Interleukin-18, transforming growth factor-β, and vascular endothelial growth factor gene polymorphisms and susceptibility to primary glomerulonephritis

Choi, H.-J.,Cho, J.-H.,Kim, J.-C.,Seo, H.-J.,Hyun, S.-H.,Kim, G.-H.,Choi, J.-Y.,Choi, H.-J.,Ryu, H.-M.,Cho, J.-H.,Park, S.-H.,Kim, Y.-L.,Han, S.,Kim, C.-D. Blackwell Publishing Ltd 2010 Tissue antigens Vol.76 No.4

<P>Several studies have showed an association of gene polymorphisms with the development of glomerulonephritis (GN). We investigated the effects of gene polymorphisms on the development of GN by analyzing polymorphisms in the interleukin (IL)-18, transforming growth factor (TGF)-β, and vascular endothelial growth factor (VEGF) genes in Korean patients with primary GN. The study included 146 normal subjects (controls) and 100 patients diagnosed with primary GN by kidney biopsy. The gene polymorphisms A-607C and G-137C in <I>IL-18</I>, C-509T and T869C in <I>TGF-</I>β<I>1</I>, and C-2578A and C405G in <I>VEGF</I> were investigated in DNA extracted from peripheral blood. Significant differences were observed between the GN and control groups in the genotype and allele frequencies of A-607C <I>IL-18</I> and C405G <I>VEGF</I>. The frequencies of the <I>IL-18</I>−607CC genotype [<I>P</I> = 0.001, odds ratio (OR) = 2.473] and the <I>VEGF</I> 405GG genotype (<I>P</I> = 0.001, OR = 2.473) were significantly increased in the GN group. The combination of <I>IL-18</I>−607CC+ and <I>VEGF</I> 405GG+ genotypes had a higher risk for developing GN in comparison with the combination of <I>IL-18</I>−607CC− and <I>VEGF</I> 405GG− genotypes (<I>P</I> < 0.001, OR = 8.642). In the haplotype analysis of the <I>IL-18</I> gene, the CG haplotype was significantly more frequent in the GN group than the control group (61.5% <I>vs</I> 46.9%, <I>P</I> = 0.002). These results show that the −607CC genotype of the <I>IL-18</I> gene and the 405GG genotype of the <I>VEGF</I> gene are associated with susceptibility to and the development of primary GN.</P>

Ion scattering spectroscopy study of the Si(001)c(4x4)-C surface reconstruction

Park J. Y.,Chae K. H.,Choi D. S.,Kim J. Y.,Kim S. S.,Seo J. H.,Whang C. N. 한국물리학회 2004 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.45 No.3

Reconstructed Si(001)c(4 4)-C surface has been studied by coaxial impact collision ion scattering spectroscopy (CAICISS). When 100L ethylene (C2H4) was exposed on Si(001)-(2 1) surface at 700 C, Si(001) dimer structures were changed by induced carbon (C) atoms. The experimental CAICISS spectra and simulation results reveal that the reconstructed Si(001)c(4 4)-C surface shows good agreement with the missing dimer model, rather than the Si-C heterodimer model, and adsorbed C atoms in uence only the reconstructed vertical plane of Si(001) surface. On comparing the azimuthal-scan curves for 100L C/Si(001) with those for clean Si(001), it can be suggested that C atoms occupy the fourth subsurface layer of Si(001) directly below the HB (bridge) site. These results are new evidence supporting the previous studies based on the C incorporation into Si(001) surface with missing dimers and the substitution of the fourth Si layers.

High-resolution 3-μm spectra of Jupiter: Latitudinal spectral variations influenced by molecules, clouds, and haze

Kim, S.J.,Geballe, T.R.,Kim, J.H.,Jung, A.,Seo, H.J.,Minh, Y.C. Academic Press 2010 Icarus Vol.208 No.2

