Molecular networks underlying ovarian aging for clinical applications

YoungHo Roh,SookRyung Kim,EunJung Choi,YoungJoo Kim,HyangGi Park,PureunNarae Kang,DaJung Chung,NaYoung Kim,MinJae Kim,AeRa Han,KwangRae Kim,Chan Park,YongPil Cheon,YoungJin Lee 한국발생생물학회 2017 한국발생생물학회 학술발표대회 Vol.2017 No.8

Due to modern trends with postponing child-bearing and getting worse living environment in women, an ovarian aging increased pregnancy failure and other complications with menopause or premature ovarian failure. Although several theories have been suggested such as mitochondrial malfunction, DNA damage/repair/methylation, caloric restriction, studies regarding ovarian aging-related molecular mechanisms for development of therapeutic methods are insufficient so far. Our objective is to determine molecular pathways of ovarian aging that result in pregnancy failure and other complications in women health to develop treatment strategies. This study is consisted of two parts: in Phase I stage, we analyzed distinct gene expression profile between young and aged mouse ovaries, and in Phase II stage several preferentially expressed genes in both ovaries were selected and analyzed their physiological functions and involved molecular networks related to ovarian aging for development of diagnostic markers and therapeutic methods. Ovaries from 10 week and 11 month-old FVB/NJ female mice with synchronized estrus cycle were collected for this study. A half of each ovary was used for RNA preparation and the other half for histological analysis. Using the Illumina HiSeq 2000 System, preferentially expressed genes were identified. Functional annotation database-based gene-set enrichment analyses and Pathway Studio® were employed to evaluate aging-related molecular networks. These findings were confirmed through qRT-PCR and immunohistochemistry. To validate RNA-Seq data, we examined expression patterns of marker genes (Amh, Bmp15 and Nobox) that were wellknown to be decreased in ovarian aging process. In young or aged ovary, preferentially expressed 876 genes were identified and extracellular matrix (ECM; p<0.001) and chromatin/nucleosome-related (p<0.001) protein-coded genes have the majority in these genes by GOTERM analysis. Amongthem, we selected several candidate genes and confirmed their expression profiles by qRT-PCR and immunohistochemistry followed by molecular network analysis. Regarding molecular interactions in these genes, PathwayStudio® was employed to predict aging-involved molecular networks in mouse ovary. Here we report a couple of candidate molecular networks and medicines (chemicals) for targeting these preferentially expressed genes/proteins. Further analyses are scheduled to produce transgenic animal models and with human ovarian tissues/cell lines.

체감형 게임 컨트롤을 위한 다각도 얼굴 포즈 인식 기술

노영호(Youngho Roh),이승원(Seungwon Lee),김대희(Daehee Kim),백준기(Joonki Paik) 대한전자공학회 2010 대한전자공학회 학술대회 Vol.2010 No.6

Differential expression of the LOX family genes in human colorectal adenocarcinomas

Kim, Youngho,Roh, Seonae,Park, Jung-Young,Kim, Yangsik,Cho, Dong Hyung,Kim, Jin Cheon Spandidos Publications 2009 ONCOLOGY REPORTS Vol.22 No.4

<P>Lysyl oxidase (LOX) is an amine oxidase that catalyzes the cross-linking of collage or elastin in the extracellular matrix, regulating the tensile strength and structural integrity of connective tissues. Recently, four paralogues (LOXL, LOXL2, LOXL3 and LOXL4) of LOX have been identified in humans, each containing the functional domains required for the amine oxidase activity toward collagen and elastin. Paradoxical roles of the LOX family members have been reported in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and type. To address expression of the LOX family genes in colorectal adenocarcinomas, we performed real-time PCR analysis with matched tumor/normal tissue specimens from 104 patients. The expression of the LOX family genes was not statistically associated with tumor location, stage, growth type, or differentiation status. However, upregulation of LOX, LOXL2 and LOXL4 was significantly correlated with absence of lymphovascular invasion (P=0.012, 0.014 and 0.005, respectively), suggesting that the oxygen tension in or around the tumors may be an important regulator for the differential expression of LOX, LOXL2 and LOXL4 in colorectal cancer. Additionally, expression of LOX, but not the other LOX family genes, was significantly upregulated in patients with a diffuse cytoplasmic expression pattern of CEA, indicating that LOX upregulation may be associated with increased invasiveness and metastatic potential in colorectal cancer.</P>

COMPARISON OF DYNAMIC STABILITY DURING WALKING AND RUNNING ON NONMOTORIZED CURVED TREADMILL ACCORDING TO CURVATURE RADIUS

