• 대한유전성대사질환학회지
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• 제20권2호
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• pp.37-43
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• 2020

페닐케톤뇨증(PKU)은 전세계적으로 가장 잘 알려지고 중요한 유전성 대사질환이다. 1950년대 이후 단백제한을 이용한 식사치료를 처음으로 시도하여 성과가 있었던 질환이며 1960년대 이후 신생아선별검사를 통해 조기진단과 조기치료가 가능하게 된 최초의 유전성대사질환이기 때문이다. 단백제한 식사치료의 효과가 좋지만 학동기, 사춘기 이후 성인시기까지 유지하는 것의 어려움이 있고 이시기에 조절이 잘 되지 않았을 경우 경련, 여러가지 정신과적인 문제들, 삶의 질의 감소 등이 문제가 되어서 오랜 기간 치료를 위한 여러 방법들이 제시되었다. 더해서 2014년 미국의학유전학회(American Medical College of Medical Genetics and Genomics, ACMG)에서 전 연령에서 혈중 페닐알라닌 수치를 120-360 umol/L로 제시를 한 이후 더욱 치료의 중요성이 올라갔다. 2000년대 페닐알라닌수산화 효소(phenylalanine hydroxylase, PAH)의 조효소인 tetrahydrobiopterin (BH4)가 치료 승인되어서 약물반응을 보이는 환자에서 치료가 시작되었으며 4세미만에서도 허가가 되어서 이른 시기부터 약물치료를 병행하여 효과를 보게 되었다. 높은 혈중 페닐알라닌수치가 혈액-뇌 장벽(Blood-brain barrier, BBB)을 통하여 뇌로 넘어가서 회백질의 변성을 나타내게 되는 문제를 막기 위해 거대중성아미노산(LNAA)를 이용한 치료가 시도되고 있다. 오랫동안 연구되었던 페닐알라닌을 trans-cinnamic acid와 암모니아로 변화를 시키는 phenylalanine ammonialyase (PAL)을 이용한 효소치료는 최근 약제로 개발되어서 2018년 이후 성인환자를 대상으로 치료가 시작되었고 잘 조절되지 않는 환자들에게 효과를 보이고 있다. PAL을 경구용으로 개발하는 것이 빠르게 진행 중이며 유전자치료에 대한 연구들도 활발하게 진행이 되고 있어 다양한 치료들이 앞으로 기대된다.

• Asian-Australasian Journal of Animal Sciences
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• 제18권11호
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• pp.1552-1556
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• 2005

The UCPs are members of the mitochondrial inner membrane transporter family, present in the mitochondrial inner membrane. Their main function is increasing the energy expenditure via diminishing the resulting production of ATP from mitochondrial oxidative phosphorylation instead of yielding dissipative heat. They are associated with the metabolism of fat and regulation of energy expenditure. The UCP gene can be viewed as the candidate gene for chicken fatness. In the present study, RT-PCR and Northern Blot methods were developed to investigate the expression of the UCP gene in ten tissues including heart, liver, spleen, lung, kidney, gizzard, intestine, brain, breast muscle and abdominal fat of chicken. The results of both RT-PCR and Northern Blot methods showed that the UCP gene expressed specific in breast muscle. The expression levels of UCP gene in breast muscles from egg-type and meat-type chickens of hatching, 2, 4, 6 and 8 wk of age were detected by RT-PCR assay and results showed that the expression levels of UCP gene were related to breeds. Expression level of UCP gene in layers was higher than that in broilers at various weeks of age except at 6 wk. The UCP gene's expression was higher at 6 wk and had no significant difference among other weeks of age in broilers; in layers the expression level of UCP gene had no significant difference among weeks of age. The experiment results also showed that insulin could increase the expression level of UCP gene by 40% compared with control group.

• Asian-Australasian Journal of Animal Sciences
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• 제22권5호
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• pp.712-720
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• 2009

The goal of this study was to elucidate the expression and segmental distribution of the glomerular cationic amino acid metabolism transporter-2 (CAT-2) and thus to improve our understanding of porcine cationic amino acid transporters and amino acid absorption. Porcine CAT-2 was cloned, sequenced and characterized. The predicted amino acid sequence of porcine CAT-2 shared 86.1% and 92.1% identity with human and mouse CAT-2A, respectively. The tissue distribution patterns and ontogenic changes of CAT-2 mRNAs were determined by real-time Q-PCR. The results showed that porcine CAT-2 was highly expressed in the heart and intestinal tract (duodenum, ileum and jejunum). In addition, the mRNA of CAT-2 was found in liver, lung, kidney, brain and muscle. Within the intestinal tract, CAT-2 mRNA was most abundant in the ileum and rarely expressed in the duodenum. In the duodenum, the levels of CAT-2 mRNA reached their peak on day 7 (p<0.05) while in the jejunum, levels were low on day 1 and 7 and increased rapidly after day 26 before peaking on days 30 and 60 (p<0.05). The levels then dramatically decreased by day 90 (p<0.05). In the ileum, levels achieved their maximum on day 30 and then decreased significantly on day 60 (p<0.05).

