• Title/Summary/Keyword: differentiation therapy

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Improvement of Neuronal Differentiation by PDE4 Inhibition in Human Bone Marrow-mesenchymal Stem Cells (인간 골수유래-중간엽 줄기세포(hBM-MSCs)에서 PDE4 억제조절을 통한 신경세포 분화 효율 개선)

  • Jeong, Da Hee;Joe, I-Seul;Cho, Goang-Won
    • Journal of Life Science
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    • v.26 no.12
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    • pp.1355-1359
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    • 2016
  • Human bone marrow mesenchymal stem cells (hBM-MSCs) can differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Previous studies, including our own, have shown that MSCs can also differentiate into neuron-like cells. However, their rate of neuronal differentiation is not sufficient for application to stem cell therapy, which requires well-defined cell types. For this purpose, we first examined the expression of neuronal lineage markers (GFAP, MAP-2, KCNH1, Nestin, NF-M, and Tuj-1) by real-time PCR, western blot, and immunocytochemical staining. The expressions of the astrocyte marker GFAP and neuronal markers NF-M and Tuj-1 increased in neuronal differentiated MSCs (dMSCs). To improve the neuronal differentiation efficiency, PDE4, an important signaling intermediator in the progression of neuronal differentiation, was modulated using well-known inhibitors such as rolipram or resveratrol and then differentiated into neuronal cells (Roli- or RSV-dMSCs). The expressions of NF-M, Tuj-1 were increased while that of GFAP decreased in Roli- and RSV-dMSCs, which were examined by real-time PCR, western blot, and immunocytochemical staining. From these experiments, we have found that the neuronal differentiation efficiency can be ameliorated by the modulation of PDE4 activity.

Lnk is an important modulator of insulin-like growth factor-1/Akt/peroxisome proliferator-activated receptor-gamma axis during adipogenesis of mesenchymal stem cells

  • Lee, Jun Hee;Lee, Sang Hun;Lee, Hyang Seon;Ji, Seung Taek;Jung, Seok Yun;Kim, Jae Ho;Bae, Sun Sik;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.20 no.5
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    • pp.459-466
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    • 2016
  • Adipogenic differentiation of mesenchymal stem cells (MSCs) is critical for metabolic homeostasis and nutrient signaling during development. However, limited information is available on the pivotal modulators of adipogenic differentiation of MSCs. Adaptor protein Lnk (Src homology 2B3 [SH2B3]), which belongs to a family of SH2-containing proteins, modulates the bioactivities of different stem cells, including hematopoietic stem cells and endothelial progenitor cells. In this study, we investigated whether an interaction between insulin-like growth factor-1 receptor (IGF-1R) and Lnk regulated IGF-1-induced adipogenic differentiation of MSCs. We found that wild-type MSCs showed greater adipogenic differentiation potential than $Lnk^{-/-}$ MSCs. An ex vivo adipogenic differentiation assay showed that $Lnk^{-/-}$ MSCs had decreased adipogenic differentiation potential compared with wild-type MSCs. Interestingly, we found that Lnk formed a complex with IGF-1R and that IGF-1 induced the dissociation of this complex. In addition, we observed that IGF-1-induced increase in the phosphorylation of Akt and mammalian target of rapamycin was triggered by the dissociation of the IGF-1R-Lnk complex. Expression levels of a pivotal transcription factor peroxisome proliferator-activated receptor gamma ($PPAR-{\gamma}$) and its adipogenic target genes (LPL and FABP4) significantly decreased in $Lnk^{-/-}$ MSCs. These results suggested that Lnk adaptor protein regulated the adipogenesis of MSCs through the $IGF-1/Akt/PPAR-{\gamma}$ pathway.