KIM, SAYUP,ROH, JONGRYUN,HYEONG, JOONHO,KIM, YOUNGHO World Scientific 2017 JOURNAL OF MECHANICS IN MEDICINE AND BIOLOGY Vol.17 No.8

<P>It is generally believed that running on a curved surface is more unstable than running on a flat surface. In this study, the dynamic stability of locomotion on a nonmotorized curved treadmill (NMCT) with three curvature radii was compared with that on a motorized flat treadmill. Sixteen healthy adult men maintained four different self-paced speeds: slow walking, fast walking, jogging, and running. Significant differences were statistically verified using two-way repeated-measures analysis of variance (ANOVA) according to the curvature radii and speeds, and the interaction effects were confirmed. Furthermore, to understand the significant differences between the speed and curvature radius, <I>post hoc</I> analyses were performed using one-way ANOVA. Except for the step width, the other parameters showed differences and correlation effects between the curvature radius and speed. As the curvature radius decreased, the stability decreased at slow speeds (slow walking) but increased at fast speeds (running). However, as the curvature radius increased, the stability increased at slow speeds (slow walking) but decreased at high speeds (running). The study results will help in suggesting the appropriate curvature radius for different user types such as athletes, the elderly, and people who require rehabilitation and will serve as preliminary data for designing the curvature radii of NMCTs.</P>

유전알고리즘을 이용한 액체로켓엔진 설계변수 최적화

이상복(Sangbok Lee),김영호(Youngho Kim),노태성(Tae-Seoung Roh) 한국추진공학회 2011 한국추진공학회 학술대회논문집 Vol.2011 No.11

유전알고리즘을 사용하여 액체로켓엔진의 연소실 압력과 노즐 확장비, O/F 비 등 주요 설계변수를 최적화하였다. 대상엔진은 LO2/RP-1을 추진제로 사용하는 개방형 가스발생기 사이클을 대상으로 하였다. 연소실의 물성치는 CEA2를 이용하였으며, 무게 산출은 참고문헌을 바탕으로 모델링 하였다. 최적설계의 목적함수는 비추력과 추력중량비를 다중목표로 설정하여 가중치 방법을 사용하였다. 유전알고리즘을 최적화 과정을 거친 결과 비추력은 최대 4%, 추력중량비는 최대 23% 정도 증가하였다. 또한 다양한 추력에 대해서 Pareto frontier line을 얻었다. A genetic algorithm (GA) has been employed to optimize the major design variables of the liquid rocket engine. Pressure of the main combustion chamber, nozzle expansion ratio and O/F ratio have been selected as design variables. The target engine has the open gas generator cycle using the LO2/RP-1 propellant. The gas properties of the combustion chamber have been obtained from CEA2 and the mass has been estimated using reference data. The objective function has been set as multi-objective function with the specific impulse and thrust to weight ratio using the weight method. The result shows about 4% improvement of the specific impulse and 23% increase of the thrust to weight ratio. The Pareto frontier line has been also obtained for various thrust requirements.

미세단조 공정의 표면에 대한 유한요소 해석과 잔류응력 측정

정창호(Changho Jung),노현규(Hyun Gyu Roh),이문구(Moon Gu Lee),이수훈(Soo-Hun Lee),홍민성(Min-sung Hong),전용호(Youngho Jeon) 한국생산제조학회 2016 한국생산제조시스템학회 학술발표대회 논문집 Vol.2016 No.04

지능형 휴머노이드 로봇의 트래킹 성능 향상에 관한 연구

장명규(Jang Myeonggyu),김영호(Kim Youngho),김예린(Kim Yealynn),박기현(Park Kihyeon),신상훈(Shin Sanghun),우종우(Woo Chongwoo),노승수(Roh Sungsu),양춘규(Yang Chungyu) 한국정보과학회 2016 한국정보과학회 학술발표논문집 Vol.2016 No.12

Histone methylation-associated transgenerational inheritance of reproductive defects in <i>Caenorhabditis elegans</i> exposed to crude oil under various exposure scenarios

Yang, Jisu,Chatterjee, Nivedita,Kim, Youngho,Roh, Ji-Yeon,Kwon, Jung-Hwan,Park, Myung-Sook,Choi, Jinhee Elsevier 2018 CHEMOSPHERE - Vol.200 No.-

