sRAGE prolonged stem cell survival and suppressed RAGE-related inflammatory cell and T lymphocyte accumulations in an Alzheimer's disease model

Oh, Seyeon,Son, Myeongjoo,Choi, Junwon,Lee, Sojung,Byun, Kyunghee Academic Press 2018 Biochemical and biophysical research communication Vol. No.

<P><B>Abstract</B></P> <P>The main causes of Alzheimer's disease (AD) have not determined and effective treatment has not been developed yet, even though extensive researches and several clinical trials have been conducted.. Fortunately, stem cell transplantation is emerging as a potential therapeutic candidate for AD, but the success of stem cell based therapy depends on the survival of transplanted cells. Here, we generated sRAGE secreting mesenchymal stem cells (sRAGE-MSCs) and then injected these MSCs or control MSCs with amyloid beta 1–42 (Aβ<SUB>1-42</SUB>) into the entorhinal cortices of male Sprague Dawley rats. The survival of transplanted cell, the number of T lymphocytes and microglia, expression of RAGE and its ligands and neuronal cell death were determined, 4 weeks after sRAGE-MSC transplantation. Transplanted sRAGE-MSCs survived longer than control MSCs and sRAGE-MSCs showed reduced level of CD4 and CD3d positive T lymphocyte. Furthermore, the number of M1 microglia in MSCs was more than that of sRAGE-MSCs as well. On the other hand, the number of M2 microglia in sRAGE-MSCs was increased compared with that of MSCs. In addition, sRAGE-MSCs decreased RAGE and RAGE ligand expressions and their interactions more effectively than those of MSCs. Finally, sRAGE-MSC transplantation protected from apoptosis and prevented decreasing numbers of neuron in Aβ<SUB>1-42</SUB> treated rat brains. These observations suggest continuous sRAGE secretion from sRAGE-MSCs might appreciably improve the effectiveness of cell therapy in Aβ<SUB>1-42</SUB> injected rat brains.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The interactions between RAGE and Aβ cause inflammatory responses and oxidative stress, and reduce cerebral blood flow. </LI> <LI> RAGE and its ligand interactions induce a cascade related to neuronal apoptosis and inflammation. </LI> <LI> The soluble form of RAGE (sRAGE) might suppress downregulation of the RAGE-mediated inflammatory/cell death pathway. </LI> <LI> sRAGE-MSCs enhanced survival more effectively than MSCs in an Aβ<SUB>1-42</SUB> induced rat model of AD. </LI> </UL> </P>

Stem Cell and Exosome Therapy in Pulmonary Hypertension

Seyeon Oh,Ji-Hye Jung,Kyung-Jin Ahn,Albert Youngwoo Jang,Kyunghee Byun,Phillip C. Yang,Wook-Jin Chung 대한심장학회 2022 Korean Circulation Journal Vol.52 No.2

Pulmonary hypertension is a rare and progressive illness with a devastating prognosis. Promising research efforts have advanced the understanding and recognition of the pathobiology of pulmonary hypertension. Despite remarkable achievements in terms of improving the survival rate, reducing disease progression, and enhancing quality of life, pulmonary arterial hypertension (PAH) is not completely curable. Therefore, an effective treatment strategy is still needed. Recently, many studies of the underlying molecular mechanisms and technological developments have led to new approaches and paradigms for PAH treatment. Management based on stem cells and related paracrine effects, epigenetic drugs and gene therapies has yielded prospective results for PAH treatment in preclinical research. Further trials are ongoing to optimize these important insights into clinical circumstances.

Fingertip Force and Muscle Activation Patterns at Varying grasp Objects

Suji Park(Suji Park),Juhyun Park(Juhyun Park),Seyeon Oh(Seyeon Oh),Chaeyeon Heo(Chaeyeon Heo),Sieun Ho(Sieun Ho),Seonhong Hwang(Seonhong Hwang) 호서대학교 기초과학연구소 2022 기초과학연구 논문집 Vol.30 No.1

