CYP2E1 regulates the development of radiation-induced pulmonary fibrosis via ER stress- and ROS-dependent mechanisms

Son, Beomseok,Kwon, TaeWoo,Lee, Sungmin,Han, IkJoon,Kim, Wanyeon,Youn, HyeSook,Youn, BuHyun American Physiological Society 2017 American Journal of Physiology: Lung cellular and Vol.313 No.5

<P>Radiation-induced pulmonary fibrosis (RIPF) is one of the most common side effects of lung cancer radiotherapy. This study was conducted to identify the molecular mechanism responsible for RIPF. We revealed that the transcriptional level of cytochrome P450 2E1 (CYP2E1) was elevated by examining expression profile analysis of RIPF mouse models. We also confirmed that CYP2E1 regulated levels of endoplasmic reticulum ( ER) stress and reactive oxygen species (ROS) in alveolar epithelial type II (AE2) cells and lung fibroblasts. Inhibition of CYP2E1 via its siRNA or inhibitor significantly attenuated epithelial-to- mesenchymal transition and apoptosis of AE2 cells, as well as myofibroblast formation induced by radiation. Finally, the effects of a CYP2E1 inhibitor on development of RIPF were evaluated by in vivo studies. Taken together, the results of the present study suggest that CYP2E1 is an important mediator of RIPF development that functions by increasing cellular ER stress and ROS levels.</P>

Circadian Clock Genes, PER1 and PER2, as Tumor Suppressors

Beomseok Son(손범석),Hyunhee Do(도현희),EunGi Kim(김은기),BuHyun Youn(윤부현),Wanyeon Kim(김완연) 한국생명과학회 2017 생명과학회지 Vol.27 No.10

암을 포함한 다양한 인간의 질병 발생이 circadian clock 유전자의 변형된 발현 양상과 깊은 연관관계를 나타내고 있다. 세포 주기와 세포 성장은 circadian rhythm과 연결되어 있으며, 이를 조절하는 clock 유전자의 비정상적인 발현은 결국 종양 발생과 암의 발달을 유발하게 된다. Circadian clock에 관한 분자적 기전은 다수의 clock activator와 clock repressor의 통합적인 조절에 따른 전사 및 번역이 포함된 음성피드백 고리로 구성되어 있다. 이러한 circadian rhythm의 자동조절 기전에 의해 전체 유전체의 약 10~15%가 전사 수준에서 영향받는 것으로 나타났다. 많은 clock 유전자들 중, Period 1 (Per1)과 Period 2 (Per2)는 clock repressor 유전자로 정상적인 생리적 리듬을 조절하는 것에 기여한다. PER1과 PER2는 cyclin, CDK, CKI를 포함하는 세포 주기 조절자의 발현에 관여함이 밝혀졌으며, 다양한 암에서 PER1과 PER2의 발현 감소가 보고되었다. 따라서, 본 논문에서는 PER1과 PER2의 circadian rhythm에서의 분자적 기능과 종양 발생과 관련된 PER1과 PER2의 하위 표적인자에 대해 살펴보고, 암 치료를 위한 새로운 치료 표적과 암의 예후를 예측하기 위한 분자 지표로써의 PER1과 PER2의 가능성에 대해 서술하고자 한다. Disruptive expression patterns of the circadian clock genes are highly associated with many human diseases, including cancer. Cell cycle and proliferation is linked to a circadian rhythm; therefore, abnormal clock gene expression could result in tumorigenesis and malignant development. The molecular network of the circadian clock is based on transcriptional and translational feedback loops orchestrated by a variety of clock activators and clock repressors. The expression of 10~15% of the genome is controlled by the overall balance of circadian oscillation. Among the many clock genes, Period 1 (Per1) and Period 2 (Per2) are clock repressor genes that play an important role in the regulation of normal physiological rhythms. It has been reported that PER1 and PER2 are involved in the expression of cell cycle regulators including cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors. In addition, correlation of the down-regulation of PER1 and PER2 with development of many cancer types has been revealed. In this review, we focused on the molecular function of PER1 and PER2 in the circadian clock network and the transcriptional and translational targets of PER1 and PER2 involved in cell cycle and tumorigenesis. Moreover, we provide information suggesting that PER1 and PER2 could be promising therapeutic targets for cancer therapies and serve as potential prognostic markers for certain types of human cancers.

