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In Vitro Ovulation and Prostaglandin Synthesis by Ovarian Follicles of Rana dybowskii
Kong, Hye-Young,Chang, Kyung-Ja,Im, Wook-Bin,Kwon, Hyuk-Bang The Korean Society for Integrative Biology 1999 Korean journal of biological sciences Vol.3 No.4
Changes in the levels of prostaglandian F$_{2a}$ (PGF$_{2a}$) and E$_2$ (PGE$_2$) in culture medium during in vitro ovulation of Rana dybowskii follicles were examined. The ovulation was induced by frog pituitary homogenate (FPH) or TPA (12-O-tetradecanoylphorbol-13-acetate, a protein kinase activator) and the levels of PGs were measured by radioimmunoassay. When the ovarian follicles were cultured, only a few oocytes were ovulated by 12 h, but half of them were ovulated by 24 h in response to FPH, whereas around 30% of oocytes were ovulated by 12 h and maximum ovulation (around 50%) occurred by 24 h in response to TPA. Without any stimulation (control), no ovulation occurred. TPA elevated the level of PGF$_{2a}$ to high levels when compared to control (basal levels), but the increase by FPH was less evident. Likewise, the levels of PGE$_2$ increased markedly in response to TPA, but rather decreased by FPH treatment. Interestingly, PGF$_{2a}$ induced ovulation but PGE$_2$ suppressed FPH- or PGF$_{2a}$-induced oocyte ovulation. Basal levels of PGs Increased steadily during culture. When theca/epithelium (THEP) layer and granulosa cell-enclosed oocytes (GCEOs) were separated by microdissection and cultured independently, higher levels of both PGs were secreted by THEP than by GCEOS. Synthesis of PGs by follicle or follicular components was strongly suppressed by exogenous cAMP or indomethacin. These results suggest that: 1) PGF$_{2a}$ plays an important role in Rana ovulation, 2) protein kinase C is involved in PGs production, and 3) thecal epithelium layer is responsible for the PGs production in Rana.
Kim, Ji-Hye,Kim, You-Kyoung,Arash, Minai-Tehrani,Hong, Seong-Ho,Lee, Jae-Ho,Kang, Bit Na,Bang, Yong-Bin,Cho, Chong-Su,Yu, Dae-Yeul,Jiang, Hu-Lin,Cho, Myung-Haing American Scientific Publishers 2012 Journal of Nanoscience and Nanotechnology Vol.12 No.7
<P>Polyethyleneimine (PEI) has been described as a highly efficient gene carrier due to its efficient proton sponge effect within endosomes. However, many studies have demonstrated that PEI is toxic and associated with a lack of cell specificity despite high transfection efficiency. In order to minimize the toxicity of PEI, we prepared chitosan-graft-spermine (CHI-g-SPE) in a previous study. CHI-g-SPE showed low toxicity and high transfection efficiency. However, this compound also had limited target cell specificity. In the present study, we synthesized galactosylated CHI-g-SPE (GCS) because this modified GCS could be delivered specifically into the liver due to hepatocyte-specific galactose receptors. The DNA-binding properties of GCS at various copolymer/DNA weight ratios were evaluated by a gel retardation assay. The GCS copolymer exhibited significant DNA-binding ability and efficiently protected DNA from nuclease attack. Using energy-filtered transmission electron microscopy (EF-TEM), we observed dense spherical, nano-sized GCS/DNA complexes with a homogenous distribution. Most importantly, GCS was associated with remarkably low cytotoxicity compared to PEI in HepG2, HeLa, and A549 cells. Moreover, GCS carriers specifically delivered the gene-of-interest into hepatocytes in vitro as well as in vivo. Our results suggest that the novel GCS described here is a safe and highly efficient carrier for hepatocyte-targeted gene delivery.</P>
Kim, Kwangwoo,Bang, So-Young,Joo, Young Bin,Kim, Taehyeung,Lee, Hye-Soon,Kang, Changwon,Bae, Sang-Cheol Journal of Rheumatology Pub. Co 2016 The Journal of rheumatology Vol.43 No.6
