• Title/Summary/Keyword: IGF1

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Angiogenesis in newly regenerated bone by secretomes of human mesenchymal stem cells

  • Katagiri, Wataru;Kawai, Takamasa;Osugi, Masashi;Sugimura-Wakayama, Yukiko;Sakaguchi, Kohei;Kojima, Taku;Kobayashi, Tadaharu
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.39
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    • pp.8.1-8.8
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    • 2017
  • Background: For an effective bone graft for reconstruction of the maxillofacial region, an adequate vascular network will be required to supply blood, osteoprogenitor cells, and growth factors. We previously reported that the secretomes of bone marrow-derived mesenchymal stem cells (MSC-CM) contain numerous growth factors such as insulin-like growth factor (IGF)-1, transforming growth factor $(TGF)-{\beta}1$, and vascular endothelial growth factor (VEGF), which can affect the cellular characteristics and behavior of regenerating bone cells. We hypothesized that angiogenesis is an important step for bone regeneration, and VEGF is one of the crucial factors in MSC-CM that would enhance its osteogenic potential. In the present study, we focused on VEGF in MSC-CM and evaluated the angiogenic and osteogenic potentials of MSC-CM for bone regeneration. Methods: Cytokines in MSC-CM were measured by enzyme-linked immunosorbent assay (ELISA). Human umbilical vein endothelial cells (HUVECs) were cultured with MSC-CM or MSC-CM with anti-VEGF antibody (MSC-CM + anti-VEGF) for neutralization, and tube formation was evaluated. For the evaluation of bone and blood vessel formation with micro-computed tomography (micro-CT) and for the histological and immunohistochemical analyses, a rat calvarial bone defect model was used. Results: The concentrations of IGF-1, VEGF, and $TGF-{\beta}1$ in MSC-CM were $1515.6{\pm}211.8pg/mL$, $465.8{\pm}108.8pg/mL$, and $339.8{\pm}14.4pg/mL$, respectively. Tube formation of HUVECs, bone formation, and blood vessel formation were increased in the MSC-CM group but decreased in the MSC-CM + anti-VEGF group. Histological findings suggested that new bone formation in the entire defect was observed in the MSC-CM group although it was decreased in the MSC-CM + anti-VEGF group. Immunohistochemistry indicated that angiogenesis and migration of endogenous stem cells were much more abundant in the MSC-CM group than in the MSC-CM + anti-VEGF group. Conclusions: VEGF is considered a crucial factor in MSC-CM, and MSC-CM is proposed to be an adequate therapeutic agent for bone regeneration with angiogenesis.

Target Proteins Involved in Aging Mechanism as an Aging Molecular Marker (노화 분자마커로서 노화기전에 관여하는 타켓 단백질)

  • Kim, Moon-Moo
    • Journal of Life Science
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    • v.26 no.8
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    • pp.983-989
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    • 2016
  • All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

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.

Platycarya strobilacea S. et Z. Extract Has a High Antioxidant Capacity and Exhibits Hair Growth-promoting Effects in Male C57BL/6 Mice

  • Kim, Eun Jin;Choi, Joo Yeon;Park, Byung Cheol;Lee, Bog-Hieu
    • Preventive Nutrition and Food Science
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    • v.19 no.3
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    • pp.136-144
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    • 2014
  • This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. This study was conducted to evaluate the effects of Platycarya strobilacea S. et Z. (PSE) extract on mouse hair growth and to determine the mechanism of action of PSE. PSE was purchased and its antioxidant activities, such as electron donating ability, total polyphenol content, and flavonoid content were tested. Toxicity during topical treatment was determined by the CCK-8 assay, a cell viability test. Fifteen 4-week-old male C57BL/6 mice were assigned to receive one of three treatments: dimethyl sulfoxide (negative control), minoxidil (positive control) or PSE. Test materials were topically applied to the shaved dorsal skin of each mouse daily for 3 weeks. After 21 days, we observed skin tissue hair follicle morphology and length, mast cell number, and stem cell factor (SCF) expression using hematoxylin and eosin (H&E), toluidine blue, and immunohistochemical staining, respectively. Furthermore, the expression of cytokines involved in hair growth [i.e., insulin-like growth factor (IGF)-1, keratinocyte growth factor (KGF), and transforming growth factor (TGF)-${\beta}1$] was determined by PCR. PSE was found to have very high antioxidant activity. The cell viability rate of PSE-treated mice was markedly higher than that of mice in the control group. We also observed an increase in hair follicle length, strong SCF staining, and a decrease in mast cell number in the PSE group. In addition, PSE-treated mice had higher IGF-1 and KGF expression and lower TGF-${\beta}1$ expression than mice in the minoxidil-treated group. These results suggest that topical application of PSE promotes hair growth by intensifying SCF, suppressing mast cell production, and increasing hair growth-promoting cytokine expression.

