• Title/Summary/Keyword: TGF-{\beta}

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Role of Radiation Therapy for Stage III Thymoma (제 3기 흉선종에서 방사선치료의 역할)

  • Chun, Ha-Chung;Lee, Myung-Za
    • Radiation Oncology Journal
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    • v.19 no.1
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    • pp.16-20
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    • 2001
  • Purpose : To evaluate the effectiveness and tolerance of the postoperative radiation therapy for patients with Stage III thymoma and to define the optimal radiotherapeutic regimen Materials and Methods : We retrospectively analyzed the records of 24 patients with Stage III thymoma who were referred for postoperative radiation therapy in our institution from June, 1987 to May, 1999. Surgical therapy consisted of total resection in one patient, subtotal resection in seventeen, and biopsy alone in six patients. Age of the patients was ranged from 20 to 62 years with mean age of 47 years. Male to female ratio was 14 to 10. Radiation therapy was delivered with linear accelerator producing either 6 MeV or 10 MeV photons. The irradiated volume included anterior mediastinum and known residual disease. The supraclavicular fossae were not irradiated. The delivered total dose was ranged from 30 to 56 Gy. One patient received 30 Gy and eighteen patients received minimum of 50 Gy. Follow up period was ranged from 12 months to 8 years with median follow up of 40 months. Results : The overall local control rate for entire group of patients was $67\%$ at 5 years. The cumulative local failure rates at one, three and five year were $18\%,\;28\%\;and\;33\%$, respectively. In patients treated with subtotal resection and biopsy alone, local control rate was $76\%\;and\;33\%$, respectively. The actuarial observed survival rate at 5 years was $57\%$, and actuarial adjusted survival at 5 years was $72\%$. The difference between 5 year survival rates for patients treated with subtotal resection and biopsy alone was not statistically significant $(62\%\;vs\;30\%)$. Conclusion : We might conclude that postoperative radiation therapy was safe and effective treatment for patients with Stage III thymoma. Postoperative radiation therapy is recommended in cases where tumor margin is close or incomplete resection is accomplished.

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Adrenomedullin Deficiency Increases the Susceptibility of Liver Fibrosis Induced by CCl4 (아드레노메둘린 결핍은 사염화탄소로 유도된 간경화 감수성을 상승시킴)

  • Ji, Ae-Ri;Hwang, Meeyul;Kim, Ah-Young;Lee, Eun-Mi;Lee, Eun-Joo;Lee, Myeong-Mi;Sung, Soo-Eun;Kim, Sang-Hyeob;Park, Jin-Kyu;Jeong, Kyu-Shik
    • Journal of Life Science
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    • v.25 no.4
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    • pp.463-472
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    • 2015
  • Adrenomedullin (AM) is a peptide expressed in all body tissues, and its related receptors are increased in liver fibrosis. In this study, we evaluated the effect of AM deficiency on liver fibrogenesis induced by $CCl_4$ using AM heterozygous (HT) mice. The animals received a single injection of $CCl_4$ or olive oil for the acute experiment, and received $CCl_4$ or olive oil three times a week for 6 weeks for the chronic experiment. Fibrosis was accessed using histopathological analysis and the western blot. The AM HT mice showed mild pericentrilobular degeneration when compared to the AM wild type (WT) mice. In the acute experiment, there was no significant difference between the AM WT and AM HT mice. However, in the chronic experiment, the $CCl_4$-treated AM HT mice showed more severe liver fibrosis than that of the CCl4-treated AM WT mice. The AST and ALT levels of the AM HT $CCl_4$ group were higher than those of the AM WT CCl4 group. Additionally, the collagen deposition, $\alpha$- SMA protein and TGF-$\beta$ protein were increased in the AM HT $CCl_4$ group when compared to the AM WT $CCl_4$ group. The AM HT mice also exhibited severe lipid peroxidation through the GSH decrement. Taken together, our data suggest that AM deficiency increases the susceptibility to liver fibrosis induced by $CCl_4$, indicating a novel therapeutic target for patients with liver fibrosis.

Effects of Myostatin Prodomains on the Reproduction of Rotifer Brachionus rotundiformis (Myostatin prodomains이 rotifer 생활사에 미치는 영향)