• Molecules and Cells
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• 제20권1호
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• pp.83-89
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• 2005

HtrA2/Omi is a mammalian mitochondrial serine protease homologous to the E. coli HtrA/DegP gene products. Recently, HtrA2/Omi was found to have a dual role in mammalian cells, acting as an apoptosis-inducing protein and being involved in maintenance of mitochondrial homeostasis. By screening a human brain cDNA library with $A{\beta}$ peptide as bait in a yeast two-hybrid system, we identified HtrA2/Omi as a binding partner of $A{\beta}$ peptide. The interaction between $A{\beta}$ peptide and HtrA2/Omi was confirmed by an immunoblot binding assay. The possible involvement of HtrA2/Omi in $A{\beta}$ peptide metabolism was investigated. In vitro peptide cleavage assays showed that HtrA2/Omi did not directly promote the production of $A{\beta}$ peptide at the ${\beta}/{\gamma}$-secretase level, or the degradation of $A{\beta}$ peptide. However, overexpression of HtrA2/Omi in K269 cells decreased the production of $A{\beta}40$ and $A{\beta}42$ by up to 30%. These results rule out the involvement of HtrA2/Omi in the etiology of Alzheimer's disease. However, the fact that overexpression of HtrA2/Omi reduces the generation of $A{\beta}40$ and $A{\beta}42$ suggests that it may play some positive role in mammalian cells.

• IMMUNE NETWORK
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• 제11권3호
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• pp.135-154
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• 2011

The great discovery of microRNAs (miRNAs) has revolutionized current cell biology and medical science. miRNAs are small conserved non-coding RNA molecules that post-transcriptionally regulate gene expression by targeting the 3' untranslated region of specific messenger RNAs for degradation or translational repression. New members of the miRNA family are being discovered on a daily basis and emerging evidence has demonstrated that miRNAs play a major role in a wide range of developmental process including cell proliferation, cell cycle, cell differentiation, metabolism, apoptosis, developmental timing, neuronal cell fate, neuronal gene expression, brain morphogenesis, muscle differentiation and stem cell division. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as cancer, psychiatric and neurological diseases, cardiovascular disease, and autoimmune disease. Interestingly, in addition, miRNA deficiencies or excesses have been correlated with a number of clinically important diseases ranging from cancer to myocardial infarction. miRNAs can repress the gene translation of hundreds of their targets and are therefore well-positioned to target a multitude of cellular mechanisms. As a consequence of extensive participation in normal functions, it is quite logical to ask the question if abnormalities in miRNAs should have importance in human diseases. Great discoveries and rapid progress in the past few years on miRNAs provide the hope that miRNAs will in the near future have a great potential in the diagnosis and treatment of many diseases. Currently, an explosive literature has focussed on the role of miRNA in human cancer and cardiovascular disease. In this review, I briefly summarize the explosive current studies about involvement of miRNA in various human cancers and cardiovascular disease.

• The Korean Journal of Physiology and Pharmacology
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• 제24권1호
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• pp.39-46
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• 2020

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.

• Nuclear Medicine and Molecular Imaging
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• 제41권3호
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• pp.252-254
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• 2007

Image fusion is fast catching attention as Wagner pointed out in his 2006 version of the recent progress and development presented at the annual meeting of Society of Nuclear Medicine. Prototypical fusion of bone scan and radiograph was already attempted at in 1961 when Fleming et al. published an article on strontium-85 bone scan. They simply superimposed dot scan on radiograph enabling simultaneous assessment of altered bone metabolism and local bone anatomy. Indeed the parallel reading of images of bone scan and radiography, CT, MRI or ultrasonography has been practiced in nuclear medicine long since. It is fortunate that recent development of computer science and technology along with the availability of refined CT and SPECT machines has permitted us to open a new avenue to digitally produce precise fusion image so that they can readily be read, exchanged and disseminated using internet. Ten years ago fusion was performed using Bresstrahlung SPECT/CT and it is now achievable by PET/CT and SPECT/CT software and SPECT/CT hardware. The merit of image fusion is its feasibility of reliable assessment of morphological and metabolic change. It is now applicable not only to stationary organs such as brain and skeleton but also to moving organs such as the heart, lung and stomach. Recently, we could create useful fusion image of cardiac SPECT and 64-channel CT angiograph. The former provided myocardial metabolic profile and the latter vascular narrowing in two patients with coronary artery stenosis and myocardial ischemia. Arterial stenosis was severe in Case 1 and mild in Case 2.

