Discovery of urinary metabolomic biomarkers for early detection of acute kidney injury

Won, A Jin,Kim, Siwon,Kim, Yoon Gyoon,Kim, Kyu-Bong,Choi, Wahn Soo,Kacew, Sam,Kim, Kyeong Seok,Jung, Jee H.,Lee, Byung Mu,Kim, Suhkmann,Kim, Hyung Sik The Royal Society of Chemistry 2016 Molecular bioSystems Vol.12 No.1

<P>The discovery of new biomarkers for early detection of drug-induced acute kidney injury (AKI) is clinically important. In this study, sensitive metabolomic biomarkers identified in the urine of rats were used to detect cisplatin-induced AKI. Cisplatin (10 mg kg(-1), i.p.) was administered to Sprague-Dawley rats, which were subsequently euthanized after 1, 3 or 5 days. In cisplatin-treated rats, mild histopathological alterations were noted at day 1, and these changes were severe at days 3 and 5. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at days 3 and 5. The levels of new urinary protein-based biomarkers, including kidney injury molecule-1 (KIM-1), glutathione S-transferase-alpha (GST-alpha), tissue inhibitor of metalloproteinase-1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, neutrophil, neutrophil gelatinase-associated lipocalin (NGAL), and osteopontin, were significantly elevated at days 3 and 5. Among urinary metabolites, trigonelline and 3-indoxylsulfate (3-IS) levels were significantly decreased in urine collected from cisplatin-treated rats prior to histological kidney damage. However, carbon tetrachloride (CCl4), a hepatotoxicant, did not affect these urinary biomarkers. Trigonelline is closely associated with GSH depletion and results in insufficient antioxidant capacity against cisplatin-induced AKI. The predominant cisplatin-induced AKI marker appeared to be reduced in urinary 3-IS levels. Because 3-IS is predominantly excreted via active secretion in proximal tubules, a decrease is indicative of tubular damage. Further, urinary excretion of 3-IS levels was markedly reduced in patients with AKI compared to normal subjects. The area under the curve receiver operating characteristics (AUC-ROC) for 3-IS was higher than for SCr, BUN, lactate dehydrogenase (LDH), total protein, and glucose. Therefore, low urinary or high serum 3-IS levels may be more useful for early detection of AKI than conventional biomarkers.</P>

UHF RFID 태그 칩용 저전력 EEPROM설계

이원재,이재형,박경환,이정환,임규호,강형근,고봉진,박무훈,하판봉,김영희,Yi, Won-Jae,Lee, Jae-Hyung,Park, Kyung-Hwan,Lee, Jung-Hwan,Lim, Gyu-Ho,Kang, Hyung-Geun,Ko, Bong-Jin,Park, Mu-Hun,Ha, Pan-Bong,Kim, Young-Hee 한국정보통신학회 2006 한국정보통신학회논문지 Vol.10 No.3

본 논문에서 는 플래쉬 셀을 사용하여 수동형 UHF RFID 태그 칩에 사용되는 저전력 1Kb 동기식 EEPROM을 설계하였다. 저전력 EEPROM을 구현하기 위한 방법으로 다음과 같은 4가지 방법을 제안하였다. 첫째, VDD(=1.5V)와 VDDP(=2.5V)의 이중 전원 공급전압 방식을 사용하였고, 둘째, 동기식 회로 설계에서 클럭(clock) 신호가 계속 클럭킹(clocking)으로 인한 스위칭 전류(switching current)가 흐르는 것을 막기 위해 CKE(Clock Enable) 신호를 사용하였다. 셋째, 읽기 사이클에서 전류 센싱(current sensing) 방식 대신 저전력 소모를 갖는 clocked inverter를 사용한 센싱 방식을 사용하였으며, 넷째, 쓰기 모드시 Voltage-up 변환기(converter) 회로를 사용하여 기준전압 발생기(Reference Voltage Generator)에는 저전압인 VDD를 사용할 수 있도록 하여 전력 소모를 줄일 수가 있었다. $0.25{\mu}m$ EEPROM 공정을 이용하여 칩을 제작하였으며, 1Kb EEPROM을 설계한 결과 읽기 모드와 쓰기 모드 시에 소모되는 전력은 각각 $4.25{\mu}W$와 $25{\mu}W$이고, 레이아웃 면적(layout area)은 $646.3\times657.68{\mu}m^2$이다. In this paper, a low-power 1Kb synchronous EEPROM is designed with flash cells for passive UHF RFID tag chips. To make a low-power EEPROM, four techniques are newly proposed. Firstly, dual power supply voltages VDD(1.5V) and VDDP(2.5V), are used. Secondly, CKE signal is used to remove switching current due to clocking of synchronous circuits. Thirdly, a low-speed but low-power sensing scheme using clocked inverters is used instead of the conventional current sensing method. Lastly, the low-voltage, VDD for the reference voltage generator is supplied by using the Voltage-up converter in write cycle. An EEPROM is fabricated with the $0.25{\mu}m$ EEPROM process. Simulation results show that power dissipations are $4.25{\mu}W$ in the read cycle and $25{\mu}W$ in the write cycle, respectively. The layout area is $646.3\times657.68{\mu}m^2$.

