• Title/Summary/Keyword: Loss-differentiation

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The Relationship between the Expression of Melanoma Differentiation-Associated Gene-7/Interleukin-24 (MDA-7/IL-24) and Clinicopathological Features in Colorectal Adenocarcinomas

  • Seo, Boram;Hong, Young Seob;Youngmin, Youngmin;Roh, Mee Sook
    • Biomedical Science Letters
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    • v.18 no.4
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    • pp.413-419
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    • 2012
  • The melanoma differentiation-associated gene-7 (MDA-7) protein, also known as interleukin-24 (IL-24), is a novel candidate of tumor suppressor that can induce apoptosis experimentally in a variety of human malignant cells. However, there have been few studies about its role in colorectal cancer. We performed immunohistochemical detection of MDA-7/IL-24 in 399 tissue samples from primary colorectal adenocarcinoma patients using a tissue microarray. Western blotting was then done to confirm the immunohistochemical observations. MDA-7/IL-24 immunoreactivity was observed in 116 (29.1%) of the 399 colorectal adenocarcinoma cases. Analysis of the MDA-7/IL-24 expression by Western blotting confirmed the immunohistochemical results. The tumors with a negative MDA-7/IL-24 expression more frequently showed poor differentiation (P=0004), lymph node metastasis (P=0.001), deep invasion (P=0.008) and high stage (P=0.001). A subset of colorectal adenocarcinoma revealed a decreased expression of MDA-7/IL-24, and this was associated with progressive pathologic features. These findings suggest that loss of MDA-7/IL-24 expression may play a role in tumor growth and progression of colorectal adenocarcinomas.

A Morphologic Study on the Differentiation of Chicken Embryo Lens (계배(鷄胚) lens의 분화(分化)에 관(關)한 형태학적(形態學的) 연구(硏究))

  • Deung, Young-Kun;Kim, Wan-Jong
    • Applied Microscopy
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    • v.22 no.1
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    • pp.103-112
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    • 1992
  • Embryonic and postembryonic chicken lenses have been analyzed morphologically to investigate the differentiation of the lens fibers by light and electron microscopes. Morphogenesis of the chick lens was initiated as lens epithelial cells were proliferated and proceeded to elongate the cells characteristically at posterior side, by which the disintegrations of nuclei were accompanied during the early developmental stages. Primary and secondary lens fibers were identified at the late developmental stages, while interconnections between neigh-boring cells well developed and denucleation commenced. On day of hatching, the chicken lens fibers contained few cell organelles within the cytoplasm and showed the homogeneity of cytoplasmic appearance. On day 10 of hatching, the lens were fully differentiated; fiber cells, in which most cell organelles except polysomes were disappeared, showed a slender and elongated prismatic shape. At that stage gap junctions were particularly developed or cytoplasmic ridges are closely interlocked between adjoining cells. In conclusion, differentiation of chick lens involves the division of epithelial cells, the elongation into fiber cells, the loss of cell organelles and the increase of gap junction.

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Anti-osteoporotic Effects of Unripe Fructus of Rubus coreanus Miquel in Osteoblastic and Osteoclastic Cells

  • Kim, Hyo Jin;Sim, Dong-Soo;Sohn, Eun-Hwa
    • Korean Journal of Plant Resources
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    • v.27 no.6
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    • pp.593-600
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    • 2014
  • Osteoporosis is a progressive bone disease characterized by low bone mass which is caused by disturbance in the balance between the activities of osteoblasts and osteoclasts. Postmenopausal osteoporosis is one of the most common disorders in women after menopause, which is linked to an estrogen deficiency and characterized by an excessive loss of trabecular bone. Rubus coreanus has been used for their various pharmacological properties in Asia as a traditional medicine. To investigate the effect of unripe fruits of R. coreanus 30% ethanol extract (RCE) on osteoblast-like cells (MG63) differentiation, we examined the effects of RCE on in vitro osteoblastic differentiation markers, alkaline phosphatase (ALP) activity and receptor activator of nuclear factor ${\kappa}$-B ligand (RANKL) and osteoprotegerin (OPG) expression. The high concentration (50 and $100{\mu}g/mL$) of RCE markedly increased ALP activity, whereas decreased the RANKL/OPG. We also investigated the effect of RCE on M-CSF plus RANKL-induced differentiation of pre-osteoclast cells (RAW 264.7). RCE treatment remarkably inhibited M-CSF/RANKL-induced formation of osteoclast-like multinuclear cells from RAW 264.7 cells. Moreover, the inhibitory effect of RCE was reduced by selective estrogen receptor-${\alpha}$ antagonist. Our research suggests that suggested that unripe fruits of R. coreanus may act beneficial effects on bone mass by regulating both osteoblast and osteoclast.

