) was added to the culture media. The levels of MMP3 in the conditioned media were then evaluated using an enzyme-linked immunosorbent assay (ELISA). In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of Type II Collagen and Pro-collagenase. Furthermore, Western blot analysis was performed to identify the roles that PG played in the ERK and p38 signaling pathways. RESULTS: The MMP3 secretion levels of S12 cells were significantly lowered in response to treatment with PG and gensenosides Rd and Rb(3) at a concentration of 100 microg/ml when compared to cells that were treated with IL-1beta. In addition, PG induced the mRNA expression of Type II Collagen dose dependently. Furthermore, phosphorylated p38 and ERK were detected in S12 articular cartilage cell line that was treated with IL-1beta. PG decreased the phosphorylation of p38, but PG did not exert any effect on phospho-ERK. CONCLUSIONS: These findings indicate that PG and gensenosides Rd and Rb(3) suppress MMP3 secretion and that gensenosides Rd and Rb(3) are the major elements involved in the suppression of MMP3 by PG. Furthermore, the suppression of MMP3 by PG occurs via the inhibition of phospho-p38 activation. Therefore, PG may exert a protective effect against the cartilage degradation of OA.

The genome-wide expression profile of Nelumbinis semen on lipopolysaccharide-stimulated BV-2 microglial cells.

This study was conducted to evaluate the protective mechanisms of Nelumbinis semen (NS) on lipopolysaccharide (LPS)-induced activation of BV-2 microglial cells. The anti-inflammatory effects of NS were determined by analyzing nitric oxide production and proinflammatory cytokines using enzyme-linked immunosorbent assay. The mechanism was evaluated in BV-2 cells with or without NS treated with LPS for various lengths of time using oligonucleotide microarray and real time reverse transcription-polymerase chain reaction. The oligonucleotide microarray analysis revealed that mitogen activated protein kinase (MAPK) signaling pathway-related genes such as Fgfr3, Fgf12, Rasal2, Nfkb2, Map2k5, Mapk1, Map3k7, and NFatc2 were down-regulated in LPS activated BV-2 cells by pretreatment with NS. In addition, significant decreases in Nos1ap gene expression were observed with NS pretreatment. Cluster linked pathway analysis using the Kyoto Encyclopedia of Genes and Genomes database revealed that the effects of NS were closely associated with the regulation of mitochondria functions. These results suggested that NS can affect the MAPK signaling pathway and mitochondrial functions in BV-2 cells activated with LPS.

Global gene analysis of Erigeron canadensis-treated TNF-alpha-, IL-4- and IL-1beta-stimulated A549 human epithelial cells.

BACKGROUND/AIMS: This study was conducted to evaluate the anti-inflammatory mechanisms of Erigeron canadensis (EC) on the tumor necrosis factor-alpha (TNF-alpha)-, interleukin (IL)-4- and IL-1beta-induced stimulation of A549 cells. METHODS: In the present study, the anti-inflammatory effects of EC on TNF-alpha-, IL-4- and IL-1beta-induced A549 cells were determined by analyzing eotaxin secretion using ELISA. In addition, the effects of ECon gene expression profiles in stimulated A549 cells were evaluated by microarray analysis. RESULTS: Oligonucleotide microarray analysis revealed that inflammatory-related genes such as NOS1, NOS2A, IL-1beta, IL-8 and CSF2 and cell adhesion-related genes such as SELE, MMP3, VCAM1, ICAM1, ITGA7 and ITGB2 were downregulated in EC-treated A549 cells that had been pretreated with TNF-alpha, IL-4 and IL-1beta. In addition, significant decreases in Eotaxin, ICAM, VCAM and IL-8 gene expression were observed in EC-treated A549 cells. CONCLUSIONS: EC has an anti-inflammatory effect in stimulated A549 cells. Microarray-based genomic survey is a high-throughput approach that is suitable for the evaluation of gene expression in cell lines that have been treated with EC.

The genome-wide expression profile of Scrophularia ningpoensis-treated thapsigargin-stimulated U-87MG cells.

