• Title/Summary/Keyword: $TGF{\beta}$

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Comparison of Histopathological Changes on the Three Drugs of Carbon Tetrachloride, Dimethylnitrosamine, Thioacetamide, and Bile Duct Ligation used for Induction of Liver Fibrosis in Rat

  • Kim, Jung-Hun;Park, Mi-Jung;Kim, Yo-El;Kim, Jin-Yeong;Sin, Jin-Hee;Park, Su-Young;Jekal, Seung-Joo
    • Korean Journal of Clinical Laboratory Science
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    • v.43 no.4
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    • pp.194-204
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    • 2011
  • This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.

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Inhibitory Effects of Dunaliella salina Extracts on Thermally-Induced Skin Aging (두날리엘라 살리나 추출물의 피부 열노화 억제 효과)

  • Joo, Ji-Hye;Seok, Ji Hyun;Hong, In-kee;Kim, Nam Kyoung;Choi, Eunmi
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.1
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    • pp.57-64
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    • 2016
  • Just like UV radiation, heat increases collagen degradation and accumulation of abnormal elastin fiber and this is termed thermal skin aging. Dunaliella salina (DS), a green alga, is known for its beta-carotene accumulation, having various applications in the health and nutritional products. However, the effects of DS on heat-induced skin aging remain unexplored. In this study, we performed anti-thermal aging tests of the ethanol extract of DS (DSE). We measured the cellular levels of type I procollagen and MMP-1 using ELISA in human dermal fibroblast cells after heat shock. DSE reduced the expression of MMP-1 protein and increased the expression of type I procollagen. In addition, DSE upregulated the mRNA expression of HSP47 reduced by heat shock, which is involved in collagen synthesis. Also, DSE reduced the expression of inflammation mediator (TGF-${\beta}$, IL-12, etc). We demonstrate that DSE regulates the heat-induced solar elastosis through the regulation of tropoelastin and fibrillin-1, two major proteins of elastic fibers, and MMP-12 expression. These results suggest that DSE may be effective for preventing thermally induced skin aging.

Caffeic Acid Phenethyl Ester Induces the Expression of NAG-1 via Activating Transcription Factor 3 (ATF3를 통한 caffeic acid phenethyl ester에 의한 NAG-1 유전자의 발현 증가)

  • Park, Min-Hee;Chung, Chungwook;Lee, Seong Ho;Baek, Seung Joon;Kim, Jong Sik
    • Journal of Life Science
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    • v.28 no.1
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    • pp.37-42
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    • 2018
  • Non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1) is a transforming growth factor beta (TGF-${\beta}$) superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. In the present study, we investigated if caffeic acid phenethyl ester (CAPE) derived from propolis could induce the expression of anti-tumorigenic gene NAG-1. Our results indicate that CAPE significantly induced NAG-1 expression in a time- and concentration-dependent manner in HCT116 cells. We also found that CAPE induced NAG-1 expression in a concentration-dependent manner in another human colorectal cancer cell line, LOVO. In addition, CAPE triggered apoptosis, which was detected with Western blot analysis using poly-(ADP-ribose) polymerase antibody. NAG-1 induction by CAPE was not dependent on transcription factor p53, which was confirmed with Western blot analysis using p53 null HCT116 cells. The luciferase assay results indicated that the new cis-elements candidates were located between -474 and -1,086 of the NAG-1 gene promoter. CAPE dramatically induced activating transcription factor 3 (ATF3) expression, but not cAMP response element-binding protein (CREB), which shares the same binding sites with ATF3. The co-transfection experiment with pCG-ATF3 and pCREB showed that only ATF3 was associated with NAG-1 up-regulation by CAPE, whereas CREB had no effect. In conclusion, the results suggest that CAPE could induce the expression of anti-tumorigenic gene NAG-1 mainly through ATF3.

Wound Healing Effects of Lespedeza cuneata Extract (야관문 추출물의 창상치유 효과)

  • Jung, Hee Kyoung;Kim, Kil-Soo;Jeong, Yoo Seok
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.3
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    • pp.374-380
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    • 2014
  • In this study, the anti-inflammatory effects of Lespedeza cuneata extract on macrophages and wound-healing in wound-induced animal experiments were investigated. In an anti-inflammatory test, 0.1 mg/mL of Lespedeza cuneata extract did not affect growth of RAW 264.7 cells, and Lespedeza cuneata extract suppressed nitric oxide (NO) generation from inflammation-induced macrophages in a concentration-dependent manner. Wounds on the skin of rats were treated with vehicle containing Lespedeza cuneata extract (SSP), vehicle (SCO), and commercial ointment (CCO). The wound and scar sizes in the SSP group were significantly reduced in comparison to the SCO and CCO groups (P<0.05). The epidermis and dermis of the SSP group also recovered faster than the SCO group based on Masson's trichrome staining. The gene expression levels of vascular endothelial growth factor (VEGF) decreased and transforming growth factor-beta 1 (TGF-${\beta}1$) increased in wound tissue from the SSP group compared to that from the SCO group. These results show that Lespedeza cuneata extract accelerates wound-healing through anti-inflammatory activity and induction of collagen regeneration as well as reduces the scar area surrounding wounds. Accordingly, Lespedeza cuneata extract could be useful as a cosmeceutical in the cosmetic industry.

