Development of a noninvasive KIM-1-based live-imaging technique in the context of a drug-induced kidney-injury mouse model

Tae-Jun Kwon,Da-Sol Lee,Md. Enamul Haque,Rang-Woon Park,Byungheon Lee,Dongkyu Kim,Yong-Hyun Jeon,Kil-Soo Kim,Sang Kyoon Kim 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7

The development of reliable methods to diagnose acute kidney injury is essential to allow the adoption of early therapeutic interventions and evaluate their effectiveness. Based on the fact that kidney injury molecule-1 (KIM-1) expression levels in kidneys are markedly upregulated early after a damage event, here we developed a noninvasive KIM- 1-based molecular imaging technique to detect kidney injury. First, we took advantage of a phage-display platform to select small peptides demonstrating a specific high binding affinity to KIM-1. The promising candidate was conjugated with fluorescent probes, and its imaging potential was validated in vitro and in vivo. This peptide, with the sequence CNRRRA, not only showed a high imaging potential in vitro, allowing a strong detection of KIM-1 expressing cells by microscopy and flow cytometry but also generated a strong kidney-specific signal in live-imaging in vivo experiments in the context of a drug-induced kidney-injury mouse model. Our data overall suggest that the CNRRRA peptide is a promising probe to use in the context of in vivo imaging for the detection of KIM-1 overexpression in damaged kidneys.

일반논문 1 : 김종익의 유언과 경성여자의학전문학교 설립과정

백운기 ( Woon Ki Paik ),김상덕 ( Sang Duk Kim ) 연세대학교 의과대학 의사학과 의학사연구소 2011 연세의사학 Vol.14 No.1

Dr. Rosetta Hall, an American missionary physician, and Dr. Jeong-hee Gil, a young Korean physician, founded the Joseon (Keijo) Women`s Training Institute in 1928. Between 1933 and 1937, Dr. Gil and her husband, Dr. Kim Tak-won, maintained and financed the medical institute. Supporting the institute placed a heavy burden on the young doctors who were just establishing their private medical practice. Despite this burden, they undertook the work necessary to elevate the institute to a full medical college. In order to generate the substantial funds needed to establish the medical college, they created a foundation for the “creation of a women`s medical college” in 1934 and solicited funding. In 1937, a philanthropist interested in furthering education, Mr. Kim Jong-ik, agreed to donate the funding necessary to elevate the institute to a medical college. Mr. Kim, however, unexpectedly contracted dysentery and died. In his will, Mr. Kim bequeathed a portion of his estate to upgrading the institute to a medical college. The executor, contrary to Mr. Kim`s intent as set forth in his will, however, did not use the funds to elevate the institute, but rather established a completely new women`s medial college. The executor`s actions were a clear violation of Drs. Kim`s and Gil`s legal rights as beneficiaries under the will. They, nonetheless, accepted the outcome, because challenging the executor`s actions under Japanese rule would have been futile as Dr. Kim was a noted anti-Japanese patriot well known to the Japanese. Moreover, Sato Gozo had been Dr. Kim`s teacher at the Keijo Medical College. Most importantly, their dream of establishing a women`s medical college in Korea had been realized regardless of how. Regardless of whether the institute had been elevated to a medical college or not, Drs. Kim Tak-won and Gil Jeong-hee made great sacrifices to further the education of women medical doctors in Korea and should be recognized for their great contributions to the creation of Korea Women`s Medical College.

Evaluation of Hot Deformation and Dynamic Recrystallization Behaviors of Advanced Reduced-Activated Alloy (ARAA)

Sang‑Wook Kim,Hyeon‑Woo Son,Taek‑Kyun Jung,Young‑Bum Chun,Yi‑Hyun Park,Ji‑Woon Lee,Soong‑Keun Hyun 대한금속·재료학회 2019 METALS AND MATERIALS International Vol.25 No.4