We present latitudinally-resolved high-resolution (R=37,000) pole-to-pole spectra of Jupiter in various narrow longitudinal ranges, in spectral intervals covering roughly half of the spectral range 2.86-3.53μm. We have analyzed the data with the aid of synthetic spectra generated from a model jovian atmosphere that included lines of CH<SUB>4</SUB>, CH<SUB>3</SUB>D, NH<SUB>3</SUB>, C<SUB>2</SUB>H<SUB>2</SUB>, C<SUB>2</SUB>H<SUB>6</SUB>, PH<SUB>3</SUB>, and HCN, as well as clouds and haze. Numerous spectral features of many of these molecular species are present and are individually identified for the first time, as are many lines of H<SUB>3</SUB><SUP>+</SUP> and a few unidentified spectral features. In both polar regions the 2.86-3.10-μm continuum is more than 10 times weaker than in spectra at lower latitudes, implying that in this wavelength range the single-scattering albedos of polar haze particles are very low. In contrast, the 3.24-3.53μm the weak polar and equatorial continua are of comparable intensity. We derive vertical distributions of NH<SUB>3</SUB>, C<SUB>2</SUB>H<SUB>2</SUB> and C<SUB>2</SUB>H<SUB>6</SUB>, and find that the mixing ratios of NH<SUB>3</SUB> and C<SUB>2</SUB>H<SUB>6</SUB> show little variation between equatorial and polar regions. However, the mixing ratios of C<SUB>2</SUB>H<SUB>2</SUB> in the northern and southern polar regions are ∼6 and ∼3 times, respectively, less than those in the equatorial regions. The derived mixing ratio curves of C<SUB>2</SUB>H<SUB>2</SUB> and C<SUB>2</SUB>H<SUB>6</SUB> extend up to the 10<SUP>-6</SUP> bar level, a significantly higher altitude than most previous results in the literature. Further ground-based observations covering other longitudes are needed to test if these mixing ratios are representative values for the equatorial and polar regions.

Characterization of Phosphoinositide-3-kinase, Class 3 (PIK3C3) Gene and Association Tests with Quantitative Traits in Pigs

Kim, J.H.,Choi, B.H.,Lim, H.T.,Park, E.W.,Lee, S.H.,Seo, B.Y.,Cho, I.C.,Lee, J.G.,Oh, S.J.,Jeon, J.T. Asian Australasian Association of Animal Productio 2005 Animal Bioscience Vol.18 No.12

This study deals with the characterization of porcine PIK3C3 and association tests with quantitative traits. PIK3C3 belongs to the class 3 PI3Ks that participate in the regulation of hepatic glucose output, glycogen synthase, and antilipolysis in typical insulin target cells such as those in the such as liver, muscle system, and fat. On the analysis of full-length mRNA sequence, the length of the PIK3C3 CDS was recorded as 2,664 bps. As well, nucleotide and amino acid identities between human and pig subjects were 92% and 99%, respectively. Five SNPs were detected over 5 exons. We performed genotyping by using a SNP C2604T on exon24 for 145 F$_2$ animals (from a cross between Korean native boars and Landrace sows) by PCR-RFLP analysis with Hpy8I used to investigate the relationship between growth and fat depot traits. In the total association analysis, which doesn' consider transmission disequilibrium, the SNP showed a significant effect (p<0.05) on body weight and carcass fat at 30 weeks of age as well as a highly significant effect (p<0.01) on back fat. In an additional sib-pair analysis, C allele still showed positive and significant effects (p<0.05) on back fat thickness and carcass fat. Moreover, the effects of C allele on the means of within-family components for carcass fat and back fat were estimated as 2.76 kg and 5.07 mm, respectively. As a result, the SNP of porcine PIK3C3 discovered in this study could be utilized as a possible genetic marker for the selection of pigs that possess low levels of back fat and carcass fat at the slaughter weight.

C3, C4 의 Nephelometric 측정 경험

조병철 ( B C Cho ),검덕희 ( D H Kim ),김민숙 ( M S Kim ),서덕규 ( D K Seo ) 대한임상검사과학회 1990 대한임상검사과학회지(KJCLS) Vol.22 No.1

RIA has been used to measure accurately a minute quantity of Ags, such as proteins. hormones, enzymes or drugs. However, due to the presence of a radication hazard and the increment of having to pool test specimens. RIA is gradually being replaced by other immunoassay that have a comparable sensitivity but do not require radiocative meterial. Turbidimetric immunoassay, latex immunoassay and fluorescence immunoassay are such examples. We at the department of clinical pathology, Asan medical center, compared CH 50 activity with C3 , C4 quantity by nephelometric method.