  • Jo, Mi-Jin;Jin, Hyung-Joo
    • Journal of Life Science
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    • v.22 no.4
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    • pp.486-491
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    • 2012
  • Myostatin (MSTN), a member of the transforming growth factor (TGF)-beta family, is a potent negative regulator of skeletal muscle growth and maintenance. The MSTN prodomain inhibits MSTN biological activity. The rotifer Brachionus rotundiformis is an excellent primary live feed for fish larvae in aquaculture; however, it is not known whether the rotifer expresses MSTN and the MSTN prodomain along with its activity. The objective of this study was to examine the effects of recombinant MSTN prodomains. Individual cultures of the rotifer B. rotundiformis were carried out to determine the effect of recombinant MSTN prodomains (pMALc2x-poMSTNpro and pMALc2x-sMSTNpro) on the pre-reproductive phase, reproductive phase, post-reproductive phase, offspring, lifespan, fecundity, and male ratio. In addition, a population culture of the rotifer was performed to confirm the effects of pMALc2x-poMSTNpro and pMALc2x-sMSTNpro on population growth. The results showed that the rotifer treated with pMALc2x-pMSTNpro had a reduced pre-reproductive phase at higher concentrations (1, 2, and 4 ${\mu}g/ml$) compared to the non-treated control group. Moreover, the pMALc2xsMSTNpro treated rotifer effectively decreased the pre-reproductive phase at a lower concentration (0.25 ${\mu}g/ml$) compared to the pMALc2x-pMSTNpro treated and control group. Interestingly, pMALc2x-poMSTNpro and pMALc2x-sMSTNpro significantly increased the population of $B.$ $rotundiformis$.

Advance Understanding and New Treatment of Alopecia Areata (원형탈모증(alopecia areata)의 최신 이해와 치료)

  • Kang, Kyung-Hwa
    • Journal of Life Science
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    • v.26 no.11
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    • pp.1345-1354
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    • 2016
  • Alopecia areata (AA) is a common and tissue-specific autoimmune disease of hair follicle resulting in the loss of hair on the scalp and elsewhere on the body. Hair follicles is a unique organ because it has its own immune system and hormonal milieu and has a different immune state at each hair cycle stage. The collapses of anagen-dependent hair follicle immune privilege arise autoimmune attack, inducing ectopic MHC class I expression in the hair follicle epithelium and autoantigen presentation to autoreactive CD8+T cells, which results in AA. Clinical and experimental studies have pointed that psychological stress may also influence the hair follicle immune/hormone systems and contribute to the induction of AA. The key pathogenesis of AA is associated with immune privilege guardians (including ACTH, ${\alpha}-MSH$, and $TGF-{\beta}$), natural killer group 2D-positive (NKG2D+) cells (including NK and CD8+T cells), and stress hormones (including CRH and substance P). Effective treatments for AA are still demanded. One of the future targets of treatment will be the modification of hair follicle immune privilege including stress. Recent studies have reported that JAK inhibitors and immunomodulators used in other autoimmune disease, such as psoriasis, atopic dermatitis, and rheumatoid arthritis, Tregs, platelet-rich plasma therapy, statins, and prostaglandin anaolgues are effective for AA. Here the article reviews the recent understanding in the pathogenesis associated with perifollicular endocrine/immunology and new treatments of AA.

Wound Healing Effect of Bacterial Synthesized Cellulose on Full Thickness Skin Defect in the Rat (박테리아 유래 셀룰로오스가 백서의 창상치유에 미치는 영향)

  • Park, Sang-Uk;Lee, Byung-Kwon;Kim, Mi-Sun;Park, Kwan-Kyu;Sung, Woo-Jung;Kim, Hyun-Yeon;Kim, Peter Chan-Woo;Shim, Jeong-Su;Lee, Yong-Jig;Kim, Seong-Ho;Kim, In-Ho;Park, Dae-Hwan
    • Archives of Plastic Surgery
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    • v.38 no.6
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    • pp.733-739
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    • 2011
  • Purpose: Cellulose is a natural substance from plants or bacteria. It is known that bacterial synthesized cellulose has an effect of wound healing. The aim of this study is to show the effect of bacterial synthesized cellulose from citrus on wound healing. Methods: Three full-thickness skin defects were made on the back of Sprague-Dawley rats. Three wounds were treated by vaseline gauze (Group V), Algisite $M^{(R)}$ (Group A) and bacterial synthesized cellulose from citrus (Group C) was used for dressing on skin defect on rats. We analyzed the gross, histological and biochemistry finding. Results: Group C showed more decrease of wound size compared to Group V (33% versus 7.2%) after 14 days. The histologic findings revealed Group C and Group A preceed the process of wound healing rather than Group V (More rapid collagen deposition and neovascularization and reduced inflammation). Also, the expressions of vascular endothelial growth factor (VEGF) and transforming growth factor (TGF)-${\beta}1$ were increased in the Group C and Group A compared with the Group V in 7 days. VEGF and TGF-${\beta}1$ expression were decreased in the Group C and Group A in 14 days, however Group V was not decreased at 14 day because of delayed wound healing process. Conclusion: Bacterial synthesized cellulose from citrus affects wound healing by reducing the inflammatory stage. And stimulates wound contracture by the deposition of extracellular matrix, thus preventing the formation of chronic wounds.

