• Title/Summary/Keyword: TGF-{\beta}

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TGF-β-activated Kinase-1: A Potential Prognostic Marker for Clear Cell Renal Cell Carcinoma

  • Wei, Can;Lai, Yong-Qing;Li, Xian-Xin;Ye, Jiong-Xian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.1
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    • pp.315-320
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    • 2013
  • Background: TGF-${\beta}$-activated kinase-1 (TAK1) has been found to be over-expressed in a variety of solid malignancies and related to tumor growth. The aim of this study was to evaluate the expression level of TAK1 in clear cell renal cell carcinoma (ccRCC) and assess its value as a novel prognostic marker. Methods: TAK1 mRNA was assessed in 51 paired ccRCC tissues and adjacent normal tissues (ADTs) by real-time PCR. Tissue TAK1 protein was also assessed in 91 ADTs and 177 samples of ccRCC immunohistochemically for evaluation of relationships with clinical characteristics. Results: RT-PCR showed that TAK1 RNA level was significantly higher in ccRCC tissues than in the paired ADTs and immunohistochemistry confirmed higher expression of TAK1 protein in ccRCC samples compared with ADTs. TAK1 protein expression in 177 ccRCC samples was significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, but not age and gender. Patients with low TAK1 levels had a better survival outcome. TAK1 expression and N stage were independent prognosis factors for the overall survival of ccRCC patients. Conclusions: Overexpression of TAK1 predicts a poor prognosis in patients with ccRCC, so that TAK1 may serve as a novel prognostic marker.

Effects of Ganoderma Lucidum Extract Ethanol Extract and Microneedle Therapy System on Hair Growth in an Alopecia Model of C57BL/6N Mice (C57BL/6N 마우스 탈모모델에서 미세다륜침과 영지추출물이 모발성장에 미치는 영향)

  • Ju, Bong Hyun;Yu, Sun Ae;Kang, Kyung Hwa;Lee, Seung Yoen
    • The Journal of Pediatrics of Korean Medicine
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    • v.28 no.2
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    • pp.72-87
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    • 2014
  • Objectives This study was carried out to investigate the effect of Ganoderma lucidum extract (GLE) and microneedle therapy system (MTS) on hair growth in an alopecia model of C57BL/6N mice. Methods Five-week old mice were depilated and separated in 4 groups ; CON (50% EtOH), MXD (5% Minoxidil), MTS and GLE + MTS. The treatments were applied twice a week for 3 weeks. The hair growth was determined photographically, the hair density, thickness and length were identified by Folliscope and the weights of body and organs were measured. In dorsal skin tissue, the expression of hair growth-related gene and protein was analyzed by RT - PCR or Western blot. In addition, the hair follicles in the dermis were observed by H&E staining. Results The promotion of hair growth was observed in GLE + MTS and MTS compared to CON. The hair density, thickness and length were also improved in GLE + MTS and MTS compared to CON. The mRNA expression of TGF-${\alpha}$, TGF-${\beta}1$, IGF-1, PRL and PL and the protein expression of VEGF and IGF-1 were increased in GLE + MTS and MTS compared to CON. The hair follicles and hair root growth were improved in GLE + MTS and MTS compared to CON. In the above results, GLE + MTS were more effective than MTS. Conclusions These results suggest that GLE and MTS has a hair growth activity and can be useful for the treatment of alopecia.

Cilostazol ameliorates diabetic nephropathy by inhibiting high-glucose-induced apoptosis

  • Chian, Chien-Wen;Lee, Yung-Shu;Lee, Yi-Ju;Chen, Ya-Hui;Wang, Chi-Ping;Lee, Wen-Chin;Lee, Huei-Jane
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.5
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    • pp.403-412
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    • 2020
  • Diabetic nephropathy (DN) is a hyperglycemia-induced progressive development of renal insufficiency. Excessive glucose can increase mitochondrial reactive oxygen species (ROS) and induce cell damage, causing mitochondrial dysfunction. Our previous study indicated that cilostazol (CTZ) can reduce ROS levels and decelerate DN progression in streptozotocin (STZ)-induced type 1 diabetes. This study investigated the potential mechanisms of CTZ in rats with DN and in high glucose-treated mesangial cells. Male Sprague-Dawley rats were fed 5 mg/kg/day of CTZ after developing STZ-induced diabetes mellitus. Electron microscopy revealed that CTZ reduced the thickness of the glomerular basement membrane and improved mitochondrial morphology in mesangial cells of diabetic kidney. CTZ treatment reduced excessive kidney mitochondrial DNA copy numbers induced by hyperglycemia and interacted with the intrinsic pathway for regulating cell apoptosis as an antiapoptotic mechanism. In high-glucose-treated mesangial cells, CTZ reduced ROS production, altered the apoptotic status, and down-regulated transforming growth factor beta (TGF-β) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB). Base on the results of our previous and current studies, CTZ deceleration of hyperglycemia-induced DN is attributable to ROS reduction and thereby maintenance of the mitochondrial function and reduction in TGF-β and NF-κB levels.

