• The Korean Journal of Nuclear Medicine
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• v.37 no.6
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• pp.374-381
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• 2003

Purpose: Determining an appropriate thresholding is crucial for PDG PET analysis since strong control of Type I error could fail to find pathological differences between eariy Alzheimer' disease (AD) patients and healthy normal controls. We compared the SPM results on FDG PET imaging of early AD using uncorrected p-value, random-field based corrected p-value and false discovery rate (FDR) control. Materials and Methods: Twenty-eight patients ($66{\pm}7$ years old) with early AD and 18 age-matched normal controls ($68{\pm}6$ years old) underwent FDG brain PET. To identify brain regions with hypo-metabolism in group or individual patient compared to normal controls, group images or each patient's image was compared with normal controls usingthe same fixed p-value of 0.001 on uncorrected thresholding, random-field based corrected thresholding and FDR control. Results: The number of hypo-metabolic voxels was smallest in corrected p-value method, largest in uncorrected p-value method and intermediate in FDG thresholding in group analysis. Three types of result pattern were found. The first was that corrected p-value did not yield any voxel positive but FDR gave a few significantly hypometabolic voxels (8/28, 29%). The second was that both corrected p-value and FDR did not yield any positive region but numerous positive voxels were found with the threshold of uncorrected p-values (6/28, 21%). The last was that FDR was detected as many positive voxels as uncorrected p-value method (14/28, 50%). Conclusions FDR control could identify hypo-metaboiic areas in group or individual patients with early AD. We recommend FDR control instead of uncorrected or random-field corrected thresholding method to find the areas showing hypometabolism especially in small group or individual analysis of FDG PET.

• Journal of Oriental Neuropsychiatry
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• v.9 no.1
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• pp.1-24
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• 1998

The effects of Hyungbangjiwhangrang on the enhancement of learning and memory of AD model rats were studied with Morris water maze and radial arm maze. Sample group was electrolytically lesioned on nbM, and then daily treated with the medicine for two months. Control group with nbM lesion, and sham group with the sham operation were treated the vehicle for same duration. The following results were observed.1. As the learning trials of Morris water maze processed repeatedly, sham group achiened 201.64${\pm}$33.13 seconds in 1st trial, 153.14${\pm}$61.80 seconds in 2nd, 106.21${\pm}$46.81 seconds in 3rd, 76.64${\pm}$48.40 seconds in 4th, and 52.29${\pm}$38.25 seconds in 5th. The control group achieved 224.08${\pm}$29.16 in 1st trial, 191.77${\pm}$67.97 seconds in 2nd, 177.77${\pm}$65.44 seconds in 3rd, 140.92${\pm}$68.27 seconds in 4th, and 126.46${\pm}$79.15 seconds in 5th. The sample group achieved 223.36${\pm}$23.33 seconds in 1st trial, 215.86${\pm}$38.93 seconds in 2nd, 190.79${\pm}$51.57 seconds in 3rd, 155.79${\pm}$62.67 seconds in 4th, and 127.93${\pm}$62.11 seconds in 5th. Therefore, these data shows that all three groups were improved in learning capacity as trials were repeated, but the shame group showed prominent improvement in learning compared with the control group(p<0.05).2. In memory retention test of Morris water maze that counts the staying time in the target area, sham group stayed for 15.36${\pm}$5.39 seconds, the control group stayed for 5.54${\pm}$5.64 seconds, and the sample group stayed for 7.43${\pm}$6.09 seconds. The analysis of the memory retention data shows that the sham group marked more significant improvement stati- stically in memory retention compared with the control group(p<0.05).3. In the learning of radial arm maze, the number and rate of animals that arrive the learning criteria amounted 12 out of 14, 85.7% in sham group, 4 out of 13, 30.8% in the control group, and 10 out of 14, 71.4% in the sample group So, the sample group shows better learning capacity significantly compared with the control group(p<0.05). With the experimental results above, Hyungbangjiwhangtang can be supposed to have the improving effects on the learning and memory of AD rats induced by eletronical injury of nbM.