Effects of Ketotifen on an Experimental Model of IgA Nephropathy (IgA 신증의 실험모델에서 케토티펜의 효과)

  • Do, Young-Sun;Soon, Eu-Jene;NamGoong, Mee-Kyung
    • Childhood Kidney Diseases
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    • v.13 no.2
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    • pp.153-160
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    • 2009
  • Purpose : The intestinal mucosal defect has been known as one of the pathogenicmechanisms of IgA nephropathy. Oral antigens usually induce the activation of Th2 cells and mast cells. These cells secrete cytokines IL-4, IL-5 and TGF-$\beta$, which increase IgA production. Although ketotifen (benzocycloheptathiophene) is an H1 antagonist and a mast cell membrane stabilizer, it could protect the gastrointestinal membrane through inhibiting the production of IL-4, IL-5, PGE2, and LTB4, and decreasing the activity of nitric oxide synthease. Therefore, we have investigated if ketotifen may protect the development of IgA nephropathy with an oral antigen. Methods : ICR mice were used as an animal model orally with Poliovax only [ketotifen (-)], the other group was given oral ketotifen [ketotifen (+)] in addition to Poliovax. Results : Mesangial IgA deposition developed in 11 out of the 18 mice in the ketotifen (-) group, while in three out of the nine mice in ketotifen (+) group. The mesangial change developed in 16 out of the 18 mice in the ketotifen (-) group, while in five out of the nine mice in the ketotifen (+) group. Serum IL-4 and IL-5 levels were not significantly lower in the latter group than in the former. Conclusion : According to the statistical results from the above, ketotifen therapy would be beneficial to reducing mesangial changes in IgA nephropathy.

Transcriptional Properties of the BMP, $TGF-\beta$, RTK, Wnt, Hh, Notch, and JAK/STAT Signaling Molecules in Mouse Embryonic Stem Cells

  • Rho Jeung-Yon;Bae Gab-Yong;Chae Jung-Il;Yu Kweon;Koo Deog-Bon;Lee Kyung-Kwang;Han Yong-Mahn
    • Reproductive and Developmental Biology
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    • v.30 no.2
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    • pp.143-156
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    • 2006
  • Major characteristics of embryonic stem cells (ESCs) are sustaining of sternness and pluripotency by self-renewal. In this report, transcriptional profiles of the molecules in the developmentally important signaling pathways including Wnt, BMP4, $TGF-\beta$, RTK, Hh, Notch, and JAK/STAT signaling pathways were investigated to understand the self-renewal of mouse ESCs (mESCs), J1 line, and compared with the NIH3T3 cell line and mouse embryonic fibroblast (MEF) cells as controls. In the Wnt signaling pathway, the expression of Wnt3 was seen widely in mESCs, suggesting that the ligand may be an important regulator for self-renewal in mESCs. In the Hh signaling pathway, the expression of Gli and N-myc were observed extensively in mESCs, whereas the expression levels of in a Shh was low, suggesting that intracellular molecules may be essential for the self-renewal of mESCs. IGF-I, IGF-II, IGF-IR and IGF-IIR of RTK signaling showed a lower expression in mESCs, these molecules related to embryo development may be restrained in mESCs. The expression levels of the Delta and HESS in Notch signaling were enriched in mESCs. The expression of the molecules related to BMP and JAK-STAT signaling pathways were similar or at a slightly lower level in mESCs compared to those in MEF and NIH3T3 cells. It is suggested that the observed differences in gene expression profiles among the signaling pathways may contribute to the self-renewal and differentiation of mESCs in a signaling-specific manner.

Isolation, Expression Pattern, Polymorphism and Association Analysis of Porcine TIAF1 Gene

  • Wang, Y.;Xiong, Y.Z.;Ren, Z.Q.;Zuo, B.;Lei, M.G.;Deng, C.Y.
    • Asian-Australasian Journal of Animal Sciences
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    • v.22 no.3
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    • pp.313-318
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    • 2009
  • TIAF1 is a TGF-${\beta}$1-induced anti-apoptotic factor that plays a critical role in blocking TNF (tumor necrosis factor) cytotoxicity in mouse fibroblasts and participates in TGF-${\beta}$-mediated growth regulation. In this study, we obtained the full-length cDNA sequence of the porcine TIAF1 gene. Real-time PCR further revealed that the TIAF1 gene was expressed at the highest level in liver and kidney with prominent expressions detected in uterus, and lower levels detected in heart, spleen, lung, stomach, small intestine, skeletal muscle and fat of Large White pigs. Sequence analysis indicated that a 6 base-pair deletion mutation existed in the exon of the TIAF1 gene between Meishan and Large White pigs. This mutation induced deletion of Gln and Val amino acids. PCR-RFLP was used to detect the polymorphism in 394 pigs of a "Large White${\times}$Meishan" $F_{2}$ resource population and four purebred pig populations. The frequencies of the A allele (with a 6 bp deletion) were dominant in Chinese Meishan and Bamei pigs, and the frequencies of the B allele (no 6 bp deletion) were dominant in Large White and Landrace pigs. Association analyses revealed that the deletion mutation had highly significant associations (p<0.01) with meat marbling score of the thorax-waist longissimus dorsi (LD) muscle (MM1) and intramuscular fat percentage (IMF), and significant associations (p<0.05) with carcass length (CL). The results presented here supply evidence that the 6 bp deletion mutation in the TIAF1 gene affects porcine meat quality and provides useful information for further porcine breeding.