SPA0355 prevents ovariectomy-induced bone loss in mice

  • Kim, Sang Hoon;Zhang, Zhongkai;Moon, Young Jae;Park, Il Woon;Cho, Yong Gon;Jeon, Raok;Park, Byung-Hyun
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.1
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    • pp.47-54
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    • 2019
  • Estrogen withdrawal in post-menopausal women leads to overactivation of osteoclasts, which contributes to the development of osteoporosis. Inflammatory cytokines are known as one of mechanisms of osteoclast activation after estrogen deficiency. SPA0355 is a thiourea derivative that has been investigated for its antioxidant and anti-inflammatory activities. However, its efficacy in bone resorption has not been previously investigated. The aim of this study was to investigate the impact of SPA0355 on the development of osteoporosis and to explore its mode of action. In vitro experiments showed that SPA0355 inhibited receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis in primary bone marrow-derived macrophages. This effect appears to be independent of estrogen receptor activation as ICI 180,782 failed to abrogate its effects on osteoclasts. Further signaling studies revealed that SPA0355 suppressed activation of the MAPKs, Akt, and $NF-{\kappa}B$ pathways. SPA0355 also increased osteoblastic differentiation, as evidenced by its effects on alkaline phosphatase activity and mineralization nodule formation. Intraperitoneal administration of SPA0355 to ovariectomized mice prevented bone loss, as verified by three-dimensional images and bone morphometric parameters derived from ${\mu}CT$ analysis. Noticeably, SPA0355 did not show hepatotoxicity and nephrotoxicity and also had little effect on hematological parameters. Taken together, the results indicate that SPA0355 may protect against bone loss in ovariectomized mice by stimulation of osteoblast differentiation and by inhibition of osteoclast resorption. Therefore, SPA0355 is a safe and potential candidate for management of postmenopausal osteoporosis.

Analysis of Operation Areas for Automatically Tuning Burst Size-based Loss Differentiation Scheme Suitable for Transferring High Resolution Medical Data (고해상도 의학 데이터 전송에 적합한 자동 제어 버스트 크기 기반 손실 차등화 기법을 위한 동작 영역 분석)

  • Lee, Yonggyu
    • Journal of Digital Convergence
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    • v.20 no.4
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    • pp.459-468
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    • 2022
  • In medical area, very high resolution images, which is loss sensitive data, are used. Therefore, the use of optical internet with high bandwidth and the transmission of high realiability is required. However, according to the nature of the Internet, various data use the same bandwidth and a new scheme is needed to differentiate effectively these data. In order to achieve the differentiation, optical delay line buffers are used. However, these buffers is constructed based on some optimal values such as the average offered load, measured data burst length, and basic delay unit. Once the buffers are installed, they are impossible to reinstall new buffers. So, the scheme changing burst length dynamically was considered. However, this method is highly unstable. Therefore, in this article, in order to guarantee the stable operation of the scheme, the analysis of operation conditions is performed. With the analysis together with the scheme, high resolution medical data with the higher class can transmit stably without loss.

Clinical Characteristics of Patients with Tinnitus Accompanied Hearing Loss (난청을 동반한 이명 환자의 임상적 특성)

  • Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.35 no.3
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    • pp.1-14
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    • 2022
  • Background : Tinnitus is common disorder with many possible causes and a symptom of many different diseases but has no effective treatment. Most of tinnitus patients experience the disorder to a degree that their quality of life and productivity are impaired. Especially tinnitus accompanied hearing loss causes severe discomfort in patients. Objectives : 1. Through symptoms of tinnitus, we tried to find out the relationship of Heo-sil(虛實) and Zuang fu bian zheng(臟腑辨證) among tinnitus patients accompanied Hearing Loss. 2. By testing THI, we tried to evaluate the quality of life of tinnitus patients group and tried to compare the quality of life between high-narrow tone and low-wide tone tinnitus patients group. 3. In the future, this study was planned to help monitor the prognosis and determine the progress of treatment for tinnitus patients who also have hearing loss. Methods : 43 patients were recruited in this study who was ill with tinnitus accompanied hearing loss. They wrote out the questionnaire about tinnitus and the Tinnitus Handicap Inventory(THI). Results : 1. In tinnitus patients, there were more men than women accompanied hearing loss. The rate of visits was higher as the age increased. 2. Most of the patients who visited the hospital had sensitive hearing loss. 3. In high-narrow tone tinnitus group, phlegm fire congesting-type are more uncomfortable than spleen-stomach weakness-type. 4. In low-wide tone tinnitus group, liver qi depression was the most uncomfortable. Conclusions : The present study suggests that tinnitus pattern may be helpful in differentiating patients with tinnitus, and the effectiveness of treatment can be predicted through differentiation. Zuang fu bian zheng(臟腑辨證) and Distinguishing between Heo(虛) and Sil(實) is expected to have positive effects on tinnitus accompanied hearing loss treatment.

Protective effect of Korean Red Ginseng against glucocorticoid-induced osteoporosis in vitro and in vivo

  • Kim, Jinhee;Lee, Hyejin;Kang, Ki Sung;Chun, Kwang-Hoon;Hwang, Gwi Seo
    • Journal of Ginseng Research
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    • v.39 no.1
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    • pp.46-53
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    • 2015
  • Background: Glucocorticoids (GCs) are commonly used in many chemotherapeutic protocols and play an important role in the normal regulation of bone remodeling. However, the prolonged use of GCs results in osteoporosis, which is partially due to apoptosis of osteoblasts and osteocytes. In this study, effects of Korean Red Ginseng (KRG) on GC-treated murine osteoblastic MC3T3-E1 cells and a GC-induced osteoporosis mouse model were investigated. Methods: MC3T3-E1 cells were exposed to dexamethasone (Dex) with or without KRG and cell viability was measured by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Realtime polymerase chain reaction was performed to evaluate the apoptotic gene expression; osteogenic gene expression and alkaline phosphatase (ALP) activity were also measured. Western blotting was performed to evaluate the mitogen-activated protein kinase (MAPK) proteins. A GC-induced osteoporosis animal model was used for in vivo study. Results and conclusion: The MTT assay revealed that Korean Red Ginseng (KRG) prevents loss of cell viability caused by Dex-induced apoptosis in MC3T3E1 cells. Real-time polymerase chain reaction data showed that groups treated with both Dex and KRG exhibited lower mRNA levels of caspase-3 and -9, whereas the mRNA levels of Bcl2, IAPs, and XIAP increased. Moreover, groups treated with both Dex and KRG demonstrated increased mRNA levels of ALP, RUNX2, and bone morphogenic proteins as well as increased ALP activity in MC3T3-E1 cells, compared to cells treated with Dex only. In addition, KRG increased protein kinase B (AKT) phosphorylation and decreased c-Jun N-terminal kinase (JNK) phosphorylation. Moreover, microcomputed tomography analysis of the femurs showed that GC implantation caused trabecular bone loss. However, a significant reduction of bone loss was observed in the KRG-treated group. These results suggest that the molecular mechanism of KRG in the GC-induced apoptosis may lead to the development of therapeutic strategies to prevent and/or delay osteoporosis.

Effect of Simple Formulas of Muscle Section in Donguibogam on Myogenic Regulatory Factors and IGF-1 Expression in C2C12 Cells