• 환경생물
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• 제29권4호
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• pp.241-250
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• 2011

현대인들은 가정생활과 직업환경 속에서 다양한 종류의 전자기파에 노출되며 전자기파 노출에 따른 생체위해성은 공중보건학적으로 중요한 이슈로 대두되었다. 현재까지 많은 체외 및 체내실험 결과에서 전자기파 노출이 세포대사, 내분비, 면역, 신경, 생식, 태아발달에 영향을 미치는 것으로 보고되었다. 세포나 개체 수준에서 시행된 실험연구에서는 전자기파 노출에 의해 세포내부 자유기의 증가, DNA 손상과 암발생, 발생기형, 생식기능 저하가 나타난다. 역학조사결과 전자기파 노출은 생명을 위협하는 질병인 백혈병, 뇌암, 근위축성 측삭경화증, 우울증, 자살, 알츠하이머와 상관성이 보고되었다. 이러한 생체기능 변화는 전자기파의 주파수, 노출기간, 강도 (에너지)에 따라 다르게 나타난다. 전자기파 노출은 곤충, 어류, 양서류, 파충류, 조류 등 야생동물에서도 동물행동, 번식, 생리기능의 변화를 초래한다. 본 소고에서는 인간보건학적 측면과 생태계에서 나타난 전자기파의 위해성을 전자기파의 종류, 노출시간에 따라 세포 및 개체 수준에서 보고된 위해성 자료를 정리하였다.

• Korean Journal of Acupuncture
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• 제29권2호
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• pp.260-270
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• 2012

Objectives : Hippocampus, a region of temporal lobe, plays an important role in the pathogenic mechanisms of brain diseases such as Alzheimer's disease, depression and temporal lobe epilepsy. This research is designed to investigate hippocampal changes after acupuncture stimulation at Shinmun(HT7) using 2-dimensional gel electrophoresis(2-DE). Methods : On postnatal-day 15, rat pups were randomly devided into Normal(NOR) or HT7 group. All of Pups kept with their mothers for 7 days, but pups in HT7 group received acupuncture stimulation at HT7 daily. On postnatal-day 21, hippocampus of each rat pup was dissceted 30 minutes after last acupuncture stimulation and the protein expressions were investigated using 2-DE. Results : After acupuncture stimulation at HT7, expression of 20 proteins were significantly increased. Succinate semialdehyde dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase-like, transketolase, aconitate hydratase and phosphoglucomutase-1 were related to glucose methabolism. Eukaryotic initiation factor(eIF) 4A-II, eIF 4A-III, mitochondrial Tu translation elongation factor and chain A of crystal structure of the 70-Kda heat shock cognate protein involve in the protein synthesis in ribosome. Tubulin ${\beta}$-4 chain, tubulin T ${\beta}$-15 and tubulin ${\alpha}$-1B chain comprise cytoskeleton. Glutathione S-transferase(GST) ${\omega}$-1, GST P and GST Yb-3 can reduce oxidative stress. ${\beta}$-soluble N-ethylmaleimide-sensitive fusion protein attachment protein is required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus, glycerol-3-phosphate dehydrogenase plays a major role in lipid biosynthesis, creatine kinase U-type catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate. Platelet-activating factor acetylhydrolase IB subunit alpha and voltage depedent anion-selective channel protein 2 were also increased. Conclusions : The results suggest that acupuncture stimulation at HT7 may enhance glucose and lipid metabolism, protein synthesis, cytoskeletal substance and anti-oxidative stress in hippocampus.

• 대한한의학방제학회지
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• 제12권2호
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• pp.77-93
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• 2004

Depression is a sort of mental disorder which is very common. To treat depression, many drugs such as TCA, MAOI are developed and used. But they have a lot of side effects, so it needs to develop drugs without side effects or with less side effects. Herbal medicines have been used to treat diseases not only physical but also mental and have less side effects. therefore, it has been thoght the need to develop herbal medicine with antidepressant effect. The purpose of this study was to reseach antidepressant effect and influence on monoamines of chunwangboshimdan thought to have antidepressant according to ancient medical book- donguibogam- and recent reports. We used 'forced swimming test(FST)' to know antidepressant effect of chunwangboshimdan and HPLC to check the influence on monoamines and their metabolites(norepinephrine, dopamine, DOPAC, HVA, serotonin, 5-HIAA) of chunwangboshimdan after divided into cerebral cortex, striatum, hypothalamus and hippocampus. The results were obtained as follows: In the study of antidepressant effect by 'forced swimming test(FST)'method, chunwang boshimdan had a significant antidepressant effect. In the study of influence on monoamines by HPLC, chunwangboshimdan mainly increased dopamine among monoamines and their metabolites(norepinephrine, dopamine, DOPAC, HVA, serotonin, 5-HIAA) significantly in 4 parts of rat's brain above-mentioned. Calculated by turnover ratio formulae of monoamine, chunwangboshimdan has more results than Imipramine. These results suggest that chunwangboshimdan has antidepressant effect that is related with the increase of monoamines by suppressing their metabolism as its mechanism.