The hot deformation behavior of advanced reduced-activation alloy (ARAA) was investigated using hot torsion tests. Thefl ow stress decreased as deformation temperature increased and as strain rate decreased. The fl ow behavior demonstratedthe typical dynamic recrystallization (DRX). Based on the constitutive analysis of peak stress, the activation energy for hotdeformation was found to be 330.3 kJ mol −1 . Peak stress was analyzed as a function of the Zener–Hollomon parameter, andcalculated and experimental values were in good agreement. A DRX kinetic model for ARAA was derived with deformationconditions based on the Avrami-type model. It was confi rmed that the volume fraction of dynamically recrystallized grainsincreased as deformation temperature increased and as strain rate decreased. The necklace structure and grain boundarybulging were observed in the deformed microstructure of ARAA. The suggested DRX mechanism for ARAA during hotworking is discontinuous DRX.

Impact of Interferon-Based Treatment on Quality of Life and Work Related Productivity from the Korean Cohort in the MOSAIC Study

( Sang Hoon Ahn ),( Won Hyeok Choe ),( Yoon Jun Kim ),( Jeong Heo ),( Dorota Latarska-smuga ),( Jiho Kang ),( Seung Woon Paik ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: Chronic Hepatitis C Virus (HCV) infection increases the risk for progressive liver disease, hepatocellular carcinoma and negatively impacts the patient’s quality of life. HCV treatment is evolving with direct acting antivirals but IFN based therapy has been the standard of care for many years and remains available in some countries. The MOSAIC study aims to characterize patients with chronic HCV infection and assess the impact of IFN-containing treatment on health-related quality of life, work related productivity and health care utilization. Methods: MOSAIC is an international prospective multicenter observational study that has been conducted in 20 countries. Consecutive patients with chronic HCV infection were enrolled and those who initiated an IFN based regimen were prospectively followed for 48 weeks. We report results from the Korean cohort Results: 100 patients were enrolled: 86 were treatment naïve and 14 were treatment experienced. 33 patients initiated an IFN based regimen: 6 patients started IFN + RBV, 26 patients started Peg-IFN + RBV, none started Peg-IFN + RBV + DAA and 1 patient received other treatment. Among the treated cohort, demographic and disease characteristics were the following: the mean age was 54.5 years; 14 patients were male. 14 had minimal or no fibrosis, 2 portal fibrosis, 3 bridging fibrosis and 6 patients suffered from cirrhosis. HCV Genotype distribution was as follows: genotype 1: 11; genotype 2: 19 and genotype 3: 3. Table 1 describes the results at baseline and changes over 4, 12 and 48 weeks and end-of-treatment (EOT) for the quality of life and work productivity outcome measures (EQ-5D-5L, HCV-PRO and WPAI). Conclusions: Results from the Korean cohort of the MOSAIC study show a moderate trend for deterioration of health-related quality of life and work productivity associated with IFN based treatment for patients with chronic HCV infection during treatment period. Acknowledgements: The design, study conduct, analysis, and financial support of MOSAIC study were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the content of the abstract. All authors had access to all relevant data and participated in writing, review, and approval of this abstract. Medical writing support was provided by Olivier Van de Steen of Medeor-consulting, funded by AbbVie. Disclosures: Sang Hoon Ahn: served as an advisor and lecturer for Bristol-Myers Squibb, Gilead Sciences, F.Hoffmann-La Roche, Merck, AbbVie, and has received unrestricted grants from Bristol-Myers Squibb, Gilead Sciences, and F. Hoffmann-La Roche for investigator- initiated trials Won Hyeok Choe: Nothing to disclosure Yoon Jun Kim: Nothing to disclosure Jeong Heo: received a grant from GSK; Research support from BMS, and Roche; Advisor for Abbvie, BMS, Gilead Sciences, Pharma Essentia, SillaJen, and Johnson & Johnson. Dorota Latarska-Smuga, Jiho Kang: are employees of AbbVie, Inc. and may hold stock or stock options. Seung Woon Paik: received grant and research support from AbbVie, BMS, Gilead, GSK, Merck, Novartis, and Roche

