• Journal of Ginseng Research
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• 제45권1호
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• pp.134-148
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• 2021

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권1호
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• pp.109-117
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• 2021

Purpose: Ménétrier disease (MD) was first described in 1888, and 50 cases have been reported until now. We aimed to discuss the etiology, diagnostics, and management of MD in children. Methods: We searched for case reports published from 2014 till 2019 in English using PubMed. Articles were selected using subject headings and key words of interest to the topic. Interesting references of the included articles were also included. Results: The pathophysiology of MD is still uncertain. However, overexpression of transforming growth factor alpha with transformation of the gastric mucosa has been observed, which may be mediated by genetics and provoked by an infectious trigger. Clinically, MD is diagnosed by abdominal pain, vomiting, anorexia, and edema secondary to hypoalbuminemia. A gastroscopy with biopsy is the gold standard for the diagnosis of MD. In children, the disease is self-limiting and only requires supportive treatment. In general, children have a good prognosis and recover spontaneously within a few weeks. Conclusion: Few pediatric cases of MD have been described in recent years, and with all different etiology. Endoscopy with biopsy remains the golden standard for the diagnosis of MD, and in children, the disease is self-limiting.

• Journal of Periodontal and Implant Science
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• 제47권2호
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• pp.66-76
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• 2017

Purpose: Oral wound healing requires gingival fibroblasts to respond to local growth factors. Epigenetic silencing through DNA methylation can potentially decrease the responsiveness of gingival fibroblasts to local growth factors. In this study, our aim was to determine whether the inhibition of DNA methylation sensitized gingival fibroblasts to transforming growth factor-${\beta}1$ (TGF-${\beta}1$). Methods: Gingival fibroblasts were exposed to 5-aza-2'-deoxycytidine (5-aza), a clinically approved demethylating agent, before stimulation with TGF-${\beta}1$. Gene expression changes were evaluated using quantitative polymerase chain reaction (PCR) analysis. DNA methylation was detected by methylation-sensitive restriction enzymes and PCR amplification. Results: We found that 5-aza enhanced TGF-${\beta}1$-induced interleukin-11 (IL11) expression in gingival fibroblasts 2.37-fold (P=0.008). 5-aza had no significant effects on the expression of proteoglycan 4 (PRG4) and NADPH oxidase 4 (NOX4). Consistent with this, 5-aza caused demethylation of the IL11 gene commonly next to a guanosine (CpG) island in gingival fibroblasts. The TGF-${\beta}$ type I receptor kinase inhibitor SB431542 impeded the changes in IL11 expression, indicating that the effects of 5-aza require TGF-${\beta}$ signaling. 5-aza moderately increased the expression of TGF-${\beta}$ type II receptor (1.40-fold; P=0.009), possibly enhancing the responsiveness of fibroblasts to TGF-${\beta}1$. As part of the feedback response, 5-aza increased the expression of the DNA methyltransferases 1 (DNMT1) (P=0.005) and DNMT3B (P=0.002), which are enzymes responsible for gene methylation. Conclusions: These in vitro data suggest that the inhibition of DNA methylation by 5-aza supports TGF-${\beta}$-induced IL11 expression in gingival fibroblasts.

• Tuberculosis and Respiratory Diseases
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• 제42권4호
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• pp.492-501
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• 1995

연구배경: TGF-$\alpha$는 세포증식을 자극하는 기능을 갖는 순기능 조절인자들 중 하나이며 autocrine 또는 paracrine기전에 의하여 그성장을 조절하며, 발암과정 및 종양세포의 성장에 중요한 역할을 한다. 반면 TGF-$\beta$는 세포의 증식을 억제하는 역기능 성장인자로 작용하며, G1기에서 S기로의 이행을 억제하여 성장의 정지에 관여하는 것으로 보고되고 있다. 방법: 저자들은 10예의 정상대조군 및 소세포암종 및 비소세포암종을 포함한 인체 폐암종 총 47예에서 TGF-$\alpha$와 TGF-$\beta$의 발현상태를 알고자 이들의 항체를 이용한 면역조직화학적 염색을 실시하여 다음과 같은 결과를 얻었다. 결과 TGF-$\alpha$는 정상 대조군 10예중 2예(20%)의 기관지 상피에서, 인체 폐암종 47예중 35예(74.5%)의 암세포질에서 산발적으로 발현이 되었다. TGF-$\beta$는 정상대조군 10예중 8예의 기관지 상피에서, 인체 폐암종 47예중 8예(17.0%)의 암세포질에서 산발적인 발현을 보였다. 결론: 이와 같은 성적은 인체 폐암종에 있어서 TGF-$\alpha$의 발현과다는 autocrine loop에 의한 수용체를 통하여 그 성장을 자극함으로써 폐암종의 발생 및 성장에 중요한 인자로 관여 한 것으로 생각되며, TGF-$\beta$의 발현감소는 세포성장의 역조절 기능의 억제로 인해 폐암종의 발생과 성장을 조장하는 것으로 생각된다.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제23권4호
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• pp.346-355
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• 2020

