• 제목/요약/키워드: Therapeutic Element

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Tau mis-splicing in the pathogenesis of neurodegenerative disorders

  • Park, Sun Ah;Ahn, Sang Il;Gallo, Jean-Marc
    • BMB Reports
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    • 제49권8호
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    • pp.405-413
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    • 2016
  • Tau proteins, which stabilize the structure and regulate the dynamics of microtubules, also play important roles in axonal transport and signal transduction. Tau proteins are missorted, aggregated, and found as tau inclusions under many pathological conditions associated with neurodegenerative disorders, which are collectively known as tauopathies. In the adult human brain, tau protein can be expressed in six isoforms due to alternative splicing. The aberrant splicing of tau pre-mRNA has been consistently identified in a variety of tauopathies but is not restricted to these types of disorders as it is also present in patients with non-tau proteinopathies and RNAopathies. Tau mis-splicing results in isoform-specific impairments in normal physiological function and enhanced recruitment of excessive tau isoforms into the pathological process. A variety of factors are involved in the complex set of mechanisms underlying tau mis-splicing, but variation in the cis-element, methylation of the MAPT gene, genetic polymorphisms, the quantity and activity of spliceosomal proteins, and the patency of other RNA-binding proteins, are related to aberrant splicing. Currently, there is a lack of appropriate therapeutic strategies aimed at correcting the tau mis-splicing process in patients with neurodegenerative disorders. Thus, a more comprehensive understanding of the relationship between tau mis-splicing and neurodegenerative disorders will aid in the development of efficient therapeutic strategies for patients with a tauopathy or other, related neurodegenerative disorders.

중추유형발생기에 근거한 뇌졸중 환자의 치료적 접근 (Therapeutic Approach for Stroke Patients based on Central Pattern Generator)

  • 김중휘;김중선
    • The Journal of Korean Physical Therapy
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    • 제14권4호
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    • pp.131-146
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    • 2002
  • In the last years, it has become possible to regain some locomotor activity in patients with incomplete spinal cord injury (SCI) through intense training on a treadmill. The ideas behind this approach owe much to insights derived from animal studies. Many studies showed that cats with complete spinal cord transection(spinalized animals) can recover locomotor function. These observations were at the basis of the concept of the central pattern generator located at spinal level. The neural system responsible for the locomotor restoration in both cats and humans is thought to be located at spinal level and is referred to as the central pattern generator(CPG). The evidence for such a spinal CPG in human is emphasis on some recent developments which support the view that there is a human spinal CPG for locomotion. An important element in afferent inputs for both spinal injured cats and humans is the provision of adequate sensory input related locomotor, which can possibly activate and/or regulate the spinal locomotor circuitry This review article deals with the afferent control of the central pattern generator. Furthermore, the application of adequate afferent inputs related locomotor for stroke patients will be able to facilitate locomotion ability, which is automatic, cyclic, rhythmic. These insights can possibly contribute to a better therapeutic approach for the rehabilitation of gait in patients with stroke.

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한의약학의 서지학적(書誌學的) 연구(I) -상한론(傷寒論)을 중심으로- (Bibliographical Study on Sanghanron (I))

  • 최명숙;임동술;이숙연
    • 약학회지
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    • 제50권4호
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    • pp.234-243
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    • 2006
  • Three important books in the oriental medicine are Huangjenaekyung (medical book), Sanghanron (pharmacological book) and Shinnongbonchokyung (herbal book). Chang, joong-kyung who is the writer of Sanghanron would be recommended as a saint physician and his book, Sanghanron is granted for a best book in this field by Chinese people. Also, Japanese physicians would estimate Sanghanron as the most magnificent book ever written by a human being. Sanghanron contains a lot of confirmations (證) of diseases, their progressing courses and exact therapeutic ways. Therefore modern physicians and pharmacists who are interested in the oriental medicine might study and practice more scientific approach of therapy for patients. The aim of this bibliographical study on Sanghanron is to explain systematically theories of this book and harmonize them with the modern medicinal study: In this study we have acquired three main results, the first is that we could get the coincidence between western & oriental way on the five therapeutic principles-sweating, vomiting, harmonizing, excreting and bleeding : the second, notice the exclusion of the Five Element Theory(the fundamental one in oriental medicine) and the third, found out the possibility of the immunological and neuroscientific explanation for pharmacological application to the oriental medicine.

