• Biomolecules & Therapeutics
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• 제20권2호
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• pp.207-213
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• 2012

The present study examined the effects of krill-derived phosphatidylserine (Krill-PS) on the learning and memory function and the neural activity in rats with trimethyltin (TMT)-induced memory deficits. The rats were administered vehicle (medium-chain triglyceride: MCT) or Krill-PS (50, 100 mg/kg, p.o.) daily for 21 days. The cognitive improving efficacy of Krill-PS in TMT-induced amnesic rats was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), acetylcholinesterase (AChE) and cAMP responsive element binding protein (CREB) immunohistochemistry. The rats with TMT injection showed impaired learning and memory of the tasks and treatment with Krill-PS produced a significant improvement of the escape latency to find the platform in the Morris water maze at the $2^{nd}$ and $4^{th}$ day compared to that of the MCT group (p<0.05). In the retention test, the Krill-PS+MCT groups showed increased time spent around the platform compared to that of the MCT group. Consistent with the behavioral data, Krill-PS 50+MCT group significantly alleviated the loss of acetylcholinergic neurons in the hippocampus and medial septum compared to that of the MCT group. Treatment with Krill-PS significantly increased the CREB positive neurons in the hippocampal CA1 area as compared to that of the MCT group. These results suggest that Krill-PS may be useful for improving the cognitive function via regulation of cholinergic marker enzyme activity and neural activity.

• Biomolecules & Therapeutics
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• 제22권3호
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• pp.176-183
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• 2014

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

• Physical Therapy Rehabilitation Science
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• 제8권3호
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• pp.125-133
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• 2019

Objective: To compare the postural control between non-specific chronic low back pain (NSCLBP) subgroups and healthy people during dynamic balance performance using a modified Star Excursion Balance Test (mSEBT). Design: Cross-sectional study. Methods: Eighteen NSCLBP subjects (9 active extension pattern [AEP], 9 flexion pattern [FP]), and 10 healthy controls were enrolled in this study. All subjects performed mSEBT on their dominant leg on a force plate. Normalized reach distance and balance parameters, including the center of pressure (COP) displacement and velocity, were recorded. Results: There were significant differences in mean reach distances in both posterolateral and posteromedial (PM) reach directions between AEP and healthy subjects (p<0.001) and between FP and healthy subjects (p<0.001). However, there were no significant differences among the three groups in the anterior reach direction. Also, the results showed no significant differences in mean COP variables (velocity and displacement) between pooled NSCLBP and healthy subjects. However, the subjects were reclassified into AEP, FP and healthy groups and the results showed a significant difference in mean COP velocity in the PM direction between AEP and FP subjects (p=0.048), and between AEP and healthy subjects (p=0.024). Conclusions: The findings in this study highlight the heterogeneity of the individuals with NSCLBP and the importance of identifying the homogenous subgroups. Individuals with AEP and FP experience deficits in dynamic postural control compared to healthy controls. In addition, the findings of this study support the concept of the Multidimensional Classification System.

• 국제물리치료학회지
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• 제10권2호
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• pp.1803-1809
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• 2019

Background: Cervical mobilization has been applied mainly for the improvement of arm and neck movements and pain reduction, and little research has been done to improve the executive function. Since this kind of so-called mechanical neck pain is one of most common symptoms, there are controversial issues about this with spine alignment. Posteroanterior (PA) mobilization from the Maitland concept is a process of examination, assessment, and treatment of neuromusculoskeletal disorder by manipulative physical therapy. Objective: To examine the short-term benefits of mobilization for patients with non-specific neck pain. Design: Dual-group Pretest-Posttest Design from the Quasi-Experimental research Methods: Fourteen participants (male 8, female 6; 20's of their age) with non-specific neck pains which are distributed all the unilateral or bilateral body side were recruited. Participants were categorized to Neck Pain with Movement Coordination Impairments (NPMCI) and Neck Pain with Mobility Deficits (NPMD) groups according to the results of physical examination. Professional physical therapist who has over 15-years-of clinical experience applicated manipulative therapy for the neck pain, an occupational therapist only conducted evaluations; K-NDI (Korean version of the Neck Disability Index), VAS (Visual Analog Scale), BDS-K (Korean version of Behavioral Dyscontrol Scale) for decreasing possible adverse effects; there were no person who reported other symptoms followed 4 weeks from the trial. Results: In the NPMCI group, data analysis indicated statistical differences between the PA mobilization interventions in NDI and BDS-K; even though, pain was reduced in VAS, this is not a significantly differ. In the NPMD group, data analysis represented statistical differences between the PA mobilization interventions in NDI, VAS and BDS-K; the scores were represented to be increased or the pain got relief. Conclusions: PA mobilization techniques according to Maitland concept have beneficial effects in patients with neck pain and other clinical positive effects which included neck disability, pain itself and motor function of upper extremity.

