• Title/Summary/Keyword: 면역 억제 치료

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Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

Compamative Study of Tracheal Anastomotic Techniques. (기관 문합 수기의 비교 실험)

  • 송원영;이연재
    • Journal of Chest Surgery
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    • v.30 no.12
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    • pp.1219-1224
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    • 1997
  • Although several reports were presented recently about bronchial arterial revascularization in clinical lung transplantation, one factor peculiar to the lung transplantation is the ischemia of the donor bronchus. Poor bronchial healing occurs frequently following clinical lung transplantation and this has been major cause of mortality and morbidity. There have been many attempts to solve bronchial anastomotic complications. Telescoping technique, one of those attempts, was advocated by San Antonio Group recently. This experiment was per(armed to evaluate the effect of telescoping anastomotic technique upon th healing of the tracheo-bronchial anastomosis. We used rabbits(weighing about 800 g) as experimental animal. Method: Resection of middle one third of cervical trachea and reanastomosis was performed by simple interrupted anastomotic technique in Group 1(n=15) and by telescoping anastomotic technique in Group 2(n= 15). Result: Anastomotic sites in the telescoping technique group showed significant increase of fibrosis in the early postoperative days(< Sdays) and remarkable band-like fibrous union compared to the simple interrupted group.

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Acupuncture at GB34 modulates laminin expression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced PD mouse model (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine를 이용한 파킨슨병 생쥐 모델에서의 laminin 발현에 대한 양릉천 자침의 조절효과)

  • Kim, Youn-Jung;Kim, Bum-Shik;Park, Hi-Joon
    • Korean Journal of Acupuncture
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    • v.25 no.1
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    • pp.155-164
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    • 2008
  • 목 적 : 본 연구의 목적은 양릉천 침 처치 시 C57BL/6 생쥐의 중뇌 흑질에 위치한 도파민성 신경세포 사멸 억제 효과를 조직화학 염색법을 이용하여 Tyrosine hydroxylase(TH)와 laminin의 발현으로 관찰하고자 한다. 실험방법 : 실험에 이용한 동물은 C57BL/6 생쥐로, 매일 25mg/kg의 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)를 5일간 주사하였고, 매일 MPTP 주사한 뒤 2시간 후에 양릉천에 침치료를 시행하였으며 MPTP 주사를 종료한 뒤 침치료는 7일동안 계속 시행하였다. 마지막 MPTP 주사 7일 후에 동물을 희생하여 뇌를 적출하고 고정하였다. 침효과를 확인하기 위해 Thyrosine hydroxylase(TH), laminin의 발현 변화 정도를 조직염색화학법으로 이용하여 확인하였다. 각 그룹간의 유의성 검증은 one-way ANOVA를 이용하였다. 결 과 : 도파민성 신경세포 선택적인 신경독소인 MPTP에 대한 양릉천 침처치에 의한 신경보호 효과를 도파민신경세포의 표지자인 TH 발현을 면역화학조직염색법으로 관찰하였다. 대조군에 비해 MPTP 처치 군의 신경세포 사멸이 유의적으로 감소하였고(P <0.05), MPTP + 침처치 군에서 증가되는 양상을 확인하였다 (P <0.05). 또한 도파민성 신경세포내에 존재하는 laminin의 발현정도 역시 대조군보다 MPTP 처치 군에서 유의적으로 감소하였고, MPTP + 침처치 군에서 증가되는 양상을 확인하였다 (P <0.05). 결 론 : MPTP에 의한 도파민성 신경세포 손상에 대한 양릉천 침처치의 신경보호 효과는 세포외 기질중의 하나인 laminin의 발현 정도를 조절하여 비롯되는 것으로 사료된다.

