• Journal of Gastric Cancer
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• 제15권3호
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• pp.201-208
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• 2015

Purpose: The AT-rich interactive domain 1A (ARID1A ) gene encodes BRG1-associated factor 250a, a component of the SWItch/Sucrose NonFermentable chromatin remodeling complex, which is considered a tumor suppressor in many tumors. We aimed to investigate the prognostic significance of ARID1A expression in gastric cancers and explore its relationship with clinicopathologic parameters such as mismatch repair protein expression. Materials and Methods: Four tissue microarrays were constructed from 191 resected specimens obtained at Soonchunhyang University Cheonan Hospital from 2006 to 2008. Nuclear expression of ARID1A was semiquantitatively assessed and binarized into retained and lost expression. Results: Loss of ARID1A expression was observed in 62 cases (32.5%). This was associated with more frequent vascular invasion (P=0.019) and location in the upper third of the stomach (P=0.001), and trended toward more poorly differentiated subtypes (P=0.054). ARID1A loss was significantly associated with the mismatch repair-deficient phenotype (P=0.003). ARID1A loss showed a statistically significant correlation with loss of MLH1 (P=0.001) but not MSH2 expression (P=1.000). Kaplan-Meier survival analysis showed no statistically significant difference in overall survival; however, patients with retained ARID1A expression tended to have better overall survival than those with loss of ARID1A expression (P=0.053). In both mismatch repair-deficient and mismatch repair-proficient groups, survival analysis showed no differences related to ARID1A expression status. Conclusions: Our results demonstrated that loss of ARID1A expression is closely associated with the mismatch repair-deficient phenotype, especially in sporadic microsatellite instability-high gastric cancers.

• Archives of Plastic Surgery
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• 제34권6호
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• pp.671-678
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• 2007

Purpose: Venous malformation(VM) which often causes pain and discomfort is the most common type of vascular malformations. Although it is presented with disfigured appearance and associated soft tissue or skeletal hypertrophy, the molecular bases of VMs are poorly understood. Differentially expressed genes(DEGs) of VMs were investigated to illuminate the molecular mechanism of the disease entity. Methods: Gene expressions of VM patients' subcutaneous tissue were studied in comparison with normal persons' by $GeneFishing^{TM}$ technique using the annealing control primers (ACPs) to identify DEGs. Candidate genes were sequenced and screened by basic local alignment search tool (BLAST) afterwards. Results: Among seventy DEGs identified, forty DEGs which had shown significantly different expression pattern were sequenced. Twenty eight out of 40 were up-regulated while 12 were down-regulated. BLAST searches revealed that 37 were known genes and 3 were unknown genes. Many genes were involved in the differentiation and remodeling of smooth muscle cells, opposed to the previous hypothesis that a lot of angiogenetic genes would be involved. Furthermore, several transcription factors and related genes, as well as cell signaling and metabolism regulators, were up regulated. Conclusion: It suggests that analysis of DEGs in VMs provide basic knowledge about its pathophysiology. and new therapeutic approaches.

• Restorative Dentistry and Endodontics
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• 제24권1호
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• pp.200-211
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• 1999

The periapical response to injury is a complex interaction of inflammatory, immune, neural, vascular and synthetic activity. TGF-${\beta}$ is a potent modulator of proliferation and differentiation in various tissue, seems to lead to an increase in extracellular matrix. MMP are a family of proteolytic enzyme that mediate the degradation of extracellular matric macromolecules, but little is known about theirs possible role in periapical tissue. The purpose of this study is to investigate the differential expression of TGF-${\beta}$ and MMP-1 in tooth follicle, periapical abscess, granuloma and cyst. The expression of TGF-${\beta}$ and MMP-1 in Periapical tissue was evaluated by immunohistochemical staining and Western blot analysis. Correlationship among the periapical lesions were stastically analyzed. The degree of MMP-1 expression in periapical abscess was higher than in any other periapical lesion, and stastically significant. TGF-${\beta}$ expression is the prominent in granuloma than other periapical lesion, which was stastically significant. The increased expression of MMP and TGF-${\beta}$ was not co-related with inflammatory cell infiltration degree of the periapical cyst. The expression degree of MMP and TGF-${\beta}$ was not co-related with periapical abscess and cyst, but expression of MMP and TGF-${\beta}$ showed strong positive co-relationship with periapical granuloma, which was stastically significant. TGF-${\beta}$ expression by Western blot analysis was prominent in granuloma and cyst, and similar to the results by imunohistochemistry. MMP-1 expression is less than TGF-${\beta}$, but there is not extreme difference between periapical lesion. These results suggest that TGF-${\beta}$ and MMP may be involved in tissue remodeling and has an important role in progress or mediation of periapical lesions.