LTE 에서의 암호화된 트래픽 모니터링을 통한 비디오 서비스 식별 공격

손민철(Mincheol Son),배상욱(Sangwook Bae),김동관(Dongkwan Kim),이지호(Jiho Lee),박철준(CheolJun Park),오범석(BeomSeok Oh),손수엘(Sooel Son),김용대(Yongdae Kim) 한국통신학회 2021 한국통신학회 학술대회논문집 Vol.2021 No.6

본 논문에서는 기지국이나 단말의 접근 권한이 없는 공격자가 기지국으로부터 방송되는 정보만을 사용하여, 기지국내의 사용자가 어떠한 동영상 스트리밍 서비스를 사용하는지 식별하는 공격을 소개한다. 본 공격에서는 기지국이 각 단말마다 할당된 하향링크 자원 및 모듈레이션/코딩 정보를 사용하여 공격자가 단말별 하향링크 데이터 양을 유추 가능하며, 동영상 스트리밍 서비스마다의 동작 설정 차이로 발생되는 트래픽 모양의 특징적인 차이를 바탕으로 결정트리 분류 기법을 활용하여 공격자가 대상 기지국 내의 사용자들이 사용중인 동영상 서비스를 식별 가능함을 보여준다.

인간 시각장(Field of View)을 고려한 웨어러블 글래스의 UX 디자인 가이드

손민지(Son, Minji),문범석(Moon, Beomseok),유승헌(Yoo, Seunghun) 한국디자인지식학회 2015 디자인지식저널 Vol.33 No.-

본 연구는 FOV(Field of View) 관련 원칙을 기반으로 하여 웨어러블 글래스의 사용자 경험을 개선할 수 있는 정보 배치 가이드 디자인을 도출하는 것을 목표로 설정하였다. 웨어러블 글래스 관련 시장 상황 조사 진행과 선행연구 조사를 통해 FOV와 관련된 시각 가이드와 현재의 웨어러블 글래스가 사용자의 시각정보 탐색 태스크를 지원하는 UX 현황에 대해 파악하였다. 이후 웨어러블 글래스 디스플레이의 시각 정보 탐색시 발생하는 인지적 문제점들을 선택 주의집중 태스크와 분산 주의 집중의 근접부합성 원리를 기반으로 도출하였다. 도출된 UX 요소들을 기반으로 현재의 대표적인 웨어러블 글래스를 디스플레이 형태와 정보 전달 방식에 따라 재구분하였으며 이를 바탕으로 현재의 시각 인지 문제점을 구조화했다. 새로이 제시돤 웨어러블 글래스관련 UX 가이드는 인간의 시야각을 전체적으로 활용한 FOV 몰입형 디스플레이가 사용된 글래스를 설정하여 정보 가이드를 디자인 하였다. 검증을 위하여 글래스의 프로토타입을 제작한 후 기억성 실험을 수행한 결과 기존 형태 대비 FOV 몰입형 UI의 기억성이 가장 높게 나타났다. 스크린의 세부 UI 요소들중 FOV 중앙과 중앙 하단에 위치하는 정보의 정답률이 높았으며, 이러한 위치에 배치된 정보가 사용자의 인지적 부담을 적게 가져온다고 볼 수 있다. 또, 현실 정보와 메타정보간 연관성과 시각 정보 탐색 태스크 관계성에 있어서도 FOV 이머시브 방식이 효율적이었으며 추후 다양한 도메인의 웨어러블 글래스 UX에 적용 가능할 것이다. This research focused on designing wearable glass UX guide that can improve users" visual information searching performance based on FOV principle. Cognitive elements on wearable glass information searching tasks were analyzed through the comparison of current wearable glasses and the human selective attention task and divided attention process theory. The result illustrated the most efficient UX for glass typed wearable device is FOV friendly large screened immersive UI and it is conveyed into new UI guide for wearables. An experiment was designed based on this prototype and cardboard VR kit. Test results reveals that users" memorability and visual searching task performance was higher with FOV immersive screen than current UI. Especially the information located along with the center line of FOV area was recognized with higher saliency. The results of this research are expected to be used as a guide in designing other domain based wearable glass or daily life wearable glass.