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Severe Anemia Caused by Parvovirus B19 Infection in Two Pediatric Kidney Transplantation Recipients (소아 신장이식 환자에서 발생한 파르보바이러스 B19에 의한 심한 빈혈에 대한 증례 보고 및 문헌 고찰)

  • Kim, Kyung-Ran;Park, Hwanhee;Kim, Doo Ri;Cho, Heeyeon;Lee, Sanghoon;Lee, Suk-Koo;Kim, Yae-Jean
    • Pediatric Infection and Vaccine
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    • v.28 no.3
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    • pp.181-188
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    • 2021
  • Anemia commonly occurs in kidney transplantation (KT) recipients. Many factors such as viral infection, bleeding, erythropoietin deficiency, and immunosuppressants are the causes of chronic anemia in KT recipients. We report 2 cases who developed severe anemia caused by parvovirus B19 infection and were successfully treated with intravenous immunoglobulin in pediatric KT recipients.

Differentiation of Entomoeba histolyticn and Entcmoeba dispor in cyst-passers by immunoblot (면역이적법을 이용한 아질아메바와 동형아메바의 감별진단)

  • 이미정;홍성태
    • Parasites, Hosts and Diseases
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    • v.34 no.4
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    • pp.247-254
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    • 1996
  • Differentiation of invasive strains of Entamoebn histolytica according to their pathogenicity has been a topic of long debate, but now the pathogenic species only is regarded as E. histolytica while the non-pathogenic species is E. dispar. The present study applied immunoblot to differentiale infections of the two species among microscopically- detected cyst-passers in Korea. The crude extract of 5. histolyticn separated in 5-20% gradient gels, revealed many fractions of 94. 81. 71, 50. 44, 38.5. 37.5, 29, 19. and 18 kDa when the cysteine proteinase inhibitor. E64, was supplemented. The serum IgG antibody of 3 proven E. histolytirc cases reacted loth the antigenic fractions of 117. 110. 99.68,66,60.54.52, 46. and 45 kDa. Sera of PCR confirmed 3 cases of E. disper reacted only to the 117 kDa fraction or the E. histolytica crude extract which was regarded as non specific. To the antitigen of monoxenic E. dispar. sera or E. dispar and E. histolytica cases showed the same immunoblot reactions. The serum IgG antibody reacted with several antigenic fractions of both E. histolytica and E. dispar. but IgM and IgE antibodies showed no reaction to either antigen. Sera of 24 symptomless amebic cyst-passers were screened with the E. histolytica alltigen; two were found to be infected by E. histolytica and 22 were by E. dispar. The present findings suggest that in Korea most of asymptomatic cyst passers of E. histolytica are carriers of E. dispar. Immunoblot using E. histolytica antigen is a good technique for the differentiation of E. histolytica and E. dispar infections.

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ω3-Polyunsaturated Fatty Acids-induced Inhibition of Tumorigenicity and Invasion by Suppression of COX-2/MMPs/VEGF through NF-kB in Colon Cancer Cells (오메가-3 지방산에 의한 COX-2/MMPs/VEGF 억제에 따른 대장암세포의 종양 형성 및 침윤 억제)

  • Shin, Soyeon;Kim, Yong-Jo;Han, Seung-Hyeon;Silwal, Prashanta;Heo, Jun-Young;Jeon, Young-Joo;Park, Seung-Kiel;Kweon, Gi-Ryang;Park, Jong-Il;Lim, Kyu
    • Journal of Life Science
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    • v.27 no.9
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    • pp.1020-1030
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    • 2017
  • Epidemiology studies have reported a reduced incidence of colon cancer among populations that consume a large quantity of ${\omega}3-polyunsaturated$ fatty acids (${\omega}3-PUFAs$) of marine origin. Herein, we demonstrated a mechanism of anticancer action of ${\omega}3-PUFAs$, showing that they suppressed invasion and tumorigenicity in colon cancer cells. Docosahexaenoic acids (DHA) inhibited the cell growth of HT29 cells. This action likely involved apoptosis, given that the DHA treatment increased the cleaved form of PARP and sub G1 cells. Moreover, the invasiveness of HT29 cells was inhibited following DHA treatment, whereas arachidonic acid (AA) had no effect. The levels of Matrix-metalloproteinase-9 (MMP-9) and MMP-2 mRNA decreased after DHA pretreatment. DHA treatment inhibited MMP-9 and MMP-2 promoter activities and reduced VEGF promoter activity. DHA pretreatment also inhibited the activities of prostaglandin-2 (PGE2)-induced MMPs and the VEGF promoter. Cyclooxygenase-2 (COX-2) overexpression increased the activity of MMPs and that of the Vascular endotherial growth factor (VEGF) promoter in HT29 cells, and DHA inhibited NF-kB and COX-2 promoter reporter activities. As shown by in vivo experiments, when mouse colon cancer cells (MCA38) were implanted into Fat-1 and wild-type mice, both the tumoral size and volume were dramatically inhibited in Fat-1 transgenic mice. Furthermore, TUNEL-positive cells increased in tumors from Fat-1 mice compared with wild mice. In immunohistochemistry, the intensity of CD31 in Fat-1 tumors was weaker. These findings suggest that ${\omega}3-PUFAs$ may inhibit tumorigenicity and angiogenesis as well as cancer cell invasion by suppression of COX-2, MMPs and VEGF via the reduction of NF-kB in colon cancer.