Tumor antigen PRAME is a potential therapeutic target of p53 activation in melanoma cells

  • Yong-Kyu Lee;Hyeon Ho Heo;Nackhyoung Kim;Ui-Hyun Park;Hyesook Youn;Eun-Yi Moon;Eun-Joo Kim;Soo-Jong Um
    • BMB Reports
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    • 제57권6호
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    • pp.299-304
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    • 2024
  • Upregulation of PRAME (preferentially expressed antigen of melanoma) has been implicated in the progression of a variety of cancers, including melanoma. The tumor suppressor p53 is a transcriptional regulator that mediates cell cycle arrest and apoptosis in response to stress signals. Here, we report that PRAME is a novel repressive target of p53. This was supported by analysis of melanoma cell lines carrying wild-type p53 and human melanoma databases. mRNA expression of PRAME was downregulated by p53 overexpression and activation using DNA-damaging agents, but upregulated by p53 depletion. We identified a p53-responsive element (p53RE) in the promoter region of PRAME. Luciferase and ChIP assays showed that p53 represses the transcriptional activity of the PRAME promoter and is recruited to the p53RE together with HDAC1 upon etoposide treatment. The functional significance of p53 activation-mediated PRAME downregulation was demonstrated by measuring colony formation and p27 expression in melanoma cells. These data suggest that p53 activation, which leads to PRAME downregulation, could be a therapeutic strategy in melanoma cells.

cAMP Response Element-Binding Protein- and Phosphorylation-Dependent Regulation of Tyrosine Hydroxylase by PAK4: Implications for Dopamine Replacement Therapy

  • Won, So-Yoon;You, Soon-Tae;Choi, Seung-Won;McLean, Catriona;Shin, Eun-Young;Kim, Eung-Gook
    • Molecules and Cells
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    • 제44권7호
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    • pp.493-499
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    • 2021
  • Parkinson's disease (PD) is characterized by a progressive loss of dopamine-producing neurons in the midbrain, which results in decreased dopamine levels accompanied by movement symptoms. Oral administration of l-3,4-dihydroxyphenylalanine (L-dopa), the precursor of dopamine, provides initial symptomatic relief, but abnormal involuntary movements develop later. A deeper understanding of the regulatory mechanisms underlying dopamine homeostasis is thus critically needed for the development of a successful treatment. Here, we show that p21-activated kinase 4 (PAK4) controls dopamine levels. Constitutively active PAK4 (caPAK4) stimulated transcription of tyrosine hydroxylase (TH) via the cAMP response element-binding protein (CREB) transcription factor. Moreover, caPAK4 increased the catalytic activity of TH through its phosphorylation of S40, which is essential for TH activation. Consistent with this result, in human midbrain tissues, we observed a strong correlation between phosphorylated PAK4S474, which represents PAK4 activity, and phosphorylated THS40, which reflects their enzymatic activity. Our findings suggest that targeting the PAK4 signaling pathways to restore dopamine levels may provide a new therapeutic approach in PD.

The Effect of an Optical Clearing Agent on Tissue Prior to 1064-nm Laser Therapy

  • Youn, Jong-In
    • Medical Lasers
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    • 제10권3호
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    • pp.146-152
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    • 2021
  • Background and Objectives Although lasers have been widely applied in tissue treatment, the light penetration depth in tissues is limited by the tissue turbidity and affected by its absorption and scattering characteristics. This study investigated the effect of using an optical clearing agent (OCA) on tissue to improve the therapeutic effect of 1064 nm wavelength laser light by reducing the heat generated on the skin surface and increasing the penetration depth. Materials and Methods A diode laser (λ = 1064 nm) was applied to a porcine specimen with and without OCA to investigate the penetration depth of the laser light and temperature distribution. A numerical simulation using the finite element method was performed to investigate the temperature distribution of the specimen compared to ex-vivo experiments using a thermocouple and double-integrating sphere to measure the temperature profile and optical properties of the tissue, respectively. Results Simulation results showed a decrease in tissue surface temperature with increased penetration depth when the OCA was applied. Furthermore, both absorption and scattering coefficients decreased with the application of OCA. In ex-vivo experiments, temperatures decreased for the tissue surface and the fat layer with the OCA, but not for the muscle layer. Conclusion The use of an OCA may be helpful for reducing surface heat generation and enhance the light penetration depth in various near-infrared laser treatments.

치매요양시설의 옥외공간 조성에 관한 기초연구 (A Basic Study on the Architectural Planning of Outdoor Space for the Elderly with Dementia)

  • 전성민;권순정
    • 의료ㆍ복지 건축 : 한국의료복지건축학회 논문집
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    • 제13권1호
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    • pp.61-71
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    • 2007
  • The Outdoor space is an essential element among healing environments for older people. The purpose of this study is to identify outdoor design issues which can improve the health conditions of the elderly living in nursing home. At first, the design principles of outdoor space for the mentally ill have been collected from the literature survey. Secondary, outdoor design requirements for the care program in nursing homes have been explored. Thirdly, good design elements have been collected from 6 nursing homes which have good outdoor space. Finally, Basic design principles of outdoor space of nursing homes in which older people with dementia live have been proposed by analysis and synthesis on the three stages before. As a result of this study, 6 dimensions in architectural planning of outdoor space for nursing homes have been presented : safety environment, various sensual stimulation, social interactions, support physical ability, accessibility, meditation.