Curcumin ameliorates cadmium-induced nephrotoxicity in Sprague-Dawley rats

Kim, Kyeong Seok,Lim, Hyun-Jung,Lim, Jong Seung,Son, Ji Yeon,Lee, Jaewon,Lee, Byung Mu,Chang, Seung-Cheol,Kim, Hyung Sik Elsevier 2018 Food and chemical toxicology Vol.114 No.-

<P><B>Abstract</B></P> <P>Chronic exposure to cadmium (Cd) causes remarkable damage to the kidneys, a target organ of accumulated Cd after oral administration. The aim of the present study was to investigate the protective effect of curcumin against Cd-induced nephrotoxicity. Sprague–Dawley male rats were divided into the following four treatment groups: control, curcumin (50 mg/kg, oral), CdCl<SUB>2</SUB>, (25 mg/kg, oral), and pre-treatment with curcumin (50 mg/kg) 1 h prior to the administration of CdCl<SUB>2</SUB> (25 mg/kg, oral) for 7 days. At 24 h after the final treatment, the animals were killed, and the biomarkers associated with nephrotoxicity were measured. Our data indicated that blood urea nitrogen (BUN) and serum creatinine (sCr) levels were significantly reduced by curcumin pre-treatment in CdCl<SUB>2</SUB>-treated animals. Histopathological studies showed hydropic swelling and hypertrophy of the proximal tubular cells in the renal cortex after Cd treatment. Pretreatment with curcumin ameliorated the histological alterations induced by Cd. The urinary excretion of kidney injury molecule-1 (Kim-1), osteopontin (OPN), tissue inhibitor of metalloproteinases 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL), and netrin-1 significantly reduced by curcumin treatment compared to that in the CdCl<SUB>2</SUB>-treated group. The administration of curcumin provided a significant protective effect against Cd-induced nephrotoxicity.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Curcumin protects against cadmium-induced renal injury. </LI> <LI> Curcumin reduces urinary excretion of AKI biomarkers. </LI> <LI> Curcumin protects against cadmium-induced apoptosis in the kidney. </LI> </UL> </P>

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Son, Ji Yeon,Kang, Yoon Jong,Kim, Kyeong Seok,Kim, Tae Hyung,Lim, Sung Kwang,Lim, Hyun Jung,Jeong, Tae Cheon,Choi, Dal Woong,Chung, Kyu Hyuck,Lee, Byung Mu,Kim, Hyung Sik Korean Society of ToxicologyKorea Environmental Mu 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

Evaluation of Renal Toxicity by Combination Exposure to Melamine and Cyanuric Acid in Male Sprague-Dawley Rats

Ji Yeon Son,Yoon Jong Kang,Kyeong Seok Kim,Tae Hyung Kim,Sung Kwang Lim,Hyun Jung Lim,Tae Cheon Jeong,Dal Woong Choi,Kyu Hyuck Chung,Byung Mu Lee,Hyung Sik Kim 한국독성학회 2014 Toxicological Research Vol.30 No.2

