Background: Niemann-Pick disease type C (NPC) is caused by the mutation of NPC genes, which leads to the abnormal accumulation of unesterified cholesterol and glycolipids in lysosomes. This autosomal recessive disease is characterized by liver dysfunction, hepatosplenomegaly, and progressive neurodegeneration. Recently, the application of induced neural stem cells (iNSCs), converted from fibroblasts using specific transcription factors, to repair degenerated lesions has been considered a novel therapy. Objectives: The therapeutic effects on NPC by human iNSCs generated by our research group have not yet been studied in vivo; in this study, we investigate those effects. Methods: We used an NPC mouse model to efficiently evaluate the therapeutic effect of iNSCs, because neurodegeneration progress is rapid in NPC. In addition, application of human iNSCs from NPC patient-derived fibroblasts in an NPC model in vivo can give insight into the clinical usefulness of iNSC treatment. The iNSCs, generated from NPC patientderived fibroblasts using the SOX2 and HMGA2 reprogramming factors, were transplanted by intracerebral injection into NPC mice. Results: Transplantation of iNSCs showed positive results in survival and body weight change in vivo. Additionally, iNSC-treated mice showed improved learning and memory in behavior test results. Furthermore, through magnetic resonance imaging and histopathological assessments, we observed delayed neurodegeneration in NPC mouse brains. Conclusions: iNSCs converted from patient-derived fibroblasts can become another choice of treatment for neurodegenerative diseases such as NPC.
Objective: This study was designed to investigate effects of Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture on body weight, body length, intellectual development Methods: We observed body weight, body length, intellectual development after feeding Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture for thirty three days, and mRNA expressions of GHRF, Somatostatin, IGF-1, NPY were analyzed by RT-PCR method. Results: The results were summarized as follows. 1. Body length was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to normal group and normal saline injection group on 4th week, 2. Lower part of hind leg length was significantly increased in Nokyongsageunhwan oral administration group compared to normal group on 3rd week, and it was significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 3. As results of observing memory aquisition using Morris water maze system, there was significantly difference in Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 4. As results of observing retention using Morris water maze system, staying time was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group. 5. The somatostatin mRNA expression in the hypothalamus was significantly decreased in Nokyongsageunhwan oral administration group compared to that of normal group. 6. The IGF-1 mRNA expression in the hypothalamus is significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group. 7. The NPY mRNA expression in the hypothalamus was significantly increased in Nokyongsageunhwan oral administration group compared to that of normal group, and it was increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group, but there was no significant difference. Conclusions: According to the above results, it appears that Nokyongsageunhwan oral administration and Nokyongsageunhwan herbal acupuncture on acupoint GB34 and GB39 showed effects on the growth and the intellectual development of rats.
Kim, Jinmok;Kim, Donguk;Park, Jinbum;Kim, Jihoon;Kim, Hyoungshick
Journal of the Korea Institute of Information Security & Cryptology
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v.25
no.4
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pp.863-872
/
2015
Kernel rootkit is recognized as one of the most severe and widespread threats to corrupt the integrity of an operating system. Without an external monitor as a root of trust, it is not easy to detect kernel rootkits which can intercept and modify communications at the interfaces between operating system components. To provide such a monitor isolated from an operating system that can be compromised, most existing solutions are based on external hardware. Unlike those solutions, we develop a kernel introspection system based on the ARM TrustZone technology without incurring extra hardware cost, which can provide a secure memory space in isolation from the rest of the system. We particularly use a secure timer to implement an autonomous switch between secure and non-secure modes. To ensure integrity of reference, this system measured reference from vmlinux which is a kernel original image. In addition, the flexibility of monitoring block size can be configured for efficient kernel introspection system. The experimental results show that a secure kernel introspection system is provided without incurring any significant performance penalty (maximum 6% decrease in execution time compared with the normal operating system).
Lee Sang Won;Kim Sang Ho;Kim Tae Heon;Kang Hyung Won;Lyu Yeoung Su
Journal of Physiology & Pathology in Korean Medicine
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v.18
no.2
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pp.507-516
/
2004
Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the commom disease in public health service. Although a variety of oriental presciptions in study POD(Polygala tenuifolia extracted from dichlorometan) have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet fully elucidated. It has been widely believed that AP peptide divided from APP causes apoptotic neurotoxicity in AD brain. However, recent evidence suggests that CT105, carboxy terminal 105 aminoacids peptide fragment of APP, may be an important factor causing neurotoxicity in AD. SK-N-SH cells expressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase contrast microscope and NO formation in the culture media, the CT105-induced cell death was significantly inhibited by POD. In addition, AD is one of brain degeneration disease. So We studied on herbal medicine that have a relation of brain degeneration. From old times, In Oriental Medicine, PO water extract has been used for disease in relation to brain degeneration. We were examined by ROS formation, neurite outgrowth assay and DPPH scravage assay. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. We studied on the regeneratory and inhibitory effects of anti-Alzheimer disease in pCT105-induced neuroblastoma cell lines by POD. Findings from our experiments have shown that POD inhibits the synthesis or activities of CT105, which has neurotoxityies and apoptotic activities in cell line. In addition, treatment of POD(>50 ㎍/㎖ for 12 hours) partially prevented CT(105)-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by the treatment with its. POD(>50 ㎍/㎖ for 12 hours) repaired CT105-induced neurite outgrowth when SK-N-SH cell lines was transfected with CT105. As the result of this study, In POD group, the apoptosis in the nervous system is inhibited, the repair against the degerneration of Neuroblastoma cells by CT105 expression is promoted. Decrease of memory induced by injection of scopolamin into rat was also attenuted by POD, based on passive avoidance test. Taken together, POD exhibited inhibition of CT105-induced apoptotic cell death. POD was found to reduce the activity of AchE and induced about the CA1 in rat hippocampus. Base on these findings, POD may be beneficial for the treatment of AD.
