Kangwon National University

About: Kangwon National University is a education organization based out in Chuncheon, South Korea. It is known for research contribution in the topics: Population & Catalysis. The organization has 9836 authors who have published 20002 publications receiving 393562 citations. The organization is also known as: KNU.

Association between glucocorticoid receptor methylation and hippocampal subfields in major depressive disorder.

Abstract: Background DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. Methods We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls. Correlations among NR3C1 promoter methylation, structural abnormalities in hippocampal subfield volumes and whole-brain cortical thickness, and clinical variables were also analyzed. Results In total, 117 participants (45 with MDD and 72 healthy controls) were recruited. Patients with MDD had significantly lower methylation than healthy controls at 2 CpG sites. In MDD, methylations had positive correlations with the bilateral cornu ammonis (CA) 2–3 and CA4-dentate gyrus (DG) subfields. However, in healthy controls, methylations had positive correlation with the subiculum and presubiculum. There were no differences in total and subfield volumes of the hippocampus between patients with MDD and healthy controls. Compared with healthy controls, patients with MDD had a significantly thinner cortex in the left rostromiddle frontal, right lateral orbitofrontal, and right pars triangularis areas. Conclusions Lower methylation in the NR3C1 promoter, which might have compensatory effects relating to CA2-3 and CA4-DG, is a distinct epigenetic characteristic in non-psychotic outpatients with MDD. Future studies with a longitudinal design and a comprehensive neurobiological approach are warranted in order to elucidate the effects of NR3C1 methylation.

Hyaluronic acid promotes angiogenesis by inducing RHAMM-TGFβ receptor interaction via CD44-PKCδ.

Abstract: Hyaluronic acid (HA) has been shown to promote angiogenesis. However, the mechanism behind this effect remains largely unknown. Therefore, in this study, the mechanism of HA-induced angiogenesis was examined. CD44 and PKCδ were shown to be necessary for induction of the receptor for HA-mediated cell motility (RHAMM), a HA-binding protein. RHAMM was necessary for HA-promoted cellular invasion and endothelial cell tube formation. Cytokine arrays showed that HA induced the expression of plasminogen activator-inhibitor-1 (PAI), a downstream target of TGFβ receptor signaling. The induction of PAI-1 was dependent on CD44 and PKCδ. HA also induced an interaction between RHAMM and TGFβ receptor I, and induction of PAI-1 was dependent on RHAMM and TGFβ receptor I. Histone deacetylase 3 (HDAC3), which is decreased by HA via rac1, reduced induction of plasminogen activator inhibitor-1 (PAI-1) by HA. ERK, which interacts with RHAMM, was necessary for induction of PAI-1 by HA. Snail, a downstream target of TGFβ signaling, was also necessary for induction of PAI-1. The down regulation of PAI-1 prevented HA from enhancing endothelial cell tube formation and from inducing expression of angiogenic factors, such as ICAM-1, VCAM-1 and MMP-2. HDAC3 also exerted reduced expression of MMP-2. In this study, we provide a novel mechanism of HA-promoted angiogenesis, which involved RHAMM-TGFβRI signaling necessary for induction of PAI-1.

Biological screening of 100 plant extracts for cosmetic use (II): anti-oxidative activity and free radical scavenging activity

Abstract: Methanol aqueous extracts of 100 plants were screened for anti-oxidative activity using Fenton's reagent/ethyl linoleate system and for free radical scavenging activity using the 1,1-diphenyl-2-picryl hydrazyl free radical generating system. The results suggest that 14 plants - Alpinia officinarum, Areca catechu, Brassica alba, Cannabis sativa, Curcuma longa, Curcuma aromatica, Eugenia caryophyllata, Evodia officinalis, Paeonia suffruticosa, Rhaphanus sativus, Rheum palmatum, Rhus verniciflua, Trapa bispinosa, Zanthoxylum piperitum - may be potential sources of anti-oxidants. Eight plants - Citrus aurantium, Cornus officinalis, Gleditsia japonica, Lindera strychnifolia, Phragmites communis, Prunus mume, Schizandra chinensis, Terminalia chebula - may be the potential source of free radical scavengers from natural plant.

Caffeic acid and its synthetic derivative CADPE suppress tumor angiogenesis by blocking STAT3-mediated VEGF expression in human renal carcinoma cells.