Melamine-induced nephrotoxicity is closely associated with crystal formation in the kidney caused by combined exposure to melamine (Mel) and cyanuric acid (CA). However, there are few dosage-finding studies for toxicological evaluation of chronic co-exposure to Mel and CA. The objective of this study was to investigate the possible mechanism by which a Mel and CA mixture lead to renal toxicity in rats. Mel and CA were co-administered to rats via oral gavage for 50 days. Nephrotoxicity was determined by measuring blood urea nitrogen (BUN) and serum creatinine (sCr) levels. Relative kidney weights were significantly increased in rats after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg) mixtures. BUN and sCr levels were significantly increased after Mel and CA co-exposure. Taken together, significant increase in KIM-1, NGAL, and calbindin levels were observed in the urine of rats exposed to Mel+CA (63/6.3 or 630/6.3 mg/kg) compared with the corresponding control group. Histological analysis revealed epithelial degeneration and necrotic cell death in the proximal tubules of the kidney after co-exposure to Mel+CA (63/6.3 or 630/6.3 mg/kg). Our data suggest that Mel-mediated renal toxicity may be influenced by CA concentrations in Mel-contaminated milk or foods.

Fabrication of a Bottom Electrode for a Nano-scale Beam Resonator Using Backside Exposure with a Self-aligned Metal Mask

Lee, Yong-Seok,Jang, Yun-Ho,Bang, Yong-Seung,Kim, Jung-Mu,Kim, Jong-Man,Kim, Yong-Kweon The Korean Institute of Electrical Engineers 2009 Journal of Electrical Engineering & Technology Vol.4 No.4

In this paper, we describe a self-aligned fabrication method for a nano-patterned bottom electrode using flood exposure from the backside. Misalignments between layers could cause the final devices to fail after the fabrication of the nano-scale bottom electrodes. A self-alignment was exploited to embed the bottom electrode inside the glass substrate. Aluminum patterns act as a dry etching mask to fabricate glass trenches as well as a self-aligned photomask during the flood exposure from the backside. The patterned photoresist (PR) has a negative sidewall slope using the flood exposure. The sidewall slopes of the glass trench and the patterned PR were $54.00^{\circ}$ and $63.47^{\circ}$, respectively. The negative sidewall enables an embedment of a gold layer inside $0.7{\mu}m$ wide glass trenches. Gold residues on the trench edges were removed by the additional flood exposure with wet etching. The sidewall slopes of the patterned PR are related to the slopes of the glass trenches. Nano-scale bottom electrodes inside the glass trenches will be used in beam resonators operating at high resonant frequencies.

A New Histone Deacetylase Inhibitor, MHY219, Inhibits the Migration of Human Prostate Cancer Cells via HDAC1

De, Umasankar,Kundu, Soma,Patra, Nabanita,Ahn, Mee Young,Ahn, Ji Hae,Son, Ji Yeon,Yoon, Jung Hyun,Moon, Hyung Ryoung,Lee, Byung Mu,Kim, Hyung Sik The Korean Society of Applied Pharmacology 2015 Biomolecules & Therapeutics(구 응용약물학회지) Vol.23 No.5

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

자연산 숭어(Mugil cephalus)의 Myxobolus sp. 감염증

김위식,이무근,박경희,정성주,오명주 한국어병학회 2003 한국어병학회지 Vol.16 No.1

2002년 2월 광양만에서 자연 서식하는 숭어에서 폐사가 발생하였다. 그 폐사 원인을 조사하는 과정에서 Myxobolus sp.의 감염을 확인하여, 본 연구에서는 병리조직학적 검사를 통한 Myxobolus sp.의 감염증을 보고하게 되었다. Myxobolus sp.의 cyst는 숭어의 장간막, 간, 아가미 및 인두낭에서 관찰되었으며, 병리조직학적 검사에서 Myxobolus sp.의 전신감염을 확인할 수 있었다. 감염 충체는 길이 10-12 ㎛, 폭 9-10 ㎛, 두께 6.4-7.2 ㎛의 크기로서 체내에 길이 4-5.2 ㎛, 폭 2.5-3.3 ㎛의 2개의 극낭을 가지고 있었다. The mortality of wild mullet, Mugil cephalus was detected in Kwang-Yang bay on February, 2002. The mullet were infected with Myxobolus sp., the cysts of Myxobolus sp. were found in the mesentery, liver, gill and pharyngeal pocket. The histological findings suggested a systemic infection by the Myxobolus sp.. The spores were measured 10-12 (10.9)㎛ in length, 9-10 (9.4) ㎛ in width, 6.4-7.2 (6.8) ㎛ in thickness, with polar capsules of 4-5.2 (4.4) ㎛ in length and 2.5-3.3 (2.9) ㎛ in width.