• 대한예방한의학회지
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• 제16권1호
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• pp.57-70
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• 2012

The apoptotic process of gastric mucosa triggered by induction of proapoptotic gene expression, such as Bax. Stress-inducing factors may affect Bcl-2/Bax ratio and thus the rate of apoptosis through modulation of the expression of both proteins depending upon the experimental model. TGF-${\beta}$ is believed to be essential in wound healing for regulation of cell growth and differentiation and is known to be involved in tissue repair and remodeling. The polypeptide growth factors, such as vascular endothelial growth factor(VEGF), regulate essential cell functions involved in tissue healing including cell proliferation, migration, and differentiation. The purpose of this study was to investigate whether the oral administration of $Hwangyeon-tang$ (HYT) would have protect effects on gastric ulcer in rat. Sprague-Dawley rats (n=40) were randomly divided into 4 groups ; Normal, Saline, Cimetidine and HYT group. The saline, cimetidine and HYT extract were orally administrated to each group and gastric ulcer was induced with HCl/EtOH solution. After 1 hour, the stomachs were collected for histological observation and immunohistochemistry. In Results, the wound healing of gastric ulcer was promoted by HYT and the significant alterations of BAX/Bcl-2, TGF-${\beta}1$ and VEGF proteins in gastric mucosa were observed. These results suggest that Fritillaria ussuriensis extract promotes wound healing and has protective effects on gastric ulcer in rats.

• 대한의용생체공학회:의공학회지
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• 제31권1호
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• pp.81-86
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• 2010

Laser irradiation is known to affect various tissues such as skin, bone, nerve, and skeletal muscle. Laser irradiation promotes ATP synthesis, facilitates wound healing, and stimulates cell proliferation and angiogenesis. In skeletal muscle, laser irradiation is related to the proliferation of skeletal muscle satellite cells. Normal skeletal muscle contains remodeling capacity from myogenic cells that are derived from mononuclear satellite cells. Their processes are activated by the expression of genes related with myogenesis such as muscle-specific transcription factors (MyoD and Myf5) and VEGF (vascular endothelial growth factor). In this study, we hypothesized that laser irradiation would enhance and regulate muscle cell proliferation and regeneration through modulation of the gene expressions related with the differentiation of skeletal muscle satellite cells. $C_2C_{12}$ myoblastic cells were exposed to continuous/non-continuous laser irradiation (660nm/808nm) for 10 minutes daily for either 1 day or 5 days. After laser irradiation, cell proliferation and gene expression (MyoD, Myf5, VEGF) were quantified. Continuous 660nm laser irradiation significantly increased cell proliferation and gene expression compared to control, continuous 808nm laser irradiation, and non-continuous 660nm laser irradiation groups. These results indicate that continuous 660nm laser irradiation can be applied to the treatment and regeneration of skeletal muscle tissue.

• Journal of Microbiology and Biotechnology
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• 제30권10호
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• pp.1543-1551
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• 2020

Panax ginseng has a wide range of activities including a neuroprotective effect, skin protective effects, enhanced DNA repairing, anti-diabetic activity, and protective effects against vascular inflammation. In the present study, we sought to discover the inhibitory effects of a mixture of natural products containing Panax ginseng, Ziziphus jujube, Rubi fructus, Artemisiae asiaticae and Scutellaria baicalensis (PZRAS) on osteoclastogenesis and bone remodeling, as neither the effects of a mixture containing Panax ginseng extract, nor its molecular mechanism on bone inflammation, have been clarified yet. PZRAS upregulated the levels of catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GSH-R) and glutathione peroxidase (GSH-Px) and reduced malondialdehyde (MDA) in LPS-treated RAW264.7 cells. Moreover, treatment with PZRAS decreased the production of IL-1β and TNF-α. PZRAS also inhibited osteoclast differentiation through inhibiting osteoclastspecific genes like MMP-2, 9, cathepsin K, and TRAP in RANKL-treated RAW264.7 cells. Additionally, PZRAS has inhibitory functions on the RANKL-stimulated activation of ERK and JNK, which lead to a decrease in the expression of NFATc1 and c-Fos. In an in vivo study, bone resorption induced by LPS was recovered by treatment with PZRAS in bone volume per tissue volume (BV/TV) compared to control. Furthermore, the ratio of eroded bone surface of femurs was significantly increased in LPS-treated mice compared to vehicle group, but this ratio was significantly reversed in PZRAS-treated mice. These results suggest that PZRAS could prevent or treat disorders with abnormal bone loss.