Glucosamine Hydrochloride and N-Acetylglucosamine Influence the Response of Bovine Chondrocytes to TGF-β3 and IGF in Monolayer and Three-Dimensional Tissue Culture

  • Pizzolatti, Andre Luiz A.;Gaudig, Florian;Seitz, Daniel;Roesler, Carlos R.M.;Salmoria, Gean Vitor
    • Tissue Engineering and Regenerative Medicine
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    • v.15 no.6
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    • pp.781-791
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    • 2018
  • BACKGROUND: Glucosamine hydrochloride (GlcN HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. METHOD: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) $TGF-{\beta}$ ($5ng\;mL^{-1}$) and IGF-I ($10ng\;mL^{-1}$), GlcN HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. RESULTS: The two glucosamines showed opposite effects in monolayer culture: GlcN HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. CONCLUSION: GlcN HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.

Novel Effect of Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1) on Hair Follicle Cells Proliferation and Hair Growth

  • Hae Chan Ha;Dan Zhou;Zhicheng Fu;Moon Jung Back;Ji Min Jang;In Chul Shin;Dae Kyong Kim
    • Biomolecules & Therapeutics
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    • v.31 no.5
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    • pp.550-558
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    • 2023
  • Hair loss is a common condition that can have a negative impact on an individual's quality of life. The severe side effects and the low efficacy of current hair loss medications create unmet needs in the field of hair loss treatment. Hyaluronan and Proteoglycan Link Protein 1 (HAPLN1), one of the components of the extracellular matrix, has been shown to play a role in maintaining its integrity. HAPLN1 was examined for its ability to impact hair growth with less side effects than existing hair loss treatments. HAPLN1 was predominantly expressed in the anagen phase in three stages of the hair growth cycle in mice and promotes the proliferation of human hair matrix cells. Also, recombinant human HAPLN1 (rhHAPLN1) was shown to selectively increase the levels of transforming growth factor-β receptor II in human hair matrix cells. Furthermore, we observed concomitant activation of the ERK1/2 signaling pathway following treatment with rhHAPLN1. Our results indicate that rhHAPLN1 elicits its cell proliferation effect via the TGF-β2-induced ERK1/2 pathway. The prompt entering of the hair follicles into the anagen phase was observed in the rhHAPLN1-treated group, compared to the vehicle-treated group. Insights into the mechanism underlying such hair growth effects of HAPLN1 will provide a novel potential strategy for treating hair loss with much lower side effects than the current treatments.

The roles of growth factors and hormones in the regulation of muscle satellite cells for cultured meat production

  • Syed Sayeed Ahmad;Hee Jin Chun;Khurshid Ahmad;Sibhghatulla Shaikh;Jeong Ho Lim;Shahid Ali;Sung Soo Han;Sun Jin Hur;Jung Hoon Sohn;Eun Ju Lee;Inho Choi
    • Journal of Animal Science and Technology
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    • v.65 no.1
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    • pp.16-31
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    • 2023
  • Cultured meat is a potential sustainable food generated by the in vitro myogenesis of muscle satellite (stem) cells (MSCs). The self-renewal and differentiation properties of MSCs are of primary interest for cultured meat production. MSC proliferation and differentiation are influenced by a variety of growth factors such as insulin-like growth factors (IGF-1 and IGF-2), transforming growth factor beta (TGF-β), fibroblast growth factors (FGF-2 and FGF-21), platelet-derived growth factor (PDGF) and hepatocyte growth factor (HGF) and by hormones like insulin, testosterone, glucocorticoids, and thyroid hormones. In this review, we investigated the roles of growth factors and hormones during cultured meat production because these factors provide signals for MSC growth and structural stability. The aim of this article is to provide the important idea about different growth factors such as FGF (enhance the cell proliferation and differentiation), IGF-1 (increase the number of myoblasts), PDGF (myoblast proliferation), TGF-β1 (muscle repair) and hormones such as insulin (cell survival and growth), testosterone (muscle fiber size), dexamethasone (myoblast proliferation and differentiation), and thyroid hormones (amount and diameter of muscle fibers and determine the usual pattern of fiber distributions) as media components during myogenesis for cultured meat production.

The Experimental Study about Antioxidant Activities of Alismatis Rhizoma Herbal Acupuncture (택사약침(澤瀉藥鍼)의 항산화효과(抗酸化效果)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Lee, Jong-moo;Lee, Byung-ryul
    • Journal of Acupuncture Research
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    • v.20 no.1
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    • pp.159-176
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    • 2003
  • Objective : The purpose of this study is to investigate the antioxidant activities of Alismatis Rhizoma herbal acupuncture by experimental methods. Methods : For this purpose, first, we put an emphasis in the control of enzymes of the antioxidant system in various changes inside the cell; these changes caused by the proliferation or the activation of the cell which were brought about by the handling of PMA and $TNF-{\alpha}$ into the THP-1 monocyte cell of the body each other. After that, we caused the acute oxidant symptom by the injection of AAPH into the mouse' abdominal cavity, and then applied the herbal acupuncture on S36 point(足三里), and finally, we measured the change of blood ingredient and the resistance against the activated oxygen of the red blood cell membrane, MDA, SOD, and catalase. Results : In vitro the revelation of $IL-1{\beta}$, IL-8, $TNF-{\alpha}$, NOS II and IL-6 were decreased and the revelation of IL-10, $TGF-{\beta}$, GM-CSFIL-12, GM-CSF and SOD were increased. The DNA-binding of $NF-{\kappa}B$ and AP-1 were activated and the formation of ROS in the THP-1 cell line was decreased. In vivo $IL-1{\beta}$ among producing the cytokine inside the plasma was meaningfully dwindled and the $INF-{\gamma}$ was meaningfully increased. The resistance of red blood cell membrane against the activated oxygen was meaningfully increased and the MDA formation was meaningfully dwindled, In the activation of hepatic antioxidase, the SOD was meaningfully increased. Conclusion : Alismatis Rhizoma herbal acupuncture by experimental methods has effected on the antioxidant activities.