Decreased Hepatic Lactotransferrin Induces Hepatic Steatosis in Chronic Non-Alcoholic Fatty Liver Disease Model

Lee, Sungmin,Son, Beomseok,Jeon, Jaewan,Park, Gaeul,Kim, Hyunwoo,Kang, Hyunkoo,Youn, HyeSook,Jo, Sunmi,Song, Jie-Young,Youn, BuHyun S. Karger AG 2018 Cellular physiology and biochemistry Vol.47 No.6

<P><B><I>Background/Aims:</I></B> Non-alcoholic fatty liver disease (NAFLD) is an emerging metabolic disease. Although it leads to severe hepatic diseases including steatohepatitis, cirrhosis, and hepatic cancer, little is known about therapy to prevent and cure hepatic steatosis, the first step of NAFLD. We conducted this investigation to unveil the mechanism of hepatic steatosis. <B><I>Methods:</I></B> We established a novel chronic NAFLD mouse model through whole body irradiation and verified the model through histological and biochemical analysis. To find molecular mechanism for hepatic steatosis, we analyzed hepatic transcriptomic profiles in this model and selected target molecule. To induce the expression of lactotransferrin (Ltf) and regulate the NAFLD, growth hormone (GH) and coumestrol was introduced to hepatocyte and mice. The universal effect of coumestrol was confirmed by administration of coumestrol to NAFLD mouse model induced by high-fructose, high-fat, and MCD diet. <B><I>Results:</I></B> It was observed that decreased hepatic Ltf expression led to excessive hepatic lipid accumulation in NAFLD mouse. Furthermore, we found that GH was decreased in irradiated mice and functioned as an upstream regulator of Ltf expression. It was observed that GH could stimulate Ltf expression and prevent uptake of dietary lipids in hepatocytes, leading to rescue of NAFLD. Finally, we suggested that coumestrol, a kind of isoflavonoid, could be used as an inducer of hepatic Ltf expression through cooperation with the GH signaling pathway both <I>in vitro</I> and <I>in vivo</I>. <B><I>Conclusions</I></B><I>:</I> Hepatic Ltf prevents hepatic steatosis through inhibition of dietary lipid uptake in radiation-induced NAFLD mouse model. We also suggest coumestrol as a drug candidate for prevention of NAFLD.</P>

Immunogenic Effect of Hyperthermia on Enhancing Radiotherapeutic Efficacy

Lee, Sungmin,Son, Beomseok,Park, Gaeul,Kim, Hyunwoo,Kang, Hyunkoo,Jeon, Jaewan,Youn, HyeSook,Youn, BuHyun MDPI 2018 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Vol.19 No.9

<P>Hyperthermia is a cancer treatment where tumor tissue is heated to around 40 °C. Hyperthermia shows both cancer cell cytotoxicity and immune response stimulation via immune cell activation. Immunogenic responses encompass the innate and adaptive immune systems, involving the activation of macrophages, natural killer cells, dendritic cells, and T cells. Moreover, hyperthermia is commonly used in combination with different treatment modalities, such as radiotherapy and chemotherapy, for better clinical outcomes. In this review, we will focus on hyperthermia-induced immunogenic effects and molecular events to improve radiotherapy efficacy. The beneficial potential of integrating radiotherapy with hyperthermia is also discussed.</P>

LDR-Induced miR-30a and miR-30b Target the PAI-1 Pathway to Control Adverse Effects of NSCLC Radiotherapy

Park, Gaeul,Son, Beomseok,Kang, JiHoon,Lee, Sungmin,Jeon, Jaewan,Kim, Joo-Hyung,Yi, Gi-Ra,Youn, HyeSook,Moon, Changjong,Nam, Seon Young,Youn, BuHyun Elsevier 2019 Molecular therapy Vol.27 No.2

Dog food including extract of Salicornia europaea reduces fat accumulation and distribution in the beagle obesity model.

