• Title/Summary/Keyword: Therapeutic function

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Recent Advancement in the Stem Cell Biology (Stem Cell Biology, 최근의 진보)

  • Harn, Chang-Yawl
    • Journal of Plant Biotechnology
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    • v.33 no.3
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    • pp.195-207
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    • 2006
  • Stem cells are the primordial, initial cells which usually divide asymmetrically giving rise to on the one hand self-renewals and on the other hand progenitor cells with potential for differentiation. Zygote (fertilized egg), with totipotency, deserves the top-ranking stem cell - he totipotent stem cell (TSC). Both the ICM (inner cell mass) taken from the 6 days-old human blastocyst and ESC (embryonic stem cell) derived from the in vitro cultured ICM have slightly less potency for differentiation than the zygote, and are termed pluripotent stem cells. Stem cells in the tissues and organs of fetus, infant, and adult have highly reduced potency and committed to produce only progenitor cells for particular tissues. These tissue-specific stem cells are called multipotent stem cells. These tissue-specific/committed multipotent stem cells, when placed in altered environment other than their original niche, can yield cells characteristic of the altered environment. These findings are certainly of potential interest from the clinical, therapeutic perspective. The controversial terminology 'somatic stem cell plasticity' coined by the stem cell community seems to have been proved true. Followings are some of the recent knowledges related to the stem cell. Just as the tissues of our body have their own multipotent stem cells, cancerous tumor has undifferentiated cells known as cancer stem cell (CSC). Each time CSC cleaves, it makes two daughter cells with different fate. One is endowed with immortality, the remarkable ability to divide indefinitely, while the other progeny cell divides occasionally but lives forever. In the cancer tumor, CSC is minority being as few as 3-5% of the tumor mass but it is the culprit behind the tumor-malignancy, metastasis, and recurrence of cancer. CSC is like a master print. As long as the original exists, copies can be made and the disease can persist. If the CSC is destroyed, cancer tumor can't grow. In the decades-long cancer therapy, efforts were focused on the reducing of the bulk of cancerous growth. How cancer therapy is changing to destroy the origin of tumor, the CSC. The next generation of treatments should be to recognize and target the root cause of cancerous growth, the CSC, rather than the reducing of the bulk of tumor, Now the strategy is to find a way to identify and isolate the stem cells. The surfaces of normal as well as the cancer stem cells are studded with proteins. In leukaemia stem cell, for example, protein CD 34 is identified. In the new treatment of cancer disease it is needed to look for protein unique to the CSC. Blocking the stem cell's source of nutrients might be another effective strategy. The mystery of sternness of stem cells has begun to be deciphered. ESC can replicate indefinitely and yet retains the potential to turn into any kind of differentiated cells. Polycomb group protein such as Suz 12 repress most of the regulatory genes which, activated, are turned to be developmental genes. These protein molecules keep the ESC in an undifferentiated state. Many of the regulator genes silenced by polycomb proteins are also occupied by such ESC transcription factors as Oct 4, Sox 2, and Nanog. Both polycomb and transcription factor proteins seem to cooperate to keep the ESC in an undifferentiated state, pluripotent, and self-renewable. A normal prion protein (PrP) is found throughout the body from blood to the brain. Prion diseases such as mad cow disease (bovine spongiform encephalopathy) are caused when a normal prion protein misfolds to give rise to PrP$^{SC}$ and assault brain tissue. Why has human body kept such a deadly and enigmatic protein? Although our body has preserved the prion protein, prion diseases are of rare occurrence. Deadly prion diseases have been intensively studied, but normal prion problems are not. Very few facts on the benefit of prion proteins have been known so far. It was found that PrP was hugely expressed on the stem cell surface of bone marrow and on the cells of neural progenitor, PrP seems to have some function in cell maturation and facilitate the division of stem cells and their self-renewal. PrP also might help guide the decision of neural progenitor cell to become a neuron.

NEW ANTIDEPRESSANTS IN CHILD AND ADOLESCENT PSYCHIATRY (소아청소년정신과영역의 새로운 항우울제)