In this study, we tried to collect and analyze the kinetic and neurological information such as finger-tip forces and EMG for several representative (the most commonly used) grasp movements to explore their force and muscle activation patterns based on the newly defined grasp taxonomy. Ten able-bodied (five males, five females) volunteered to participate and they performed five different grasp tasks: holding a bottle (Bottle), turning a doorknob (Knob), cutting with a knife (Knife), brushing with a toothbrush (Toothbrush), holding a thick book (Book) after we attached five force sensitive resistor (FSR) sensors on the tip of fingers and four surface electromyogram (sEMG) electrodes on the lower arm of the subject’s dominant hand. Root Mean Square (RMS) and Mean Absolute Value (MAV) from the mean maximum values of sEMG(%) and fingertip force(kgf) of all ten subjects were extracted as features. The classification from the feature dataset using convolutional neural network (CNN) was applied and analyzed the results of accuracy and repeatability. The mean maximum values of EMG and fingertip forces during five different grasp tasks, and the MAV and RMS which were extracted features from the above were compared with task pairs. They showed significant differences in comparison of four pairs of tasks which were Bottle and Knife (p = 0.005 in both MAV and RMS), Bottle and Toothbrush (p = 0.005in both MAV and RMS), Bottle and Book (p = 0.013 in both MAV and RMS), Knob and Toothbrush (p = 0.047 in MAV and p = 0.028 in RMS). The classification accuracy of the Bottle grasp task was the largest at 60% (true positive predictive rate is 60% and false postive rate is 40%), while the other tasks showed an 30-40% of accuracy. Repeatability was 60% in the Bottle task and 50% in the Knob task, and those of the other tasks were ranged 30-40%. Overall, it is believed that the small number of samples in the study is the main reason of the low accuracy and repeatability of the classification. A total of nine variables (four sEMG and five forces) showed different significances in paired mean comparisons for five grasp tasks (graspping a bottle, turning a doorknob, cutting with a knife, brushing teeth with a toothbrush, holding a thick book). A comparison of the reduced variable from feature extraction also showed different classification accuracy for five grasp tasks.

전기방사 키틴 나노섬유로 강화된 실크 피브로인 기반 투명 복합 필름

장세연 ( Seyeon Jang ),송명오 ( Myeong-oh Song ),강석주 ( Seok Ju Kang ),진정호 ( Jungho Jin ) 한국키틴키토산학회 2021 한국키틴키토산학회지 Vol.26 No.1

본 연구에서는 전기방사 공정을 이용해 제작한 키틴 멤브레인에 실크 피브로인 수용액을 함침하여 투명한 키틴-실크피브로인 복합체 필름을 제작하였다. 키틴과 실크 피브로인의 복합화에 따라 화학 및 결정구조, 광학적 특성, 기계적 특성이 어떻게 달라지는지 알아보았다. 키틴-실크 피브로인 복합체 필름에서는 키틴 멤브레인과 실크 피브로인 필름의 특징적인 peak들이 복합화되어 나타나는 것을 확인하였다. 키틴 멤브레인은 0%(파장: 550 nm)의 투과도를 나타내지만, 키틴과 유사한 굴절률을 갖는 실크 피브로인을 키틴 멤브레인 내부에 고르게 함침함으로써 89%(파장: 550 nm)의 투과도를 갖는 투명한 복합체 필름을 형성할 수 있었다. 또한 키틴-실크 피브로인 복합체는 키틴과 실크 피브로인 사이의 상호작용과 실크 피브로인의 β-sheet 형성에 의해 단일 실크 피브로인 필름보다 높은 강도와 연신율을 가지는 것을 확인하였다. Here, we introduce transparent chitin-silk fibroin composite film, which shows excellent optical and mechanical properties. We fabricated transparent chitin-silk fibroin composite film by impregnating the chitin membranes with an aqueous silk fibroin solution. Chitin membrane is simply produced by an electrospinning process. The chitin-silk fibroin composite film was analyzed by Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), UV-vis spectrometry, and tensile test. It was confirmed through the SEM image that the chitin membrane was completely impregnated with an aqueous silk fibroin solution. The chitin membrane impregnated with an aqueous silk fibroin solution has a transmittance of 89%. Moreover, the mechanical properties of the chitin-silk fibroin composite films were improved compared to the silk fibroin film.

Synthesis and Potent Anti-leukemic Activity of Novel 5'-Norcarbocyclic C-nucleoside Phosphonic Acids

Kim, Seyeon,Kim, Eunae,Oh, Chang-Hyun,Yoo, Kyung Ho,Hong, Joon Hee Korean Chemical Society 2014 Bulletin of the Korean Chemical Society Vol.35 No.12

The first synthetic route to 5'-norcarbocyclic C-nucleoside [7-oxa-7,9-dideazadenosine (furo[3,2-d]pyrimidine) and 9-deazaadenosine (pyrrolo[3,2-d]pyrimidine)] phosphonic acids from commercially available 1,3-dihydroxy cyclopentane was described. The key C-C bond formation from sugar to base precursor was performed using Knoevenagel-type condensation from a ketone derivative. Synthesized C-nucleoside phosphonic acids were tested for anti-HIV activity as well as anti-leukemic activity. Compound 26 showed significant anti-leukemic activity.