A Case Study of Family Therapy for Marriage Migrant Woman who Experienced Family Violence - Focusing on Chinese Woman Who Participated in Counseling alone - (가정폭력 피해 결혼이주여성의 가족치료 사례연구: 단독으로 상담에 참여한 중국출신 여성을 중심으로)

  • Moon, Jung Hwa
    • Korean Journal of Family Social Work
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    • no.55
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    • pp.91-128
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    • 2017
  • The purpose of this study is to develop an effective intervention strategy for marriage migrant woman in family therapy. For this purpose, we collected counseling cases of professional counselors who successfully completed counseling and attempted the qualitative analysis of treatment intervention strategies and effects. The results of the study were obtained by dividing the meaning units in the immigrant woman's statements made during the counseling process composed of a total of 6 sessions. The counselors were analyzed to have tried the following intervention strategies. They attempted the following six strategies: Helping emotional differentiation by searching for unresolved emotional problems, dealing with undifferentiation due to family projection process and love triangle, dealing with multi-generational transfer process of the original family relationship patterns and coping mechanism, shedding lihgt on ineffectiveness of inconsistent communication due to emotional oppression applying a communication model of MRI, switching client's awareness through reorganization, suggesting a way of communication that leads to real self. Such counselors' attempts resulted in positive changes and treatment effects were found to include first, cognitive insights and motivation for change, second, improved communication skills and third, anxiety reduction and self-differentiation. Due to their husbands' refusal to participate in counseling, marriage migrant women often get involved in counseling alone, so they tend to worry that the effectiveness of family therapy may be low but it was found that the proper intervention of the counselor could improve the ability of the wife to resolve conflicts, which would be a great help in solving problems such as family violence and this study is meaningful in that it provided the appropriate therapeutic intervention strategies needed.

Development of Cell Therapeutics against Ischemic Vascular Diseases Using Mesenchymal Stem Cells: From Bench to Bed (중간엽줄기세포(MSC)를 이용한 허혈성 혈관질환 치료를 위한 세포치료제 개발: 기초연구에서 임상연구)

  • Lee, Eun Ji;Park, Shin Hu;Seo, Jeong Ho;An, Hyo Gyung;Nam, Si Hyun;Kwon, Sang-Mo
    • Journal of Life Science
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    • v.32 no.7
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    • pp.567-577
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    • 2022
  • Recently, the prevalence of ischemic diseases, such as ischemic heart disease, cerebral ischemia, and peripheral arterial disease, has been continuously increasing due to the aging population. The current standardized treatment for ischemic diseases is reperfusion therapy through pharmacotherapy and surgical approaches. Although reperfusion therapy may restore the function of damaged arteries, it is not effective at restoring the function of the surrounding tissues that have been damaged due to ischemia. Therefore, it is necessary to develop a new treatment strategy that can safely and effectively treat ischemic damage and restore the function of surrounding tissues. To overcome these limitations, stem cell-based therapy to regenerate the damaged region has been studied as a promising strategy for ischemic vascular diseases. Mesenchymal stem cells (MSCs) can be isolated from diverse tissues and have been shown to be promising for the treatment of ischemic disease by regenerating damaged tissues through immunomodulation, the promotion of angiogenesis, and the secretion of various relevant factors. Moreover, new approaches to enhancing MSC function, such as cell priming or enhancing transplantation efficiency using a 3D culture method, have been studied to increase stem cell therapeutic efficacy. In this review, we provide various strategies by which MSCs are used to treat ischemic diseases, and we discuss the challenges of MSC transplantation, such as the differentiation, proliferation, and engraftment of MSCs at the ischemic site.

Impact of Postoperative Chemoradiotherapy and Chemoradiotherapy Alone for Esophageal Cancer in North-West Iran