폐좌상시 폐단락률과 PEEP치료의 효과

김영식,황성오,최경훈,안무업,오중환,임경수,윤정환,강성준 大韓應急醫學會 1992 대한응급의학회지 Vol.3 No.1

To evaluate the physiologic extent of pulmonary contusion and effect of PEEP therapy for pulmonary contusion, we studied 16 patients received PEEP therapy with pulmonary contusion from nonpenetrating chest trauma. Hemodynamic parameters including pulmonary vascular resistance index and intrapulmonary shunt fraction were calculated from standard measurement, and arterial oxygen tension was measured. Pulmonary vascular resistance index and intrapulmonary shunt fraction were increased in patient group. Arterial oxygen tension was decreased with increase of the intrapulmonary shunt fraction(R=0.75). Arter minimal PEEP therap(5-10 ㎝H₂O), pulmonary vascular resistance index was remained unchanged and intrapulmonary shunt fraction was decreased without significant changes of pulmonary hemodynamics. Increment of arterial tension was increased with decrease of intrapulmonary shunt fraction(R=0.43). Decreased stroke volume index suggested of cardiac injury such as cardiac contusion in patient group. These results of our study suggested that increased intrapulmonary shunt fraction caused arterial hypoxia in pulmonary contusion and arterial oxygen tension was increased as a result of reduced intrapulmonary shunt by PEEP therapy.

생약 배합에 따른 탈모 방지 및 발모 촉진에 관한 연구

김무영,곽제훈,박정미,이진태,안봉전 경산대학교 생명자원개발연구소 2002 생명자원과 산업 Vol.6 No.-

본 연구에서 생약 추출물을 이용한 탈모 방지 및 발모 촉진에 대한 효과를 검증하고자 Norwood's V형 1명, Ⅵ형 1명, Ⅶ형 2명의 성인 남자 4명과 Ludwig's Ⅱ형의 여자 2명 모두 6명을 대상으로 8개월간 생약 도포와 복용을 동시에 실시하여 두피 변화와 발모 효과에 관찰하였다. 생약 추출물을 도포하고 복용한 이후, 탈모 수가 점차 줄어들고 있어 탈모 방지에 효과가 있는 것으로 나타났으며, 지정한 부위의 모발 생성을 찾아 볼 수 있었다. 도포 및 복용 실험 전 피검자들의 1㎠ 당 평균 모발수는 평균 150개의 모발이 생성되고 있는 정상인의 1/3 수준에도 이르지 못하는 약 44개였으나, 생약 추출물의 도포와 복용 실험에 들어간 지 3개월 후에는 두피 1㎠ 당 평균 약 57개로, 6개월 후에는 평균 약 88개로 각각 증가하였다. 도포 및 복용 후 발모로 인해 대인관계에 자신감을 느낄 수 있었으며, 미용에 관심을 더 갖게 되는 등 피검자들이 실험에 만족하고 있는 것으로 나타났다. 현재 생약 추출물은 식품 개발과 함께 의약품, 향미료, 화장품, 염료 등 다양한 상품으로 개발되고 있듯이, 본 연구에 활용한 생약 추출물도 모근의 혈액 순환을 촉진시켜 건강한 두피 유지와 모발 생성, 미용 생체 활성 물질로 응용할 여지가 크다고 생각된다. This study was conducted to examine the effect of herb extract on hair loss prevention and hair growth promotion. Four baldheaded men and two partly baldheaded women were selected as the subjects of this study. After they took the herb medicine and sprayed the herb extractant, the change of hair and scalp condition, hair roots, the number of hairs, and thickness of hairs was examined. It appeared that the amount of hair loss decreased gradually and new thin hairs were generated after receiving the treatment. Before the treatment, the average number of hairs in 1㎠ was approximately 44, which was below one third of that of normal people who had about 150 hairs in the 1㎠. After spraying and taking the herb extract for three months, the average number of hairs increased to 57, and it increased to 88 after another three months. It gradually improved and finally maintained healthy condition. According to their response, they felt confident in personal relations due to hair generation and growth. They were also concerned about beauty more than before. More than half of them were satisfied with the treatment. As herb extracts have being developed as various products such as medicine, perfume, cosmetics, and dyes, the herb extract which was used in this study can be applied to maintenance of healthy scalp, generation of hair, and active materials for beauty.