• Biomolecules & Therapeutics
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• v.2 no.3
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• pp.223-228
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• 1994

In this study, we examined gangliosides from streptozotocin-induced diabetic rat brain. To obtain the diabetic rat brain, we sacrified the rat three days after injecting the streptozotocin into venus in tail. We measured blood glucose level according to Somogy-Nelson method and measured insulin level using $^{125}$ I-insulin RIA kit. The gangliosides were extracted according to Folch-Suzuki method from the rat brain. We also examined the effect of major lipid components extracted from deer antler on diabetic rat brain. The results showed that the major lipids components lowered both blood glucose and insulin level in normal rat. However only the blood glucose level in diabetic rat was lowered with major lipid components. In diabetic rat brain, gangliosides metabolism were changed. The amount of GMla was increased while GDla, GDlb, and GTlb were not synthesized. Furthermore, undefined ganglioside was found. In major lipid component-treated diabetic rat brain, the ganglioside metabolism proceeded as same as the normal rat. On the contrary, in bovine brain gangliosides-treated diabetic rat brain, the gangliosides metabolism was not recovered to normal one.

• Journal of Nutrition and Health
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• v.26 no.6
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• pp.680-691
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• 1993

Rats were fed for an 8-week period a low riboflavin diet(5ug riboflavin/day) or a control diet(30ug/day) supplied either ad libitum or by pair feeding in order to study the effect of riboflavin on the metabolism of lipids and neurotransmitters. Erythrocyte glutathione reductase (EGR) and monomine oxidase(MAO) activity in the liver and brain were assayed. EGR activity coefficient in riboflavin deficient rats was significantly higher than in ad libitum controls whereas MAO activity was decreased in the deficient rats. Fatty acid composition showed a different trend in the serum, liver and brain. In the serum, the concentrations of essential fatty acids and $\omega$-3 fatty acids(eicosapentaenoic acid, docosahexaenoic acid)were decreased about 20-40% in the deficient and pair-fed than in the ad libitum controls. Brain serotonin and 5-HIAA(5-hydroxyindole acetic acid) concentrations were decreased in the riboflavin deficient rats. Learning ability measured by a water maze and exploratory activity using the open field test were not impaired in the deficient rats. These results indicate that brain lipid metabolism was protected in subclinical riboflavin deficiency, however, riboflavin deficiency affected brain serotonin content.

• IMMUNE NETWORK
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• v.22 no.5
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• pp.39.1-39.18
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• 2022

RNA metabolism plays a central role in regulating of T cell-mediated immunity. RNA processing, modifications, and regulations of RNA decay influence the tight and rapid regulation of gene expression during T cell phase transition. Thymic selection, quiescence maintenance, activation, differentiation, and effector functions of T cells are dependent on selective RNA modulations. Recent technical improvements have unveiled the complex crosstalk between RNAs and T cells. Moreover, resting T cells contain large amounts of untranslated mRNAs, implying that the regulation of RNA metabolism might be a key step in controlling gene expression. Considering the immunological significance of T cells for disease treatment, an understanding of RNA metabolism in T cells could provide new directions in harnessing T cells for therapeutic implications.

• Molecules and Cells
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• v.28 no.3
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• pp.201-207
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• 2009

Silibinin is a polyphenolic flavonoid compound isolated from milk thistle (Silybum marianum), with known hepatoprotective, anticarcinogenic, and antioxidant effects. Herein, we show that silibinin inhibits receptor activator of $NF-{\kappa}B$ ligand (RANKL)-induced osteoclastogenesis from RAW264.7 cells as well as from bone marrow-derived monocyte/macrophage cells in a dose-dependent manner. Silibinin has no effect on the expression of RANKL or the soluble RANKL decoy receptor osteoprotegerin (OPG) in osteoblasts. However, we demonstrate that silibinin can block the activation of $NF-{\kappa}B$, c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein (MAP) kinase, and extracellular signal-regulated kinase (ERK) in osteoclast precursors in response to RANKL. Furthermore, silibinin attenuates the induction of nuclear factor of activated T cells (NFAT) c1 and osteoclast-associated receptor (OSCAR) expression during RANKL-induced osteoclastogenesis. We demonstrate that silibinin can inhibit $TNF-{\alpha}$-induced osteoclastogenesis as well as the expression of NFATc1 and OSCAR. Taken together, our results indicate that silibinin has the potential to inhibit osteoclast formation by attenuating the downstream signaling cascades associated with RANKL and $TNF-{\alpha}$.

• BMB Reports
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• v.41 no.8
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• pp.609-614
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• 2008

The concentrations and catalytic activities of enzymes control metabolic rates. Previous studies have focused on enzyme concentrations because there are no genome-wide techniques used for the measurement of enzyme activity. We propose a method for evaluating the significance of enzyme activity by integrating metabolic network topologies and genome-wide microarray gene expression profiles. We quantified the enzymatic activity of reactions and report the 388 significant reactions in five perturbation datasets. For the 388 enzymatic reactions, we identified 70 that were significantly regulated (P-value < 0.001). Thirty-one of these reactions were part of anaerobic metabolism, 23 were part of low-pH aerobic metabolism, 8 were part of high-pH anaerobic metabolism, 3 were part of low-pH aerobic reactions, and 5 were part of high-pH anaerobic metabolism.

• Molecules and Cells
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• v.45 no.11
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• pp.781-788
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• 2022

Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders. We will conclude with a potential mechanism of proline metabolism in neuronal function and mental health.

