SOD2 and Sirt3 Control Osteoclastogenesis by Regulating Mitochondrial ROS : ROLE OF SOD2 AND SIRT3 IN OSTEOCLASTOGENESIS

Kim, Haemin,Lee, Yong Deok,Kim, Hyung Joon,Lee, Zang Hee,Kim, Hong-Hee Wiley-Blackwell Publishing, Inc. 2017 Journal of Bone and Mineral Research Vol. No.

<P>Reactive oxygen species (ROS) are an indispensable element of cellular signal transduction in various cell types, including bone cells. In particular, osteoclasts (OCs), cells specialized for bone resorption, utilize ROS as second messengers during receptor activator of NF-kappa B ligand (RANKL)-induced differentiation and activation. In addition, because of the high energy demands of bone-resorbing activity, OCs contain large amounts of mitochondria, the source of the majority of total ROS. In this study, we focused on the regulation of ROS generated from mitochondria during osteoclastogenesis. We observed that the level of mitochondrial superoxide dismutase 2 (SOD2), an enzyme responsible for reducing superoxide radicals in mitochondria, was increased by RANKL. siRNA-mediated knockdown (KD) of SOD2 increased ROS levels and enhanced OC differentiation. Conversely, overexpression of SOD2 reduced osteoclastogenesis by decreasing ROS levels. Moreover, we found that NAD-dependent deacetylase sirtuin 3 (Sirt3), an activator of SOD2 in mitochondria, was induced by RANKL. Sirt3-targeted siRNA decreased SOD2 activity by reducing deacetylation of lysine 68 of SOD2, leading to increased osteoclastogenesis. Furthermore, in vivo KD of SOD2 or Sirt3 in ICR mouse calvariae decreased bone volume and increased OC surface, supporting the results of in vitro experiments. Taken together, our findings demonstrate for the first time to our knowledge that the regulation of mitochondrial ROS by SOD2 and Sirt3 plays an important role in fine-tuning the OC differentiation program. (C) 2016 American Society for Bone and Mineral Research.</P>

Extracellular S100A4 negatively regulates osteoblast function by activating the NF-κB pathway

( Haemin Kim ),( Yong Deok Lee ),( Min Kyung Kim ),( Jun-oh Kwon ),( Min-kyoung Song ),( Zang Hee Lee ),( Hong-hee Kim ) 생화학분자생물학회(구 한국생화학분자생물학회) 2017 BMB Reports Vol.50 No.2

Patients with inflammatory bone disease or cancer exhibit an increased risk of fractures and delayed bone healing. The S100A4 protein is a member of the calcium-binding S100 protein family, which is abundantly expressed in inflammatory diseases and cancers. We investigated the effects of extracellular S100A4 on osteoblasts, which are cells responsible for bone formation. Treating primary calvarial osteoblasts with recombinant S100A4 resulted in matrix mineralization reductions. The expression of osteoblast marker genes including osteocalcin and osterix was also suppressed. Interestingly, S100A4 stimulated the nuclear factor-kappaB (NF-κB) signaling pathway in osteoblasts. More importantly, the ex vivo organ culture of mouse calvariae with recombinant S100A4 decreased the expression levels of osteocalcin, supporting the results of our in vitro experiments. This suggests that extracellular S100A4 is important for the regulation of bone formation by activating the NF-κB signaling pathway in osteoblasts. [BMB Reports 2017; 50(2): 97-102]

Multifunctional Theranostic Nanomedicine for Photoacoustic Imaging-Guided Combination Tumor Treatment

Kim, Jamin,Kim, Haemin,Moon, Hyungwon,Lee, Hohyeon,Chang, Jin Ho,Kim, Jungwook,Kim, Hyuncheol American Scientific Publishers 2016 Journal of Nanoscience and Nanotechnology Vol.16 No.11

<P>The use of small interfering RNA (siRNA) with chemotherapeutic drugs has a synergistic effect of inhibiting target genes. Furthermore, theranostics, which enables therapeutic drug delivery and provides immediate diagnosis, is also emerging as a promising technique. In line with this novel concept, we have developed an albumin-based nanomedicine capable of combination therapy (chemo-and gene therapy) and photoacoustic imaging. The multifunctional (combination therapy and photoacoustic imaging) theranostic nanomedicine contains paclitaxel (PTX), siRNA, and indocyanine green (ICG). Sulfhydryl-modified siRNA and sulfhydryl-modified human serum albumin form more stable nanoparticles mainly through the disulfide bond, unlike prevalent nanomedicines (e. g., lipid-based nanomedicine or siRNA bioconjugates). The albumin-based multifunctional nanomedicine shows double gene inhibition ability and a synergistic effect of chemoand gene therapy. Inhibition of the expression of target genes (Bcl-2, VEGF, etc.) and simultaneous treatment with PTX exhibit a synergistic effect compared to single treatment in vitro and in vivo. Furthermore, using ICG, photoacoustic imaging was very efficient. Our study demonstrates that this multifunctional theranostic nanomedicine could perform co-delivery of PTX and siRNA and yield a synergistic effect for target cells. By virtue of combination gene therapy, this the ranostic nanomedicine has great potential to cure various diseases, including cancer, and aid the prognosis of target tumor cells or tissues by photoacoustic imaging. To the best of our knowledge, this is the first report of the development of a multifunctional theranostic nanomedicine for combination therapy and non-invasive photoacoustic imaging.</P>

