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Oxidative Inactivation of Peroxiredoxin Isoforms by H2O2 in Pulmonary Epithelial, Macrophage, and other Cell Lines with their Subsequent Regeneration (폐포상피세포, 대식세포를 비롯한 각종 세포주에서 H2O2에 의한 Peroxiredoxin 동위효소들의 산화에 따른 불활성화와 재생)

  • Oh, Yoon Jung;Kim, Young Sun;Choi, Young In;Shin, Seung Soo;Park, Joo Hun;Choi, Young Hwa;Park, Kwang Joo;Park, Rae Woong;Hwang, Sung Chul
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.1
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    • pp.31-42
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    • 2005
  • Background : Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce $H_2O_2$ and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess $H_2O_2$, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. Methods : This study examined the effect of exogenous, excess $H_2O_2$ on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. Result : The addition of excess $H_2O_2$ to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the $H_2O_2$ treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated $H_2O_2$ treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. Conclusion : The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.

Perspective of Bronchial Responsiveness According to an Inhaled Anti-inflammatory Treatment in Cough Asthma (기침형 천식에서 향염증 흡입제 치료 경과에 따른 기도과민성 변화에 대한 고찰)

  • Moon, Seung-Hyug;Ki, Shin-Young;Kim, Yong-Hoon;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.45 no.5
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    • pp.1012-1021
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    • 1998
  • Background : It is known that airway inflammation is present in most patients with asthma, but the relationship between symptoms and the severity and nature of airway inflammation has not been established. Cough variant asthma is defined as an asthma in which the dominant symptom is cough, and the condition can be successfully treated with inhaled steroids. This study was performed to evaluate the time course of bronchial responsiveness according to an inhaled anti-inflammatory therapy and the factors which affect the resolution of bronchial responsiveness, and an efficacy of nedocromil to cough asthma. Method: A prospective study for the investigation of bronchial responsiveness according to an inhaled anti-inflammatory treatment in sixty-one cough asthmatics was performed. Twenty-three entered budesonide ($400{\mu}g{\times}2/day$), twenty-two entered nedocromil ($4mg{\times}2/day$) and sixteen patients entered combined group. The bronchial hyperresponsiveness (BHR) was estimated by methacholine challenge test using counted breath method. The symptom was estimated by 'symptom score'. Reevaluation of BHR and symptom was performed at 2 month after treatment, and if BHR was not resoluted at this time, regarded as a non-responder, and then follow-up of BHR and symptom was performed at 4- and/or 6 month after treatment. Results: The improvement of BHR and symptom was significant in 2 month (p<0.05), but there was no change of them during follow-up period of 4- and/or 6 month in non-responders. In comparison of allergic markers such as serum total IgE, peripheral eosinophil count and skin test reactivity between responders and non-responders, there was no difference in each other. However, in comparison of other factors such as cumulative pack-years, symptom duration, age, gender, and the initial degree of PC20, there was a significant difference in each other(p<0.05). The percent of patients with the resolution of BHR in 2 month was not different in each group(p=0.95). There was no significant difference in the degree of improvement of BHR and symptom in each group. Conclusion: Bronchial responsiveness and symptom was not significantly improved in non-responders during follow-up period of 4- and/or 6 month. The effect of inhaled nedocromil was equivalent to that of inhaled steroid in cough asthmatics, and the response to combined treatment is not superior to that achieved by either of these agents used alone.

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Evaluation of Dose Change by Using the Deformable Image Registration (DIR) on the Intensity Modulated Radiation Therapy (IMRT) with Glottis Cancer (성문암 세기조절 방사선치료에서 변형영상정합을 이용한 선량변화 평가)