Expression of Fas/FasL in CD8+ T and CD3+ Foxp3+ Treg Cells - Relationship with Apoptosis of Circulating CD8+ T Cells in Hepatocellular Carcinoma Patients

  • Guo, Cun-Li;Yang, Xiu-Hua;Cheng, Wen;Xu, Yi;Li, Jie-Bing;Sun, Yi-Xin;Bi, Yu-Mei;Zhang, Lei;Wang, Qiu-Cheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.6
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    • pp.2613-2618
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    • 2014
  • Aims: Dysfunction of the host immune system in cancer patients can be due to a number of factors, including lymphocyte apoptosis. Several studies showed that $Foxp3^+T$ cells take part in inducing this process by expressing FasL in tumor patients. However, the relationship between apoptosis, $CD8^+T$ cells and $Foxp3^+T$ cells in HCC patients is still unclear. The present study was designed to investigate the correlation between apoptosis levels and Fas/FasL expression in $CD8^+T$ lymphocytes and $Foxp3^+T$ cells in patients with HCC. Methods: $CD8^+T$ cells and $CD3^+Foxp3^+T$ cells were tested from peripheral blood of HCC patients and normal controls and subjected to multicolor flow cytometry. The expression of an apoptosis marker (annexin V) and the death receptor Fas in $CD8^+T$ cells and FasL in $CD3^+Foxp3^+T$ cells were evaluated. Serum TGF-${\beta}1$ levels in patients with HCC were measured by enzyme-linked immunosorbent assay. The relationship between apoptosis and Fas expression, as well as FasL expression in $CD3^+Foxp3^+T$ cells was then evaluated. Results: The frequency of $CD8^+T$ cells binding annexin V and Fas expression in $CD8^+T$ cells, were all higher in HCC patients than normal controls and the proportion of apoptotic $CD8^+T$ cells correlated with their Fas expression. Serum TGF-${\beta}1$ levels correlated inversely with $CD3^+Foxp3^+T$ cells. Conclusions: Fas/FasL interactions might lead to excessive turnover of $CD8^+T$ cells and reduce anti-tumor immune responses in patients with HCC. Further investigations of apoptosis induction in $Fas^+CD8^+T$ cells in vitro are required.

Ganoderma lucidum Pharmacopuncture for the Treatment of Acute Gastric Ulcers in Rats

  • Park, Jae-Heung;Jang, Kyung-Jun;Kim, Cheol-Hong;Lee, Yoo-Hwan;Lee, Soo-Jung;Kim, Bum-Hoi;Yoon, Hyun-Min
    • Journal of Pharmacopuncture
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    • v.17 no.3
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    • pp.40-49
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    • 2014
  • Objectives: The gastric ulcer is a common disorder of the stomach and duodenum. The basic physiopathology of a gastric ulcer results from an imbalance between some endogenous aggressive and cytoprotective factors. This study examined whether Ganoderma lucidum pharmacopuncture (GLP) would provide protection against acute gastric ulcers in rats. Methods: Sprague-Dawley rats were divided randomly into 4 groups of 8 rats each: normal, control, normal saline (NP) and GLP groups. The experimental acute gastric ulcer was induced by using an EtOH/HCl solution and the normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated once with injections of saline and GLP, respectively. Two local acupoints were used: CV12 (中脘) which is the alarm point of the Stomach Meridian, and ST36 (足三里), which is the sea point of the Stomach Meridian. The stomachs from the rats in each group were collected and analyzed for gross appearance and histology. Also, immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$ was performed. Results: Histological observations of the gastric lesions in the control group showed comparatively extensive damage of the gastric mucosa and necrotic lesions had penetrated deeply into the mucosa. The lesions were long, hemorrhagic, and confined to the glandular portions. The lesions were measured microscopically by using the clear depth of penetration into the gastric mucosal surface. The length and the width of the ulcer were measured and the inhibition percentage was calculated. Wound healing of the acute gastric ulcer was promoted by using GLP, and significant alterations of indices in gastric mucosa were observed. Such protection was shown by gross appearance, histology and immunohistochemistry staining for BAX, Bcl-2 and TGF-${\beta}1$. Conclusion: These results suggest that GLP administered at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol-induced acute gastric ulcer.