Purpose: Peroxisome proliferator-activated receptor gamma (PPAR-γ) has a key role in hepatic fibrogenesis by virtue of its effect on the hepatic stellate cells (HSCs). Although many studies have shown that PPAR-γ agonists inhibit liver fibrosis, the mechanism remains largely unclear, especially regarding the cross-talk between PPAR-γ and other potent fibrogenic factors. Methods: This experimental study involved 25 male Wistar rats. Twenty rats were subjected to bile duct ligation (BDL) to induce liver fibrosis, further divided into an untreated group (BDL; n=10) and a group treated with the PPAR-γ agonist thiazolidinedione (TZD), at 14 days post-operation (BDL+TZD; n=10). The remaining 5 rats had a sham operation (sham; n=5). The effect of PPAR-γ agonist on liver fibrosis was evaluated by histopathology, protein immunohistochemistry, and mRNA expression quantitative polymerase chain reaction. Results: Histology and immunostaining showed markedly reduced collagen deposition, bile duct proliferation, and HSCs in the BDL+TZD group compared to those in the BDL group (p<0.001). Similarly, significantly lower mRNA expression of collagen α-1(I), matrix metalloproteinase-2, platelet-derived growth factor (PDGF)-B chain, and connective tissue growth factor (CTGF) were evident in the BDL+TZD group compared to those in the BDL group (p=0.0002, p<0.035, p<0.0001, and p=0.0123 respectively). Moreover, expression of the transforming growth factor beta1 (TGF-β1) was also downregulated in the BDL+TZD group (p=0.0087). Conclusion: The PPAR-γ agonist inhibits HSC activation in vivo and attenuates liver fibrosis through several fibrogenic pathways. Potent fibrogenic factors such as PDGF, CTGF, and TGF-β1 were downregulated by the PPAR-γ agonist. Targeting PPAR-γ activity may be a potential strategy to control liver fibrosis.

• Asian-Australasian Journal of Animal Sciences
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• 제15권9호
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• pp.1244-1249
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• 2002

Myostatin (growth differentiation factor (GDF)-8), is one member of the transforming growth factor $\beta$ superfamily. Investigations of GDF-8 null mice and double-muscled cattle revealed that GDF-8 has a profound influence upon skeletal muscle growth. Therefore, the GDF-8 effect upon the productive performance of pigs is worth exploring. In the present study, the nucleotide sequences and expression levels of GDF-8 genes in European pigs (Landrace and Duroc) and Asian pigs (Taoyuan and Small-ear) were evaluated. Based upon their genetic background these breeds possess significantly distinct growth rate and muscle productionphenotypes. Our sequence data showed that the nucleotide sequences of European and Asian pigs were 100% similar. Postnatal expression of GDF-8 gene in skeletal muscles, from birth to 12 mo of age, among different breeds was measured. GDF-8 expression levels in the longissimus muscle of neonatal European breed littermates were the highest, however it declined significantly (p<0.05) at 1 and 3 mo, and then increased gradually at 6 to 12 mo. The Asian breeds, however, GDF-8 expression level increased markedly at 3 mo and maintained a constant level thereafter. The results indicate that rather than polymorphism within the GDF-8 functional sequence between European and Asia breeds, it was relative to the gene regulation in postnatal muscle growth.

• Archives of Plastic Surgery
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• 제33권1호
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• pp.1-4
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• 2006

Cryopreserved fibroblast implants represent a major advancement for healing of chronic wounds. Bone marrow stromal cells, which include the mesenchymal stem cells, have a low immunity-assisted rejection and are capable of expanding profoundly in a culture media. Therefore, they have several advantages over fibroblasts in clinical use. The ultimate goal of this study was to compare the wound healing accelerating growth factor secretion of the bone marrow stromal cells with that of the fibroblasts and this pilot study particularly focuses on the growth factor secretion to accelerate wound healing. Bone marrow stromal cells and fibroblasts were isolated from the same patients and grown in culture. At 1, 3, and 5 days post-incubating, secretion of basic fibroblast growth factor(bFGF), vascular endothelial growth factor (VEGF), and transforming growth factor beta(TGF-${\beta}$) were compared. In TGF-${\beta}$ secretion fibroblasts showed 12~21% superior results than bone marrow stromal cells. In contrast, bFGF levels in the bone marrow stromal cells were 47~89% greater than that in fibroblasts. The VEGF levels of the bone marrow stromal cells was 7~12 fold greater than that of the fibroblasts. Our results suggest that the bone marrow stromal cells have great potential for wound healing accelerating growth factor secretion.