  • Kim, Woo Chul;Min, Chul Kee;Lee, Suk;Choi, Sang Hyoun;Cho, Kwang Hwan;Jung, Jae Hong;Kim, Eun Seog;Yeo, Seung-Gu;Kwon, Soo-Il;Lee, Kil-Dong
    • Progress in Medical Physics
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    • v.25 no.3
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    • pp.167-175
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    • 2014
  • The purpose of this study is to evaluate the variation of the dose which is delivered to the patients with glottis cancer under IMRT (intensity modulated radiation therapy) by using the 3D registration with CBCT (cone beam CT) images and the DIR (deformable image registration) techniques. The CBCT images which were obtained at a one-week interval were reconstructed by using B-spline algorithm in DIR system, and doses were recalculated based on the newly obtained CBCT images. The dose distributions to the tumor and the critical organs were compared with reference. For the change of volume depending on weight at 3 to 5 weeks, there was increased of 1.38~2.04 kg on average. For the body surface depending on weight, there was decreased of 2.1 mm. The dose with transmitted to the carotid since three weeks was increased compared be more than 8.76% planned, and the thyroid gland was decreased to 26.4%. For the physical evaluation factors of the tumor, PITV, TCI, rDHI, mDHI, and CN were decreased to 4.32%, 5.78%, 44.54%, 12.32%, and 7.11%, respectively. Moreover, $D_{max}$, $D_{mean}$, $V_{67.50}$, and $D_{95}$ for PTV were increased or decreased to 2.99%, 1.52%, 5.78%, and 11.94%, respectively. Although there was no change of volume depending on weight, the change of body types occurred, and IMRT with the narrow composure margin sensitively responded to such a changing. For the glottis IMRT, the patient's weight changes should be observed and recorded to evaluate the actual dose distribution by using the DIR techniques, and more the adaptive treatment planning during the treatment course is needed to deliver the accurate dose to the patients.

Cerebrolysin Attenuates Astrocyte Activation Following Repetitive Mild Traumatic Brain Injury: Implications for Chronic Traumatic Encephalopathy (만성외상성뇌병증과 관련된 반복적 경도 외상성뇌손상(rmTBI)모델에서 cerebrolysin의 별아교 세포활성 억제효과)

  • Kang, Hyun Bae;Kim, GiHun;Kim, HyunJoong;Han, Sa Rang;Chae, Dong Jin;Song, Hee-Jung;Kim, Dong Woon
    • Journal of Life Science
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    • v.23 no.9
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    • pp.1096-1103
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    • 2013
  • Chronic traumatic encephalopathy (CTE), which is common in athletes, is a progressive neurodegenerative disease and a long-term consequence of repetitive closed head injuries. CTE is regarded as a chronic brain syndrome due to the effects of repetitive traumatic brain injury (TBI). Because neurotrophic factors are neuroprotective in models of brain and spinal cord injuries, we examined the effects of cerebrolysin, a mixture of various neurotrophic factors, on brain pathology in a mouse model of repetitive mild TBI (rmTBI), which is a good model of CTE. Five groups were created and treated as follows: groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control. We found that p-tau expression was increased in the pyramidal layer of the cortex and hippocampus, particularly the CA3 region, but not in the CA1 region and the dentate gyrus (DG). Intra-tail vein administration of cerebrolysin ($10{\mu}l$ of 1 mg/ml) after/during rmTBI treatment reduced p-tau expression in both the cortex and hippocampus. Histological analysis revealed mild astrocyte activation (increased expression of glial fibrillary acidic protein (GFAP)) but not microglia activation (ionized calcium binding adaptor molecule 1 (iba-1) expression) and peripheral macrophage infiltration (CD45). Additionally, administration of cerebrolysin after rmTBI resulted in reduced astrocyte activation. These observations in rmTBI demonstrated that cerebrolysin treatment reduces phosphorylation of tau and astrocyte activation, attenuates brain pathology, and mitigates function deficits in TBI. Taken together, our observations suggest that cerebrolysin has potential therapeutic value in CTE.

Inhibitory Effects of Myagropsis myagroides Ethanol Extract on 2,4-Dinitrochlorobenzene-Induced Atopic Dermatitis-Like Skin Lesions in Mice (2,4-Dinitrochlorobenzene 유도 아토피 피부염 모델 마우스에 대한 외톨개 모자반(Myagropsis myagroides) 에탄올 추출물의 억제 효과)

  • Kim, Koth-Bong-Woo-Ri;Kang, Bo-Kyeong;Ahn, Na-Kyung;Choi, Yeon-Uk;Bae, Nan-Young;Park, Ji-Hye;Park, Sun-Hee;Kim, Min-Ji;Ahn, Dong-Hyun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.8
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    • pp.1121-1127
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    • 2015
  • This study investigated the effects of Myagropsis myagroides ethanol extract (MMEE) on 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD)-like skin lesions in BALB/c mice. The effects of MMEE on DNCB-induced BALB/c mice were evaluated by examining skin symptom severity, levels of total immunoglobulin E (IgE), tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$), interleukin (IL)-4, and IL-10 in serum, and levels of IL-4, IL-5, IL-13, and $interferon-{\gamma}$ ($IFN-{\gamma}$) in splenocytes. MMEE significantly reduced the total clinical severity score, total IgE levels, as well as $TNF-{\alpha}$ and IL-4 production in an AD mouse model but increased IL-10 production. Production of IL-4, IL-5, and IL-13 in splenocytes was reduced by MMEE, whereas $IFN-{\gamma}$ production increased. These results suggest that MMEE can inhibit the development of AD-like skin lesions in BALB/c mice by modulating the immune response and may be an effective potential therapeutic agent for AD.