  • Yang, In Jun;Tettey, Clement;Shin, Heung Mook
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.28 no.4
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    • pp.411-416
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    • 2014
  • Simple formulas (單方) of muscle section in Donguibogam (東醫寶鑑) have long been prescribed for strengthening muscle and/or prevention of age-related muscle loss. However, biological activity and mechanisms by which they influence myoblast differentiation have not been studied. Therefore, in this study, we evaluated the effects of 14 simple formulas on myoblast differentiation in C2C12 myoblast cells under non-cytotoxic ($0.5mg/m{\ell}$) conditions. C2C12 cells were treated with water extracts of simple formulas for 72 h, and RT-PCR was performed to determine the gene expression levels of myogenic regulatory factors (MRFs), including myoD, myogenin, MRF4, myf5, and insulin like growth factor-1 (IGF-1). Treatment with Colocasiae Rhizoma (CR), Pini Semen (PS), and Sesami Semen (SS) resulted in a significant increase in expression of myogenin in C2C12 cells. Treatment with Allii Macrostemi Bulbus (AM), Colocasiae Rhizoma (CR), and Pini Semen (PS) also resulted in increased expression of MRF4 in C2C12 cells. In addition, enhanced expression of IGF-1 was observed in treatment with Eucommiae cortex (EC), Dioscoreae Rhizoma (DR), Colocasiae Rhizoma (CR), Pini Semen (PS), and Sesami Semen (SS) in C2C12 cells. These results indicate that simple formulas of muscle section in Donguibogam could potentially enhance myoblast differentiation at least in part via increasing expression of myogenin, and/or MRF4 and/or IGF-1.

Effect of Extrinsic Factors on Differentiated Cardiomyocyte-like Cells from Human Embryonic Stem Cells

  • Gil, Chang-Hyun;Jang, Jae-Woo;Lee, Won-Young;Park, Ze-Won;Lee, Jae-Ho;Chung, Sun-Hwa;Chae, Jung-Il;Chung, Hyung-Min
    • Reproductive and Developmental Biology
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    • v.33 no.4
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    • pp.263-271
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    • 2009
  • Cardiovascular diseases (CVDs) are one of the most cause of death around the world and fields of interest for cardiac stem cells. Also, current use of terminally differentiated adult cardiomyocytes for CVDs has limited regenerative capacity therefore any significant cell loss may result in the development of progressive heart failure. Human embryonic stem cells (hESCs) derived from blastocyst-stage embryos spontaneously have ability to differentiate via embryo-like aggregates (endoderm, ectoderm and mesoderm) in vitro into various cell types including cardiomyocyte. However, most effective molecule or optimized condition which can induce cardiac differentiation of hESCs is rarely studied. In this study, we developed both spontaneous and inductive cardiomyocyte-like cells differentiation from hESCs by treatment of induced-factors, 5-azacytidine, BMP-4 and cardiogenol C. On the one hand, spontaneous and inductive cardiomyocyte-like cells showed that cardiac markers are expressed for further analysis by RT-PCR and immunocytochemistry. Interestingly, BMP-4 greatly improved homogeneous population of the cardiomyocyte-like cells from hESCs CHA15 and H09. In conclusion, we verified that spontaneously differentiated cells showed cardiac specific markers which characterize cardiac cells, treated extrinsic factors can manage cellular signals and found that hESCs can undergo differentiation into cardiomyocytes better than spontaneous group. This finding offers an insight into the inductive factor of differentiated cardiomyocytes and provides some helpful information that may offer the potential of cardiomyocytes derived from hESCs using extrinsic factors.

Tumor Necrosis factor-α Promotes Osteogenesis of Human Bone Marrow-derived Mesenchymal Stem Cells through JNK-dependent Pathway (Tumor necrosis factor-α에 의한 골수 유래 중간엽 줄기세포의 골세포로의 분화 촉진에서 JNK의 역할)

  • Kim, Mi-Ra;Song, Hae-Young;Kim, Jae-Ho
    • Journal of Life Science
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    • v.16 no.7 s.80
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    • pp.1207-1213
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    • 2006
  • Tumor necrosis $factor-{\alpha}\;(TNF-{\alpha})$ has been implicated in skeletal diseases by promoting bone loss in inflammatory bone diseases. In the present study, we examined the effects of $TNF-{\alpha}$ on osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells (hBMSCs). $TNF-{\alpha}$ dose-dependently promoted matrix mineralization of hBMSCs with a maximal stimulation at 2ng/ml. $TNF-{\alpha}$ increased expression of alkaline phosphatase, which plays a crucial role for the matrix deposition. The $TNF-{\alpha}-stimulated$ osteoblastic differentiation was not affected by $NF_kB$ inhibitors, BAY and SN50. However, a JNK-specific inhibitor, SP600125 completely abolished the $TNF-{\alpha}-stimulated$ matrix mineralization and expression of alkaline phosphatase. These results suggest that $TNF-{\alpha}$ enhances osteoblastic differentiation of hBMSCs through JNK-dependent pathway.