Immunomodulatory Effect of Mesenchymal Stem Cell-Derived Exosomes in Lipopolysaccharide-Stimulated RAW 264.7 Cells (Lipopolysaccharide로 자극한 RAW 264.7 세포에서 성체줄기세포 유래 엑소좀(exosome)의 면역 조절 효과)

  • Jung, Soo-Kyung;Park, Mi Jeong;Lee, Jienny;Byeon, Jeong Su;Gu, Na-Yeon;Cho, In-Soo;Cha, Sang-Ho
    • Microbiology and Biotechnology Letters
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    • v.44 no.3
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    • pp.383-390
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    • 2016
  • Mesenchymal stem cells (MSCs) are multipotent stem cells that can be differentiated into a variety of cell types, including adipocytes, osteoblasts, chondrocytes, β-pancreatic islet cells, and neuronal cells. MSCs have been reported to exhibit immunomodulatory effects in many diseases. Many studies have reported that MSCs have distinct roles in modulating inflammatory and immune responses by releasing bioactive molecules. Exosomes are cell-derived vesicles present in biological fluids, including the blood, urine, and cultured medium of cell cultures. In this study, we investigated the immunomodulatory effects of mouse adipose tissue-derived MSCs (mAD-MSCs), cultured medium (MSC-CM) of mAD-MSCs, and mAD-MSC-derived exosomes (MSC-Exo) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. We observed that the expression levels of IL-1β, TNF-α, and IL-10 were significantly increased in LPS-stimulated RAW 264.7 cells compared to those in LPS-unstimulated RAW 264.7 cells. Additionally, these values were significantly (p < 0.05) decreased in mAD-MSCs-RAW 264.7 cell co-culture groups, MSC-CM-treated groups, and MSC-Exo-treated groups. MSCs can modulate the immune system in part by secreting cytokines and growth factors. We observed that immunomodulatory factors such as IL-1β, TNF-α, and IL-10 were secreted by mAD-MSCs under co-culturing conditions of mAD-MSCs with activated RAW 264.7 cells. In addition, mAD-MSC-derived exosomes exhibited similar immunomodulatory effects in activated RAW 264.7 cells. Therefore, our results suggest that mAD-MSCs have an immunomodulatory function through indirect contact.

A Case Report: Limitation of Mouth Opening in Dermatomyositis (개구장애를 동반한 피부근염 환자 증례)

  • Kim, Hye-Kyung;Kim, Ki-Suk;Kim, Mee-Eun
    • Journal of Oral Medicine and Pain
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    • v.35 no.2
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    • pp.155-163
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    • 2010
  • Dermatomyositis (DM) is an idiopathic inflammatory connective tissue disorder and a systemic autonomic immune disease which shows a progressive muscle weakness and characteristic rash. It is identified by a characteristic rash accompanying, or more often preceding muscle weakness. Pathognomonic skin lesions are a blue-purple discoloration on the upper eyelids with edema (heliotropic rash), a flat red rash on the face and upper trunk, and erythema of the knuckles with a raised violaceous scaly eruption (Gottron's papule). The myopathy represents inflammatory and degenerative changes primarily affecting proximal muscles. DM often involves GI tract and respiratory system with as risk of 15-25% internal malignancy. It's managed with sun protection since muscle weakness as well as a rash could be aggravated by sun exposure. Systemic corticosteroid is an initial therapy and other immunosuppressive agent has been used as alternatives. Facial muscles are unaffected and masticatory muscles are rarely affected in DM. We present trismus close to muscle contracture in a patient with DM. Therefore, it needs continuous mouth-opening exercise to prevent progressive muscle contracture and to ensure normal mouth opening.