Effects of Synchronicity of Carbohydrate and Protein Degradation on Rumen Fermentation Characteristics and Microbial Protein Synthesis

Seo, J.K.,Kim, M.H.,Yang, J.Y.,Kim, H.J.,Lee, C.H.,Kim, K.H.,Ha, Jong K. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.3

A series of in vitro studies were carried out to determine i) the effects of enzyme and formaldehyde treatment on the degradation characteristics of carbohydrate and protein sources and on the synchronicity of these processes, and ii) the effects of synchronizing carbohydrate and protein supply on rumen fermentation and microbial protein synthesis (MPS) in in vitro experiments. Untreated corn (C) and enzyme-treated corn (EC) were combined with soy bean meal with (ES) and without (S) enzyme treatment or formaldehyde treatment (FS). Six experimental feeds (CS, CES, CFS, ECS, ECES and ECFS) with different synchrony indices were prepared. Highly synchronous diets had the greatest dry matter (DM) digestibility when untreated corn was used. However, the degree of synchronicity did not influence DM digestibility when EC was mixed with various soybean meals. At time points of 12 h and 24 h of incubation, EC-containing diets showed lower ammonia-N concentrations than those of C-containing diets, irrespective of the degree of synchronicity, indicating that more efficient utilization of ammonia-N for MPS was achieved by ruminal microorganisms when EC was offered as a carbohydrate source. Within C-containing treatments, the purine base concentration increased as the diets were more synchronized. This effect was not observed when EC was offered. There were significant effects on VFA concentration of both C and S treatments and their interactions. Similar to purine concentrations, total VFA production and individual VFA concentration in the groups containing EC as an energy source was higher than those of other groups (CS, CES and CFS). The results of the present study suggested that the availability of energy or the protein source are the most limiting factors for rumen fermentation and MPS, rather than the degree of synchronicity.

Synthesis and biological evaluation of C-ring truncated deguelin derivatives as heat shock protein 90 (HSP90) inhibitors

Kim, H.S.,Hong, M.,Ann, J.,Yoon, S.,Nguyen, C.T.,Lee, S.C.,Lee, H.Y.,Suh, Y.G.,Seo, J.H.,Choi, H.,Kim, J.Y.,Kim, K.W.,Kim, J.,Kim, Y.M.,Park, S.J.,Park, H.J.,Lee, J. Elsevier/Pergamon 2016 Bioorganic & medicinal chemistry Vol.24 No.22

Based on the lead compound L-80 (compound 2), a potent heat shock protein 90 (HSP90) inhibitor, a series of C-ring truncated deguelin analogs were designed, synthesized and evaluated for Hypoxia Inducible Factor-1α (HIF-1α) inhibition as a primary screening method. Their structure-activity relationship was investigated in a systematic manner by varying the A/B ring, linker and D/E ring, respectively. Among the synthesized inhibitors, compound 5 exhibited potent HIF-1α inhibition in a dose-dependent manner and significant antitumor activity in human non-small cell lung carcinoma (H1299), with better activities than L-80. It also inhibited in vitro hypoxia-mediated angiogenic processes in human retinal microvascular endothelial cells (HRMEC). The docking study of 5 showed a similar binding mode as L-80: it occupied the C-terminal ATP-binding pocket of HSP90, indicating that the anticancer and antiangiogenic activities of 5 were derived from HIF-1α destabilization by inhibiting the C-terminal ATP-binding site of hHSP90.

Dipeptidyl petidase-IV inhibitor (gemigliptin) inhibits tunicamycin-induced endoplasmic reticulum stress, apoptosis and inflammation in H9c2 cardiomyocytes

Hwang, H.J.,Jung, T.W.,Ryu, J.Y.,Hong, H.C.,Choi, H.Y.,Seo, J.A.,Kim, S.G.,Kim, N.H.,Choi, K.M.,Choi, D.S.,Baik, S.H.,Yoo, H.J. North-Holland 2014 Molecular and cellular endocrinology Vol.392 No.1

The direct effects of dipeptidyl peptidase-IV (DPP-IV) inhibitors on endoplasmic reticulum (ER) stress-induced apoptosis and inflammation in cardiomyocytes have not been elucidated. H9c2 cell viability, which was reduced by tunicamycin, was increased after DPP-IV inhibitor gemigliptin treatment. Gemigliptin significantly decreased the tunicamycin-mediated increase in glucose regulated protein 78 (GRP78) expression and ER stress-mediated signaling molecules such as protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C-EBP homologous protein (CHOP) and inositol-requiring enzyme 1α (IRE1α)/c-Jun N-terminal kinase (JNK)-p38. Furthermore, gemigliptin effectively induced Akt phosphorylation in a dose-dependent manner. Using flow cytometry and Hoechst staining, we showed that treatment with Akt inhibitor significantly blocked the anti-apoptotic effects mediated by gemigliptin. The reduction in tunicamycin-induced GRP78 level and PERK/CHOP pathway activity by gemigliptin was reversed after treatment with Akt inhibitor. In conclusion, gemigliptin effectively inhibited ER stress-induced apoptosis and inflammation in cardiomyocytes via Akt/PERK/CHOP and IRE1α/JNK-p38 pathways, suggesting its direct protective role in cardiovascular diseases.