Effect of Dietary Glycoprotein Extracted from Porphyra yezoensis on Growth Performance and Resistance against Edwardsiella tarda in Olive Flounder Paralichthys olivaceus Juveniles (김(Porphyra yezoensis)에서 추출한 당단백질의 사료내 첨가가 넙치(Paralichthys olivaceus) 치어 성장 및 Edwardsiella tarda 저항성에 미치는 영향)

  • Kim, Kang-Woong;Choi, Jeong-Wook;Kim, Kyoung-Duck;Han, Hyon-Sob;An, Cheul-Min;Lee, Bong-Joo;Choi, Youn Hee;Nam, Taek Jeong
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.45 no.6
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    • pp.606-611
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    • 2012
  • This study examined the effects of dietary glycoprotein extracted from Porphyra yezoensi on growth performance and resistance against the pathogenic bacteria Edwardsiella tarda in olive flounder. A porphyra-originated glycoprotein (P) was extracted using sequential processes of water and ethanol treatment. P extracts were added to a fish-meal-based diet at concentrations of 0.0, 0.5, and 1.0% (designated as Con, $P_{0.5}$, and $P_{1.0}$, respectively). Fish were fed one of the three experimental diets for 10 weeks. All fish groups exhibited over 96.7% survival during the experimental period. Results indicated that the fish fed diets containing P showed an increase in growth performance, including enhanced weight gain, specific growth rate, and feed efficiency. An increase in insulin-like growth factor (IGF-1) was observed in the fish fed the $P_{1.0}$ diet, as compared to those fed Con. At the end of the 10-week feeding trial, all fish were infected with E. tarda, and accumulated mortality was monitored for 8 days. Fish fed the Con diet exhibited increasing mortality from day 3 to the end of the challenge test, whereas the mortality of P-fed fish ceased at day 5. We suggest that supplementation with P-originated glycoprotein in aquafeed may increase growth performance and resistance against pathogenic bacteria in olive flounder juveniles.

Effect of Wild Plant Extracts Based on Korea Traditional Prescription on Endurance Exercise Performance during Calorie Restriction Period (초저열량식이로 인한 체력 저하에서 산야초추출물의 지구력 증진 효과)

  • Kim, Joong-Hark;Kim, Hwa-Young;Chang, Hey-Eun;Chung, Ji-Sang;Hwang, Sung-Joo;Park, Mi-Hyoun;Hong, Seong-Gil
    • Korean Journal of Food Science and Technology
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    • v.38 no.1
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    • pp.147-151
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    • 2006
  • Effects of wild plant extract (Lak) based on Korea traditional prescription on maximal exercise performance and endurance were evaluated using calorie-restriction animal model. In acute forced swimming test with 10% body weight attached to tail, dietary Lak supplementation increased exercise performance endurance by increasing concentrations of ATP and insulin-like growth factor-1 (IGF-1) under calorie-restriction condition, and decrement of blood lactic acid concentration and increment of muscle ATP content were observed. These results suggest Lak is very effective for decreasing side-effects of obesity therapy using very low calorie diet.

Collagen Extraction Using Supercritical CO2 from Animal-Derived Waste Tissue (동물 유래 폐지방으로부터 초임계 CO2를 이용한 콜라겐 추출)

  • No, Seong-Rae;Shin, Yong-Woo;You, Seong-sik
    • Korean Chemical Engineering Research
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    • v.60 no.3
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    • pp.386-391
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    • 2022
  • This study is about a technique for obtaining collagen by extracting fat by treating collagen-containing liposuction effluent in the presence of supercritical fluid. Using a supercritical solvent, a collagen extract could be obtained from animal-derived fat in a short time (about 6 hours), and about 2-3% of collagen by mass compared to the raw material could be obtained. The presence of collagen in the extract obtained by supercritical extraction was confirmed by SDS-PAGE, and it was confirmed that it was type 1 collagen having a relatively large molecular weight. In addition, the growth factors of IGF-1, bFGF, VEGF and NGF were analyzed to find out which growth factors were present in the collagen obtained by supercritical extraction, and it was found that these growth factors were contained in the extract. There was no significant difference in DNA content per mg of sample before and after supercritical treatment. Further in-depth studies are likely to be needed on decellularization technology using the supercritical process. In conclusion, the extracellular matrix obtained through the solvent extraction process using a supercritical fluid contains growth factors above a certain amount even after decellularization and removal of fat, so that it was found that not only biocompatibility is greatly increased, but also tissue regeneration can be rapidly induced.