Tuberous Sclerosis Complex with Crohn's Disease (크론병과 병발한 결절성경화증 1예)

  • Kim, Min Hee;Lee, Yoon Jin;Kim, Jae Young;Yi, Yoon Young;Kang, Joon Won
    • Journal of the Korean Child Neurology Society
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    • v.26 no.4
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    • pp.284-287
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    • 2018
  • Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutation of one of two genes, TSC1 (encoding hamartin, 9q34) and TSC2 (encoding tuberin, 16p13). It invades the central nervous system and various parts of the body, causing various symptoms. Crohn's disease (CD) is a chronic immune-mediated disease that has not been clearly elucidated. It is thought to be caused by an excessive immune response of the body to bacteria that normally exist in the digestive tract with genetic factors. No cases have been reported in which both of the above-mentioned diseases occurred simultaneously. We report a case of CD in a patient with TSC. A 12-year-old boy was brought to our hospital because of abdominal pain. Skin lesions were observed in the TSC. Fundus examination revealed a hamartoma in the right retina. Brain magnetic resonance imaging revealed a subendothelial giant cell astrocytoma (SEGA). On the basis of these findings, he was diagnosed as having TSC. Blood test results showed increased levels of inflammatory markers. On abdominal ultrasonography, his colon walls were observed to be thickened with increased vascularity of the proximal ascending colon, ileocecal valve, and terminal ileum. Colonoscopy revealed discontinuous ulcerations and inflammations of the ileum, IC valve, and cecum, similar to those found in CD. Everolimus was administered orally for the SEGA but was discontinued frequently owing to the exacerbation of CD. The possibility of CD should be kept in mind in patients with TSC considering to undergo treatment for SEGA.

Anti-arthritic Activity of Artemisia princeps Pampanini on Complete Freund's Adjuvant-induced Arthritis (Artemisia princeps Pampanini의 complete freund's adjuvant 유발 관절염에 대한 개선 효과)

  • Kim, Ha-Rim;Kim, Sol;Kim, Seon-Young
    • Journal of Life Science
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    • v.31 no.8
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    • pp.736-744
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    • 2021
  • Artemisia princeps Pampanini is an herbal medicine widely used to immune function-related diseases, such as anti-oxidative, anti-inflammatory, and antibacterial agents. In this study, we investigated the anti-inflammatory effects of AP extract and underlying mechanisms were evaluated in RAW 264.7 cells. The effects of AP extract were also studied in a complete Freund's adjuvant (CFA)-induced arthritis and lipopolysaccharide (LPS)-induced inflammation mouse model. In RAW 264.7 cells, AP extracts significantly inhibited the LPS-induced nitric oxide (NO) production and inducible NO synthase and cyclooxygenase-2 protein expression. The LPS-induced phosphorylation of mitogen-activated protein kinases and nuclear factor-κB was also significantly blocked by AP extract in RAW 264.7 cells. Oral administration of AP extract suppressed the increase in mouse paw edema and spleen index compared to CFA-treated mice group. Histologically, the infiltration of inflammatory cells was increased in cartilage and synovium in the CFA-treated mouse group, whereas it was suppressed in the AP extract-administered group. Furthermore, AP extract treatment significantly reduced the inflammatory cytokine, tumor necrosis factor-α, levels in CFA and LPS-treated mouse. In conclusion, the anti-inflammatory and anti-arthritis effect of AP extract was confirmed in both in vitro and in vivo models, suggesting that Artemisia princeps Pampanini may be a candidate material for arthritis treatment.