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Lee, Dahae,Kang, Ki Sung,Yu, Jae Sik,Woo, Jung-Yoon,Hwang, Gwi Seo,Eom, Dae-Woon,Baek, Seung-Hoon,Lee, Hye Lim,Kim, Ki Hyun,Yamabe, Noriko The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by $60{\mu}M$ FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with $60{\mu}M$ FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by $60{\mu}M$ FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Protective effect of Korean Red Ginseng against FK506-induced damage in LLC-PK1 cells

Dahae Lee,Ki Sung Kang,Jae Sik Yu,Jung-Yoon Woo,Gwi Seo Hwang,Dae-Woon Eom,Seung-Hoon Baek,Hye Lim Lee,Ki Hyun Kim,Noriko Yamabe 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.3

Background: Compound FK506 is an immunosuppressant agent that is frequently used to prevent rejection of solid organs upon transplant. However, nephrotoxicity due to apoptosis and inflammatory response mediated by FK506 limit its usefulness. In this study, the protective effect of Korean Red Ginseng (KRG) against FK506-induced damage in LLC-PK1 pig kidney epithelial cells was investigated. Methods: LLC-PK1 cells were exposed to FK506 with KRG and cell viability was measured. Western blotting and RT-PCR analyses evaluated protein expression of MAPKs, caspase-3, and KIM-1. TLR-4 gene expression was assessed. Caspase-3 activities were also determined. The number of apoptotic cells was measured using an image-based cytometric assay. Results: The reduction in LLC-PK1 cell viability by 60mM FK506 was recovered by KRG cotreatment in a dose-dependent manner. The phosphorylation of p38, p44/42 MAPKs (ERK), KIM-1, cleaved caspase-3, and TLR-4 mRNA expression was increased markedly in LLC-PK1 cells treated with 60mM FK506. However, with the exception of p-ERK, elevated levels of p-p38, KIM-1, cleaved caspase-3, and TLR-4 mRNA expression were significantly decreased after cotreatment with KRG. Activity level of caspase-3 was also attenuated by KRG cotreatment. Moreover, image-based cytometric assay showed that apoptotic cell death was increased by 60mM FK506 treatment, whereas it was decreased after cotreatment with KRG. Conclusion: Taken together, these results suggest that the molecular mechanism of KRG in the FK506-induced nephrotoxicity may lead to the development of an adjuvant for the inhibition of adverse effect FK506 in the kidney.

Protective effect of ginsenoside Rb1 against tacrolimus-induced apoptosis in renal proximal tubular LLC-PK1 cells

Lee, Dahae,Lee, Dong-Soo,Jung, Kiwon,Hwang, Gwi Seo,Lee, Hye Lim,Yamabe, Noriko,Lee, Hae-Jeong,Eom, Dae-Woon,Kim, Ki Hyun,Kang, Ki Sung The Korean Society of Ginseng 2018 Journal of Ginseng Research Vol.42 No.1

Background: The aim of the present study was to evaluate the potential protective effects of six ginsenosides (Rb1, Rb2, Rc, Rd, Rg1, and Rg3) isolated from Panax ginseng against tacrolimus (FK506)-induced apoptosis in renal proximal tubular LLC-PK1 cells. Methods: LLC-PK1 cells were treated with FK506 and ginsenosides, and cell viability was measured. Protein expressions of mitogen-activated protein kinases, caspase-3, and kidney injury molecule-1 (KIM-1) were evaluated by Western blotting analyses. The number of apoptotic cells was measured using an image-based cytometric assay. Results: Reduction in cell viability by $60{\mu}M$ FK506 was ameliorated significantly by cotreatment with ginsenosides Rg1 and Rb1. The phosphorylation of p38, extracellular signal-regulated kinases, and KIM-1, and cleavage of caspase-3, increased markedly in LLC-PK1 cells treated with FK506 and significantly decreased after cotreatment with ginsenoside Rb1. The number of apoptotic cells decreased by 6.0% after cotreatment with ginsenoside Rb1 ($10{\mu}M$ and $50{\mu}M$). Conclusion: The antiapoptotic effects of ginsenoside Rb1 on FK506-induced apoptosis were mediated by the inhibition of mitogen-activated protein kinases and caspase activation.