  • Lee, Soo-Jung
    • Journal of the Korean Academy of Child and Adolescent Psychiatry
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    • v.14 no.1
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    • pp.12-25
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    • 2003
  • Objectives:As increasing number of new antidepressants have been being introduced in clinical practice, pharmacological understanding has been broadened. These changes mandate new information and theories to be incorporated into the treatment process of children with depressive disorders. In light of newly coming knowledge, this review intended to recapitulate the characteristics of new antidepressants and to consider the pivotal issues to develope guidelines for the treatment of depression in childhood and adolescence. Methods:Searching the Pub-Med online database for the articles with the key words of 'new', 'antidepressants' and 'children' ninety-seven headings of review articles were obtained. The author selected the articles of pertinent subjects in terms of either treatment guideline or psychopharmacology of new antidepressants. When required, articles about the clinical effectiveness of individual antidepressants were separatedly searched. In addition, the safety information of new antidepressants was acquired by browsing the official sites of the United States Food and Drugs Administration and Department of Health and Human Services. Results:1) For the clinical course, treatment phase, and treatment outcome, the reviews or treatment guidelines adopted the information from adult treatment guidelines. 2) Systematic and critical reviews unambiguously concluded that selective serotonin reuptake inhibitors(SSRIs) excelled tricyclic antidepressants( TCAs) for both efficacy and side effect profiles, and were recommend for the first-line choice for the treatment of children with depressive disorders. 3) New antidepressants generally lacked treatment experiences and randomized controlled clinical trials. 4) SSRIs and other new antidepressants, when used together, might result in pharmacokinetic and/or pharmacodynamic drug-to-drug interaction. 5) The difference of the clinical effectiveness of antidepressants between children and adults should be addressed from developmental aspects, which required further evidence. Conclusion:Treatment guidelines for the pharmacological treatment of childhood and adolescence depression could be constructed on the basis of clinical trial findings and practical experiences. Treatment guidelines are to best serve as the frame of reference for a clinician to make reasonable decisions for a particular therapeutic situation. In order to fulfill this role, guidelines should be updated as soon as new research data become available.

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Risk Assessment of Dermatolymphangioadenitis by Lymphoscintigraphy in Patients with Lower Extremity Lymphedema (하지림프부종 환자에서 림프신티그라피를 이용한 피부림프선염 위험도 평가)

  • Choi, Joon-Young;Hwang, Ji-Hye;Park, Jung-Mi;Lee, Kyung-Han;Kim, Sang-Eun;Kim, Dong-Ik;Lee, Byung-Boong;Kim, Byung-Tae
    • The Korean Journal of Nuclear Medicine
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    • v.33 no.2
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    • pp.143-151
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    • 1999
  • Purpose: Dermatolymphangioadenitis (DLA) is a common and serious complication of lymphedema which deteriorates lymphatic function. The purpose of this study was to assess the risk of DLA by lymphos-cintigraphy in patients with lower extremity lymphedema. Materials and Methods: The subjects were 59 edematous lower extremities of 50 patients without previous episode of DLA and 12 lower extremities of 6 controls. Whole body images were acquired 1 min and 2 hr after subcutaneous injection of 37 MBq of Tc-99m-antimony sulfide colloid into interdigital spaces of both feet before therapy for lymphedema. The lymphosintigraphic and clinical variables were compared between groups with or without occurrence of DLA during clinical follow up. Results: There were 20 episodes of DLA in 12 extremities during clinical follow-up (19 :6 months). On univariate analysis, there were significant differences in ilioinguinal lymph node uptake, uptake pattern of main lymphatic vessel, clinical stage and therapy compliance between the two groups. After multivariate analysis, only the uptake pattern of main lymphatic vessel and therapy compliance fore confirmed to be independent variables. In other words, non-visualized main lymphatic vessel and poor compliance to therapy were more frequent in extremities with subsequent occurrence of DLA. Conclusion: Lymphoscintigraphy can be used to predict the risk of DLA and may thus be helpful for determining the initial therapeutic plan in patients with lower extremity lymphedema.

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The Results of Combined Modality Treatment with Transurethral Resection, Cisplatin and Radiation Therapy for Invasive Bladder Cancer (침윤성 방광암에서 경요도적절제술 및 Cisplatin과 방사선의 병용치료의 효과)

  • Oh, Yoon-Kyeong
    • Radiation Oncology Journal
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    • v.9 no.2
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    • pp.311-317
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    • 1991
  • Ten patients with deep muscle-invading bladder carcinoma (clinical stages T3a to T4b) who were not candidates for cystectomy were treated with combined modality treatment with transurethral resection, cisplatin chemotherapy and pelvic irradiation from 1989 through 1990, and were analyzed retrospectively. All patients were not candidates for cystectomy because the tumors were judged unresectable or they were not fit for a radical cystectomy. Of the patients 5 had clinical stage T3a, 3 stage T3b and 2 stage T4b disease. The minimum follow-up was 16 months. The complete response rate is 60$\%$ for all patients. The complete responses were achieved in 4 of 5(80$\%$) with stage cT3a, in 2 of 3(67$\%$)with stage cT3b and in none of 2(0$\%$) with stage cT4b. The partial responses were achieved in 2, so an overall response rate was 80$\%$. All six patients with grade I or II transitional cell carcinoma showed complete responses. Four patients with higher grade tumors showed partial responses in 2 and no response in 2, and all died of their bladder cancer. Six patients who showed complete responses after treatment are alive and only one of them showed a local recurrence 10 months after treatment. Distant metastases developed in 3 patients: lungs in 2(cT4b) of those who were never locally free of disease and spine in 1 patient (cT3b) among those with a partial response. Two patients died of metastases to lungs. During the follow-up diarrhea occurred in one which was improved after conservative treatment. On the basis of this analysis it is suggested that combined modality treatment seems to be a tolerable regimen and can be offered with a relatively high probability of success and conservation of bladder function in those with less advanced tumors by clinical stage and low grade.