The protein microarray in maternal serum complicated with early onset fetal growth restriction/preeclampsia: preliminary data

( Haemin Kim ),( Hyo-shin Kim ),( Hyun-hwa Cha ),( Yoo-min Kim ),( Ji-hee Sung ),( Won Joon Seong ),( Soo-young Oh ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: Early onset fetal growth restriction (FGR) and/or preeclampsia (PE) are the major causes to perinatal morbidity and mortality. Although, the pathophysiology of these obstetric complications has not been revealed yet, we hypothesized that there could be several undiscovered autoantibodies associated with these diseases. In this study, we aimed to develop autoantibodies in maternal serum complicated with early onset FGR and/or PE. Methods: Serum samples from two respective cases of disease (before 32 weeks of gestation) and control (between 24 and 26 weeks of gestation) were analyzed using a slide based high-density protein microarray which can detect 1,800 of proteins. We obtained an A-score based on the signal intensity of 1,800 protein spots and selected the upper 1 percentile protein showing significant bindings. Results: We observed significant bindings in 32 proteins and strong bindings in four proteins (GSTT1, ZBTB16, ILF2 and MX1) in disease group. In control group, there were significant bindings in 27 proteins and strong bindings in seven proteins (EEF1G, GSTT1, HOOK1, MEIS2, MLH1, MX1 and PRKCZ). Interestingly, there was strong bindings in GSTT-1 (Glutathione S-transferase theta-1), which involved in glutathione metabolic process in cytoplasm, both disease and control group implying the importance of glutathione metabolism during pregnancy. Conclusion: We could observe several antibodies showing significant bindings in maternal serum. Further test is performing.

Threshold of 50g screening test for gestational diabetes mellitus in twin pregnancy-should it be the same as singleton?

( Hyo-shin Kim ),( Haemin Kim ),( Hyun Mi Kim ),( Mi Ju Kim ),( Hyun-hwa Cha ),( Won Joon Seong ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: The differences in the effect of gestational diabetes mellitus (GDM) between twin and singleton is recognized, there is a growing awareness that unique guidelines for twin pregnancies should be established. We aimed to evaluate the effect of GDM on twin pregnancies; and to find a reasonable threshold of 50g-oral glucose tolerance test (OGTT) for twin pregnancies, with performance similar to that in singleton (74 - 83% sensitivity and 72 - 85% specificity). Methods: This was retrospective cohort study of all women who delivered twins in a single institute for 8-year period between January 2014, and March 2022. We recruited women as two groups, GDM group and non-GDM group, to comparing pregnancy and neonatal outcomes. With the results of 50g-OGTT, ROC analysis was performed to find a threshold for twin pregnancies. Results: We included 209 twin pregnancies (404 neonates) who delivered in our institution between January 2014 and December 2021. Of them, 27 women (6.6%) were diagnosed with GDM, and only three women required insulin treatment. Pre-pregnancy body weight and BMI were significantly higher in GDM group, however gestational weight gain was significantly lower in GDM group. Among the perinatal outcomes, there was no significant difference except transient tachypnea of the newborn (TTN) (28.3% vs. 16.5%, p = 0.038, OR=1.99). As the threshold for 50g-OGTT, a value of 151 mg/dL has 85.7% sensitivity and 88.2% specificity; and improved false positive rate (22.3% to 11.8%) and positive predictive rate (39.2% to 52.9%) than 140 mg/dL. Conclusion: Considering that GDM in twin pregnancies is not significantly increase the critical adverse outcomes, we suggest a value of 151 mg/dL for 50g-OGTT in twin pregnancies as a value with similar performance to that in singleton pregnancies.