  • Mirinezhad, Seyed Kazem;Somi, Mohammad Hossein;Shirmohamadi, Masoud;Seyednejad, Farshad;Jangjoo, Amir Ghasemi;Ghojazadeh, Morteza;Mohammadzadeh, Mohammad;Naseri, Ali Reza;Nasiri, Behnam
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.6
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    • pp.3921-3924
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    • 2013
  • Background: To investigate the role of surgical treatment for locally advanced esophageal cancer, we compared the outcomes of chemoradiotheroy alone (CRT) to postoperative chemoradiotherapy (S/CRT), using, Regional Radiotherapy Center, database. Materials and Methods: This retrospective study was conducted in North-West of Iran, included of 255 consecutive patients with esophageal cancer. Eligible operable and non-operable, were treated with S/CRT and CRT respectively. Radiotherapy (RT) was delivered at 1.8-2 Gy/day for five consecutive days in a given week. Chemotherapy (CT) consisted of cisplatin and 5-fluorouracil. Results: From March 2006 to March 2011 255 patients: male/female 129/96, median age 68 (35-90), squamous/adeno 213/12, received CRT/S+CRT 166/59, median radiation dose $45{\pm}13.6Gy$, Median survival 13.5 (11-15), overall survival (OS) One/Two/Three 57/21/16%, Died/alive 158/97, Univariate analysis prognostic factors: age/stag/differentiation/dose of RT/fraction/treatment, Multivariate analysis predictor factor: dose of RT/fraction. Conclusions: Although this treatment offers some possibility for improvement of patients with esophageal cancer, there remains a significant need for development of new drug and new therapeutic approaches that can substantially impact survival.

Immature thymocyte antigen, JL1, as a possible immunodiagnostic and immunotherapeutic target for leukemia

  • Shin, Young Kee;Choi, Eun Young;Kim, Seok Hyung;Park, Seong Hoe
    • IMMUNE NETWORK
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    • v.1 no.1
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    • pp.1-6
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    • 2001
  • The identification of tumor-specific antigens has represented a critical milestone in cancer diagnosis and therapy. Clinical research in this area for leukemia has also been driven over the past few decades by the hope that surface antigens with restricted tissue expression would be identified. Disappointingly, only a small number of the leukemic antigens identified to date, meet sufficient criteria to be considered viable immunophenotypic markers. In this paper, we nominate anti-JL1 monoclonal antibody as an immunodiagnostic and immunotherapeutic candidate for leukemia. The JL1 molecule appears to be a novel cell surface antigen, which is strictly confined to a subpopulation of limited stages during the hematopoietic differentiation process. Despite the restricted distribution of the JL1 antigen in normal tissues and cells, anti-JL1 monoclonal antibody specifically recognizes various types of leukemia, irrespective of immunophenotypes. On the basis of these findings, we propose JL1 antigen as a tumor-specific marker, which shows promise as a candidate molecule for diagnosis and immunotherapy in leukemia, and one that spares normal bone marrow stem cells.

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A Clinical Study on One Case of Exotropia Caused by Unilateral-internuclear- ophthalmoplegia due to Pontine Infarction (뇌교 경색에 의한 일측성핵간마비로 유발된 외사시 환자에 대한 증례보고)

  • Park, Hoi-Jin;Kim, Su-Hyun;Ahn, Ho-Jin;Ock, Min-Keun;Jung, Kyung-Suk
    • Journal of Acupuncture Research
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    • v.23 no.3
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    • pp.241-247
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    • 2006
  • Objectives : This study is to report one case of the patient who has exotropia caused by unilateral internuclear ophthalmoplegia due to pontine infarction, which is a rare disease so there has few research about the effect of acupuncture therapy on it, treated with the SAAM(舍巖) Acupuncture Sojangjeonggyeok(小湯正洛) Methods & Results : In the point of differentiation of Syndrome, these subjects were diagnosed as deficiency of Yin and blood(陰血不足). We treated her with SAAM Acupuncture Sojangjeonggyeok(小湯正洛), herb medication(淸肝湯, 六味地黃湯), and the symptoms were resolved clearly by above treatment during about a week. Conclusion : This case shows proper oriental medical treatment based on the exact differentiation of symptoms has good effect on this disease as one of conservative therapies.

