Activating transcription factor-2 supports the antioxidant capacity and ability of human mesenchymal stem cells to prevent asthmatic airway inflammation

Ju Hyein,Yun HongDuck,Kim YongHwan,Nam Yun Ji,Lee Seungun,Lee Jinwon,Jeong Seon Min,Heo Jinbeom,Kwon Hyungu,Cho You Sook,Jeong Gowun,Ryu Chae-Min,Shin Dong-Myung 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-

Glutathione (GSH), an abundant nonprotein thiol antioxidant, participates in several biological processes and determines the functionality of stem cells. A detailed understanding of the molecular network mediating GSH dynamics is still lacking. Here, we show that activating transcription factor-2 (ATF2), a cAMP-response element binding protein (CREB), plays a crucial role in maintaining the level and activity of GSH in human mesenchymal stem cells (MSCs) by crosstalking with nuclear factor erythroid-2 like-2 (NRF2), a well-known master regulator of cellular redox homeostasis. Priming with ascorbic acid 2-glucoside (AA2G), a stable vitamin C derivative, increased the expression and activity of ATF2 in MSCs derived from human embryonic stem cells and umbilical cord. Subsequently, activated ATF2 crosstalked with the CREB1-NRF2 pathway to preserve the GSH dynamics of MSCs through the induction of genes involved in GSH synthesis (GCLC and GCLM) and redox cycling (GSR and PRDX1). Accordingly, shRNA-mediated silencing of ATF2 significantly impaired the self-renewal, migratory, proangiogenic, and anti-inflammatory capacities of MSCs, and these defects were rescued by supplementation of the cells with GSH. In addition, silencing ATF2 attenuated the ability of MSCs to alleviate airway inflammatory responses in an ovalbumin-induced mouse model of allergic asthma. Consistently, activation of ATF2 by overexpression or the AA2G-based priming procedure enhanced the core functions of MSCs, improving the in vivo therapeutic efficacy of MSCs for treating asthma. Collectively, our findings suggest that ATF2 is a novel modulator of GSH dynamics that determines the core functionality and therapeutic potency of MSCs used to treat allergic asthma.

S-614 A case of intracavitary pulmonary aspergillosis treated with instillation of voriconaz ole

( Hyein Lee ),( Bin Hwangbo ),( Hyojae Kang ),( Joohae Kim ),( Young Ju Choi ) 대한내과학회 2016 대한내과학회 추계학술대회 Vol.2016 No.1

Medical Treatment of symptomatic intracavitary pulmonary aspergillosis is difficult. Oral or intravenous anti-fungal agents have limited roles. Bronchial artery embolization or surgery is considered for intractable hemoptysis. Intracavitary instillation of amphotericin B through the per cutaneous catheter has been attempted for pulmonary aspergillosis with hemoptysis, showing favorable short-term outcome. We experienced a case of a 69-year-old man with chronic infection of aspergillosis in a huge right upper lobe cavity which was developed after endobronchial brachy-therapy. The patient complained chronic cough and cheat pain. Treatment with systemic voriconalzole and bronchoscopic intracavitary instillation of amphotericin B was failed. Fungal colonies were disappeared after treatment with instillation of voriconazole through fiberoptic bronchoscopy. This is the first case report of intacavitary aspergillosis treated with bronchospcic instillation of voriconazole.

Characterization of the novel bacterial strain isolated from tomato rhizosphere resistant to bacterial wilt disease

Hyein Park,Jidam Lee,Min-Jung Kwak,Pyeong An Lee,Soojin Kim,Soon-Kyeong Kwon,Ju Yeon Song,Seon-Woo Lee,Jihyun F. Kim 한국농약과학회 2018 한국농약과학회 학술발표대회 논문집 Vol.2018 No.10

Analysis of Antioxidant Effect in Espressos from Eminent Coffee Brands in Korea

Hyein Jeong,Siyoung Lee,Min Jae Kim,Byeong Su Kim,Seon Ho An,Ju Yong Kim,Jae Hwan Kim,Sumi Chung,You Jin Hwang,Joe Eun Son,Ki Won Lee 한국식품영양과학회 2014 한국식품영양과학회 학술대회발표집 Vol.2014 No.10