A study on Pre-and Post-surgical Patterns of Mandibular Movement and EMG in Skeletal Class III Prognathic Patients who underwent Intraoral Vertical Ramus Osteotomy (하악 전돌증 환자의 구내 하악골 상행지 골절단술전후의 하악골 운동양상 및 저작근 근전도 변화에 관한 연구)

  • Park, Young-Chel;Hwang, Chung-Ju;Yu, Hyung-Seog;Han, Hee-Kyung
    • The korean journal of orthodontics
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    • v.27 no.2
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    • pp.283-296
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    • 1997
  • Stomatognathic system is a complex one that is composed of TMJ, neuromuscular system, teeth and connective tissue, and all its components are doing their parts to maintain their physiological relationships. Mandible, in particular, performs various functions such as mastication, speech, and deglutition, the muscular activities that determine such functions are signalled by numerous types of proprioceptors that exist in periodontal membrane, TMJ, and muscles to be controlled by complicated pathways and mechanics of peripheral and central nervous system. Orthodontic treatment, especially when accompanied by orthognathic surgery, brings dramatic changes of stornatognat is system such as intraoral proprioceptors and muscle activities and thus, changes in patterns of mandibular function result The author tried to analyze changes in patterns of mandibular movement and physiologic activities of surrounding muscles in Skeletal Class III ortlrognathic surgery patients who presently show a great increase in numbers. The purpose of this study was to draw some objective guidelines in evaluating funclierual aspects of orthognathic surgery patients. Mandibular functional analysis using Biopak was performed for skeletal Class III prognathic patients who underwent IVRO(lntraoral Vertical Ramus Osteotmy), and the following results were obtained: 1. Resting EMG was greater in pre-surgical group than the control group, and it showed gradual decrease after the surgery. Clenching EMG of masseter and anterior temporalis of pre-surgical group was smaller than those of control group, they also increased post-surgically, and significant difference was found between pre-surgical and post-surgical(6 months) groups. 2. Resting EMG of anterior ternporalis was greater than that of all the other muscles, but there was no significant difference. Clenching EMG of anterior temporalis and masseter were greater than those of the other muscles with statistical difference. In swallowing, digastric muscle showed the highest EMG with statistical significance. 3. Limited range of mandibular movement was shown in pre-surgical group. Significant increase in maximum mouth opening was observed six months post-surgically, and significant increase in protrusive movement was observed three months post-surgically.

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Decomposition and Nutrient Dynamics of Leaf Litter of Camellia japonica L. in Korea (동백나무(Camellia japonica L.) 낙엽의 분해와 영양원소의 동태)

  • Cha, Sangsub;Lee, Kyung-Eui;Lee, Sang-Hoon;Choi, Moonjong;Shim, Jae Kuk
    • Korean Journal of Environment and Ecology
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    • v.30 no.1
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    • pp.110-117
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    • 2016
  • Litter fall is a source of nutrients and carbon transfer in terrestrial ecosystems. Litter decomposition provides nutrients needed for plant growth, sustains soil fertility, and supplies $CO_2$ to the atmosphere. We collected the leaf litter of evergreen broadleaf tree, Camellia japonica L., and carried out a decomposition experiment using the litterbag method in Ju-do, Wando-gun, Korea for 731 days from Dec 25, 2011 to Dec 25, 2013. The leaf litter of C. japonica remained 42.6% of the initial litter mass after experiment. The decay constant (k) of C. japonica leaf litter was $0.427yr^{-1}$. The carbon content of C. japonica leaf litter was 44.6%, and the remaining carbon content during the decomposition tended to coincide with the changes in litter mass. The initial nitrogen and phosphorus content was 0.47% and 324.7 mg/g, respectively. The remaining N in decaying litter increased 1.66-fold in the early decomposition stage, then gradually decreased to 1.18-fold after 731 days. The content of P showed the highest value (1.64-fold of initial content) after 456 days, which then fell to a 1.15-fold after 731 days. The remaining Ca, K, Mg and Na content in C. japonica leaf litter tended to decrease during decomposition. The remaining K showed a remaining mass of 8.9% as a result of rapid reduction. The initial C/N and C/P ratio of C. japonica leaf litter was 94.87 and 1368.5, respectively. However, it tended to decrease as decomposition progressed because of the immobilization of N and P (2.78 and 2.68-fold of initial content, respectively) during the leaf litter decaying. The study results showed that N and P was immobilized and other nutrients was mineralized in C. japonica leaf litter during experimental period.

