• Journal of Ginseng Research
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• 제45권3호
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• pp.390-400
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• 2021

Background: We recently showed that gintonin, an active ginseng ingredient, exhibits antibrain neurodegenerative disease effects including multiple target mechanisms such as antioxidative stress and antiinflammation via the lysophosphatidic acid (LPA) receptors. Amyotrophic lateral sclerosis (ALS) is a spinal disease characterized by neurodegenerative changes in motor neurons with subsequent skeletal muscle paralysis and death. However, pathophysiological mechanisms of ALS are still elusive, and therapeutic drugs have not yet been developed. We investigate the putative alleviating effects of gintonin in ALS. Methods: The G93A-SOD1 transgenic mouse ALS model was used. Gintonin (50 or 100 mg/kg/day, p.o.) administration started from week seven. We performed histological analyses, immunoblot assays, and behavioral tests. Results: Gintonin extended mouse survival and relieved motor dysfunctions. Histological analyses of spinal cords revealed that gintonin increased the survival of motor neurons, expression of brain-derived neurotrophic factors, choline acetyltransferase, NeuN, and Nissl bodies compared with the vehicle control. Gintonin attenuated elevated spinal NAD(P) quinone oxidoreductase 1 expression and decreased oxidative stress-related ferritin, ionized calcium-binding adapter molecule 1-immunoreactive microglia, S100β-immunoreactive astrocyte, and Olig2-immunoreactive oligodendrocytes compared with the control vehicle. Interestingly, we found that the spinal LPA1 receptor level was decreased, whereas gintonin treatment restored decreased LPA1 receptor expression levels in the G93A-SOD1 transgenic mouse, thereby attenuating neurological symptoms and histological deficits. Conclusion: Gintonin-mediated symptomatic improvements of ALS might be associated with the attenuations of neuronal loss and oxidative stress via the spinal LPA1 receptor regulations. The present results suggest that the spinal LPA1 receptor is engaged in ALS, and gintonin may be useful for relieving ALS symptoms.

• Biomolecules & Therapeutics
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• 제32권1호
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• pp.154-161
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• 2024

Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disorder that causes progressive paralysis. L-Citrulline is a nonessential neutral amino acid produced by L-arginine via nitric oxide synthase (NOS). According to previous studies, the pathogenesis of ALS entails glutamate toxicity, oxidative stress, protein misfolding, and neurofilament disruption. In addition, L-citrulline prevents neuronal cell death in brain ischemia; therefore, we investigated the change in the transport of L-citrulline under various pathological conditions in a cell line model of ALS. We examined the uptake of [¹⁴C]L-citrulline in wild-type (hSOD1wt/WT) and mutant NSC-34/ SOD1^G93A (MT) cell lines. The cell viability was determined via MTT assay. A transport study was performed to determine the uptake of [¹⁴C]L-citrulline. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was performed to determine the expression levels of rat large neutral amino acid transported 1 (rLAT1) in ALS cell lines. Nitric oxide (NO) assay was performed using Griess reagent. L-Citrulline had a restorative effect on glutamate induced cell death, and increased [¹⁴C]L-citrulline uptake and mRNA levels of the large neutral amino acid transporter (LAT1) in the glutamate-treated ALS disease model (MT). NO levels increased significantly when MT cells were pretreated with glutamate for 24 h and restored by co-treatment with L-citrulline. Co-treatment of MT cells with L-arginine, an NO donor, increased NO levels. NSC-34 cells exposed to high glucose conditions showed a significant increase in [¹⁴C]L-citrulline uptake and LAT1 mRNA expression levels, which were restored to normal levels upon co-treatment with unlabeled L-citrulline. In contrast, exposure of the MT cell line to tumor necrosis factor alpha, lipopolysaccharides, and hypertonic condition decreased the uptake significantly which was restored to the normal level by co-treating with unlabeled L-citrulline. L-Citrulline can restore NO levels and cellular uptake in ALS-affected cells with glutamate cytotoxicity, pro-inflammatory cytokines, or other pathological states, suggesting that L-citrulline supplementation in ALS may play a key role in providing neuroprotection.