Association Between Mushroom intake and Risk of All-Cause and Cause-Specific Mortality: Using Korean Genome and Epidemiology Study (KoGES) Cohort

Hyein Jung,Su Bin Hwang,Hyeon Ju Park,Sangah Shin 한국식품영양과학회 2022 한국식품영양과학회 학술대회발표집 Vol.2022 No.10

Adverse Drug Events Associated With Remdesivir in Real-World Hospitalized Patients With COVID-19, Including Vulnerable Populations: A Retrospective Multicenter Study

Kang Hyein,Kang Chang Kyung,Im Jae Hyoung,Cho Yoonsook,Kang Dong Yoon,Lee Ju-Yeun 대한의학회 2023 Journal of Korean medical science Vol.38 No.44

Background: Remdesivir is a US Food and Drug Administration-approved drug for coronavirus disease 2019 (COVID-19). Clinical trials were conducted under strictly controlled situations for a selected population, and their reported adverse events may not fully represent conditions in real-world patients. We aimed to estimate the incidence of adverse drug events (ADEs) associated with remdesivir in hospitalized patients with COVID-19, including vulnerable subpopulations, such as those with impaired renal or hepatic function and pregnant women. Methods: This retrospective observational study included hospitalized patients with confirmed COVID-19 treated with remdesivir between January and December 2021 at ten hospitals. ADEs and severe ADEs (Common Toxicity Criteria for Adverse Events grade ≥ 3) were operationally defined and analyzed through laboratory investigations. The incidence of ADEs was compared with that of each matched control in subpopulations with renal or hepatic impairment and pregnant women. Results: Among 2,140 patients, 1,416 (66.2%) and 295 (13.8%) experienced at least one ADE and severe ADE, respectively. The most frequent ADE was 'hepatic injury' (42.9%), followed by anemia (27.6%). The most common severe ADEs were 'hypokalemia' (5.3%), 'hepatic injury' (2.9%), and 'anemia' (3.6%). There was no significant difference in the incidence of ADEs in patients relative to their respective matched-control groups, including those with renal impairment (80.0% vs. control 71.8%, P = 0.063), hepatic impairment (70.4% vs. control 75.0%, P = 0.623) and pregnant women (78.6% vs. control 63.7%, P = 0.067). However, severe ADE incidence was significantly higher in patients with renal impairment (40.8% vs. 16.0%, P < 0.001). The most common severe ADEs in those were 'anemia' (15.3%), 'hypokalemia' (10.5%), and 'thrombocytopenia' (8.9%). There was no statistically significant difference in the incidence of severe ADEs in patients with hepatic impairment or in pregnancy (P = 0.230; P = 0.085). Conclusion: A significant proportion of patients with COVID-19 treated with remdesivir experienced ADEs and severe ADEs. Given the high incidence of severe ADEs, caution is required in patients with renal impairment. Further studies are needed to investigate ADEs in pregnant women and patients with hepatic impairment.

노인차별 경험과 자기연령주의(self-ageism)