• Tuberculosis and Respiratory Diseases
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• 제78권3호
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• pp.239-245
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• 2015

Background: Chronic obstructive pulmonary disease is characterized by emphysema, chronic bronchitis, and small airway remodeling. The alveolar destruction associated with emphysema cannot be repaired by current clinical practices. Stem cell therapy has been successfully used in animal models of cigarette smoke- and elastase-induced emphysema. However, the optimal dose of mesenchymal stem cells (MSCs) for the most effective therapy has not yet been determined. It is vital to determine the optimal dose of MSCs for clinical application in emphysema cases. Methods: In the present study, we evaluated the therapeutic effects of various doses of MSCs on elastase-induced emphysema in mice. When 3 different doses of MSCs were intravenously injected into mice treated with elastase, only $5{\times}10^4$ MSCs showed a significant effect on the emphysematous mouse lung. We also identified action mechanisms of MSCs based on apoptosis, lung regeneration, and protease/antiprotease imbalance. Results: The MSCs were not related with caspase-3/7 dependent apoptosis. But activity of matrix metalloproteinase 9 increased by emphysematous lung was decreased by intravenously injected MSCs. Vascular endothelial growth factor were also increased in lung from MSC injected mice, as compared to un-injected mice. Conclusion: This is the first study on the optimal dose of MSCs as a therapeutic candidate. This data may provide important basic data for determining dosage in clinical application of MSCs in emphysema patients.

• Clinical and Experimental Pediatrics
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• 제48권8호
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• pp.886-893
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• 2005

목 적 : 가와사키병은 어린 소아에서 전신성 혈관염을 일으키는 가장 흔한 원인이다. 가와사키병이 발병한 경우 여러 혈관 성장인자들의 분비가 촉진되어 내막층의 증식과 신생 혈관 생성작용이 진행되면서 관상동맥이 재구성된다. 수년간 가와사키병의 치료제로 IVIG와 코르티코스테로이드가 사용되었으나 그 치료기전이 명확히 밝혀진 바는 없다. 이런 IVIG와 코르티코스테로이드가 가와사키병의 관상동맥합병증을 감소시키는데 어떠한 기전으로 작용하는지 알아보고자 본 연구에서는 Matrigel을 이용하여 in vitro에서 VEGF에 의해 유도된 내막세포 분화에 대한 IVIG와 methylprednisolone의 효과를 보고자 하였다. 방 법 : Matrigel을 이용하여 in vitro에서 VEGF에 의해 유도된 내막세포 분화에 대한 IVIG와 methylprednisolone의 효과를 보고자 VEGF, VEGF와 IVIG, VEGF와 VEGF antibody, VEGF와 methylprednisolone, VEGF, IVIG와 methylprednisolone을 각각 넣어주고, HUVECs를 18시간 동안 배양 후 튜브의 총 길이를 측정하였다. 결 과 : 1) IVIG의 농도를 25 mg/mL, 그리고 40 mg/mL로 증량하였을 경우 IVIG를 투여하지 않은 대조군에 비하여 통계학적으로 각각 유의한 세포수(HUVECs) 감소 효과를 관찰할 수 있었으며(P<0.001), 40 mg/mL를 처리한 경우가 25 mg/mL를 처리한 경우보다 세포수 감소 효과가 더 뚜렷하였다(P<0.05). 세포배양 시간에 따른 억제 효과는 25 mg/mL과 40 mg/mL에서 배양 후 24시간과 48시간 모두에서 대조군과 비교하여 통계학적으로 유의한 효과를 보였다(P<0.001). 2) VEGF 20 ng/mL를 처리한 군에 IVIG 40 mg/mL 또는 여러 농도의 methylprednisolone($10^{-12}M$, $10^{-9}M$ or $10^{-6}M$)을 처치해 주었을 때 튜브 형성이 유의하게 억제되었으며(P<0.05), methylprednisolone의 경우 그 억제 정도가 농도에 비례하여 일어났으나 IVIG 투여시 보다는 억제 효과가 약하였다. 한편, IVIG와 methylprednisolone와 병합투여한 경우는 methylprednisolone 농도에 상관없이 모두 튜브 형성을 잘 억제하였으며(P<0.001), IVIG만 단독 투여한 것과 통계적 차이는 없었다. 결 론 : 본 연구에서는 in vitro에서 VEGF가 HUVECs의 분화를 유도하고 분화된 내막세포의 맥관 형성이 IVIG와 methylprednisolone에 의해 저해된다는 것을 보여주었다. 이는 가와사키병의 관상동맥합병증이 생기는 기전 중 VEGF와 내막세포의 분화로 인해 일어나는 관상동맥의 재구성을 IVIG와 methylprednisolone이 억제한다는 것을 시사하며 치료 기전 중 하나로 제시될 수 있다.