경성여자의학전문학교 창립의 주체였던 김탁원,길정희부부는 왜 실제 설립 과정에서 제외되었는가?

백운기 ( Woon Kee Baik ),김상덕 ( Sang Duk Kim ) 연세대학교 의과대학 의사학과 의학사연구소 2010 연세의사학 Vol.13 No.1

Chosun (a.k.a. Keijo) Women``s Medical Training Institute was founded in 1928 as a joint effort between an American missionary physician named Dr. Rosetta Sherwood Hall and one of Korea’s first female physicians, Dr. Kil Chung-Hee. In 1932, in anticipation of her retirement, Dr. Hall transferred full responsibility for the Institute to Dr. Kil and her husband Dr. Kim Taik-Won, a neuropsychiatrist. Unfortunately, following Dr. Hall``s departure to America in 1933, funding from Dr. Hall’s missionary society was discontinued. This prompted an evacuation of the Institute’s lecture halls and teaching laboratories. As a result of this change in finances, the Institute’s operations were transported to, and maintained exclusively at, Drs. Kim and Kil``s private residence. During this interim period, the institute was sustained financially by this husband and wife team. In addition to these new found financial difficulties, there were ongoing political hardships. In an effort to alleviate these various difficulties, the couple decided to pursue the task of upgrading the Institute to a standard medical college. As a first step toward this goal, in 1934, the couple established a foundation for the “creation of a women``s medical college”. This undertaking (i.e., the creation of a medical college) required a large amount of funding. Therefore, the couple became actively engaged in the solicitation of funding for this purpose. In 1937, an education philanthropist named Mr. Kim Chong-Ik agreed to donate substantial funds for the purpose of establishing the women’s medical college. As fate would have it, however, / 49 he unexpectedly contracted dysentery and died suddenly. The application for the creation of a women``s medical college was filed and approved in 1938 by the Japanese Governor-General. Thus, the first class of students in the newly created medical college was enrolled on May 1, 1938. Curiously, however, neither Dr. Kim nor Dr. Kil was named in the charter. Although one could presuppose various reasons to explain how this omission occurred, there is one undeniable aspect of history that makes clear and cogent sense in this regard. It is now known that Dr. Kim was a leading activist for Korean independence from Japan during the 1920’s and 1930’s. He was regarded as an agitator by the Japanese occupation government and viewed as an undesirable, rebellious, anti-Japanese element. The South Korean government, in recognition of his heroic deeds during that period of Japanese occupation, posthumously awarded the Ae-Jok Jan(humanitarian award) to Dr. Kim Taik-Won on August 15, 2007. On July 4, 2008, his remains were subsequently transferred, along with his professional partner and wife Dr. Kil Chung-Hee, to the Korean National Cemetery in Daejon, South Korea. If one considers the political climate that existed in Korea in the late 1930’s under Japanese occupation, it stands to reason that any medical college application that included an anti-Japanese activist such as Kim Taik-Won would be doomed to fail. I believe that the absence of Drs. Kim Taik-Won and Kil Chung-Hee’s names from the medical college charter was a rational, politically motivated act of omission.

Physical exercise improves cognitive function by enhancing hippocampal neurogenesis and inhibiting apoptosis in male offspring born to obese mother

Kim, Tae-Woon,Park, Hye-Sang Elsevier 2018 Behavioural brain research Vol.347 No.-