• 대한한의학회지
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• 제25권4호
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• pp.188-199
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• 2004

Transglutaminase 2 (TGase 2) is an enzyme that is widely used in many biological systems for generic tissue stabilization purposes or immediate defenses for wounds. Many reports have showed that TGase 2 is aberrantly activated in tissues and cells and contributes to a variety of diseases, including neurodegenerative diseases and autoimmune diseases. In most cases, the TGase 2 appears to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. However, in other cases such as celiac disease, arthritis, lupus, amyotrophic lateral sclerosis, TGase 2 is involved in the generation of autoantibodies. This suggests the possibility that the inappropriate expression and/or presentation of TGase 2 to T cells might contribute to these diseases in genetically predisposed individuals. Others and we have found that TGase 2 expression is also increased in the inflammation process. We also demonstrated reverse of inflammation by TGase inhibition. Furthermore we discovered the genuine role of TGase 2 in immune cell activation. Increase of TGase activity induces or exacerbates inflammation via NF-κB activation without I-κBα kinase signalings. This review will examine a possibility of TGase inhibitors as therapeutic agents in a variety of inflammatory diseases.

• Animal cells and systems
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• 제14권1호
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• pp.1-10
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• 2010

Previously we showed that CHIP, a co-chaperone of Hsp70 and E3 ubiquitin ligase, can promote the degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis (fALS) via a mechanism not involving SOD1 ubiquitylation. Here we present evidence that CHIP functions in the interaction of mutant SOD1 with 26S proteasomes. Bag-1, a coupling factor between molecular chaperones and the proteasomes, formed a complex with SOD1 in an hsp70-dependent manner but had no direct effect on the degradation of mutant SOD1. Instead, Bag-1 stimulated interaction between CHIP and the proteasome-associated protein VCP (p97), which do not associate normally. Over-expressed CHIP interfered with the association between mutant SOD1 and VCP. Conversely, the binding of CHIP to mutant SOD1 was inhibited by VCP, implying that the chaperone complex and proteolytic machinery are competing for the common substrates. Finally we observed that mutant SOD1 strongly associated with the 19S complex of proteasomes and CHIP over-expression specifically reduced the interaction between S6/S6' ATPase subunits and mutant SOD1. These results suggest that CHIP, together with ubiquitin-binding proteins such as Bag-1 and VCP, promotes the degradation of mutant SOD1 by facilitating its translocation from ATPase subunits of 19S complex to the 20S core particle.

• Annals of Clinical Neurophysiology
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• 제13권1호
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• pp.1-12
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• 2011

Transcranial magnetic stimulation (TMS) is a non-invasive tool used to study aspects of human brain physiology, including motor function and the pathophysiology of various brain disorders. A brief electric current passed through a magnetic coil produces a high-intensity magnetic field, which can excite or inhibit the cerebral cortex. Although various brain regions can be evaluated by TMS, most studies have focused on the motor cortex where motor evoked potentials (MEPs) are produced. Single-pulse and paired-pulse TMS can be used to measure the excitability of the motor cortex via various parameters, while repetitive TMS induces cortical plasticity via long-term potentiation or long-term depression-like mechanisms. Therefore, TMS is useful in the evaluation of physiological mechanisms of various neurological diseases, including movement disorders and epilepsy. In addition, it has diagnostic utility in spinal cord diseases, amyotrophic lateral sclerosis and demyelinating diseases. The therapeutic effects of repetitive TMS on stroke, Parkinson disease and focal hand dystonia are limited since the duration and clinical benefits seem to be temporary. New TMS techniques, which may improve clinical utility, are being developed to enhance clinical utilities in various neurological diseases.

• Journal of Acupuncture Research
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• 제30권5호
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• pp.247-252
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• 2013

Objectives : The purpose of this study was to observe the clinical effects of acupuncture therapy and Ecklonia cava extract on sleep disturbance in ALS patients. Methods : In this study one patient received acupuncture therapy and took Ecklonia cava extract. The effects of the combined administration of these treatments were evaluated using Numeric Rating Scale and Pittsburgh Sleep Quality Index. Results : The NRS score for sleep disturbance decreased from 10 to 1 and the PSQI score decreased from between 12~13 to 8. After treatment, the patient stopped taking sleeping pills and antidepressant. Conclusions : Combined administration of acupuncture therapy and Ecklonia cava extract could be effective in improving sleep disturbances in ALS patient.