Electrochromic (EC) devices are capable of reversibly changing their optical properties upon charge injection and extraction induced by the external voltage. The characteristics of the EC device, such as low power consumption, high coloration efficiency, and memory effects under open circuit status, make them suitable for use in a variety of applications including smart windows and electronic papers. Coloration due to reduction or oxidation of redox chromophores can be used for EC devices (e-paper), but the switching time is slow (second level). Recently, with increasing demand for the low cost, lightweight flat panel display with paper-like readability (electronic paper), an EC display technology based on dye-modified $TiO_2$ nanoparticle electrode was developed. A well known organic dye molecule, viologen, was adsorbed on the surface of a mesoporous $TiO_2$ nanoparticle film to form the EC electrode. On the other hand, ZnO is a wide bandgap II-VI semiconductor which has been applied in many fields such as UV lasers, field effect transistors and transparent conductors. The bandgap of the bulk ZnO is about 3.37 eV, which is close to that of the $TiO_2$ (3.4 eV). As a traditional transparent conductor, ZnO has excellent electron transport properties, even in ZnO nanoparticle films. In the past few years, one-dimension (1D) nanostructures of ZnO have attracted extensive research interest. In particular, 1D ZnO nanowires renders much better electron transportation capability by providing a direct conduction path for electron transport and greatly reducing the number of grain boundaries. These unique advantages make ZnO nanowires a promising matrix electrode for EC dye molecule loading. ZnO nanowires grow vertically from the substrate and form a dense array (Fig. 1). The ZnO nanowires show regular hexagonal cross section and the average diameter of the ZnO nanowires is about 100 nm. The cross-section image of the ZnO nanowires array (Fig. 1) indicates that the length of the ZnO nanowires is about $6\;{\mu}m$. From one on/off cycle of the ZnO EC cell (Fig. 2). We can see that, the switching time of a ZnO nanowire electrode EC cell with an active area of $1\;{\times}\;1\;cm^2$ is 170 ms and 142 ms for coloration and bleaching, respectively. The coloration and bleaching time is faster compared to the $TiO_2$ mesoporous EC devices with both coloration and bleaching time of about 250 ms for a device with an active area of $2.5\;cm^2$. With further optimization, it is possible that the response time can reach ten(s) of millisecond, i.e. capable of displaying video. Fig. 3 shows a prototype with two different transmittance states. It can be seen that good contrast was obtained. The retention was at least a few hours for these prototypes. Being an oxide, ZnO is oxidation resistant, i.e. it is more durable for field emission cathode. ZnO nanotetropods were also applied to realize the first prototype triode field emission device, making use of scattered surface-conduction electrons for field emission (Fig. 4). The device has a high efficiency (field emitted electron to total electron ratio) of about 60%. With this high efficiency, we were able to fabricate some prototype displays (Fig. 5 showing some alphanumerical symbols). ZnO tetrapods have four legs, which guarantees that there is one leg always pointing upward, even using screen printing method to fabricate the cathode.
Journal of the Korean Society of Food Science and Nutrition
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v.43
no.6
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pp.799-806
/
2014
The present study was conducted to evaluate the effects of extract from Eriobotrya japonica leaves (EJE) on cognitive impairment induced by scopolamine, a muscarinic antagonist, in rats. Scopolamine injection (1 mg/kg, i.p.) impaired performance in rats in the passive avoidance test as well as in water maze test and severely reduced cholinergic system reactivity, as indicated by reduced acetylcholine levels and increased acetylcholinesterase activity. Daily administration of EJE significantly increased step-through latency in the passive avoidance test, reduced escape latency, and increased time spent in the platform quadrant in the Morris water maze test. EJE protected against scopolamine-induced cholinergic system deficit, including reduced acetylcholine levels and increased acetylcholinesterase activity in whole brain homogenates. These results suggest that EJE provides a significant anti-amnesic effect against scopolamine-induced cholinergic system deficits and cognitive impairment.
Sin, Seung Mi;Kim, Ji Hyun;Cho, Eun Ju;Kim, Hyun Young
Journal of Applied Biological Chemistry
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v.64
no.3
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pp.299-307
/
2021
Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ25-35-induced cognitive impairment.