<P><B>Abstract</B></P> <P>As part of a study to explore the long-term effects of the Hebei Spirit oil spill accident, transgenerational toxicity and associated epigenetic changes were investigated in the nematode <I>Caenorhabditis elegans.</I> Under experimental conditions, worms were exposed to Iranian heavy crude oil (IHC) under three different scenarios: partial early-life exposure (PE), partial late-life exposure (PL), and whole-life exposure (WE). Growth, reproduction, and histone methylation were monitored in the exposed parental worms (P0) and in three consecutive unexposed offspring generations (F<SUB>1-3</SUB>). Reproductive potential in the exposed P0 generation in the WE treatment group was reduced; additionally, it was inhibited in the unexposed offspring generations of the P0 worms. This suggests that there was transgenerational inheritance of defective reproduction. Comparison of developmental periods of exposure showed that IHC-treated worms in the PL group had a greater reduction in reproductive capacity than those in the PE group. Decreased methylation of histone H3 (H3K9) was found in the IHC-exposed parental generation. A heritable reduction in reproductive capacity occurred in wildtype <I>N2</I> but was not found in a H3K9 histone methyltransferase (HMT) mutant, <I>met-2</I>(<I>n4256</I>), suggesting a potential role for HMT in transgenerational toxicity. Our results suggest that the reproductive toxicity after IHC exposure could be heritable and that histone methylation is associated with the transmission of the inherited phenotype.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Transgenerational toxicity of Iranian heavy crude oil (IHC) was investigated in the nematode <I>Caenorhabditis elegans</I> in the four consecutive generations under different exposure scenarios. </LI> <LI> <I>C. elegans</I> reproduction potential was inhibited by the IHC in the unexposed generations and in the exposed parental generation. </LI> <LI> Whole-life exposure condition exhibited transgenerational inheritance of defective reproduction. </LI> <LI> Decreased methylation of histone H3K9 was found in the exposed generation; however, a heritable diminution in reproduction did not occur in the H3K9 histone methyltransferase defective mutant. </LI> <LI> Reproductive toxicity caused by IHC exposure was found to be transmitted to subsequent unexposed generations, and methylation of histone H3K9 seems to be involved in it. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Hydrogen isotope exchange behavior of protonated lithium metal compounds

Park, Chan Woo,Kim, Sung-Wook,Sihn, Youngho,Yang, Hee-Man,Kim, Ilgook,Lee, Kwang Se,Roh, Changhyun,Yoon, In-Ho Korean Nuclear Society 2021 Nuclear Engineering and Technology Vol.53 No.8

The exchange behaviors of hydrogen isotopes between protonated lithium metal compounds and deuterated water or tritiated water were investigated. The various protonated lithium metal compounds were prepared by acid treatment of lithium metal compounds with different crystal structures and metal compositions. The protonated lithium metal compounds could more effectively reduce the deuterium concentration in water compared with the corresponding pristine lithium metal compounds. The H⁺ in the protonated lithium metal compounds was speculated to be more readily exchangeable with hydrons in the aqueous solution compared with Li⁺ in the pristine lithium metal compounds, and the exchanged heavier isotopes were speculated to be more stably retained in the crystal structure compared with the light protons. When the tritiated water (157.7 kBq/kg) was reacted with the protonated lithium metal compounds, the protonated lithium manganese nickel cobalt oxide was found to adsorb and retain twice as much tritium (163.9 Bq/g) as the protonated lithium manganese oxide (69.9 Bq/g) and the protonated lithium cobalt oxide (75.1 Bq/g) in the equilibrium state.

Physalis alkekengi L. var. francheti alleviates neuronal cell death caused by activated microglia in vitro

Park Byoung Hee,Kwon Oh Wook,Kim In Sung,Lee Hae Min,Roh Yeon Jin,Kim Minseo,Jo Youngho,Cho Hwayeon,Park Jung Kuk,Zhi Zheng,Lee Byung Cheon 한국응용생명화학회 2021 Applied Biological Chemistry (Appl Biol Chem) Vol.64 No.1

Microglia are the macrophages that reside in the brain. Activated microglia induces further activation of astrocytes and neuronal cells for mounting an immune response. However, activated microglia release neurotoxic mediators causing neuroinflammation, which is associated with chronic etiology of neurodegenerative diseases. We investigated the effect of ethanol extract of Physalis alkekengi L. var. francheti fruit (PAFE) on neuronal cell death mediated by activated microglia. PAFE decreased NO production and IL-6 secretion in LPS-stimulated BV-2 and primary microglial cells without reducing cell viability. Consistently, treatment with PAFE decreased iNOS and COX-2 expression and ERK phosphorylation in LPS-stimulated BV-2 cells. Finally, apoptosis of N2a cells grown in conditioned media prepared from LPS-stimulated BV-2 cells containing PAFE was inhibited via downregulation of the Bax/Bcl-2 ratio. Taken together, PAFE alleviates neuronal cell death by reducing neurotoxic mediators such as NO and IL-6 from activated microglia. Therefore, it could be a potential candidate to treat neurodegenerative diseases caused by chronic neuroinflammation.