• Journal of the Institute of Electronics Engineers of Korea CI
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• v.49 no.1
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• pp.16-22
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• 2012

In this paper, we proposed a method of baseline correction for analysis of Raman spectra of platelets from Alzheimer's disease (AD) transgenic mice. Measured Raman spectra include the meaningful information and unnecessary noise which is composed of baseline and additive noise. The Raman spectrum is divided into the local region including several peaks and the spectrum of the region is modeled by curve fitting using Gaussian model. The additive noise is clearly removed from the process of replacing the original spectrum with the fitted model. The baseline correction after interpolating the local minima of the fitted model with linear, piecewise cubic Hermite and cubic spline algorithm. The baseline corrected models extract the feature with principal component analysis (PCA). The classification result of support vector machine (SVM) and maximum $a$ posteriori probability (MAP) using linear interpolation method showed the good performance about overall number of principal components, especially SVM gave the best performance which is about 97.3% true classification average rate in case of piecewise cubic Hermite algorithm and 5 principal components. In addition, it confirmed that the proposed baseline correction method compared with the previous research result could be effectively applied in the analysis of the Raman spectra of platelet.

• Journal of Oriental Neuropsychiatry
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• v.21 no.2
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• pp.125-140
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• 2010

Objectives : The purpose of this study is to examine from various angles the protective effect of Gastrodia elata Blume (GEB) against nerve cell death induced by $\beta$-amyloid by using the cell line SH-SY5Y, which is commonly utilized for toxicity testing in nerve cells, and to find out its mechanism of action. Methods : To begin with, as a result of assessing the rate of cell survival by employing MTT reduction assay, the treatment with $\beta$-amyloid at different concentrations caused cytotoxicity, which was inhibited by preprocessing GEB extract. In addition, after $\beta$-amyloid was processed with the cell SH-SY5Y, apoptosis progressed, which was reduced effectively by processing GEB extract. Results : When cytotoxicity was caused by using hydrogen peroxide, a representative ROS, in order to examine the antioxidant effect of GEB, its protective effect was also observed. Apart from ROS, reactive nitrogen species (RNS) are also known to play a crucial role in nerve cell death. The treatment with the NO donor SNAP increased the production of nitric oxide and the expression of iNOS, which was also inhibited by GEB extract. Meanwhile, as an attempt to find out the mechanism of action explaining the antioxidant effect, the intracellular antioxidant enzyme expressions were measured by RT-PCR, which showed that GEB extract increased the expressions of heme oxygenase-1, GAPDH and $\gamma$-glutamate cysteine ligase. Lastly, GEB extract had a protective effect against impaired memory induced by scopolamine in animal models (in vivo). Conclusions : These findings indicate that GEB has a protective effect against the death of cranial nerve cells, suggesting possibilities for the prevention and treatment of AD.

• Journal of Sasang Constitutional Medicine
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• v.21 no.3
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• pp.138-153
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• 2009

1. Objectives: Yeolda-Hanso tang (YH) has long been used as traditional herbal formula in Korea as various diseases. Now we modified Yeolda-Hanso tang (YH) for neurodegenerative diseases treatment and named New-Yeolda-Hanso tang (NYH). We investigated neuroprotective effects of NYH on NGF-differentiated PC12 cells cytotoxicity induced by $\beta$-Amyloid peptide (A$\beta$25-35) and evaluated the ability of NYH to prevent and treat for neurodegenerative diseases via autophagy enhancement. 2. Methods and Results: 1) Protective effect of NYH on PC12 cells cytotoxity induced by A$\beta$25-35. PC12 cells survival was measured by MTT and lactate dehydrogenase (LDH) assay. $20{\mu}M$ $\beta$-Amyloid peptide (A$\beta$25-35) induced cytotoxicity on NGF-differentiated PC12 cells. NYH attenuated the cytotoxic effects of A$\beta$25-35 in a dose-dependent manner. 2) Pharmacological induction of Autophagy by NYH in PC12 cells Autophagy induction and activation was measured by immunoblot assay. Marker of autophagy, LC3 II expression and the ratio of LC3-II/I was slightly increased in the protein treated with YH, and significantly augmented in the protein treated with NYH. NYH-induced increase of LC3-II protein level was inhibited by 3MA. 3) Induction of Autophagy by NYH on A$\beta$25-35-induced injury in PC12 cells In MTT assay, $100{\mu}g/ml$ re-treated NYH attenuated $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. Protection effect of NYH was blocked by autophagy inhibitor 3MA. In immunoblot assay, $1200{\mu}g/ml$ pre-treated NYH activated autophagy in $20{\mu}M$ A$\beta$25-35-induced cytotoxicity in PC12 cells. The observed effect was partially blocked by 3MA. 3. Conclusions: All the results indicated that NYH possesses neuroprotective potential partially mediated by autophagy enhancement and NYH may be considered to be a promising new herbal formula to prevent and treat for neurodegenerative diseases including Alzheimer's disease (AD).