• Journal of Chest Surgery
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• 제43권4호
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• pp.394-398
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• 2010

배경: 저자들은 자연 기흉 환자의 폐 기포에서 transforming growth factor-beta 1 receptor II (TGF-${\beta}1$RII)와 transforming growth factor-beta 1 (TGF-${\beta}1$) ligand를 면역조직화학염색법으로 조사하여 상기 유전 물질이 과 발현되어 폐 기포 형성에 관여될 수 있음을 보고한 바 있다. 그러나 TGF-${\beta}1$ ligand는 혈액 내에도 존재하고 있으므로 혈액내의 TGF-${\beta}1$ ligand 양이 폐 기포 조직의 형성에도 관여가 될 수 있는 가능성 여부를 알아보기 위하여 연구를 하였다. 대상 및 방법: 자연 기흉으로 폐 기포 절제술을 실시한 환자 19명에서 폐 기포 조직과 혈액을 채취하였다. 대조군으로 25∼27세의 정상인 5명에서 혈액을 채취하였다. 획득된 폐 기포 조직은 formalin 용액에 고정하였으며 파라핀에 포매하여 $5{\sim}6{\mu}m$ 두께로 블록을 만들었으며 면역조직화학염색방법으로 염색하여 관찰하였다. 채취된 혈액에서 ELISA assay로 혈액내의 TGF-${\beta}1$의 양을 측정하였다. 결과: 19명 중 16명에서 TGF-${\beta}1$에 양성이었으며 10명에서 TGF-${\beta}1$RII에 양성의 소견을 보였다. TGF-${\beta}1$에 양성인 16명 중 9명에서 TGF-${\beta}1$RII에 양성으로 확인되었다. 강하게 염색된 부위는 폐 기포 조직과 정상 폐 조직의 경계선 부위였다. 폐 기포 조직에서 TGF-${\beta}1$과 TGF-${\beta}1$RII가 동시에 양성인 환자 9명의 혈액내의 TGF-${\beta}1$의 양은 $38.36{\pm}16.2ng/mL$이었으며 대조군은 $54.06{\pm}15ng/mL$이었다. 결론: 폐 기포를 갖는 수술 환자 군의 혈액내의 TGF-${\beta}1$의 양이 대조군보다 높지 않은 수치를 보이는 것으로 보아 혈액 내 TGF-${\beta}1$ 양은 폐 기포 형성에 직접적으로 관여될 가능성은 적고, 폐 조직에서 국소적으로 과 발현되는 TGF-${\beta}1$RII and TGF-${\beta}1$ ligand가 폐 기포 형성에 더 많이 관계하는 것으로 예상한다.

• KSBB Journal
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• 제14권1호
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• pp.9-16
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• 1999

Transforming growth factor $\beta$1(TGF-$\beta$1)은 여러 가지 생물학적 활성을 가지는 관계로 의학적 치료제로서 사용될 가능성이 크다. 본 연구에서는 혈소판추출, 젤여과, 양이온교환 크로마토그래피 및 역상 HPLC등 네 단계의 정제과정으로 이루어져 있는 정제공정을 이용한 TGF-$\beta$1을 값싸고 효울적으로 정제하였다. 이 과정을 거쳐 최종적으로 얻어진 TGF-$\beta$1은 비환원조건하에서 SDS-PAGE를 행한 결과 구매된 TGF-$\beta$1 표준품과 일치한 위치에서 한 개의 band가 관찰되어 순수하다는 것을 확인하였으며 또한 이것이 Westem blot를 통하여 TGF-$\beta$1 항체와 결합하는 것으로부터 TGF-$\beta$1임을 확인하였다 또한, mink lung epithelial cell line 을 이용한 성장저해 실험을 통해 정제된 TGF-$\beta$1이 구매되TGF-$\beta$1 표준품보다 조금 높은 활성을 가지는 것을 확인하였다 최종적으로 농축혈소판 10단위로부터 약 3.7$\mu$g의 정제된 TGF-$\beta$1이 얻어져 그 최종수율은 약 21%였다.

• 한국산학기술학회:학술대회논문집
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• 한국산학기술학회 2011년도 추계학술논문집 1부
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• pp.330-333
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• 2011

Allomatrix (Wright Medical Tech, Inc., USA), is a newly designed, injectable putty with a reliable demineralized bone matrix(DBM), derived from human bone. The compound contains 86% DBM and other bone growth factors such as bone morphogenic protein (BMP)-2, BMP-4, insulin-like growth factor (IGF)-1, and transforming growth factor (TGF)-${\beta}1$. It has excellent os-teoinduction abilities. In addition, DBM is known to have osteoconduction capacity as a scaffold due to its collagen matrix. This product contains a powder, which is a mix of DBM and surgical grade calcium sulfate as a carrier. A practitioner can blend the powder with calcium sulfate solution, making a putty-type material which has the advantages of ease of handling, better fixation, and no need for a membrane, because it can function as membrane itself. This study reports the clinical and radiographic results of various guided bone regeneration cases using Allomatrix, demonstrating its strong potential as a graft material.