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Role of Nuclear Factor Erythroid 2-Related Factor 2 in Chronic Obstructive Pulmonary Disease

  • Ban, Woo Ho;Rhee, Chin Kook
    • Tuberculosis and Respiratory Diseases
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    • 제85권3호
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    • pp.221-226
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    • 2022
  • Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation due to chronic airway inflammation and destruction of the alveolar structure from persistent exposure to oxidative stress. The body has various antioxidant mechanisms for efficiently coping with such oxidative stress. The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) is a representative system. Dysregulation of the Nrf2-ARE pathway is responsible for the development and promotion of COPD. Furthermore, COPD severity is also closely related to this pathway. There has been a clinical impetus to use Nrf2 for diagnostic and therapeutic purposes. Therefore, in this work, we systematically reviewed the clinical significance of Nrf2 in COPD patients, and discuss the value of Nrf2 as a potential COPD biomarker.

정지환(定志丸)의 기억 및 인지기능 향상에 대한 효능 연구 (Therapeutic Potential of Jeongjihwan for the Prevention and Treatment of Amnesia)

  • 정태영;정원춘;박종현
    • 동의생리병리학회지
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    • 제25권1호
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    • pp.37-47
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    • 2011
  • This study was aimed to investigate the memory enhancing effect of Jeongjihwan against scopolamine-induced amnesia in C57BL/6 mice. To determine the effect of Jeongjihwan on the memory and cognitive function, we have injected scopolamine (1 mg/kg, i.p.) into C57BL/6 mice 30 min before beginning of behavior tests. We have conducted Y-maze, Morris water-maze, passive avoidance and fear conditioning tests to compare learning and memory functions. Scopolamine-induced behavior changes of memory impairment were significantly restored by oral administration of Jeongjihwan (100 or 200 mg/kg/day). To elucidate the molecular mechanism underlying the memory enhancing effect of Jeongjihwan, we have examined the antioxidant defense system and neurotrophic factors. Jeongjihwan treatment attenuated intracellular accumulation of reactive oxygen species and up-regulated mRNA and protein expression of antioxidant enzymes as assessed by RT-PCR and western blot analysis, respectively. Jeongjihwan also increased protein levels of brain-derived neurotrophic factor (BDNF) compared with those in the scopolamine-treated group. Furthermore, as an upstream regulator, the activation of cAMP response element-binding protein (CREB) via phosphorylation was assessed by Western blot analysis. Jeongjihwan elevated the phosphorylation of CREB (p-CREB), which seemed to be mediated partly by extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase B/Akt. These findings suggest that Jeongjihwan may have preventive and therapeutic potential in the management of amnesia.

음성 정보를 이용한 자폐아 치료용 로봇의 동작 설계 (Therapeutic Robot Action Design for ASD Children Using Speech Data)

  • 이진규;이보희
    • 전기전자학회논문지
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    • 제22권4호
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    • pp.1123-1130
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    • 2018
  • 이전 연구에서 자폐성 장애의 여러 특징적 증상을 갖는 아이들의 치료를 위해 사용될 수 있는 로봇을 설계 및 제작하여 현장실험이 진행 되었으며 기존 로봇은 터치에 의한 아이들과 상호작용을 통해 감정 표현 동작을 한다. 이러한 터치 상호작용에 감정 교육 및 치료를 위해 인공신경망을 이용한 동작 설계를 하였다. 하지만 이러한 물리적 접촉은 치료 활동의 초기에 사용되기 어려워 초기 치료 효과를 기대하기 어려웠다. 이에 본 논문에서는 동작 방식을 보완하여 음성 정보를 이용한 빠른 상호작용을 통해 치료 활동이 초기에 가능하고 유연한 대처와 다양한 상황에서 로봇이 사용될 수 있는 동작 설계를 기술한다. 이에 필요한 요소로서 음성 데이터 수집 방법 및 인공신경망을 이용한 음성 인식 구조가 설계되었으며 실험을 통하여 분류 결과를 분석하였다. 이렇게 설계된 인공신경망은 향후 다양한 음성 데이터를 수집하여 정확도를 향상시키고 현장실험을 통하여 동작의 효용성을 살펴볼 것이다.