<P>Objective. Cyclophosphamide (CYC) is an immunosuppressant drug widely used to treat various diseases including lupus nephritis, but its efficacy highly varies from individual to individual. This pharmacogenomics association study searched for genetic variations associated with CYC efficacy. Methods. Genome-wide association scan was performed for 109 Korean patients with systemic lupus erythematosus with lupus nephritis (classes III-V) who received intravenous CYC induction therapy. Genetic differences between responders and nonresponders were examined using Cochran-Armitage trend tests, and genotype imputation was used for defining the association locus. Results. Genetic polymorphisms in the Fc gamma receptor gene (FCGR) cluster at human chromosome 1q23, previously associated with lupus nephritis susceptibility, were associated with the response to CYC treatment for lupus nephritis. Significant response association was found for 3 perfectly correlated (r(2) = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 x 10(-8)). Carriage of the minor alleles in these SNP was found only in nonresponders (31%) and none in responders (0%). Conclusion. This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy.</P>
Joo, Young Bin,Kim, Yul,Park, Youngho,Kim, Kwangwoo,Ryu, Jeong Ah,Lee, Seunghun,Bang, So-Young,Lee, Hye-Soon,Yi, Gwan-Su,Bae, Sang-Cheol BioMed Central 2017 ARTHRITIS RESEARCH AND THERAPY Vol.19 No.-
<P><B>Background</B></P><P>Radiographic progression is reported to be highly heritable in rheumatoid arthritis (RA). However, previous study using genetic loci showed an insufficient accuracy of prediction for radiographic progression. The aim of this study is to identify a biologically relevant prediction model of radiographic progression in patients with RA using a genome-wide association study (GWAS) combined with bioinformatics analysis.</P><P><B>Methods</B></P><P>We obtained genome-wide single nucleotide polymorphism (SNP) data for 374 Korean patients with RA using Illumina HumanOmni2.5Exome-8 arrays. Radiographic progression was measured using the yearly Sharp/van der Heijde modified score rate, and categorized in no or severe progression. Significant SNPs for severe radiographic progression from GWAS were mapped on the functional genes and reprioritized by post-GWAS analysis. For robust prediction of radiographic progression, tenfold cross-validation using a support vector machine (SVM) classifier was conducted. Accuracy was used for selection of optimal SNPs set in the Hanyang Bae RA cohort. The performance of our final model was compared with that of other models based on GWAS results and SPOT (one of the post-GWAS analyses) using receiver operating characteristic (ROC) curves. The reliability of our model was confirmed using GWAS data of Caucasian patients with RA.</P><P><B>Results</B></P><P>A total of 36,091 significant SNPs with a <I>p</I> value <0.05 from GWAS were reprioritized using post-GWAS analysis and approximately 2700 were identified as SNPs related to RA biological features. The best average accuracy of ten groups was 0.6015 with 85 SNPs, and this increased to 0.7481 when combined with clinical information. In comparisons of the performance of the model, the 0.7872 area under the curve (AUC) in our model was superior to that obtained with GWAS (AUC 0.6586, <I>p</I> value 8.97 × 10<SUP>-5</SUP>) or SPOT (AUC 0.7449, <I>p</I> value 0.0423). Our model strategy also showed superior prediction accuracy in Caucasian patients with RA compared with GWAS (<I>p</I> value 0.0049) and SPOT (<I>p</I> value 0.0151).</P><P><B>Conclusions</B></P><P>Using various biological functions of SNPs and repeated machine learning, our model could predict severe radiographic progression relevantly and robustly in patients with RA compared with models using only GWAS results or other post-GWAS tools.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1186/s13075-017-1414-x) contains supplementary material, which is available to authorized users.</P>