Intravesical Instillation of c-MYC Inhibitor KSI-3716 Suppresses Orthotopic Bladder Tumor Growth

Jeong, K.C.,Kim, K.T.,Seo, H.H.,Shin, S.P.,Ahn, K.O.,Ji, M.J.,Park, W.S.,Kim, I.H.,Lee, S.J.,Seo, H.K. Williams and Wilkins Co 2014 The Journal of urology Vol.191 No.2

Purpose: c-MYC is a promising target for cancer therapy but its use is restricted by unwanted, devastating side effects. We explored whether intravesical instillation of the c-MYC inhibitor KSI-3716 could suppress tumor growth in murine orthotopic bladder xenografts. Materials and Methods: The small molecule KSI-3716, which blocks c-MYC/MAX binding to target gene promoters, was used as an intravesical chemotherapy agent. KSI-3716 action was assessed by electrophoretic mobility shift assay, chromatin immunoprecipitation, transcription reporter assay and quantitative reverse transcriptase-polymerase chain reaction. Inhibition of cell proliferation and its mechanism was monitored by cell cytotoxicity assay, EdU incorporation assay and flow cytometry. The in vivo efficacy of KSI-3716 was examined by noninvasive luminescence imaging and histological analysis after intravesical instillation of KSI-3716 in murine orthotopic bladder xenografts. Results: KSI-3716 blocked c-MYC/MAX from forming a complex with target gene promoters. c-MYC mediated transcriptional activity was inhibited by KSI-3716 at concentrations as low as 1 μM. The expression of c-MYC target genes, such as cyclin D2, CDK4 and hTERT, was markedly decreased. KSI-3716 exerted cytotoxic effects on bladder cancer cells by inducing cell cycle arrest and apoptosis. Intravesical instillation of KSI-3716 at a dose of 5 mg/kg significantly suppressed tumor growth with minimal systemic toxicity. Conclusions: The c-MYC inhibitor KSI-3716 could be developed as an effective intravesical chemotherapy agent for bladder cancer.

Interaction of small G protein signaling modulator 3 with connexin 43 contributes to myocardial infarction in rat hearts

Lee, C.Y.,Choi, J.W.,Shin, S.,Lee, J.,Seo, H.H.,Lim, S.,Lee, S.,Joo, H.C.,Kim, S.W.,Hwang, K.C. Academic Press 2017 Biochemical and biophysical research communication Vol. No.

Connexin 43 (Cx43), a ubiquitous connexin expressed in the heart and skin, is associated with a variety of hereditary conditions. Therefore, the characterization of Cx43-interacting proteins and their dynamics is important to understand not only the molecular mechanisms underlying pathological malfunction of gap junction-mediated intercellular communication but also to identify novel and unanticipated biological functions of Cx43. In the present study, we observed potential targets of Cx43 to determine new molecular functions in cardio-protection. MALDI-TOF mass spectrometry analysis of Cx43 co-immunoprecipitated proteins showed that Cx43 interacts with several proteins related to metabolism. In GeneMANIA network analysis, SGSM3, which has not been previously associated with Cx43, was highly correlated with Cx43 in heart functions, and high levels of SGSM3 appeared to induce the turnover of Cx43 through lysosomal degradation in myocardial infarcted rat hearts. Moreover, we confirmed that lysosomal degradation of Cx43 is dependent upon the interaction between SGSM3 and Cx43 in H9c2 cardiomyocytes. The functional importance of the interaction between SGSM3 and Cx43 was confirmed by results showing that Cx43 expression was enhanced by SGSM3 siRNA knockdown in H9c2 cells. In summary, the results of this study elucidate the molecular mechanisms in which Cx43 with SGSM3 is degraded in myocardial infarcted rat hearts, which may contribute to the establishment of new therapeutic targets to modulate cardiac function in physiological and pathological conditions.