Protection against RAGE-mediated neuronal cell death by sRAGE-secreting human mesenchymal stem cells in 5xFAD transgenic mouse model

Son, Myeongjoo,Oh, Seyeon,Park, Hyunjin,Ahn, Hyosang,Choi, Junwon,Kim, Hyungho,Lee, Hye Sun,Lee, Sojung,Park, Hye-Jeong,Kim, Seung U.,Lee, Bonghee,Byun, Kyunghee Elsevier 2017 Brain, behavior, and immunity Vol.66 No.-

<P><B>Abstract</B></P> <P>Alzheimer's disease (AD), which is the most commonly encountered neurodegenerative disease, causes synaptic dysfunction and neuronal loss due to various pathological processes that include tau abnormality and amyloid beta (Aβ) accumulation. Aβ stimulates the secretion and the synthesis of Receptor for Advanced Glycation End products (RAGE) ligand by activating microglial cells, and has been reported to cause neuronal cell death in Aβ<SUB>1–42</SUB> treated rats and in mice with neurotoxin-induced Parkinson’s disease.</P> <P>The soluble form of RAGE (sRAGE) is known to reduce inflammation, and to decrease microglial cell activation and Aβ deposition, and thus, it protects from neuronal cell death in AD. However, sRAGE protein has too a short half-life for therapeutic purposes. We developed sRAGE-secreting umbilical cord derived mesenchymal stem cells (sRAGE-MSCs) to enhance the inhibitory effects of sRAGE on Aβ deposition and to reduce the secretion and synthesis of RAGE ligands in 5xFAD mice. In addition, these cells improved the viability of injected MSCs, and enhanced the protective effects of sRAGE by inhibiting the binding of RAGE and RAGE ligands in 5xFAD mice. These findings suggest sRAGE protein from sRAGE-MSCs has better protection against neuronal cell death than sRAGE protein or single MSC treatment by inhibiting the RAGE cell death cascade and RAGE-induce inflammation.</P> <P><B>Highlights</B></P> <P> <UL> <LI> sRAGE enhanced viability of MSCs in 5xFAD mice. </LI> <LI> sRAGE-MSCs showed low Aβ<SUB>1–42</SUB> levels and protective effects from RAGE-mediated neuronal cell death microglia activation in 5xFAD mice. </LI> <LI> Comparing sRAGE protein and MSCs, the sRAGE protein effectively modulated expression of RAGE ligands and control MSC has protective effects from neuron apoptosis in 5xFAD mice. </LI> </UL> </P>

Gamma-aminobutyric acid-salt attenuated high cholesterol/high salt diet induced hypertension in mice

Myeongjoo Son,Seyeon Oh,Hye Sun Lee,Junwon Choi,Bae-Jin Lee,Joung-Hyun Park,Chul Hyun Park,Kuk Hui Son,Kyunghee Byun 대한약리학회 2021 The Korean Journal of Physiology & Pharmacology Vol.25 No.1

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABAsalt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

Ishophloroglucin A, derived from Ishige okamurae, regulates high-fat-dietinduced fat accumulation via the leptin signaling pathway, associated with peripheral metabolism

Nalae Kang,Seyeon Oh,Hyun-Soo Kim,Hyosang Ahn,Junwon Choi,Soo-Jin Heo,Kyunghee Byun,You-Jin Jeon 제주대학교 해양과학연구소 2020 해양과환경연구소 연구논문집 Vol.44 No.-

Leptin, a well-known appetite hormone, plays a role in fat metabolism in peripheral tissues including the adipose, liver, and muscle tissues. In this study, we investigated the antiobesity and fat accumulation regulatory effects of Ishophloroglucin A, derived from the brown seaweed Ishige okamurae, which acts via the leptin signaling pathway in the peripheral tissues of a high-fat-diet-induced obese mouse model. Obesity in C57BL/6J mice was induced by feeding them with a high-fat diet for 10 weeks and Ishophloroglucin A (2.5 mg/kg) was orally treated for the last 4 weeks. Body weights were monitored once per week during the experimental period. After the experiment, several serum biochemical parameters were measured using commercial kits and the white adipose, liver, and muscle tissues were observed using immunohistochemistry methods. Ishophloroglucin A significantly reduced glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, and leptin level, which increase as a result of high-fat diet. Also, Ishophloroglucin A clearly activated the leptin signaling pathway in all examined peripheral tissues, reduced the adipose tissue size, and alleviated steatosis in the liver and muscle tissues. These results implied that Ishophloroglucin A treatment for 4 weeks positively induced molecular mechanisms and histologic changes related with leptin signaling. These findings suggested that constant Ishophloroglucin A treatment clearly regulates obesity and peripheral fat accumulation via the leptin signaling pathway in high-fat-diet-induced obese mice.