• Journal of Nutrition and Health
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• v.26 no.3
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• pp.231-247
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• 1993

This study was designed to confirm the effect of dietary protein level and oral administration of tryptophan on brain serotonin metabolism. Two animal experiments were conducted. The objectives and results of research were as follows : In the first experiment, it was investigated whether administration of reserpine to Sprague-Dawley rats fed 6% or 20% casein diet induced decrease in serum tryptophan and large neutral amino acid(LNAA) concentrations, tryptophan/LNAA concentration ratio, brain tryptophan, serotonin and 5-hydroxyindoleacetic acid(5-HIAA) contents. Brain serotonin content of 6% casein diet group was lower than those of 20% casein diet group. Both 6% and 20% casein diet groups administered with reserpine to induce the analogous depression, showed the notable decrease in brain serotonin content when they were compared with 20% casein diet group not administered with reserpine. Serum tryptophan/LNAA ration and brain 5-HIAA content showed a tendency similar to the change of serotonin content, but the mean difference among all groups was not significant. From these results, it could be said that when the dietary protein level was low, brain serotonin content was decrease. The second experimnt was to see the change in serum tryptophan concentration and tryptophan/LNAA ratio and brain tryptophan, serotonin and 5-HIAA content when tryptophan was administered orally to the animals treated with reserpine. Serum tryptophan concentration tended to increase in both reserpine-treated 6% and 20% casein diet groups administered with tryptophan, especially in the 6% casein diet group. Serum tryptophan/LNAA concentration ratio tended to incrase in reserpine-tteated 6% casein diet group, while decrease in reserpine-treated 20% casein diet group. Brain tryptophan content was increased in both reserpine-treated 6% and 20% casein diet groups. However, brain serotonin content of reserpine-treated 6% casein diet group showed a tendency to decrease, while that of reserpine-treated 20% casein group increase. Consequently, the effect of tryptophan administration on increase of brain tryptophan and serotonin content in animals treated with reserpine was far more excellent in 20% casein diet groups. It was concluded that dietary protein intake and tryptophan administration increase brain serotonin level. Accordingly, it was possible to confirm that brain function, particularly in aspect of behavior related to the serotonin, was changed with manipulation of dietary composition.

• Journal of Korean Neurosurgical Society
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• v.50 no.3
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• pp.173-178
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• 2011

Objective : The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain. Methods : Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns. Results : According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.Conclusion : Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.

• Journal of Genetic Medicine
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• v.9 no.2
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• pp.84-88
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• 2012

Purpose: Neurofibromatosis type 1 (NF1), which is caused by mutations of the NF1 gene, is the most frequent single gene disorder to affect the nervous system. Unidentified bright objects (UBOs) are commonly observed on brain magnetic resonance imaging (MRI) in patients with NF1. However, their clinical and pathologic significance is not well understood. The purpose of this study was to investigate the correlation between UBOs and cerebral glucose metabolism measured by $^{18}F$-2-Fluoro-2-deoxy-D-glucose ($^{18}F$-FDG) positron emission tomography (PET) in Korean patients with NF1. Materials and Methods: Medical records of 75 patients (34 males and 41 females) with NF1 who underwent brain MRI and PET between 2005 and 2011 were evaluated retrospectively. Clinical data including demographics, neurological symptoms, and brain MRI and PET findings, were reviewed. Results: UBOs were detected in the brain MRI scans of 31 patients (41%). The region most frequently affected by UBOs was the basal ganglia. The most frequent brain PET finding was thalamic glucose hypometabolism (45/75, 60%). Of the 31 patients with UBOs, 26 had thalamic glucose hypometabolism on brain PET, but the other 5 had normal brain PET findings. Conversely, of the 45 patients with thalamic glucose hypometabolism on brain PET, 26 showed UBOs on their brain MRI scans, but 19 had normal findings on brain MRI scans. Conclusion: UBOs on brain MRI scans and thalamic glucose hypometabolism on PET appear to be 2 distinctive features of NF1 rather than correlated symptoms. Because the clinical significance of these abnormal imaging findings remains unclear, a longitudinal follow-up study of changes in clinical manifestations and imaging findings is necessary.

• The Korean Journal of Nuclear Medicine
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• v.35 no.4
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• pp.231-240
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• 2001

Purpose: Normal aging results in detectable changes in the brain structure and function. We evaluated the changes of regional cerebral glucose metabolism in the normal aging process with FDG PET. Materials and Methods: Brain PET images were obtained in 44 healthy volunteers (age range 20-69 'y'; M:F = 29:15) who had no history of neuropsychiatric disorders. On 6 representative transaxial images, ROIs were drawn in the cortical and subcortical areas. Regional FDG uptake was normalized using whole brain uptake to adjust for the injection dose and correct for nonspecific declines of glucose metabolism affecting all brain areas equally. Results: In the prefrontal, temporoparietal and primary sensorimotor cortex, the normalized FDG uptake (NFU) reached a peak in subjects in their 30s. The NFU in the prefrontal and primary sensorimotor cortex declined with age after 30s at a rate of 3.15%/decade and 1.93%/decade, respectively. However, the NFU in the temporoparietal cortex did not change significantly with age after 30s. The anterior (prefrontal) posterior (temporoparietal) gradient peaked in subjects in their 30s and declined with age thereafter at a rate of 2.35%/decade. The NFU in the caudate nucleus was decreased with age after 20s at a rate of 2.39%/decade. On the primary visual cortex, putamen, and thalamus, the NFU values did not change significantly throughout the ages covered. These patterns were not significantly different between right and left cerebral hemispheres. Of interest was that the NFU in the left cerebellar cortex was increased with age after 20s at a rate of 2.86%/decade. Conclusion: These data demonstrate regional variation of the age-related changes in the cerebral glucose metabolism, with the most prominent age-related decline of metabolism in the prefrontal cortex. The increase in the cerebellar metabolism with age might reflect a process of neuronal plasticity associated with aging.