Changfan Jin,Beomseok Rhee,Seon-Yeong Park,Gi-Young Son,Sokho Kim 한국산업식품공학회 2022 학술대회 및 심포지엄 Vol.2022 No.11

Biocidal effect of thymol and carvacrol on aquatic organisms: Possible application in ballast water management systems

Kim, Hyunwoo,Lee, Sungmin,Son, Beomseok,Jeon, Jaewan,Kim, Daehoon,Lee, wonku,Youn, HyeSook,Lee, Jae-Myung,Youn, BuHyun Elsevier 2018 MARINE POLLUTION BULLETIN Vol.133 No.-

<P><B>Abstract</B></P> <P>Ballast water is essential for maintaining the balance and integrity of a ship. However, exchanging ballast water resulted in discharging water of different origins in vessel recipient ports, and this may have caused ecosystem disturbance or aquatic pollution. The ballast water management (BWM) system is essential for the purification and disinfection of the ballast water that is taken up. Because current BWM systems widely use biocides for the treatment of aquatic organisms, the biocides may result in unintended toxicity of the discharged ballast water. In this study, we suggested thymol and carvacrol as chemical biocides for BWM systems and investigated their effectiveness using <I>Artemia salina</I> and <I>Escherichia coli</I>. Thymol and carvacrol showed biocidal effects in our study. A combination of these substances showed a synergistic increase in the biocidal effects. Moreover, carvacrol naturally degrades after disinfection, which indicates that natural substances may be promising candidates to increase the efficacy and reduce unwanted side effects of the BWM system.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Thymol showed specifically high biocidal effect on <I>Artemia salina</I> </LI> <LI> Carvacrol showed specifically high biocidal effect on <I>Escherichia coli</I> </LI> <LI> Combination treatment of thymol and carvacrol showed synergistic biocidal effects </LI> <LI> Carvacrol naturally degraded and lost biocidal effect in 4 days </LI> </UL> </P>

NRBF2-mediated autophagy contributes to metabolite replenishment and radioresistance in glioblastoma

Kim Jeongha,Kang Hyunkoo,Son Beomseok,Kim Min-Jung,Kang JiHoon,Park Kang Hyun,Jeon Jaewan,Jo Sunmi,Kim Hae Yu,Youn HyeSook,Youn BuHyun 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-

Overcoming therapeutic resistance in glioblastoma (GBM) is an essential strategy for improving cancer therapy. However, cancer cells possess various evasion mechanisms, such as metabolic reprogramming, which promote cell survival and limit therapy. The diverse metabolic fuel sources that are produced by autophagy provide tumors with metabolic plasticity and are known to induce drug or radioresistance in GBM. This study determined that autophagy, a common representative cell homeostasis mechanism, was upregulated upon treatment of GBM cells with ionizing radiation (IR). Nuclear receptor binding factor 2 (NRBF2)—a positive regulator of the autophagy initiation step—was found to be upregulated in a GBM orthotopic xenograft mouse model. Furthermore, ATP production and the oxygen consumption rate (OCR) increased upon activation of NRBF2-mediated autophagy. It was also discovered that changes in metabolic state were induced by alterations in metabolite levels caused by autophagy, thereby causing radioresistance. In addition, we found that lidoflazine—a vasodilator agent discovered through drug repositioning—significantly suppressed IR-induced migration, invasion, and proliferation by inhibiting NRBF2, resulting in a reduction in autophagic flux in both in vitro models and in vivo orthotopic xenograft mouse models. In summary, we propose that the upregulation of NRBF2 levels reprograms the metabolic state of GBM cells by activating autophagy, thus establishing NRBF2 as a potential therapeutic target for regulating radioresistance of GBM during radiotherapy.