Angiotensin-converting enzyme 2 expression level in placenta of women with gestational diabetes mellitus

( Hyun Mi Kim ),( Mi Ju Kim ),( Hyun-hwa Cha ),( Hee Jeong Kim ),( Haemin Kim ),( Hyo-shin Kim ),( Won Joon Seong ) 대한산부인과학회 2022 대한산부인과학회 학술대회 Vol.108 No.-

Objective: The aim of this study was to evaluate the expression level of Angiotensin converting enzyme 2 (ACE2) in the placenta in women with gestational diabetes mellitus (GDM) delivered at term and to compare the results with normal pregnant women. Methods: This is a retrospective study in women who delivered at our center from 2015 to 2020. The placenta deposited in the biobank was used and was obtained from a woman who delivered a singleton at full-term. GDM was diagnosed using a two-step approach with the Carpenter-Coustan. Women with overt DM were excluded. RNA was extracted from the placenta and cDNA was synthesized. Then the expression level of the ACE2 gene was compared through real-time PCR analysis. A relative quantitative analysis of level of ACE2 gene expression compared to the endogenous control group was performed. The relative quantitative values between the normal pregnant group and GDM groups were compared. Results: A total of 29 placental samples were collected from normal pregnant women, and 20 placental samples were collected from GDM women. In the GDM group, there were 10 pregnant women who used insulin. The relative quantity of ACE 2 expression level had not statistically significance difference between the normal group and the GDM group (-1.7±0.5 vs. -1.5±0.6, p=0.116). Among the GDM groups, ACE 2 expression levels were compared according to whether or not insulin was used, but there was no statistically significance difference between the group the non-insulin group and the administered group (-1.6±0.5 vs. -1.3±0.6, p=0.164). Conclusion: ACE2, which is thought to play an important role in glycemic control and to have a beneficial effect on endothelial function, did not differ significantly in the expression level in the placenta of women with GDM.

CUSTOMER EQUITY IN TRADITIONAL MARKETS: CROSS-CULTURAL STUDY BETWEEN CHINA AND KOREA

Huanzhang Wang,Sang Jin Kim,Kyung Hoon Kim,Haemin Seok 글로벌지식마케팅경영학회 2016 Global Marketing Conference Vol.2016 No.7

The Chinese ecosystem (especially in traditional markets) has been completely subverted by on-line stores such as Taobao and JingDong after 2010. This research is to understand how to improve traditional markets since 92.5% practitioners in the retail industry conduct business in traditional markets. By the mean time Korean traditional markets attract more customers. In this research the multi-group analysis is used to analyze the difference between Chines customers and Korean customers upon customer equity in traditional markets. The research objectives are: First, to understand the relationships among service quality, customer equity drivers and customer satisfaction in Chinese and Korean traditional markets; Second, find out how to improve the three drivers of customer equity through these variables mentioned above in traditional markets. In this study the relationships among service quality, the drivers of customer equity, customer satisfaction and customer lifetime value were studied based on the analysis of the data which were collected in Chinese and Korean traditional markets.

Development of Polyurethane Elastomers Using Vanillin-Based Polyol Chain Extender

Haemin GANG,Daewoo LEE,Kwon-young CHOI,Han na KIM,Hoon RYU,Dai-soo LEE,byung-gee KIM 한국생물공학회 2017 한국생물공학회 학술대회 Vol.2017 No.4

Thermal therapeutic method for selective treatment of deep-lying tissue by combining laser and high-intensity focused ultrasound energy.

Kim, Haemin,Kang, Jeeun,Chang, Jin Ho Optical Society of America 2014 Optics letters Vol.39 No.9

<P>Photothermal therapy is performed by delivering laser radiation into the target lesion containing tissue chromophores so as to induce localized heating. For high treatment efficacy, the laser wavelength should be selected to maximize the absorption of incident laser radiation in the tissue chromophores. However, even with the optimal laser wavelength, both the absorption and the scattering of laser energy in tissue openly hamper treatment efficacy in deep-lying lesions. To overcome the limitation, we propose a dual thermal therapeutic method in which both laser and acoustic energies are transmitted to increase therapeutic depth while maintaining high target selectivity of photothermal therapy. Through skin-mimicking phantom experiments, it was verified that the two different energies are complementary in elevation of tissue temperature, and the treatment depth using laser radiation is increased along with acoustic energy.</P>

Review : Postharvest Biological Control of Colletotrichum acutatum on Apple by Bacillus subtilis HM1 and the Structural Identification of Antagonists

( Haemin Kim ),( Kuijae Lee ),( Jongchan Chae ) 한국미생물 · 생명공학회 2015 Journal of microbiology and biotechnology Vol.25 No.11

Bacillus subtilis HM1 was isolated from the rhizosphere region of halophytes for its antifungal activity against Colletotrichum acutatum, the causative agent of anthracnose. Treatment of postharvest apples with the cell culture or with a cell-free culture supernatant reduced disease severity 80.7% and 69.4%, respectively. Both treatments also exhibited antifungal activity against various phytopathogenic fungi in vitro. The antifungal substances were purified and analyzed by acid precipitation, gel filtration, high-performance liquid chromatography, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). Three compounds were identified as fengycin, iturin, and surfactin. The MALDI-TOF/ TOF mass spectrum revealed the presence of cyclized fengycin homologs A and B, which were distinguishable on the basis of the presence of either alanine or valine, respectively, at position 6 of the peptide sequence. In addition, the cyclized structure of fengycin was shown to play a critical role in antifungal activity.