CHILDHOOD TRAUMA:RESILIENCE AND RISK FACTORS ON DEVELOPMENTAL TRAJECTORY (소아기 외상 : 발달경로에 따른 보호 및 위험인자)

  • Kim, Young-Shin
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.13 no.1
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    • pp.15-23
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    • 2002
  • Knowledge regarding the resilience factors and risk factors of the childhood trauma on the developental trajectory is in its infancy due to the lack of prospective follow-up studies in the childhood trauma and limited understanding of the complex reciprocal interactions between childhood trauma, develop-ent and various aspects of children's environment. These difficulties in the conceptual framework and research methods in the childhood trauma are partly reflected in the inconsistencies, even controversies, of the results in the childhood trauma researches. Despite these difficulties, common aspects of the risk factors and resilience of the childhood trauma on the development can be identified from the previous studies. The resilience to the negative outcome on the development by childhood trauma includes:sex female before puberty, male after puberty or infancy), high socioeconomic status, no organic problem, easy temperament, no previous experience with early loss or separation, younger age at the trauma, better problem solving capacity, high self-esteem, internal locus of control, high coping skills, ability to identify interpersonal relationships, ability to play, sense of humor, having capable parents, having a warm relaionship with at least one of the parents, high education and participating in the organized religious activities. These commonalities of the results suggest that risk and resilient factors of the childhood trauma are interdependent, each factor has multiplicity in the impacts on the children's development according to the developmental stage of the child, family and children's other environment, trauma and stressor have diverse effects according to their intensity and risk and resilience factors could have synergistic or antagonistic effects to each other. To develop comprehensive understanding on the relationship between childhood trauma and developmental psychopathology, risk and resilience factors and to develop effective and efficient prevention and intervention, research on the effect of the stress on the neurodevelopment, on the individual differences of the response to the trauma including genetic factors and constitution, and on the brain plasticity should be accompanied in the future.

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FMDV 2C Protein of Foot-and-mouth Disease Virus Increases Expression of Pro-inflammatory Cytokine TNFα via Endoplasmic Reticulum Stress (구제역바이러스의 FMDV 2C 단백질은 소포체 스트레스를 통해서 염증 유도 사이토카인 TNFα의 발현을 증가시킴)

  • Kang, Hyo Rin;Seong, Mi So;Nah, Jin Ju;Ryoo, Soyoon;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
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    • v.30 no.3
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    • pp.285-290
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    • 2020
  • Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

Anti-cancer Effects of Cultivated Orostachys japonicus on Human Colon Cancer Cell Line SW480 (인체대장암세포주 SW480에 대한 재배 와송의 항암효과 연구)

  • Park, Sookyoung;Won, Jinyoung;Park, Kanghui;Hong, Yonggeun
    • Journal of Life Science
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    • v.28 no.7
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    • pp.819-826
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    • 2018
  • Orostachys japonicus (OJ) is a medicinal herb with immunoregulatory, anti-aging, anti-oxidative, and many other therapeutic properties. The purpose of this study was to elucidate the anti-cancer property of cultivated OJ. SW480 cell viability was significantly reduced by cumulative exposure to OJ extract. We also observed inhibitory effects of OJ after 72 hr through the growth and migration of SW480 cells using scratch assay. SW480 cells in OJ-free medium began to move into the scratch site at 24 hr; however, cells in medium containing OJ did not migrate into the scratch site until 48 hr. Male C57BL/6 mice (4 weeks old) were orally administered OJ extract for 31 days before injection of SW480 cells. At 7, 14, and 28 days after subcutaneous injection of SW480 cells, tumor weight and volume were analyzed. The body weight of the OJ-treated group was continuously increased during administration of the OJ extract relative to the control group. Injection of SW480 cells caused a reduction in body weight in all groups; however, the OJ-treated group exhibited a significant increase in body weight after 14 days. Tumor weight and volume were lower in the OJ-treated group than in the control group after 28 days. Although these results suggest that OJ suppresses the proliferation and migration of human colon cancer cells, additional studies are required to provide preclinical evidence before launching clinical trials evaluating OJ as an anti-cancer biohealth product.