• Parasites, Hosts and Diseases
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• 제57권3호
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• pp.225-232
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• 2019

Innate lymphoid cells (ILCs) are key players during an immune response at the mucosal surfaces, such as lung, skin, and gastrointestinal tract. Giardia lamblia is an extracellular protozoan pathogen that inhabits the human small intestine. In this study, ILCs prepared from the lamina propria of mouse small intestine were incubated with G. lamblia trophozoites. Transcriptional changes in G. lamblia-exposed ILCs resulted in identification of activation of several immune pathways. Secretion of interleukin (IL)-17A, IL-17F, $IL-1{\beta}$, and interferon-${\gamma}$ was increased, whereas levels of IL-13, IL-5, and IL-22, was maintained or reduced upon exposure to G. lamblia. Goup 3 ILC (ILC3) was found to be dominant amongst the ILCs, and increased significantly upon co-cultivation with G. lamblia trophozoites. Oral inoculation of G. lamblia trophozoites into mice resulted in their presence in the small intestine, of which, the highest number of parasites was detected at the 5 days-post infection. Increased ILC3 was observed amongst the ILC population at the 5 days-post infection. These findings indicate that ILC3 from the lamina propria secretes IL-17 in response to G. lamblia, leading to the intestinal pathology observed in giardiasis.

• 대한임상검사과학회지
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• 제47권1호
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• pp.51-58
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• 2015

Ethanol has long been implicated in triggering apoptotic neurodegeneration. Alcohol also may indirectly harm the fetus by imparing the mother's physiology. We examined the effects of ethanol on immature brain of mice. Three-weeks-old female ICR strain mice daily intraperitoneally injected with ethanol at the concentration of 4 and 20% in saline for 0, 6, and 24 hours and 1 and 4 weeks. The mice were weighted and sacrificed, and the brains were ectomized for the present histological, immunohistochemical and TUNEL assays. Based on the histologic hematoxylin and eosin stain, immunohistochemical expression of glutamate receptor protein and neuronal cell adhesion molecule (NCAM) were evaluated. The cerebral cortex of the ethanol-treated group showed few typical symptoms of apoptosis such as chromosome condensation and disintegration of the cell bodies. TUNEL staining revealed DNA fragmentation in the 6 and 24 hours. This results demonstrated that acute ethanol administration causes neuronal cell death. I found that either glutamate receptor inhibition or activation could induce cerebellar degeneration as ethanol effect. Neuronal death also can be induced by excess activity of certain neurotransmitter, including glutamate. Neurons must establish cell-to-cell contact during growth and development in order to survive, migrate to their final destination, and develop appropriate connections with neighboring cell. Purkinje cell in cerebellar are especially vulnerable to the cell death and degeneration. After ethanol treatment in cerebellar, NCAM had decreased by 4 weeks. This result suggest that apoptosis seems to be involved in the slow elimination of neuron and cerebellar degeneration.

• 운동영양학회지
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• 제16권2호
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• pp.93-100
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• 2012

Alzheimer's disease (AD) is the most common cause of dementia in adults. Microtubule associated protein tau is abnormally phosphorylated in AD and aggregates as paired helical filaments (PHFs) in neurofibrillary tangles (NFTs). NFTs are the most common intraneuronal inclusion in the brains of patients with AD and have been implicated in mediating neuronal cell death and cognitive deficit. Aberrant phosphorylation of tau is an early pathological event in AD, but the underlying mechanisms are unclear. MAP kinases are a family of Serine/Threonine (Ser/Thr) kinases that involved hyper - phosphorylation of tau in AD. The purpose of this study was to investigate the effect of treadmill exercise on phosphorylation of tau level and activation of MAPKs including JNK, ERK, p38-MAPK. To address this, Tg mouse model of AD, Tg-NSE/hTau 23, which expresses human tau 23 in the brain, was chosen. Animals were subjected to treadmill exercise for 12 weeks from 24 months of age. Treadmill exercise in Tg group improved cognitive function compared with Tg-SED group in watermaze test. In addition, treadmill exercised Tg mice significantly reduced the activation of JNK54/46, p38-MAPK and tau (Ser404, Ser202, Thr231), and increased activation of ERK44/42 in cerebral cortex. These results suggest that treadmill exercise may provide a therapeutic potential to alleviate the tau pathology like AD.