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Treat-to-Target Strategy for Asian Patients with Early Rheumatoid Arthritis: Result of a Multicenter Trial in Korea

  • Song, Jason Jungsik;Song, Yeong Wook;Bae, Sang Cheol;Cha, Hoon-Suk;Choe, Jung-Yoon;Choi, Sung Jae;Kim, Hyun Ah;Kim, Jinseok;Kim, Sung-Soo;Lee, Choong-Ki;Lee, Jisoo;Lee, Sang-Heon;Lee, Shin-Seok;Lee, Soo-Kon;Lee, Sung Won;Park, Sung-Hwan;Park, Won;Shim, Seung Cheol;Suh, Chang-Hee;Yoo, Bin;Yoo, Dae-Hyun;Yoo, Wan-Hee
    • Journal of Korean Medical Science
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    • v.33 no.52
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    • pp.346.1-346.11
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    • 2018
  • Background: To evaluate the therapeutic benefits of the treat-to-target (T2T) strategy for Asian patients with early rheumatoid arthritis (RA) in Korea. Methods: In a 1-year, multicenter, open-label strategy trial, 346 patients with early RA were recruited from 20 institutions across Korea and stratified into 2 groups, depending on whether they were recruited by rheumatologists who have adopted the T2T strategy (T2T group) or by rheumatologists who provided usual care (non-T2T group). Data regarding demographics, rheumatoid factor titer, anti-cyclic citrullinated peptide antibody titer, disease activity score of 28 joints (DAS28), and Korean Health Assessment Questionnaire (KHAQ) score were obtained at baseline and after 1 year of treatment. In the T2T group, the prescription for disease-modifying antirheumatic drugs was tailored to the predefined treatment target in each patient, namely remission (DAS28 < 2.6) or low disease activity (LDA) ($2.6{\leq}DAS28$ < 3.2). Results: Data were available for 163 T2T patients and 162 non-T2T patients. At the end of the study period, clinical outcomes were better in the T2T group than in the non-T2T group (LDA or remission, 59.5% vs. 35.8%; P < 0.001; remission, 43.6% vs. 19.8%; P < 0.001). Compared with non-T2T, T2T was also associated with higher rate of good European League Against Rheumatism response (63.0% vs. 39.8%; P < 0.001), improved KHAQ scores (-0.38 vs. -0.13; P = 0.008), and higher frequency of follow-up visits (5.0 vs. 2.0 visits/year; P < 0.001). Conclusion: In Asian patients with early RA, T2T improves disease activity and physical function. Setting a pre-defined treatment target in terms of DAS28 is recommended.

Brazilin downregulates CCL20 expression via regulation of STAT3 phosphorylation in TNF-α/IL-17A/IFN-γ-induced HaCaT cells (TNF-α/IL-17A/IFN-γ 유도된 HaCaT 세포에서 브라질린의 STAT3 인산화 억제를 통한 CCL20 저해 효과)

  • Kim, Mi Ran;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.185-192
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    • 2021
  • Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

Ameliorative Effects of Soybean Leaf Extract on Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes and a C57BL/6 Mouse Model (콩잎 추출물의 근위축 개선 효과)

  • Hye Young Choi;Young-Sool Hah;Yeong Ho Ji;Jun Young Ha;Hwan Hee Bae;Dong Yeol Lee;Won Min Jeong;Dong Kyu Jeong;Jun-Il Yoo;Sang Gon Kim
    • Journal of Life Science
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    • v.33 no.12
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    • pp.1036-1045
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    • 2023
  • Sarcopenia, a condition characterized by the insidious loss of skeletal muscle mass and strength, represents a significant and growing healthcare challenge, impacting the mobility and quality of life of aging populations worldwide. This study investigated the therapeutic potential of soybean leaf extract (SL) for dexamethasone (Dexa)-induced muscle atrophy in vitro and in an in vivo model. In vitro experiments showed that SL significantly alleviated Dexa-induced atrophy in C2C12 myotube cells, as evidenced by preserved myotube morphology, density, and size. Moreover, SL treatment significantly reduced the mRNA and protein levels of muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (MAFbx), key factors regulating muscle atrophy. In a Dexa-induced atrophy mouse model, SL administration significantly inhibited Dexa-induced weight loss and muscle wasting, preserving the mass of the gastrocnemius and tibialis anterior muscles. Furthermore, mice treated with SL exhibited significant improvements in muscle function compared to their counterparts suffering from Dexa-induced muscle atrophy, as evidenced by a notable increase in grip strength and extended endurance on treadmill tests. Moreover, SL suppressed the expression of muscle atrophy-related proteins in skeletal muscle, highlighting its protective role against Dexa-induced muscle atrophy. These results suggest that SL has potential as a natural treatment for muscle-wasting conditions, such as sarcopenia.