• Biomolecules & Therapeutics
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• v.17 no.1
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• pp.70-78
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• 2009

Coptis japonica (C. japonica) is a perennial medicinal plant that has anti-inflammatory activity. C. japonica contains numerous biologically active alkaloids including berberine, palmatine, epi-berberine, and coptisine. The most well-known anti-inflammatory principal in C. japonica is berberine. For example, berberine has been implicated in the inhibition of iNOS induction by cytokines in microglial cells. However, the efficacies of other alkaloids components on microglial activation were not investigated yet. In this study, we investigated the effects of three alkaloids (palmatine, epi-berberine and coptisine) from C. japonica on lipopolysaccharide (LPS)-induced microglial activation. BV2 microglial cells were immunostimulated with LPS and then the production of several inflammatory mediators such as nitric oxide (NO), reactive oxygen species (ROS) and matrix metalloproteinase-9 (MMP-9) were examined as well as the phosphorylation status of Erk1/2 mitogen activated protein kinase (MAPK). Palmatine and to a lesser extent epi-berberine and coptisine, significantly reduced the release of NO, which was mediated by the inhibition of LPS-stimulated mRNA and protein induction of inducible nitric oxide synthase (iNOS) from BV2 microglia. In addition to NO, palmatine inhibited MMP-9 enzymatic activity and mRNA induction by LPS. Palmatine also inhibited the increase in the LPS-induced MMP-9 promoter activity determined by MMP-9 promoter luciferase reporter assay. LPS stimulation increased Erk1/2 phosphorylation in BV2 cells and these alkaloids inhibited the LPS-induced phosphorylation of Erk1/2. The anti-inflammatory effect of palmatine in LPS-stimulated microglia may suggest the potential use of the alkaloids in the modulation of neuroinflammatory responses, which might be important in the pathophysiological events of several neurological diseases including Alzheimer's disease (AD), multiple sclerosis (MS), Parkinson's disease (PD) and stroke.

• Journal of Life Science
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• v.30 no.4
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• pp.331-342
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• 2020

The suppression of neuroinflammatory responses in microglial cells can be considered a key target for improving the progression of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). Asparagus cochinchinensis has traditionally been used as a medicine to treat fever, cough, kidney disease, breast cancer, inflammatory diseases, and brain diseases. In this study, we investigated the neuroprotective mechanism of an aqueous extract from A. cochinchinensis root (AEAC), particularly its anti-inflammatory effects on lipopolysaccharide (LPS)-activated BV-2 microglial cells. BV-2 cells were treated with four different concentrations of AEAC. No significant toxicity was detected in BV-2 cells treated with AEAC. Nitric oxide (NO), cyclooxygenase-2 (COX-2) mRNA, and inducible nitric oxide synthase (iNOS) mRNA levels were 21% lower in the AEAC+LPS group than in the Vehicle+LPS group. Lower proinflammatory (TNF-α and IL-1β) and anti-inflammatory cytokine (IL-6 and IL-10) levels were also detected in the AEAC+LPS group than in the Vehicle+LPS group, albeit at varying rates. Moreover, the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group compared to the Vehicle+LPS group, enhancement of the phosphorylation of mitogen-activated protein kinase (MAPK) members after LPS treatment was significantly recovered in the AEAC-pretreated group, while cell cycle arrest at the G2/M phase caused by LPS treatment was less severe in the AEAC+LPS group. The increase in reactive oxygen species (ROS) generation induced by LPS treatment was also lower in the AEAC-pretreated group than in the Vehicle+LPS group. This is the first study to show that AEAC exerts anti-neuroinflammatory activity against LPS stimulation by regulating the MAPK signaling pathway, the cell cycle, and ROS production.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.5
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• pp.662-669
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• 2011