• Journal of Ginseng Research
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• 제44권1호
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• pp.79-85
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• 2020

Background: Helicobacter pylori increases reactive oxygen species (ROS) and induces oxidative DNA damage and apoptosis in gastric epithelial cells. DNA damage activates DNA damage response (DDR) which includes ataxia-telangiectasia-mutated (ATM) activation. ATM increases alternative reading frame (ARF) but decreases mouse double minute 2 (Mdm2). Because p53 interacts with Mdm2, H. pylori-induced loss of Mdm2 stabilizes p53 and induces apoptosis. Previous study showed that Korean Red Ginseng extract (KRG) reduces ROS and prevents cell death in H. pylori-infected gastric epithelial cells. Methods: We determined whether KRG inhibits apoptosis by suppressing DDRs and apoptotic indices in H. pylori-infected gastric epithelial AGS cells. The infected cells were treated with or without KRG or an ATM kinase inhibitor KU-55933. ROS levels, apoptotic indices (cell death, DNA fragmentation, Bax/Bcl-2 ratio, caspase-3 activity) and DDRs (activation and levels of ATM, checkpoint kinase 2, Mdm2, ARF, and p53) were determined. Results: H. pylori induced apoptosis by increasing apoptotic indices and ROS levels. H. pylori activated DDRs (increased p-ATM, p-checkpoint kinase 2, ARF, p-p53, and p53, but decreased Mdm2) in gastric epithelial cells. KRG reduced ROS and inhibited increase in apoptotic indices and DDRs in H. pylori-infected gastric epithelial cells. KU-55933 suppressed DDRs and apoptosis in H. pylori-infected gastric epithelial cells, similar to KRG. Conclusion: KRG suppressed ATM-mediated DDRs and apoptosis by reducing ROS in H. pylori-infected gastric epithelial cells. Supplementation with KRG may prevent the oxidative stress-mediated gastric impairment associated with H. pylori infection.

• 생명과학회지
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• 제23권9호
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• pp.1096-1103
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• 2013

만성외상성뇌병증(Chronic traumatic encephalopathy, CTE)은 운동선수와 매우 밀접하게 관련되어 있으며 장기간에 걸쳐 반복적인 외상성뇌손상(traumatic brain injury, TBI)로 인한 퇴행성뇌질환이다. 신경영양인자(neurotrophic factor)는 여러 종류가 알려져 있으며 이들은 뇌와 척수의 물리적 손상시에 신경보호효과가 있다. 따라서, 신경영양인자의 혼합물인 cebrolysin을 이용하여 CTE질환에 가장 적합하다고 여겨지는 repetitive mild TBI (rmTBI) 모델에서 cerebrolysin의 신경보호효과를 알아보고자 하였다. 실험군은 5군(groups 1 and 2: rmTBI for 4 weeks following cerebrolysin injection for 4 weeks; groups 3 and 4: rmTBI for 8 weeks with or without cerebrolysin injection for 4 weeks; group 5: control)으로 나누어 진행하였다. CTE의 가장 대표적 표시인자인 tau 단백질의 인산화를 조직학적으로 조사한 결과, 대뇌겉질과 해마내 CA3 영역에서 phospho-tau단백질의 발현이 증가되었으며 cerebrolysin ($10{\mu}l$ of 1 mg/ml)를 미정맥으로 투여시 p-tau발현이 감소되었다. CTE의 병인으로 알려진 별아교세포와 미세아교세포의 활성을 각각의 표시인인 GFAP, iba-1을 이용하여 면역조직화학염색을 시행하였다. 별아교세포의 활성은 rmTBI에 의하여 증가하였으며 cerebrolysin에 의해 회복되었으나 미세아교세포의 활성은 관찰되지 않았다. 또한 rmTBI모델에서 체내 탐식세포(macrophage)의 뇌내유입유무를 관찰하고자 CD45 염색을 시행하였으나 유의한 차이를 관찰하지 못하였다. 이상의 결과를 종합하면, cerebrolysin이 rmTBI에 의한 tau단백질의 인산화 및 별아교세포의 활성을 조절하는 것으로 사료된다. 따라서 cerebrolysin이 CTE 환자에 대한 치료 약물의 후보가 될 수 있음을 시사한다.

• 대한의생명과학회지
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• 제24권2호
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• pp.64-75
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• 2018

CCN3 (also known as NOV, Nephroblastoma overexpressed) proteins are involved in various pathologies during different developmental stages. We have previously shown that intracellular levels and normal extracellular secretion of CCN3 are important for neuronal differentiation. Furthermore, we demonstrated that a single amino acid in the CCN3 TSP-1 domain is important for extracellular secretion and that palmitoylation of CCN3 is required in this process. However, the effect of abnormal CCN3 accumulation on cells remains to be studied. Here, we found mutations in the TSP-1 domain of CCN3 that led to intracellular accumulation and abnormal aggregation of CCN3. It was observed that this mutation resulted in a phenomenon similar to neurodegeneration when overexpressed in the developing mouse cortex. This mutation also confirmed the activation of apoptotic gene expression in Neuro2a cells. In addition, we confirmed the in vivo transcriptional changes induced by this mutation using microarray analysis. We observed a significant increase in the expression of Anp32a, an apoptosis-related gene. Collectively, these results indicate that a single mutation in CCN3 can lead to abnormal cell death if it shows intracellular accumulation and abnormal aggregation.