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Screening and Characterization of Lactobacillus casei MCL Strain Exhibiting Immunomodulation Activity

  • Choi, Jae-Kyoung;Lim, Yea-Seul;Kim, Hee-Jin;Hong, Yeong-Ho;Ryu, Buom-Yong;Kim, Geun-Bae
    • Food Science of Animal Resources
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    • v.32 no.5
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    • pp.635-643
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    • 2012
  • As an appraisal for the application of a new starter culture, more than 200 lactic acid bacteria strains were isolated from raw milk and healthy human feces. The strains showing excellent growth and acid production ability in 10% skim milk media were selected and identified as Lactobacillus casei based on the results of their API carbohydrate fermentation patterns, as well as 16S rDNA sequence analysis. To assess the effect of L. casei strains on irritable bowel disease (IBD), the inhibitory effect of the selected strains against the nitric oxide (NO) production of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells was measured. Among the tested L. casei strains, L. casei MCL was observed to have the greatest NO inhibitory activity. Additionally, L. casei MCL was found to inhibit mRNA expression of pro-inflammatory cytokines (interleukin-$1{\beta}$, IL-6, TNF-${\alpha}$), as well as cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) involved in pathophysiologic processes such as inflammation. The mRNA expression of anti-inflammatory cytokines, including IL-10 and transforming growth factor-$1{\beta}$ (TGF-${\beta}$) of L. casei MCL, was confirmed using quantitative real-time PCR. In conclusion, L. casei MCL showed decreases in the expression of pro-inflammatory cytokines and up-regulated expression of the anti-inflammatory cytokine.

Reduction of Inflammation and Enhancement of Motility after Pancreatic Islet Derived Stem Cell Transplantation Following Spinal Cord Injury

  • Karaoz, Erdal;Tepekoy, Filiz;Yilmaz, Irem;Subasi, Cansu;Kabatas, Serdar
    • Journal of Korean Neurosurgical Society
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    • v.62 no.2
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    • pp.153-165
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    • 2019
  • Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

THE EFFECTS OF TGF-$\beta$1 ON THE BONE REGENERATION IN GUINEA PIG MANDIBLE (형질변형성장인자가 손상골 재생능에 미치는 영향에 관한 실험적 연구)

  • Lee Byung-Do;Hwang Eui-Hwan;Lee Sang-Rae;Hong Jung-Pyo
    • Journal of Korean Academy of Oral and Maxillofacial Radiology
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    • v.25 no.2
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    • pp.423-435
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    • 1995
  • The purpose of this study was to observe the effect of TGF-βl, which promotes differentiation and proliferation of osteoblasts, on bone regeneration. Experimental bone defects that measured 3 mm in diameter were created on the mandibles of guinea pig by removal of bone with the use of trephine burs. In one side of mandibular body, the experimental groups, bone defects were grafted with Biogran(Orthovita Co., U.S.A) and TGF-β1(R&D System Co., U.SA). In the remaining side of the mandiblar body, the control groups, bone defects were grafted with only Biogran. Guinea pigs in the control and experimental groups were serially terminated by fours on the 3 days, the 1 week, the 2 weeks, the 3 weeks, and the 4 weeks after experiment, and both sides of the mandibular bodies were removed and fixed with 10% neutral formalin. They were decalcified and embedded in paraffin as using the usual method. The specimen sectioned and stained with hematoxylin and eosin. Also, they were radiographed with a soft X -ray apparatus. The obtained results were as follows; 1. Hemorrhagic condition, observed in the granulation tissues, disappeared on the 1 week after experiment in both groups, and more prominent in the experimental group. The granulation tissues of the experimental group had larger number of cells than those of the control group. 2. Osteoblastic differentiation in the margin of grafted material and adjacent bone was observed on the 1 week after experiment in both groups. Also, bone formation was observed in immature form on the 1 week after experiment. and more prominent in the experimental group. 3. In the polarizing microscopic examination, bone matrix was very loose on the 1 week after experiment, but increase in density with time, and more prominent in the experimental group. 4. In the microradiographic examination, newly formed bone was observed in the experimental group on the 2 weeks after experiment, and this was observed earlier than in the control group. Newly formed bone was increased with time and defected area was markedly decreased on the 4 weeks after experiment.

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