Replication of genome-wide association studies on asthma and allergic diseases in Korean adult population

Allergic diseases such as asthma, allergic rhinitis, and atopicdermatitis are heterogeneous diseases characterized by multiplesymptoms and phenotypes. Recent advancements in geneticstudy enabled us to identify disease associated genetic factors.Numerous genome-wide association studies (GWAS) have revealedmultiple associated loci for allergic diseases. However,the majority of previous studies have been conducted in populationsof European ancestry. Moreover, the associations of singlenucleotide polymorphisms (SNPs) with allergic diseaseshave not been studied amongst the large-scale general Koreanpopulation. Herein, we performed the replication study to validatethe previous variants, known to be associated with allergicdiseases, in the Korean population. In this study, we categorizedthree allergic related phenotypes, one allergy and two asthmarelated phenotypes, based on self-reports of physician diagnosisand their symptoms from 8,842 samples. As a result, we foundnominally significant associations of 6 SNPs with at least one allergicrelated phenotype in the Korean population. [BMB reports2012; 45(5): 305-310

In situ induction of dendritic cell–based T cell tolerance in humanized mice and nonhuman primates

Administration of an ICAM-1–specific antibody arrests dendritic cells in a semi-immature state and facilitates antigen-specific T cell tolerance to islet allografts in humanized mice and Rhesus monkeys

Efficacy of psychosocial interventions for pregnancy rates of infertile women undergoing in vitro fertilization: a systematic review and meta-analysis

Purpose This study aimed to analyze the efficacy of psychosocial interventions for improving pregnancy rates in infertile women undergoing in vitro fertilization (IVF) treatment through a systematic review and meta-analysis. Methods Twelve studies were included in the meta-analysis. To estimate the effect size, a meta-analysis of the studies was performed using RevMan 5.3. The possibility of publication bias was evaluated using funnel plots and Egger’s method. Results A statistically significant effect size (standardized mean difference [SMD] = 1.39; 95% confidence interval [CI] = 1.11–1.71; p = 0.004; I2 = 19%) was found for the 12 studies that investigated the effects of psychosocial interventions on clinical pregnancy rates. The psychosocial interventions that had a significant effect on pregnancy rates were mind-body interventions (SMD = 1.37; 95% CI = 1.01–1.85; p = 0.040; I2 = 0%) and cognitive behavioral therapy (SMD = 2.19; 95% CI = 1.17–4.13; p = 0.010). Conclusions The results suggest that psychosocial interventions affect pregnancy rates. Moreover, they indicate that mind-body interventions and cognitive behavioral therapy are beneficial for improving the pregnancy outcome in infertile women undergoing IVF

Systematic Analysis of the Molecular Mechanisms of Cold and Hot Properties of Herbal Medicines

Effective treatments for patients experiencing temperature-related symptoms are limited. The hot and cold effects of traditional herbal medicines have been utilized to treat and manage these symptoms, but their molecular mechanisms are not fully understood. Previous studies with arbitrarily selected herbs and ingredients may have produced biased results. Here, we aim to systematically elucidate the molecular mechanisms of the hot and cold properties of herbal medicines through an unbiased large-scale investigation of herbal ingredients, their target genes, and the transcriptome signatures induced by them. Using data regarding 243 herbs retrieved from two herbal medicine databases, we statistically identify (R)-Linalool, (-)-alpha-pinene, peruviol, (L)-alpha-terpineol, and cymol as five new hot-specific ingredients that share a common target, a norepinephrine transporter. However, no significant ingredients are cold-specific. We also statistically identify 14 hot- and 8 cold-specific new target genes. Pathway enrichment analysis of hot-specific target genes reveals the associated pathways including neurotransmitter reuptake, cold-induced thermogenesis, blood pressure regulation, adrenergic receptor signaling, and cation symporter activity. Cold-specific target genes are associated with the steroid pathway. Transcriptome analysis also shows that hot herbs are more strongly associated with coagulation and synaptic transmission than cold herbs. Our results, obtained from novel connections between herbal ingredients, target genes, and pathways, may contribute to the development of pharmacological treatment strategies for temperature-related pain using medicinal plants

Interaction between the mouse homologue of CD99 and its ligand PILR as a mechanism of T cell receptor-independent thymocyte apoptosis

Here, we show that the interaction between two membrane proteins, the mouse homologue of CD99 (designated D4) and its ligand, paired immunoglobulin-like type 2 receptor (PILR), is one of the major mechanisms of thymocyte apoptosis. Using the polymeric fusion protein of PILR and IgG1 (PILR-Ig), we demonstrated that D4 ligation in the absence of T cell receptor (TCR) engagement leads to the induction of apoptosis, mainly at the double-positive stage of thymocytes. This was further confirmed by a blocking study in which blocking the interaction between D4 and PILR by soluble D4 protein led to reduced apoptosis in the fetal thymic organ culture with wild type and TCRα-/- mice. Furthermore, the dissection of intracellular signaling pathway demonstrated that D4 cross-linking led to caspase activation without any change in mitochondrial membrane potential. Based on these data, we propose a mechanism for thymocyte depletion in which the interaction between D4 and PILR delivers an active signal

Image_1_Regulation of CIRP by genetic factors of SP1 related to cold sensitivity.tif

Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 mediate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p-5, false discovery rate 2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.</p

Table_4_Regulation of CIRP by genetic factors of SP1 related to cold sensitivity.docx

Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 mediate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p-5, false discovery rate 2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.</p

Table_2_Regulation of CIRP by genetic factors of SP1 related to cold sensitivity.docx

Cold-inducible RNA-binding-protein (CIRP) is a cold shock protein that plays a protective role in genotoxic stress response. CIRP modulates inflammation in human diseases, inhibits cell proliferation, and protects cells from genotoxic damage during cellular stress. The mild cold responsive element and specificity protein 1 (SP1) play a role in Cirp expression at low temperatures. Although previous studies have provided insights into the immune functions of SP1 or CIRP, the mechanisms by which CIRP and SP1 mediate inflammatory responses remain largely unknown. Therefore, in the current study, we examined whether Cirp expression is affected by genetic factors related to temperature sensitivity as well as under low temperature. We performed a genome-wide association study on cold sensitivity in 2,000 participants. Fifty-six genome-wide significant trait-locus pairs were identified (p-5, false discovery rate 2 > 0.8) relationship and expression quantitative trait locus-associated signals with the nearest Sp1 gene. We confirmed that the minor alleles of rs11170510 and rs58123204 were associated with increased Sp1 expression. Additionally, Sp1 overexpression led to CIRP translocation from the nucleus to the cytoplasm. CIRP protein levels increased in serum samples that had minor alleles of rs11170510 and rs58123204. Levels of various pro-inflammatory cytokines were also significantly increased in human peripheral blood mononuclear cells with minor alleles of rs11170510 and rs58123204. These results suggest that genetic factors related to cold sensitivity regulate CIRP expression and function and provide valuable insights into prediction of potential diseases through analysis of inherent genetic factors in humans.</p