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Characteristics of Purinergic Receptor Expressed in Human Retinoblastoma Cells

  • Kim, Dae-Ran;Kong, In-Deok
    • Biomedical Science Letters
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    • v.13 no.4
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    • pp.333-339
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    • 2007
  • Recently, much attention has been paid to human retinoblastoma since it provide a good model system for studying mechanisms underlying cell growth, differentiation, proliferation, and apoptosis, and for developing cancer therapy. However, until now it is unclear whether purinergic receptors are involved in the calcium mobilization in the retinoblastoma cells. In this regard, we measured possible purinergic signaling in WERI-Rb-1 cells using $Ca^{2+}$ imaging technique and RT-PCR method. ATP-induced $[Ca^{2+}]_i$ transients was maintained to about $90.7{\pm}1.0%$ of the control (n=48) even in the absence of extracellular calcium. The ATP-induced intracellular calcium response was only attained to $10.4{\pm}1.8%$ (n=55) of peak amplitude of the control after preincubation of 1 ${\mu}MU-73122$, a PLC inhibitor, but it was not affected by 1 ${\mu}MU-73343$, a inactive form of U-73122. And also ATP-induced $[Ca^{2+}]_i$ rise was almost attenuated by 20 ${\mu}M$ 2-APB, a putative $IP_3$ receptor inhibitor. Two subtypes of $IP_3$ receptor $(IP_{3-1}R,\;IP_{3-2}R)$ were identified by a RT-PCR method. These findings suggest that purinergic stimuli can cause calcium mobilization via $PLC-IP_3$ pathway after the activation of P2Y receptors in the retinoblastoma cells, which may play important roles in cell proliferation, differentiation, growth, and cell death.

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Effects of Mercuric Chloride on the Differentiation Cerebral Neuron of Chick Embryo ( I ) (계배 대뇌의 신경세포 분화에 미치는 수은의 영향 ( I ))

  • Kim, Saeng-Gon;Cho, Kwang-Phil;Kim, Jeong-Sang
    • Applied Microscopy
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    • v.24 no.2
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    • pp.26-36
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    • 1994
  • To investigate the effects of mercuric chloride ($HgCl_2$) on the differentiation in the cerebral neuron of chick embryo 7 days, the ultrastructural changes in nerve cells injected with a various doses of mercuric chloride were observed with transmission electron microscope. The enzyme activity of the some dehydrogenases, and adenosine triphophate (ATP) were also analyzed. The results obtained are as follows; The ultrastructural changes in 1.0mg-injected group, the nuclear envelope were irregular, and the RER, Golgi complexes and mitochondria were not well developed. In 2.0mg-injected group, the nuclear envelope were partly destroyed or detached, and mitochondria were decreased in number and their cristae were destroyed, too. The RER and Golgi complexes were less developed than those of the normal groups. In general, the activities of dehydrogenases were declined by increasing the dose of mercuric chloride. Lactate dehydrogenase (LDH) activity fatted to below 85% of the normal group in 1.0mg-injected group, and 69% in 2.0mg-injected group. Malate dehydrogenase (MDH) activity was decreased greatly to 76% in 2.0mg-injected group. Succinate dehydrogenase (SDH) activity fatted to 85% in 1.0mg-injected group, and 74% in 2.0mg-injected group. ATP content in 1.0mg-injected group was almost near to the normal level, but it was increased significantly in 2.0mg-injected group.

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Diallyl Disulfide (DADS) Induces Upregulation of PTEN in Human Leukemia Cells

  • Chung, Weon-Kuu;Lee, Byoung-Kil;Lee, Young-Rae;Park, Jin-Ny;Kwon, Hyoung-Chul
    • Journal of Food Hygiene and Safety
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    • v.24 no.1
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    • pp.38-45
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    • 2009
  • The differentiation of leukemia cells into mature cells is a major target of the human leukemia therapy. As differentiated leukemia cells lose their proliferative and tumor-forming abilities, differentiation inducers may be useful for the treatment of leukemia. In this study, the experiments were designed to determine whether diallyl disulfide (DADS) regulates expressions of tumor suppressor protein PTEN (phosphatase and tension homologue) in HL60 cells. DADS causes upregulation of PTEN in a time- and dose-dependent manner, which was correlated with decrease of phospho-Akt level. These results suggest that DADS induces upregulation of PTEN in human leukemia cells. These results suggest that DADS may be a useful anticancer agent for management of human leukemia.