An experiment was conducted with broiler (Cobb 400) male chicks (n = 480) to determine the effect of betaine (Bet) supplementation (0 and 800 mg/kg) to diets containing five concentrations (15, 18, 20, 22 and 24 g/kg crude protein, CP) of methionine (Met) in a $2{\times}5$ factorial study for performance, carcass traits, immune responses, and serum parameters. Each diet was fed ad libitum from 1 to 42 d of age to 8 replicates of 6 chicks. Birds were housed in battery brooders placed in an open-sided poultry shed. Body weight gain, feed intake, feed conversion efficiency and slaughter variables were recorded at 21 and 42 d of age. Serum biochemical profile, antibody production against Newcastle disease (ND) and lymphocyte proliferation ratio (LPR) were analysed at 42 d of age. Supplementing Bet to diets containing sub-optimal concentrations of Met (15 g/kg) improved weight gain and breast yield at 21 d of age (p<0.01), and feed conversion efficiency at 42 d of age (p<0.05). Feed efficiency at 21 d of age, body weight gain at 42 d of age, slaughter variables except breast yield at 21 d of age and ND antibody titres were not affected (p>0.05) by the interaction. LPR increased (p<0.05) with Bet supplementation at 20 g Met/kg CP equal to those broilers fed 24 g Met without Bet. Bet supplementation enhanced the concentrations of protein, globulin and cholesterol in serum of broilers fed sub-optimal concentrations of Met. Results suggested that Bet supplementation (800 mg/kg diet) enhanced growth (21 d), feed conversion efficiency (42 d), breast yield and lymphocyte proliferation in broilers fed a diet containing 15 g Met/kg CP.

• Food Quality and Culture
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• v.1 no.1
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• pp.46-57
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• 2007

The purpose of the present study was to examine the nutrient intake status of elderly dementia patients. We surveyed the dietary intake of 50 demented elderly patients receiving a regular diet, who were hospitalized in a geriatric hospital in Yongin, Gyeonggi-do. The average age of the subjects was $79.6{\pm}6.5$ for the males and $80.5{\pm}6.3$ for the females. The average heights were $169.5{\pm}6.0\;cm$ (males) and $154.6{\pm}5.2\;cm$ (females), and the average weights were $58.5{\pm}7.4$ (males) and $51.7{\pm}8.9\;kg$ (females). Depending on the type of dementia, the male patients showed significant differences in their intakes of vegetable protein, fiber, total iron, and non-heme iron between the Alzheimer's disease (AD) and the vascular dementia (VD) groups, and the female patients showed significant differences in their intakes of total protein, phosphorus, zinc, and vitamin $B_6$ between the two groups. The male patients showed significant differences in their intakes of animal-source calcium and carotene according to ability to self-feed. According to physical activity, the male patients showed significant differences in vegetable fat and vitamin A intake, and the females showed significant differences in their intakes of total protein, animal protein, fiber, ash, total calcium, vegetable-source calcium, animal-source calcium, phosphorous, total iron, non-heme iron, heme iron, sodium, vitamins $B_1$, $B_2$, $B_6$, niacin, vitamin C, folate, and potassium. We found that the patients consumed excessive protein, but low amounts of calcium, vitamin $B_2$, and folate. Also, the patients' physical activity abilities appeared to affect their nutrient intakes.

• The Korean Journal of Physiology and Pharmacology
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• v.8 no.4
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• pp.173-179
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• 2004

Amyloid ${\beta}-peptide\;(A{\beta})$ contributes to the pathogenesis of Alzheimer's disease (AD), causing neuronal death through apoptosis. In this study, the neuroprotective role of BF-7, extracted form sericultural product, was examined against $A{\beta}-induced$ toxicity in cultured human neuronal cell SKN-SH. In order to know if the BF-7 has positive role on the cognition and memory in human, the mixture of BF-7, DHA and EPA (BDE) was examined using Rey Kim and K-WAIS test with 50 healthy high school student. We report here that BDE significantly attenuated $A{\beta}-induced$ apoptosis through the reduction of ROS accumulation, and diminished caspase-like protease activity. Moreover, the memory index and memory preservation, and attentative concentration of BDE treated group for 1 month were significantly improved, in contrast to the case of placebo control treated with DHA and EPA. This result represent that the BF-7 play significant positive role on learning memory. Taken together, our result suggested the natural product BF-7 is a good substance for the brain functionally and physiologically.