Abstract: Tumor angiogenesis is required for tumor development and isstimulated by angiogenic inducers like VEGF (vascular endothe-lial growth factor). Our previous study demonstrated that STAT3(signal transducer and activator of transcription 3) up-regulatesHIF-1a(hypoxiainduciblefactor-1a)proteinstabilityandenhan-ces HIF-1-mediated VEGF expression in hypoxic solid tumorcells, thus suggesting that the inhibition of STAT3 signaling mayhave clinical applications. In this study, we examined in vitro andinvivo,whethercaffeicacid(CA)oritsderivativeCADPE[3-(3,4-dihydroxy-phenyl)-acrylicacid2-(3,4-dihydroxy-phenyl)-ethyles-ter] exert anticancer activity by targeting STAT3. It was foundthat CA or CADPE significantly inhibit STAT3 activity, and thatthis in turn down-regulates HIF-1a activity. Consequently, se-quential blockade of STAT3 and HIF-1a resulted in the down-regulation of VEGF by inhibiting their recruitment to the VEGFpromoter. In mice bearing a Caki-I carcinoma, both CA andCADPE retarded tumor growth and suppressed STAT3 phos-phorylation, HIF-1a expression, vascularization and STAT3-inducible VEGF gene expression in tumors. Taken together, ourresults demonstrate that CA and CADPE are potential inhibitorsofSTAT3 andthattheysuppresstumorangiogenesis byinhibitingthe activity of STAT3, the expression of HIF-1a and VEGF.IntroductionIn a previous study, we found that signal transducer and activator oftranscription 3 (STAT3) plays a pivotal role in the regulation of hyp-oxia inducible factor-1a (HIF-1a) protein stability and that it enhan-ces the HIF-1-mediated expression of vascular endothelial growthfactor (VEGF) by interacting with HIF-1a in human renal carcinomacells (1). These findings demonstrate that STAT3 is a critical up-regulator of hypoxia-mediated VEGF expression in solid tumor cells.VEGF has been well established to have a crucial role in angio-genesis and tumor progression (2), and VEGF inhibition has producedpromising results as a tumor anti-angiogenesis therapy in animalmodels and cancer patients (3). Hypoxia commonly develops withinsolid tumors because tumor cell proliferation is faster than the rate ofblood vessel formation, and thus leads to a compromised tumor bloodsupply (4). Moreover, hypoxia also stimulates VEGF expression intumors and promotes angiogenesis to meet the metabolic requirementfor growth (5). Thus, factors that regulate hypoxic angiogenesis rep-resent viable anticancer therapeutic targets. HIF-1 is one such target,as it is a key transcription factor that regulates VEGF expression. HIF-1 is a heterodimer composed of HIF-1a and HIF-1b subunits (6), andits biologic activity depends on the amount of HIF-1a, which is tightlyregulated by oxygen tension. Under normoxic conditions, HIF-1aprotein is unstable. Many studies have challenged the developmentof anticancer drug targeting HIF-1a which is inducible under hypoxicconditions (7).Recently, STAT3 was found to be a direct transcriptional activatorof the VEGF gene, and demonstrated to up-regulate VEGF expressionin diverse human cancers (8), which suggests that STAT3 activitycontributes significantly to VEGF overproduction in tumors. STAT3is activated by phosphorylation at tyrosine residue 705 (Y705), whichleads to dimer formation, its nuclear translocation, DNA binding andtarget gene transcription (9). Phosphorylation of STAT3 at tyrosine705 (Y705) is critically its dimerization and nuclear translocation;both prerequisites of STAT3 activation (10). Thus, we considered thatinhibiting this phosphorylation at residue 705 might reduce VEGFexpression in tumor cells. During a search for inhibitors of STAT3activity, we found that caffeic acid (CA) and its synthetic derivative,CADPE [3-(3,4-Dihydroxy-phenyl)-acrylic acid 2-(3,4-dihydroxy-phenyl)-ethyl ester], are both active. CA has been reported to possessa wide spectrum of biological effects, e.g. antioxidant activity (11–13)and anti-inflammatory properties (14,15), which are similar to theeffects of many other anticancer agents.In the present study, the observations made revealed that CA or itsderivative CADPE inhibit tumor growth and angiogenesis by inhibit-ing the activity of STAT3, the expression of HIF-1a and VEGF ina mouse xenograft model. These findings indicate that CA or its de-rivative CADPE activity as an anticancer molecules and that STAT3-dependent repression of HIF-1a and VEGF may be used to control anexcess angiogenesis in various solid tumor cells.Materials and methods

Expression Profiling of Tobacco Leaf Trichomes Identifies Genes for Biotic and Abiotic Stresses

Abstract: Nicotiana tabacum (tobacco) plants have short and long glandular trichomes. There is evidence that tobacco trichomes play several roles in the defense against biotic and abiotic stresses. cDNA libraries were constructed from control and cadmium (Cd)-treated leaf trichomes. Almost 2,000 expressed sequence tag (EST) cDNA clones were sequenced to analyze gene expression in control and Cdtreated leaf trichomes. Genes for stress response as well as for primary metabolism scored highly, indicating that the trichome is a biologically active and stress-responsive tissue. Reverse transcription–PCR (RT–PCR) analysis demonstrated that antipathogenic T-phylloplanin-like proteins, glutathione peroxidase and several classes of pathogenesis-related (PR) proteins were expressed specifi cally or dominantly in trichomes. Cysteine-rich PR proteins, such as non-specifi c lipid transfer proteins (nsLTPs) and metallocarboxypeptidase inhibitors, are candidates for the sequestration of metals. The expression of osmotin and thaumatin-like proteins was induced by Cd treatment in both leaves and trichomes. Confocal laser scanning microscopy (CLSM) showed that glutathione levels in tip cells of both long and short trichomes were higher than those in other types of leaf cells, indicating the presence of an active sulfur-dependent protective system in trichomes. Our results revealed that the trichomespecifi c transcriptome approach is a powerful tool to investigate the defensive functions of trichomes against both abiotic and biotic stress. Trichomes are shown to be an enriched source of useful genes for molecular breeding towards stress-tolerant plants.