The endoplasmic reticulum (ER) is a principal site for protein synthesis, protein folding, calcium storage, and calcium signaling. Thapsigargin (TG), an inducer of ER stress, inhibits ER-associated Ca(2+)-ATPase and disrupts Ca(2+) homeostasis. ER stress plays an important pathogenetic role in Alzheimer's disease, Parkinson's disease, Huntington's disease, Lou Gehrig's disease, and prion protein diseases. This study was conducted to evaluate the protective mechanisms of Scrophularia ningpoensis (SN) extracts and chemicals on TG-stimulated U-87MG cells. In this study, the recovery activities of E-harpagoside (EHA), harpagide (HA), 8-O-E-p-methoxycinnamoylharpagide (MH), aucubin (AB), cinnamic acid (CA), p-coumaric acid (pCA), p-methoxycinnamic acid methyl ester (MME), caffeic acid (CFA), ferulic acid (FA), and (E)-p-methoxycinnamic acid (MA) on TG-stimulated U-87MG cells were evaluated. The results revealed that SN, MME, CFA, and MH showed considerable recovery effects. Therefore, SN, MME, CFA, and MH were selected to evaluate the gene expression profile of U-87MG cells by using microarray analysis and real-time RT-PCR. The results of this analysis revealed that cell cycle, proliferation, protein folding, and anti-apoptosis-related genes were up-regulated in SN, MME, CFA, and MH-treated U-87MG cells. In addition, significant decreases in apoptosis, the MAPK signaling pathway, and mitochondria-related gene expressions were observed in SN-, MME-, CFA-, and MH-treated U-87MG cells. Thus, SN, MME, CFA, and MH might affect neurodegenerative diseases.

Effects of triterpenoids from Poria cocos Wolf on the serotonin type 3A receptor-mediated ion current in Xenopus oocytes.

Poria cocos Wolf (P. cocos Wolf) is used to treat chronic gastritis, edema, nephrosis, gastric atony, acute gastroenteric catarrh, dizziness, emesis and vomiting. Triterpenoids are a class of natural compounds produced by P. cocos Wolf that contain acyclic 30-carbon precursors. In this study, we investigated the effect of triterpenoids (PA, Pachymic acid; DA, dehydroeburicoic acid; HA, 3beta-hydroxylanosta-7,9(11),24-trien-21-oic acid) on human 5-hydroxytryptamine 3A (5-HT(3A)) receptor channel activity, which is one of the ligand-gated ion channel families. The two-electrode voltage-clamp technique was used to examine the 5-HT3A mediated current. The inhibitory effect of triterpenoids on 5HT-induced inward current (I(5-HT)) occurred in a concentration dependent and reversible manner. Furthermore, the half-inhibitory concentrations (IC(50)) of PA, DA and HA were 3.2+/-0.2, 5.5+/-0.6 and 1.4+/-0.2 microM, respectively. This corresponded to an order of potency for the inhibition of I(5-HT) in oocytes expressing human 5-HT(3A) receptor of HA>PA>DA. Finally, inhibition of I(5HT) by triterpenoids occurred in a non-competitive manner, while inhibition by HA and PA showed more voltage-dependency. Taken together, these results indicate that triterpenoids may regulate the expressed 5-HT(3A) receptors in Xenopus oocytes. Furthermore, this regulation of the ligand-gated ion channel activity by triterpenoids may be one of the pharmacological actions of P. cocos Wolf.

Susceptibility for ischemic stroke in Korean population is associated with polymorphisms of the Fc gamma receptor IIA.

Fc gamma receptor IIA could influence atherogenic processes through the production of superoxide anions, cytokines, and proteolytic enzymes as well as by oxidation of lipoproteins and enhancement of foam cell formation. In this study, we performed an interaction analysis between FCGR2A polymorphisms and ischemic stroke using direct DNA sequencing after the selection of Fc gamma receptor IIA gene based on genome-wide association study. Four of the FCGR2A polymorphisms, rs7511868 [odds ratio (OR) = 3.21; P = 0.027], rs6427595 (OR = 3.12; P = 0.008), rs7512140 (OR = 5.71; P = 0.002), and rs6696854 (OR = 3.65; P = 0.004) were significantly associated with ischemic stroke. These four polymorphisms still showed significant association after stratification analysis using the Mantel-Haenszel method. In the multivariate logistic regression, the adjusted OR estimates for rs6427595, rs7512140, and rs6696854 were 3.04 (P = 0.016), 4.84 (P = 0.015), and 3.80 (P = 0.006), respectively. The diplotype consisting of two homozygous haplotypes (H2 = AAAC) was significantly associated with ischemic stroke (OR = 17.39; P < 0.001). These results suggest that FCGR2A polymorphisms may be associated with a genetic susceptibility to ischemic stroke in a Korean population.

Recent progress in toxicogenomics research in South Korea.