• 한방안이비인후피부과학회지
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• 제20권2호통권33호
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• pp.36-46
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• 2007

Objective : In this study, the effect of Atractylodes japonica against LPS induced inflammation in mouse microglia BV2 cells was investigated. Method : Microglia BV2 Cells viability was determined using the MTT assay. We used water, ethanol extract from Atractylodes japonica and studied on the anti-inflammatory effect of lipopolysaccharide-induced inflammation using reverse transcription polymerase chain reaction (RT-PCR), western blot, and nitric oxide detection on mouse microglia BV2 cells. Result : The MTT assay revealed that it's extract has no significant cytotoxicity in the microglia BV2 cell. Various solvent extract from Atractylodes japonica inhibited nitrite production, iNOS protein and mRNA expression levels. And also it's extracts significantly reduced lipopolysaccharide-induced COX-2 activation in RT-PCR and western blot in lipopolysaccharide-induced microglia BV2 cells Conclusion : In this study, it's extracts was shown to suppress NO production by inhibiting iNOS expression and COX-2 activity. With this effects of anti-inflammation, we suggests that, it's extracts may be a useful candidate for the development of a drug on the related inflammatory diseases in brain.

• 동의신경정신과학회지
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• 제20권2호
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• pp.31-46
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• 2009

Objectives : This experiment was designed to investigate the effect of Gojineumja(Guzhenyinzi, GJEJ) on damaged neural tissue in cultured glial cells and in the mouse brain tissue. Methods : The effects of the GJEJ on activation of astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide were investigated. The effects of the GJEJ on levels of glial fibrillary acidic protein(GFAP)-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine were investigated. Results : 1. GJEJ reduced levels of activated astrocytes and caspase 3-positive cell counts in cultured glial cells administered with ${\beta}$-amyloid peptide. 2. GJEJ reduced levels of GFAP-positive reactive astrocyets and caspase 3-positive cells in the hippocampal subfields in the rats administered with scopolamine. Conclusions : The present data. suggest that GJEJ may have a protective function of neuronal and non-neuronal cells in damaged neural tissue caused by AD-like stimulations. Further studies on identification of effective molecular components of GJEJ and their interactions with damaged neural cells would be important for understanding molecular mechanism and may be further applicable for the development of therapeutic strategies.

• Nutrition Research and Practice
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• 제17권6호
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• pp.1128-1142
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• 2023

BACKGROUND/OBJECTIVES: Inonotus obliquus has been used as antidiabetic herb around the world, especially in the Russian and Scandinavian countries. Diabetes is widely believed to be a key factor in Alzheimer's disease (AD), which is widely considered to be type III diabetes. To investigate whether I. obliquus can also ameliorate AD, it would be interesting to identify new clues for AD treatment. We tested the anti-AD effects of raw Inonotus obliquus polysaccharide (IOP) in a mouse model of AD (3×Tg-AD transgenic mice). MATERIALS/METHODS: SPF-grade 3×Tg-AD mice were randomly divided into three groups (Control, Metformin, and raw IOP groups, n = 5 per group). β-Amyloid deposition in the brain was analyzed using immunohistochemistry for AD characterization. Gene and protein expression of pertinent factors of the ubiquitin-proteasome system (UPS) was determined using real-time quantitative polymerase chain reaction and Western blotting. RESULTS: Raw IOP significantly reduced the accumulation of amyloid aggregates and facilitated UPS activity, resulting in a significant reduction in AD-related symptoms in an AD mouse model. The presence of raw IOP significantly enhanced the expression of ubiquitin, E1, and Parkin (E3) at both the mRNA and protein levels in the mouse hippocampus. The mRNA level of ubiquitin carboxyl-terminal hydrolase isozyme L1, a key factor involved in UPS activation, also increased by approximately 50%. CONCLUSIONS: Raw IOP could contribute to AD amelioration via the UPS pathway, which could be considered as a new potential strategy for AD treatment, although we could not exclude other mechanisms involved in counteracting AD processing.

• Environmental Analysis Health and Toxicology
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• 제21권3호
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• pp.275-282
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• 2006

In order to get insight into the mechanism of cadmium (Cd)-induced brain injury, we investigated the effects of Cd on the induction of COX-2 in bEnd.3 mouse brain endothelial cells. Cd induced COX-2 expression and $PGE_2$ release, which were attenuated by thiol-reducing antioxidant N-acetylcysteine (NAC) indicating oxidative components might contribute to these events. Indeed, Cd increased cellular reactive oxygen species (ROS) level and DNA binding activity of nuclear factor-kB (NF-kB), an oxidative stress sensitive transcription factor. Cd-induced $PGE_2$ production and COX-2 expression were significantly attenuated by Bay 11 7082, a specific inhibitor of NF-kB and by SB203580, a specific inhibitor of p38 mitogen activated protein kinase (MAPK). These data suggest that Cd induces COX-2 expression through activation of NF-kB and p38 MAPK, the oxidative stress-sensitive signaling molecules, in brain endothelial cells.