김주현(Juhyun Kim),오혜인(Hyein Oh),주경희(Kyonghee Ju) 한국노년학회 2020 한국노년학 Vol.40 No.4

본 연구는 연령차별을 경험한 노인들이 스스로 부정적 차별 인식을 내면화하는 일련의 과정에 집중하는 연구이다. 노인들이일상생활에서 경험하는 연령차별의 모습을 규명하고 이같은 차별경험이 ‘자기연령주의(self-ageism)’를 통해서 어떤 결과로 이어지는지를탐색하기 위해 근거이론방법을 활용하였다. 분석결과에 따르면 노인들은 명시적 차별 뿐 아니라 암묵적 차별에도 반응하는데 이 과정에서 노인의 고통(빈곤, 질병, 무위, 고독)의 강도가 높고 객관적인 차별상황에 속에서 차별대응에 실패한 기억이 강할수록 더욱 높은수준의 자기연령주의를 갖게 되는 것으로 나타났다. ‘자기연령주의’는 나이에 의한 ‘차별’을 당한 노인들이 스스로에 대한 부정적 이미지를 내재화함으로써, 현실에서 다양한 거부/분리/멈춤 등의 행동을 통해 삶의 질적 측면에서의 불이익을 감수하는 현상이다. 건강, 제도적지원, 보듬어주는 사람들과 같은 지지적 자원들이 존재하는 경우에 노인들은 보다 적극적인 방식으로 작용/상호작용을 통해 자기연령주의를 극복할 여지를 보이지만, 반면 이러한 자원들의 부족으로 스스로 동기부여하지 못하는 노인들의 경우 자기연령주의로 인한 부정적환류에 갇혀버리게 됨으로서 침체되고 위축된 삶을 살아가게 된다. 이런 상태에서 스스로를 동기화(motivation)해서 신체, 인지, 정서, 사회적 반응을 해나가는 것은 매우 쉽지 않은 일이다. 그러므로 분석과정에서 특별히 두 가지 부분, 맥락적 조건과 중재적 조건에 주목하며미시적으로는 노인의 동기화와 회복력(resilience) 향상을 위한 프로그램을 제안하였고, 거시적으로는 전 생애주기와 관련한 복지 및건강서비스 체계 보완, 커뮤니티케어를 통한 접근성과 통합성 확대, 인식개선과 차별금지법과 같은 시스템 마련의 필요성을 주장하였다 This study focuses on the process of internalizing the perception of negative discrimination among elderly people who have experienced age discrimination. The grounded theory method was used to identify the age discrimination experienced by the elderly in their daily lives and to explore the consequences of such discrimination through self-ageism. According to the analysis results, the elderly respond not only to explicit discrimination but also to implicit discrimination. In this process, the stronger the pain of old age (poverty, disease, ignorance, and solitude) and the stronger the memory of failing to respond to discrimination, the higher the level of self-ageism. Self-ageism has internalized the negative image of the elderly, who have been discriminated against by age, resulting in disadvantages in terms of quality of life through various reject/separate/suspension actions in reality. In the presence of supportive resources such as health, institutional support, and caregivers, the elderly have room to overcome self-ageism through more active ways. However elderly people who cannot motivate themselves and they lack these resources, elderly are trapped in negative refluxcaus ed by self-ageism and sustained a depressed and shrinking life. In this state, it is not easy to motivate themselves and make physical, cognitive, emotional and social responses. Therefore, in this analysis, we specifically noted two aspects, contextual conditions and interventional conditions, and proposed programs for synchronizing senior citizens and improving resiliency from a microscopic point of view, and argued for the need to develop systems such as supplementing welfare and health service systems related to the entire life cycle, expanding accessibility and ’age-integration’ through ’Community Care’, awareness improvement and anti-discrimination laws.

초기 청소년기 정서행동문제의 종단적 변화에 따른 잠재프로파일 분류 및 전이 영향요인 분석

김빛나 ( Bitna Kim ),장혜인 ( Hyein Jang ),박주희 ( Ju Hee Park ) 대한가정학회 2022 Human Ecology Research(HER) Vol.60 No.1

Using a person-centered approach, the current study investigated latent profiles for the emotional and behavioral problems of students in sixth-grade in elementary school and second grade of middle school. The aim was to explore latent transition patterns and verify the factors affecting the transitions. The participants were 1,937 adolescents who responded to the 3^rd year (6^th grade of elementary school; Time 1), 4^th year (1^st grade of middle school), and 5^th year (2^nd grade of middle school; Time 2) of the Korean Children Youth Panel Study. Latent profile and latent transition analyses were performed. The results were as follows: first, the latent profile of emotional and behavioral problems changed from Time 1 to Time 2. The latent groups at Time 1 were classified into low, moderate, high, and externalizing-dominant, whereas at Time 2, five groups were identified: low, moderate, high, externalizing-dominant, and withdrawal-dominant. Second, transition analyses revealed that although 22.3-57.0% of latent groups remained unchanged, there were significant changes over time between groups, as a new group (‘withdrawal-dominant’) emerged in Time 2. Third, different factors influenced the latent profile transition of emotional and behavioral problems depending on the transition pattern. Higher levels of self-esteem, better relationships with peers and teachers, and lower levels of parental inconsistency meant emotional and behavioral problems had not worsened at Time 2. The results suggest that early interventions are needed during the transition from childhood to early adolescence.