• Biomolecules & Therapeutics
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• 제30권3호
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• pp.232-237
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• 2022

Autism spectrum disorder (ASD) having core characteristics of social interaction problems and repetitive behaviors and interests affects individuals at varying degrees and comorbidities, making it difficult to determine the precise etiology underlying the symptoms. Given its heterogeneity, ASD is difficult to treat and the development of therapeutics is slow due to the scarcity of animal models that are easy to produce and screen with. Based on the theory of excitation/inhibition imbalance in the brain with ASD which involves glutamatergic and/or GABAergic neurotransmission, a pharmacologic agent to modulate these receptors might be a good starting point for modeling. N-methyl-D-aspartic acid (NMDA) is an amino acid derivative acting as a specific agonist at the NMDA receptor and therefore imitates the action of the neurotransmitter glutamate on that receptor. In contrast to glutamate, NMDA selectively binds to and regulates the NMDA receptor, but not other glutamate receptors such as AMPA and kainite receptors. Given this role, we aimed to determine whether NMDA administration could result in autistic-like behavior in adolescent mice. Both male and female mice were treated with saline or NMDA (50 and 75 mg/kg) and were tested on various behavior experiments. Interestingly, acute NMDA-treated mice showed social deficits and repetitive behavior similar to ASD phenotypes. These results support the excitation/inhibition imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model of ASD-like behaviors.

• BMB Reports
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• 제56권3호
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• Journal of Preventive Medicine and Public Health
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• 제56권2호
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• pp.145-153
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• 2023

Objectives: Although it is difficult to define the quality of stroke care, acute ischemic stroke (AIS) patients with moderate-to-severe neurological deficits may benefit from thrombectomy-capable hospitals (TCHs) that have a stroke unit, stroke specialists, and a substantial endovascular thrombectomy (EVT) case volume. Methods: From national audit data collected between 2013 and 2016, potential EVT candidates arriving within 24 hours with a baseline National Institutes of Health Stroke Scale score ≥6 were identified. Hospitals were classified as TCHs (≥15 EVT case/y, stroke unit, and stroke specialists), primary stroke hospitals (PSHs) without EVT (PSHs-without-EVT, 0 case/y), and PSHs-with-EVT. Thirty-day and 1-year case-fatality rates (CFRs) were analyzed using random intercept multilevel logistic regression. Results: Out of 35 004 AIS patients, 7954 (22.7%) EVT candidates were included in this study. The average 30-day CFR was 16.3% in PSHs-without-EVT, 14.8% in PSHs-with-EVT, and 11.0% in TCHs. The average 1-year CFR was 37.5% in PSHs-without-EVT, 31.3% in PSHs-with-EVT, and 26.2% in TCHs. In TCHs, a significant reduction was not found in the 30-day CFR (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.76 to 1.12), but was found in the 1-year CFR (OR, 0.84; 95% CI, 0.73 to 0.96). Conclusions: The 1-year CFR was significantly reduced when EVT candidates were treated at TCHs. TCHs are not defined based solely on the number of EVTs, but also based on the presence of a stroke unit and stroke specialists. This supports the need for TCH certification in Korea and suggests that annual EVT case volume could be used to qualify TCHs.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.11-18
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• 2020

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

• ALGAE
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• 제31권1호
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• pp.73-84
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• 2016

Marine organisms are frequently used to be harmful and have lower side effects than synthetic drugs. The cognitive improving efficacy of gamma aminobutyric acid-enriched fermented Saccharina japonica (FSJ) on the memory deficient rats, which were induced by trimethyltin chloride (TMT), was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), cAMP response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) immunohistochemistry. The neurite outgrowth of Neuro2a cells was assessed in order to examine the underlying mechanisms of the memory enhancing effects of FSJ. Treatment with FSJ tended to shorten the latency to find the platform in the acquisition test of the Morris water maze at the second and fourth day compared to the control group. In the probe trial, the FSJ treated group increased time spent in the target quadrant, compared to that of the control group. Consistent with the behavioral data, these treatments recovered the loss of ChAT, CREB, and BDNF immunepositive neurons in the hippocampus produced by TMT. Treatment with FSJ markedly stimulated neurite outgrowth of the Neuro2a cells as compared to that of the controls. These findings demonstrate that FSJ may be useful for improving the cognitive function via regulation of neurotrophic marker enzyme activity.

• 대한조현병학회지
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• 제24권1호
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• pp.26-35
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• 2021

Objectives: Social function deficit is known as a core feature of schizophrenia. This study aimed to investigate differences in empathic tendencies and theory of mind (ToM) skills between healthy controls and young individuals with schizophrenia, and to examine the associations between empathic tendencies, ToM skills and schizotypy, and executive function in schizophrenia. Methods: Thirty patients with schizophrenia and 30 healthy controls were enrolled and assessed using the interpersonal relationship index (IRI; perspective taking, fantasy, empathic concern, and personal distress subscales), ToM-Picture Story Task (ToM-PST; sequence and cognitive questionnaire), Wisconsin schizotypy scale (revised physical anhedonia and perceptual aberration), and Stroop tests for empathic tendencies, ToM skills, schizotypy, and executive function. Results: In individuals with schizophrenia, the IRI for perspective taking and ToM-PST score for cognitive function were lower, and the IRI for personal distress was higher than those in healthy controls. The IRIs for perspective taking and fantasy were related to revised physical anhedonia, and that for empathic concern was associated with revised physical anhedonia and perceptual aberration. The ToM-PST score for sequence was associated with the Stroop test score for schizophrenia. Conclusion: These findings indicate deficits in empathic tendencies and ToM skills, which may be independently and primarily associated with schizotypy and executive function in young individuals with schizophrenia.