Kim, Min Jeong;Lee, Ah Young;Cho, Dong Shik;Cho, Eun Ju
Journal of the Korea Academia-Industrial cooperation Society
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v.20
no.5
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pp.241-251
/
2019
In the present study, we investigated the effect of microcurrent against cognitive impairment in Alzheimer's disease (AD) mice model. The cognitive impairment was induced by intracerebroventricularly injection of amyloid beta ($A{\beta}$) to ICR mouse brain, and four kinds of micorocurrent wave were applied to AD mice. We observed the improved cognitive ability in microcurrent-applied AD mice through novel object recognition test and Morris water maze test, compared to $A{\beta}$-injected control group. The contents of malondialdehyde generated by $A{\beta}$ in the brain were also reduced by microcurrent application. These effects of microcurrent were related to the modulation of $A{\beta}$ producing and brain-derived neurotrophic factor (BDNF). Microcurrent down-regulated ${\beta}$-secretase, presenilin 1, and presenilin 2 which were related amyloidogenic pathway, and up-regulated human brain-derived neurotrophic factor in the mice brain, especially Wave4 group [STEP FORM wave form (0, 1.5, 3, 5V), wave superposition]. These results suggest that microcurrent application could provide help for improvement learning and memory ability, at least partly.
In order to measure the volatile organic compounds (VOCs) of a sample which is too large to use commercially available chamber, a stainless steel vacuum chamber (VC) (with an internal diameter of 205 mm and a height of 50 mm) was manufactured and the temperature of the chamber was controlled using an oven. After concentrating the volatiles of the sample in the chamber by helium gas, it was made possible to remove residual volatile substances present in the chamber under reduced pressure ((2 ± 1) × 10-2 mmHg). The chamber was connected to a purge & trap (P&T) using a 6 port valve to concentrate the VOCs, which were analyzed by gas chromatography-mass spectrometry (GC-MS) after thermal desorption (VC-P&T-GC-MS). Using toluene, the toluene recovery rate of this device was 85 ± 2 %, reproducibility was 5 ± 2 %, and the detection limit was 0.01 ng L-1. The method of removing VOCs remaining in the chamber with helium and the method of removing those with reduced pressure was compared using Korean drinking water regulation (KDWR) VOC Mix A (5 μL of 100 ㎍ mL-1) and butylated hydroxytoluene (BHT, 2 μL of 500 ㎍ mL-1). In case of using helium, which requires a large amount of gas and time, reduced pressure ((2 ± 1) × 10-2 mmHg) only during the GC-MS running time, could remove VOCs and BHT to less than 0.1 % of the original injection concentration. As a result of analyzing volatile substances using VC-P&T-GC-MS of six types of cell phone case, BHT was detected in four types and quantitatively analyzed. Maintaining the chamber at reduced pressure during the GC-MS analysis time eliminated memory effect and did not affect the next sample analysis. The volatile substances in a cell phone case were also analyzed by dynamic headspace (HT3) and GC-MS, and the results of the analysis were compared with those of VC-P&T-GC-MS. Considering the chamber volume and sample weight, the VC-P&T configuration was able to collect volatile substances more efficiently than the HT3. The VC-P&T-GC-MS system is believed to be useful for VOCs measurement of inhomogeneous large sample or devices used inside clean rooms.
Xianan Dong ;Liangliang Kong ;Lei Huang ;Yong Su ;Xuewang Li;Liu Yang;Pengmin Ji ;Weiping Li ;Weizu Li
Journal of Ginseng Research
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v.47
no.3
/
pp.458-468
/
2023
Background: As a complication of Type II Diabetes Mellitus (T2DM), the etiology, pathogenesis, and treatment of cognitive dysfunction are still undefined. Recent studies demonstrated that Ginsenoside Rg1 (Rg1) has promising neuroprotective properties, but the effect and mechanism in diabetes-associated cognitive dysfunction (DACD) deserve further investigation. Methods: After establishing the T2DM model with a high-fat diet and STZ intraperitoneal injection, Rg1 was given for 8 weeks. The behavior alterations and neuronal lesions were judged using the open field test (OFT) and Morris water maze (MWM), as well as HE and Nissl staining. The protein or mRNA changes of NOX2, p-PLC, TRPC6, CN, NFAT1, APP, BACE1, NCSTN, and Ab1-42 were investigated by immunoblot, immunofluorescence or qPCR. Commercial kits were used to evaluate the levels of IP3, DAG, and calcium ion (Ca2+) in brain tissues. Results: Rg1 therapy improved memory impairment and neuronal injury, decreased ROS, IP3, and DAG levels to revert Ca2+ overload, downregulated the expressions of p-PLC, TRPC6, CN, and NFAT1 nuclear translocation, and alleviated Aβ deposition in T2DM mice. In addition, Rg1 therapy elevated the expression of PSD95 and SYN in T2DM mice, which in turn improved synaptic dysfunction. Conclusions: Rg1 therapy may improve neuronal injury and DACD via mediating PLC-CN-NFAT1 signal pathway to reduce Aβ generation in T2DM mice.
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