Intensive Proteomic Approach to Identify Secreted Peptides/Proteins from 3T3-L1 Adipocytes using Gel Electrophoresis and Liquid Chromatograph Separation Methods (젤 전기영동 및 액체 크로마토그래피 분리 방법을 이용하여 지방 세포로부터 분비되는 단백질들에 대한 프로테오믹스 연구 방법)

  • Hwang, Hyun-Ho;Baek, Moon-Chang
    • YAKHAK HOEJI
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    • v.55 no.3
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    • pp.203-212
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    • 2011
  • Adipocytes have been known to secrete a number of important proteins called adipokines with roles in energy metabolism, reproduction, cardiovascular function and immunity. In this study we have attempted to identify intensively secretory proteins from 3T3-L1 adipocytes. 3T3-L1 preadipocytes were differentiated into mature adipocytes and then the cells were left in serum-free medium. The supernatant was filtrated and dialyzed. Lyophilized secretome was fractionated by two different methods, 1-D SDS PAGE and RP-FPLC. The tryptic peptides from the gel slices and the FPLC fractions were analyzed by nanoLC/ESI-MS/MS. We identified a total of 303 identical proteins from two methods, 251 proteins from 1-D gel and 184 proteins from RP-FPLC. 86 of them were listed as a secretory protein Finally, we identified many known or unknown secreted proteins existed in the low level including adiponectin, angiotensinogen, bone morphogenetic protein-1 (BMP-1), macrophage migration inhibitory factor (MIF), insulin like growth factor-II (IGF-II), interleukin-6 (IL-6), follistatin-related protein-1, minecan, and resistin. The existence of some of secreted proteins has been confirmed in RNA level. This proteomic experiment is useful for the intensive screening of secretory proteins in many kinds of other cells.

Autophagy-Is it a preferred route for lifespan extension?

  • Dwivedi, Meenakshi;Ahnn, Joo-Hong
    • BMB Reports
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    • v.42 no.2
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    • pp.65-71
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    • 2009
  • Autophagy, which is a process of self eating, has gained interest in the past decade due to its both beneficial and controversial roles in various biological phenomena. The discovery of autophagy genes (ATG) in yeast has led to focused research designed to elucidate the mechanism and regulation of this process. The role of autophagy in a variety of biological phenomena, including human disease, is still the subject of debate. However, recent findings suggest that autophagy is a highly regulated process with both beneficial and negative effects. Indeed, studies conducted using various model organisms have demonstrated that increased autophagy leads to an extended lifespan. Despite these findings, it is still unknown if all pathways leading to extended lifespan converge at the process of autophagy or not. Here, an overview of modern developments related to the process of autophagy, its regulation and the molecular machinery involved is presented. In addition, this review focuses on one of the beneficial aspects of autophagy, its role in lifespan regulation.

Genomic approaches for the understanding of aging in model organisms

  • Park, Sang-Kyu
    • BMB Reports
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    • v.44 no.5
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    • pp.291-297
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    • 2011
  • Aging is one of the most complicated biological processes in all species. A number of different model organisms from yeast to monkeys have been studied to understand the aging process. Until recently, many different age-related genes and age-regulating cellular pathways, such as insulin/IGF-1-like signal, mitochondrial dysfunction, Sir2 pathway, have been identified through classical genetic studies. Parallel to genetic approaches, genome-wide approaches have provided valuable insights for the understanding of molecular mechanisms occurring during aging. Gene expression profiling analysis can measure the transcriptional alteration of multiple genes in a genome simultaneously and is widely used to elucidate the mechanisms of complex biological pathways. Here, current global gene expression profiling studies on normal aging and age-related genetic/environmental interventions in widely-used model organisms are briefly reviewed.