Effect of fermented sarco oyster extract on age induced sarcopenia muscle repair by modulating regulatory T cells

Kyung-A Byun,Seyeon Oh,Sosorburam Batsukh,Kyoung-Min Rheu,이배진,Kuk Hui Son,Kyunghee Byun 한국수산과학회 2023 Fisheries and Aquatic Sciences Vol.26 No.6

Sarcopenia is an age-related, progressive skeletal muscle disorder involving the loss of muscle mass and strength. Previous studies have shown that γ-aminobutyric acid (GABA) from fermented oysters aids in regulatory T cells (Tregs) cell expansion and function by enhancing autophagy, and concomitantly mediate muscle regeneration by modulating muscle inflammation and satellite cell function. The fermentation process of oysters not only increases the GABA content but also enhances the content of branched amino acids and free amino acids that aid the level of protein absorption and muscle strength, mass, and repair. In this study, the effect of GABA-enriched fermented sarco oyster extract (FSO) on reduced muscle mass and functions via Treg modulation and enhanced autophagy in aged mice was investigated. Results showed that FSO enhanced the expression of autophagy markers (autophagy-related gene 5 [ATG5] and GABA receptor-associated protein [GABARAP]), forkhead box protein 3 (FoxP3) expression, and levels of anti-inflammatory cytokines (interleukin [IL]-10 and transforming growth factor [TGF]-β) secreted by Tregs while reducing pro-inflammatory cytokine levels (IL-17A and interferon [IFN]-γ). Furthermore, FSO increased the expression of IL-33 and its receptor IL-1 receptor-like 1 (ST2); well-known signaling pathways that increase amphiregulin (Areg) secretion and expression of myogenesis markers (myogenic factor 5, myoblast determination protein 1, and myogenin). Muscle mass and function were also enhanced via FSO. Overall, the current study suggests that FSO increased autophagy, which enhanced Treg accumulation and function, decreased muscle inflammation, and increased satellite cell function for muscle regeneration and therefore could decrease the loss of muscle mass and function with aging.

The Influence of Knowledge Gap on Personal and Attributed AIDS Stigma

Byoungkwan Lee,Hyun Jung Oh,Seyeon Keum,Younjae Lee,이병관,오현정,금세연,이윤재 한국헬스커뮤니케이션학회 2012 헬스커뮤니케이션연구 Vol.6 No.-

현재 에이즈 낙인 관련 연구는 그 감염 및 발병률이 높은 저개발 도상국가를 중심으로 진행되어, 한국과 같이 감염인의 숫자가 상대적으로 적은 선진국에서 어떻게 에이즈를 낙인화 하는 가에 대한 연구가 부족한 실정이다. 본 연구는 이러한 문제의식을 바탕으로 에이즈 지식 수준의 차이가 한국인들의 에이즈 낙인 (개인적 낙인과 사회적 낙인) 수준에 미치는 영향을 설명하 기 위한 모델을 제안 및 검증하였다. 본 연구는 또한 감염에 대한 두려움을 에이즈 지식과 에이즈 낙인을 연결하는 매개변인으로 설정하고, 세 변인 간의 관계를 분석하였다. 2008년 에이 즈 공익 캠페인 효과조사를 위해 745명을 대상으로 한 전화 조사 데이터를 분석한 결과는 다음과 같다. 우선, 에이즈 지식은 감염에 대한 두려움 및 개인적 낙인에 부정적 영향을 주는 부적 예측 변인이었으며, 감염에 대한 두려움은 개인적 낙인 및 사회적 낙인의 부적 예측 변인으 로 나타났다. 성별과 연령 역시 감염에 대한 두려움과 유의미한 상관관계가 있었으며, 교육 수준의 경우 에이즈 지식 및 개인적 낙인에 긍정적인 영향을 미치는 것으로 나타났다. Although AIDS stigma has been widely studied in developing countries where the prevalence of HIV/AIDS infection is high, less is known about how people living in countries where HIV-infected people are scarce perceive and manifest AIDS stigma in their society. To fill this gap, this study tested a comprehensive model that explicates the influence of AIDS knowledge gap on personal and attributed stigma among people living in Korea. The study considered fear of contagion as a mediator between AIDS knowledge gap and AIDS stigma. With the data (N = 745) collected to evaluate the impact of 2008 Korean AIDS campaign, a structural equation model was utilized to test the hypothesized relationships between AIDS knowledge gap, fear of contagion, personal stigma, and attributed stigma. The findings indicate that AIDS knowledge is negatively associated with fear of contagion and personal stigma. Fear of contagion is also negatively associated with both personal and attributed stigma. Sex and age significantly predicted fear of contagion and education level was positively associated with AIDS knowledge and personal stigma.