<P><B>Abstract</B></P> <P>Maternal obesity induces hippocampal functional changes and leads to deficits in cognitive functions, such as learning and memory in offspring. We investigated the protective effects of physical exercise against cognitive function deficit in offspring born to obese mothers. Neurotrophic factors, neurogenesis, and apoptosis were analyzed in the hippocampus and dentate gyrus of offspring. Four-week-old female rats were fed a high-fat diet (HFD) for 20 weeks: 12 weeks prior to mating, and 8 weeks during pregnancy and breast-feeding. Male offspring rats were randomly divided into four groups: Control group (CON), exercise and control group (ECON), male offspring born to obese mother group (MOM), and exercise and MOM group (EMOM). In the exercise groups, treadmill exercise was performed 6 times per week for 4 weeks. Male offspring rats were subjected to the Morris water maze tests and step-down avoidance to assess spatial learning and memory, and short-term memory. The result showed that deficits in spatial learning and memory, and short-term memory in male offspring born to obese mothers was associated with decreases in brain-derived neurotrophic factor (BDNF) levels and neurogenesis, and an increase in apoptosis in the hippocampal dentate gyrus. Physical exercise improved spatial learning and memory, and short-term memory by enhancing BDNF levels and neurogenesis, and by inhibiting apoptosis in the hippocampal dentate gyrus of male offspring born to obese mothers. Our results suggest that physical exercise may be a preventive measure against or a treatment for cognitive function impairment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Physical exercise improved learning and memory in male offspring born to maternal obesity. </LI> <LI> Physical exercise enhanced BDNF, TrkB and neurogenesis in male offspring born to maternal obesity. </LI> <LI> Physical exercise inhibited apoptosis and cell death in male offspring born to maternal obesity. </LI> </UL> </P>

A Two-Step-Recess Process Based on Atomic-Layer Etching for High-Performance <tex> $\hbox{In}_{0.52}\hbox{Al}_{0.48}\hbox{As}\hbox{/}\hbox{In}_{0.53} \hbox{Ga}_{0.47}\hbox{As}$</tex> p-HEMTs

Kim, Tae-Woo,Kim, Dae-Hyun,Park, Sang-Duk,Shin, Seung Heon,Jo, Seong June,Song, Ho-Jin,Park, Young Min,Bae, Jeoun-Oun,Kim, Young-Woon,Yeom, Geun-Young,Jang, Jae-Hyung,Song, Jong-In IEEE 2008 IEEE transactions on electron devices Vol.55 No.7

<P> We investigated 60-nm <TEX>$\hbox{In}_{0.52}\hbox{Al}_{0.48}\hbox{As}\hbox{/} \break\hbox{In}_{0.53}\hbox{Ga}_{0.47}\hbox{As}$</TEX> pseudomorphic high-electron mobility transistors (p-HEMTs) fabricated by using a Ne-based atomic-layer-etching (ALET) technology. The ALET process produced a reproducible etch rate of 1.47 <TEX>$\hbox{\bf{\AA}}$</TEX> /cycle for an InP etch stop layer, an excellent InP etch selectivity of 70 against an <TEX>$ \hbox{In}_{0.52}\hbox{Al}_{0.48}\hbox{As}$</TEX> barrier layer, and an rms surface-roughness value of 1.37 <TEX>$\hbox{\bf{\AA}}$</TEX> for the exposed <TEX>$\hbox{In}_{0.52}\hbox{Al}_{0.48}\hbox{As}$</TEX> barrier after removing the InP etch stop layer. The application of the ALET technology for the gate recess of 60-nm <TEX>$\hbox{In}_{0.52} \hbox{Al}_{0.48}\hbox{As}\hbox{/}\hbox{In}_{0.53}\hbox{Ga}_{0.47}\hbox{As}$</TEX> p-HEMTs produced improved device parameters, including transconductance <TEX>$(G_{M})$</TEX>, cutoff frequencies <TEX>$(f_{T})$</TEX>, and electron saturation velocity <TEX>$(\upsilon_{\rm sat})$</TEX> in the channel layer, which is mainly due to the high etch selectivity and low plasma-induced damage to the gate area. The 60-nm <TEX>$\hbox{In}_{0.52}\hbox{Al}_{0.48}\hbox{As}\hbox{/}\hbox{In}_{0.53}\hbox{Ga}_{0.47}\hbox{As}$</TEX> p-HEMTs fabricated by using the ALET technology exhibited <TEX>$G_{M, {\rm Max}} = \hbox{1.17}\ \hbox{S/mm}$</TEX> , <TEX>$f_{T} = \hbox{398}\ \hbox{GHz}$</TEX> , and <TEX>$\upsilon_{\rm sat} = \hbox{2.5}\ \times \hbox{10}^{7}\ \hbox{cm/s}$</TEX>. </P>