Preventive Effect on Development of Diabetes and Renoprotective Effect of Acanthopanax Senticosus Aqua-acupuncture in Multiple Low-dose Streptozotocin-Induced Diabetic Rats (가시오가피약침(五加皮藥鍼)이 당뇨유발억제(糖尿誘發抑制) 및 신장보호활성(腎臟保護活性)에 미치는 영향)

  • Chung, Chong-un;Lee, Yun-ho;Kang, Sung-keel
    • Journal of Acupuncture Research
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    • v.20 no.3
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    • pp.1-14
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    • 2003
  • Objective : The aim of the study was to investigate the preventive effect of Acanthopanax senticosus(AS) aqua-acupuncture into Sinsu(BL23) of the multiple low-does strepozotocin(STZ)-induced diabetic rats. Methods : The experimental animals were divided into 4 groups : normal group of rats, control group of multiple low-does STZ-induced diabetic rats, NSAA group with 0.4ml normal saline(NS) aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats, and ASAA group with 0.4ml of 20% AS aqua-acupunctured subcutaneously into Sinsu in multiple low-does STZ-induced diabetic rats. Each of AS and NS aqua-acupuncture was done subcutaneously into both loci of Sinsu taking turns everyday for 3 weeks. Thereafter the levels of serum glucose, body weight, index of kidney hypertrophy, urine glucose, urinary albumin excretion, creatinine clearance, mesangial cell and TGF-${\beta}1$ expression in glomeruli and tubular cells were measured on the determined day. Conclusions : 1. Both ASAA and NSAA groups decreased the serum glucose levels in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant decreases than NSAA group. 2. Both ASAA and NSAA groups prevented the development of diabetes in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group prevented more markedly the development of diabetes than NSAA group. 3. Both ASAA and NSAA groups prevented the reduction of body weight in multiple low-dose STZ-induced diabetic rats as compared to the control group, and ASAA group showed the same as the normal group. 4. Both ASAA and NSAA groups did not show any changes of the creatinine clearance in multiple low-does STZ-induced diabetic rats. 5. Both ASAA and NSAA groups prevented the excretion of urinary glucose and albumin in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group showed more significant prevention than NSAA group. 6. Both ASAA and NSAA groups prevented the expansion of glomerular cells and the protein expression of transforming growth factor-${\beta}1$ in multiple low-dose STZ-induced diabetic rats as compared to the cintrol group, and ASAA group prevented more significantly than NSAA group.

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THE EFFECT OF SEVERAL ROOT-END FILLING MATERIALS ON MG63 OSTEOBLAST-LIKE CELLS (수종의 치근단역충전 재료가 MG63 osteoblast-like cells에 미치는 영향)

  • Lee, Jeong-Ho;Shon, Won-Jun;Lee, Woo-Cheol;Baek, Seung-Ho
    • Restorative Dentistry and Endodontics
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    • v.35 no.3
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    • pp.222-228
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    • 2010
  • The purpose of this study was to compare mineral trioxide aggregate (MTA; Dentsply, Tulsa Dental, Tulsa, OK, USA), which is widely used as root-end filling material, with DiaRoot BioAggregate (DB; Innovative BioCaramix Inc, Vancouver, BC, Canada), newly developed product, by using MG63 osteoblast-like cells. MTA, DB, and Intermediate Restorative Material (IRM; Dentsply Caulk, Milford, DE, USA) were used for root-end filling material while tissue culture plastic was used for control group. Each material was mixed and, the mixtures were left to set for 24 hours. MG63 cells were seeded to each group and then they were cultured for attachment for 4 hours. Following the attachment of cells to the root-end filling material, early cellular response was observed. After another 12 hours'culture, the level of attachment between cells and material was observed and in order to identify the effect of each material to bone formation, transforming growth factor beta1 ($TGF{\beta}1$) and osteocalin (OC) were estimated by using enzyme-linked immunosorbent assay (ELISA), and the amount of alkaline phosphatase (ALP) was also measured. The data were analyzed using one-way ANOVA. As a result, only at OC and the number of cells which were attached to materials, there was no statistical difference between MTA and DB. At other items, there was statistically significant difference in all groups. Although DB has not shown exactly the same cellular response like that of MTA, the number of attached cells shows that biocompatibility of the material and OC indicates bone formation rate. Therefore, if DB is used for root end filling material, it is expected to lead to similar results to MTA.