Valproic acid enforces the priming effect of sphingosine-1 phosphate on human mesenchymal stem cells

Lim, Jisun,Lee, Seungun,Ju, Hyein,Kim, Yonghwan,Heo, Jinbeom,Lee, Hye-Yeon,Choi, Kyung-Chul,Son, Jaekyoung,Oh, Yeon-Mok,Kim, In-Gyu,Shin, Dong-Myung UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.40 No.3

<P>Engraftment and homing of mesenchymal stem cells (MSCs) are modulated by priming factors including the bioactive lipid sphingosine-1-phosphate (S1P), by stimulating CXCR4 receptor signaling cascades. However, limited <I>in vivo</I> efficacy and the remaining priming molecules prior to administration of MSCs can provoke concerns regarding the efficiency and safety of MSC priming. Here, we showed that valproic acid (VPA), a histone deacetylase inhibitor, enforced the priming effect of S1P at a low dosage for human umbilical cord-derived MSCs (UC-MSCs). A DNA-methylation inhibitor, 5-azacytidine (5-Aza), and VPA increased the expression of <I>CXCR4</I> in UC-MSCs. In particular, UC-MSCs primed with a suboptimal dose (50 nM) of S1P in combination with 0.5 mM VPA (VPA+S1P priming), but not 1 <I>µ</I>M 5-Aza, significantly improved the migration activity in response to stromal cell-derived factor 1 (SDF-1) concomitant with the activation of both MAPK<SUP>p42/44</SUP> and AKT signaling cascades. Both epigenetic regulatory compounds had little influence on cell surface marker phenotypes and the multi-potency of UC-MSCs. In contrast, VPA+S1P priming of UC-MSCs potentiated the proliferation, colony forming unit-fibroblast, and anti-inflammatory activities, which were severely inhibited in the case of 5-Aza treatment. Accordingly, the VPA+S1P-primed UC-MSCs exhibited upregulation of a subset of genes related to stem cell migration and anti-inflammation response. Thus, the present study demonstrated that VPA enables MSC priming with S1P at a low dosage by enhancing their migration and other therapeutic beneficial activities. This priming strategy for MSCs may provide a more efficient and safe application of MSCs for treating a variety of intractable disorders.</P>

Small hypoxia-primed mesenchymal stem cells attenuate graft-versus-host disease

Kim, YongHwan,Jin, Hye Jin,Heo, Jinbeom,Ju, Hyein,Lee, Hye-Yeon,Kim, Sujin,Lee, Seungun,Lim, Jisun,Jeong, Sang Young,Kwon, JiHye,Kim, Miyeon,Choi, Soo Jin,Oh, Wonil,Yang, Yoon Sun,Hwang, Hyun Ho,Yu, H Nature Publishing Group UK 2018 Leukemia Vol.32 No.12

<P>Mesenchymal stem cells (MSCs) are of particular interest for the treatment of immune-related diseases due to their immunosuppressive capacity. Here, we show that Small MSCs primed with Hypoxia and Calcium ions (SHC-MSCs) exhibit enhanced stemness and immunomodulatory functions for treating allogeneic conflicts. Compared with naïve cultured human umbilical cord blood-derived MSCs, SHC-MSCs were resistant to passage-dependent senescence mediated via the monocyte chemoattractant protein-1 and p53/p21 cascade and secreted large amounts of pro-angiogenic and immunomodulatory factors, resulting in suppression of T-cell proliferation. SHC-MSCs showed DNA demethylation in pluripotency, germline, and imprinted genes similarly to very small embryonic-like stem cells, suggesting a potential mutual relationship. Genome-wide DNA methylome and transcriptome analyses indicated that genes related to immune modulation, cell adhesion, and the cell cycle were up-regulated in SHC-MSCs. Particularly, polo-like kinase-1 (<I>PLK1</I>), zinc-finger protein-143, dehydrogenase/reductase-3, and friend-of-GATA2 play a key role in the beneficial effects of SHC-MSCs. Administration of SHC-MSCs or <I>PLK1</I>-overexpressing MSCs significantly ameliorated symptoms of graft-versus-host disease (GVHD) in a humanized mouse model, resulting in significantly improved survival, less weight loss, and reduced histopathologic injuries in GVHD target organs compared with naïve MSC-infused mice. Collectively, our findings suggest that SHC-MSCs can improve the clinical treatment of allogeneic conflicts, including GVHD.</P>