• Clinical and Experimental Pediatrics
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• 제49권2호
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• pp.192-197
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• 2006

목 적 : 천식은 기도의 만성 염증성 질환으로 기도개형은 천식에서 가장 중요한 병태생리이다. 혈관의 신생 및 혈관투과성을 증가시키는 것으로 알려진 VEGF가 천식의 중증도와 기침의 지속기간에 따라 차이가 있는지 알아보고, 폐렴과 같은 급성 하기도 질환에서도 증가하는지 알아보고자 하였다. 방 법 : 2001년 1월부터 2002년 1월까지 강북삼성병원 소아과에 천식 및 폐렴으로 내원한 36명의 환아와 건강검진을 위해 소아과 외래를 방문한 건강한 어린이 22명을 대상으로 하였다. 천식 환아는 중증도에 따라 경증 천식군과 중등증 및 중증 천식의 두 군으로 나누고, 또한 내원 시까지의 기침의 지속기간에 따라 2주 미만, 2주에서 4주, 4주 이상의 세 군으로 분류한 후 각각 혈청 VEGF 농도를 비교하였으며, 혈소판 및 백혈구수, CRP, IgE 농도, 총호산구수, 대상군의 나이와의 상관관계를 조사하였다. 결 과 : 평균 혈청 VEGF 농도는 경증 천식군, 중등증 및 중증 천식군, 폐렴군, 대조군에서 각각 $278.4{\pm}191.6pg/mL$, $751.6{\pm}534.2pg/mL$, $775.6{\pm}340.0pg/mL$, $311.2{\pm}198.1pg/mL$로 중등증 및 중증 천식군과 폐렴군에서 경증 천식군 및 대조군보다 혈청 VEGF 농도가 유의하게 높았다(P<0.05). 기관지 천식을 앓고 있는 환아 중 기침 기간에 따라 혈청 VEGF 농도를 비교해 본 결과 2주 이상 4주 이하 동안 기침을 한 군 및 4주 이상 기침을 한 군에서 혈청 VEGF 농도는 각각 $709.2{\pm}589.3pg/mL$, $896.9{\pm}594.9pg/mL$로 2주 미만 기침을 한 그룹의 $307.1{\pm}198.4pg/mL$에 비하여 의미있게 높았다(P<0.05). 혈청 VEGF 농도와 혈소판 수치 및 백혈구수와는 양의 상관관계를 보였으며(P<0.05), CRP, IgE 농도, 총호산구수 및 대상군의 나이와는 의미 있는 상관관계가 없었다. 결 론 : 혈청 VEGF는 기관지 천식에서 중증도 및 염증의 지속기간과 연관이 있으며, 급성 하기도 질환의 급성 염증반응에도 중요한 역할을 한다.

• 생명과학회지
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• 제32권2호
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• pp.175-188
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• 2022

혈관과 섬유증 기관들의 평활근과 세포외기질에 대한 릴랙신의 조절기능이 입증되어왔다. 본 총설에서는 저항성 소동맥과 방광을 포함한 섬유증 기관들의 세포외기질에 작용하는 릴랙신의 다양한 기전들을 고찰한다. 릴랙신은 혈관 평활근육의 수축을 억제하고, 콜라겐과 같은 세포외기질의 구성성분들을 감소키켜 혈관벽의 수동적 신전성을 증가시킴으로써, 혈관확장을 유도한다. 릴랙신이 동맥의 혈관확장을 유도하는 주된 세포기전은 RXFP1/PI3K의 활성화, Akt 인산화 및 eNOS 활성화를 통한 내피세포-의존성 산화질소의 생성에 의해 매개된다. 추가적으로, 릴랙신은 또한 다른 대체경로들을 작동하여 신장과 장간막 동맥의 혈관확장을 증가시킨다. 신장 소동맥에서, 릴랙신은 내피세포의 MMPs 및 EtB 수용체의 활성화와 VEGF 및 PlGF의 생성을 촉진하여, 평활근의 수축성과 콜라겐의 침착을 억제함으로써 혈관확장을 초래한다. 이와 달리, 장간막 소동맥에서, 릴랙신은 bradykinin (BK)-유도 이완을 시간-의존적으로 증강시킨다. BK-매개 이완의 신속 증가는 IK_Ca 이온통로와 뒤이은 EDH 유발에 의존하는 반면, BK에 의한 지속적 이완은 COX 활성과 PGI₂에 의존한다. 릴랙신의 항섬유화 효과는 염증유발 면역세포의 침투, endothelial-to-mesenchymal transition (EndMT) 및 근섬유아세포의 분화와 활성을 억제하여 매개된다. 릴랙신은 또한 근섬유아세포 내 NOS/NO/cGMP/PKG-1 경로를 활성화하여, TGF-β1-유도 ERK1/2 및 Smad2/3 신호의 활성과 ECM 콜라겐의 침착을 억제한다.