Wound Healing Effects of Rose Placenta in a Mouse Model of Full-Thickness Wounds

  • Kim, Yang Woo;Baek, Seung Ryeol;Lee, Eun Sook;Lee, Sang Ho;Moh, Sang Hyun;Kim, Soo Yun;Moh, Ji Hong;Kondo, Chieko;Cheon, Young Woo
    • Archives of Plastic Surgery
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    • v.42 no.6
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    • pp.686-694
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    • 2015
  • Background Rosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice. Methods Sixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta ($250{\mu}g$) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test. Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-${\beta}1$ expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA. Conclusions Rose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

Regulatory Dendritic Cells Induced by Mesenchymal Stem Cells Ameliorate Dextran Sodium Sulfate-Induced Chronic Colitis in Mice

  • Jo, Hannah;Eom, Young Woo;Kim, Hyun-Soo;Park, Hong Jun;Kim, Hee Man;Cho, Mee-Yon
    • Gut and Liver
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    • v.12 no.6
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    • pp.664-673
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    • 2018
  • Background/Aims: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. Methods: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. Results: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), and interferon-${\gamma}$ (IFN-${\gamma}$), was decreased, but that of CD11b, IL-10, and transforming growth factor-${\beta}$ (TGF-${\beta}$) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-${\alpha}$, and IFN-${\gamma}$ decreased, but that of IL-10, TGF-${\beta}$, and Foxp3 increased in the MSC- and MSC-DC-injected groups. Conclusions: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.

Effect of Greater Celandine (Chelidonium majus L.) on Rat Hepatic Stellate Cells with Liver Fibrosis (백굴채(白屈菜)가 간섬유화 과정 중 간성상세포에 미치는 영향)

  • Lee, Hong-Il;Kim, Young-Chul
    • The Journal of Internal Korean Medicine
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    • v.32 no.4
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    • pp.504-518
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    • 2011
  • Objectives : This study was performed to investigate the anti-fibrogenic effect of greater celandine on cultured rat hepatic stellate cells. Materials and Methods : Hepatic stellate cells (HSC-T6) were treated with various concentrations of greater celandine extract for 24, 48, and 72 hours. The extraction was done with distilled water. After the treatment, cell viability, proliferation, mRNA of the ${\alpha}SMA$, TIMP-1, TIMP-2, collagen I ${\alpha}$ 1, MMP-2, IL-6, TGF-${\beta}1$, PDGFr-${\beta}1$, Bcl-2, Bax, Bcl-xl, caspase-3, caspase-9 and the activities of SOD and catalase were measured by using MTT assay, BrdU assay, real-time PCR, superoxide dismutase assay and catalase assay. Results : The viability, proliferation, mRNA expression and synthesis of collagen of the hepatic stellate cells were inhibited as the concentration increased, which indicates the herb has an inhibitory effect on fibrogenesis of the liver by regulating the fibrosis associated genes in transcription. Conclusions : These results suggest that greater celandine would be beneficial in the treatment of fibrotic patients as well as for patients with chronic hepatitis.

Genetic Polymorphisms and Cancer Susceptibility of Breast Cancer in Korean Women

  • Kang, Dae-Hee
    • BMB Reports
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    • v.36 no.1
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    • pp.28-34
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    • 2003
  • Breast cancer is the most prevalent cancer among women in Western countries, and its prevalence is also increasing in Asia. The major risk factor for breast cancer can be traced to reproductive events that influence the lifetime levels of hormones. However, a large percentage of breast cancer cases cannot, be explained by these risk factors. The identification of susceptibility factors that predispose individuals to breast cancer (for instance, if they are exposed to particular environmental agents) could possibly give further insight into the etiology of this malignancy and provide targets for the future development of therapeutics. The most interesting candidate genes include those that mediate a range of functions. These include carcinogen metabolism, DNA repair, steroid hormone metabolism, signal transduction, and cell cycle control. We conducted a hospital-based case-control study in South Korea to evaluate the potential modifying role of the genetic polymorphisms of selected low penetrance genes that are involved in carcinogen metabolisms (i.e., CYP1A1, CYP2E1, GSTM1/T1/P1, NAT1/2, etc.), estrogen synthesis and metabolism (i.e., CYP19, CYP17, CYP1B1, COMT, ER-$\alpha$, etc.), DNA repair (i.e., XRCC1/3, ERCC2/4, ATM, AGT, etc.), and signal transduction as well as others (i.e., TGF-$\beta$, IGF-1, TNF-$\beta$, IL-1B, IL-1RN, etc.). We also took into account the potential interaction between these and the known risk factors of breast cancer. The results of selected genes will be presented in this mini-review.