BACKGROUND: The importance of toxicogenomics was recognized early in Korea and a group of researchers was trying to build up a research infrastructure and educational system. However, since the scale of the Korean pharmaceutical industry, which was expected to play the key role in toxicogenomics was small compared to that of advanced countries, industry-sponsored large-scale research projects and supporting infrastructures have been lacking in Korea. RESULTS: To improve this situation, the Korean government has exerted special efforts to promote toxicogenomics research and development the last few years as an initiative to stimulate a premature drug development industry on par with global competition and launched several large scale research projects recently. Researchers are also trying to keep pace with government efforts by organizing local scientist groups, training young toxicogenomics scientists, and widening the toxicogenomic research efforts to environmental toxicity as well. Research and development from bioinformatics and genomics venture companies are also contributing to uplifting the competitiveness of the toxicogenomics industry. CONCLUSION: Toxicogenomics in Korea is making steady progress in many directions. It is gaining ground by government and related industries as well, the research is diversified to embrace environmental genomics, and local research groups are making strategic links to international research groups such as the MicroArray Quality Control (MAQC) consortium. We expect the advancement of the Korean toxicogenomics research program will be beneficial not only to the local society alone, but also to international scientists as a whole.

Inhibitory effects of Schizandrae Fructus on eotaxin secretion in A549 human epithelial cells and eosinophil migration.

Eosinophilia have been implicated in a broad range of diseases, most notably allergic conditions (e.g. asthma, rhinitis and atopic dermatitis) and inflammatory diseases. These diseases are characterized by an accumulation of eosinophils in the affected tissue. Defining the mechanisms that control the recruitment of eosinophil is fundamental to understanding how these diseases progress and identifying a novel target for drug therapy. Accordingly, this study was conducted to evaluate the regulatory effect of Schizandrae Fructus (SF) on the expression of eotaxin, an eosinophil-specific chemokine released in respiratory epithelium following allergic stimulation, as well as its effects on eosinophil migration. To accomplish this, human epithelial lung cells (A549 cell) were stimulated with a combination of TNF-alpha (100ng/ml) and IL-4 (100ng/ml) for 24h. The cells were then restimulated with TNF-alpha (100ng/ml) and IL-1beta (10ng/ml) to induce the expression of chemokines and adhesion molecules involved in eosinophil chemotaxis for another 24h. Next, the samples were treated with various concentrations of Schizandrae Fructus (SF) (1, 10, 100, 1000microg/ml) or one of the major constituents of SF, schizandrin (0.1, 1, 10, 100microg/ml), after which following inhibition effect assay was performed triplicates in three independence. The levels of eotaxin in secreted proteins were suppressed significantly by SF (100 and 1000microg/ml, p<0.01) and schizandrin (10 and 100microg/ml, p<0.01). In addition, SF (1, 10, 100 and 1000microg/ml) decreased mRNA expression levels in A549 cells significantly (p<0.01). Eosinophil recruitment to lung epithelial cells was also reduced by SF, which indicates that eotaxin plays a role in eosinophil recruitment. Furthermore, treatment with SF suppressed the expression of another chemokine, IL-8 (0.1 and 1microg/ml SF, p<0.01), as well as intercellular adhesion molecule-1 (10 and 100microg/ml SF, p<0.01) and vascular cell adhesion molecule-1 (0.1 and 1microg/ml SF, p<0.05), which are all related to eosinophil migration. Taken together, these findings indicate that SF may be a desirable medicinal plant for the treatment of allergic diseases.

Microarray analysis of gene expression profiles in response to treatment with bee venom in lipopolysaccharide activated RAW 264.7 cells.

AIM OF THE STUDY: The therapeutic application of bee venom (BV) has been used in traditional medicine to treat diseases such as arthritis, rheumatism and pain. Macrophages produce molecules that are known to play roles in inflammatory responses. MATERIAL AND METHODS: We performed microarray analysis to evaluate the global gene expression profiles of RAW264.7 macrophage cells treated with BV. In addition, six genes were subjected to real-time PCR to confirm the results of the microarray. The cells were treated with lipopolysaccharide (LPS) or BV plus LPS for 30 min or 1h. RESULTS: 124 genes were found to be up-regulated and 158 were found to be down-regulated in cells that were treated with BV plus LPS for 30 min, whereas 211 genes were up-regulated and 129 were down-regulated in cells that were treated with BV plus LPS for 1h when compared with cells that were treated with LPS alone. Furthermore, the results of real-time PCR were similar to those of the microarray. BV inhibited the expression of specific inflammatory genes that were up-regulated by nuclear factor-kappa B in the presence of LPS, including mitogen-activated protein kinase kinase kinase 8 (MAP3K8), TNF, TNF-alpha-induced protein 3 (TNFAIP3), suppressor of cytokine signaling 3 (SOCS3), TNF receptor-associated factor 1 (TRAF1), JUN, and CREB binding protein (CBP). CONCLUSIONS: These results demonstrate the potent activity of BV as a modulator of the LPS-mediated nuclear factor-kappaB (NF-kappaB)/MAPK pathway in activated macrophages. In addition, these results can be used to understand other effects of BV treatment.