• 대한후두음성언어의학회지
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• 제27권1호
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• pp.54-57
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• 2016

Percutaneous dilatational tracheostomy (PDT) has become an increasingly popular method of establishing an airway for patients in need of chronic ventilator assistance. We report a rare case of a 42-year-old female who developed extensive subcutaneous emphysema, bilateral pneumothoraces, pneumomediastinum, and pneumoperitoneum after percutaneous dilatational tracheostomy. The patient suffered from amyotrophic lateral sclerosis, and underwent PDT after a period of mechanical ventilation. During PDT, tracheostomy tube was inserted into the paratracheal space. Follow-up chest radiography and computed tomography of chest and abdomen revealed extensive subcutaneous emphysema, bilateral pneumothoraces, pneumomediastinum, and pneumoperitoneum. The patient was treated successfully with insertion of the thoracostomy tube and conservative care.

• 동의신경정신과학회지
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• 제18권3호
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• pp.237-247
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• 2007

People with somatoform disorder have a number of different symptoms that typically last for several years. Their symptoms can't be traced to a specific physical cause. In people with somatoform disorder, medical test results are either normal or don't explain the person's symptoms. The symptoms of somatoform disorder are similar to the symptoms of other illnesses. People with this disorder may have several medical evaluations and tests to be sure that they don't have another illness. In this case, we described a 56-year old man who was diagnosed as R/O) ALS, because he has many similar symptoms of ALS (amyotrophic lateral sclerosis) such as gait disturbance, dysarthria, dyspnea. But we diagnosed his case as somatoform disorder and treated with herbal medication, acupuncure treatment ,negative cupping and relaxation training. Through these treatment, the patient showed improvement of chief complains and accessory symptoms.

• 대한한의학회지
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• 제24권4호
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• pp.139-148
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• 2003

Objectives : Polyneuropathies are diseases of multiple peripheral nerves. They are usually characterized by symmetrical, bilateral distal motor and sensory impairment with a graded increase in severity distally. It is generally regarded that the natural courses are poor, so we wanted to study the effects of Oriental medical treatment on a patient with polyneuropathy. Methods : We treated by conservative Oriental medical treatment a woman of 68 years who was diagnosed as a polyneuropathy and was hospitalized at Seoul Oriental Hospital, Kyungwon University, from 12th Mar. to 31st May, 2003. Changes of functional disability were checked by Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS), muscle atrophy was checked by measuring circumference of the thighs, calves, arms, and sensory impairment was checked by a sensory test. Results : 1. Functional disability caused by motor impairment was reduced after the Oriental medical treatment 2. Muscle atrophy was reduced after the Oriental medical treatment 3. Sensory impairment was reduced after the Oriental medical treatment Conclusion : We treated a patient who was diagnosed with polyneuropathy for over 80 days and recorded good effects of Oriental medical treatment on polyneuropathy.

• 한국정보통신학회:학술대회논문집
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• 한국정보통신학회 2018년도 춘계학술대회
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• pp.696-699
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• 2018

본 논문은 FPGA를 이용해서 몸을 움직이지 못하는 루게릭병 환자들을 위해 동공을 추적하여 의사 소통을 할 수 있게 해주는 시스템을 소개한다. OpenCV를 이용한 얼굴 및 눈동자 추적과 DE1-SoC보드를 이용하여 눈의 움직임 검출과 문자를 출력한다. 본 논문에서는 웹캠을 사용하고 눈동자를 추적하고 눈동자의 좌표 값에 따라 눈동자의 움직임을 파악하고 사용자의 의도에 맞는 문자를 출력한다. 비교적 개발비용이 저렴하고 업데이트 가능한 FPGA를 사용하고, 블루투스를 이용하여 핸드폰으로 쉽게 문자를 출력할 수 있는 시스템을 제안한다.