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Justicidin A Reduces β-Amyloid via Inhibiting Endocytosis of β-Amyloid Precursor Protein

  • Chun, Yoon Sun;Kwon, Oh-Hoon;Oh, Hyun Geun;Cho, Yoon Young;Yang, Hyun Ok;Chung, Sungkwon
    • Biomolecules & Therapeutics
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    • v.27 no.3
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    • pp.276-282
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    • 2019
  • ${\beta}$-amyloid precursor protein (APP) can be cleaved by ${\alpha}$-, and ${\gamma}$-secretase at plasma membrane producing soluble ectodomain fragment ($sAPP{\alpha}$). Alternatively, following endocytosis, APP is cleaved by ${\beta}$-, and ${\gamma}$-secretase at early endosomes generating ${\beta}$-amyloid ($A{\beta}$), the main culprit in Alzheimer's disease (AD). Thus, APP endocytosis is critical for $A{\beta}$ production. Recently, we reported that Monsonia angustifolia, the indigenous vegetables consumed in Tanzania, improved cognitive function and decreased $A{\beta}$ production. In this study, we examined the underlying mechanism of justicidin A, the active compound of M. angustifolia, on $A{\beta}$ production. We found that justicidin A reduced endocytosis of APP, increasing $sAPP{\alpha}$ level, while decreasing $A{\beta}$ level in HeLa cells overexpressing human APP with the Swedish mutation. The effect of justicidin A on $A{\beta}$ production was blocked by endocytosis inhibitors, indicating that the decreased APP endocytosis by justicidin A is the underlying mechanism. Thus, justicidin A, the active compound of M. angustifolia, may be a novel agent for AD treatment.

Curcumin modulates the apolipoprotein B mRNA editing by coordinating the expression of cytidine deamination to uridine editosome components in primary mouse hepatocytes

  • He, Pan;Tian, Nan
    • The Korean Journal of Physiology and Pharmacology
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    • v.23 no.3
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    • pp.181-189
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    • 2019
  • Curcumin, an active ingredient of Curcuma longa L., can reduce the concentration of low-density lipoproteins in plasma, in different ways. We had first reported that curcumin exhibits hypocholesterolemic properties by improving the apolipoprotein B (apoB) mRNA editing in primary rat hepatocytes. However, the role of curcumin in the regulation of apoB mRNA editing is not clear. Thus, we investigated the effect of curcumin on the expression of multiple editing components of apoB mRNA cytidine deamination to uridine (C-to-U) editosome. Our results demonstrated that treatment with $50{\mu}M$ curcumin markedly increased the amount of edited apoB mRNA in primary mouse hepatocytes from 5.13%-8.05% to 27.63%-35.61%, and significantly elevated the levels of the core components apoB editing catalytic polypeptide-1 (APOBEC-1), apobec-1 complementation factor (ACF), and RNA-binding-motif-protein-47 (RBM47), as well as suppressed the level of the inhibitory component glycine-arginine-tyrosine-rich RNA binding protein. Moreover, the increased apoB RNA editing by $50{\mu}M$ curcumin was significantly reduced by siRNA-mediated APOBEC-1, ACF, and RBM47 knockdown. These findings suggest that curcumin modulates apoB mRNA editing by coordinating the multiple editing components of the edito-some in primary hepatocytes. Our data provided evidence for curcumin to be used therapeutically to prevent atherosclerosis.

Calculation of Kappa-Averaged Collision Strengths of Silicon VIII Ion for a Non-Maxwellian Distribution

  • He, Jian;Zhang, Qingguo
    • Journal of the Korean Physical Society
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    • v.73 no.9
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    • pp.1310-1314
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    • 2018
  • Non-Maxwellian distributions are found in the laboratory and space plasmas. For an accurate study of plasmas, the Kappa-averaged collision strengths of silicon VIII ion for $4^0S_{3/2}-2^0D_{3/2}$, $4^0S_{3/2}-2^0D_{5/2}$ and $2^0D_{3/2}-2^0D_{5/2}$ transitions are calculated for Kappa distributions with ${\kappa}=2$, 3 and 5 and for temperatures from $10^{4.5}K$ to $10^{6.5}K$. Results indicate that significant differences occur between the averaged collision strengths for the Maxwellian and the Kappa distributions. Fuythermore, and for each ${\kappa}$ value, the Kappa-averaged collision strengths vary in a complicated way with temperature for the $4^0S_{3/2}-2^0D_{3/2}$ and $4^0S_{3/2}-2^0D_{5/2}$ transitions while they decrease with increasing temperature for the $2^0D_{3/2}-2^0D_{5/2}$ transition. The calculation is significant if plasmas are to be studied for a non-Maxwellian distribution.

Establishment and Application of a Femtosecond-laser Two-photon-polymerization Additive-manufacturing System

  • Li, Shanggeng;Zhang, Shuai;Xie, Mengmeng;Li, Jing;Li, Ning;Yin, Qiang;He, Zhibing;Zhang, Lin
    • Current Optics and Photonics
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    • v.6 no.4
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    • pp.381-391
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    • 2022
  • Two-photon-polymerization additive-manufacturing systems feature high resolution and precision. However, there are few reports on specific methods and possible problems concerning the use of small lasers to independently build such platforms. In this paper, a femtosecond-laser two-photon-polymerization additive-manufacturing system containing an optical unit, control unit, monitoring unit, and testing unit is built using a miniature femtosecond laser, with a detailed building process and corresponding control software that is developed independently. This system has integrated functions of light-spot detection, interface searching, micro-/nanomanufacturing, and performance testing. In addition, possible problems in the processes of platform establishment, resin preparation, and actual polymerization for two-photon-polymerization additive manufacturing are explained specifically, and the causes of these problems analyzed. Moreover, the impacts of different power levels and scanning speeds on the degree of polymerization are compared, and the influence of the magnification of the object lens on the linewidth is analyzed in detail. A qualitative analysis model is established, and the concepts of the threshold broadening and focus narrowing effects are proposed, with their influences and cooperative relation discussed. Besides, a linear structure with micrometer accuracy is manufactured at the millimeter scale.

The Comparative Studies for the Anti-stress Effect of Guibitang and Ascorbic Acid on Heating and Swimming Stress (열(熱)Stress 및 유영(游泳)Stress에 대(對)한 귀비탕(歸脾湯)과 Ascorbic Acid의 항(抗)Stress효능(效能) 비교연구(比較硏究))

  • Lee Hwa-Sin;Whang Wei-Wan
    • Journal of Oriental Neuropsychiatry
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    • v.6 no.1
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    • pp.19-39
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    • 1995
  • In order to compare the anti-stress effect of Guibitang with that of ascorbic acid, after these medicines were administered to guinea pigs induced by heating and swimming stress, the changes of the weight of body and organ, and content of plasma catecholamines, serum total cholesterol, free cholesterol, triglyceride, protein, glucose and cortisol were measured. The results were as follows : 1. The weight of the body was increased with statistical significance in the groups administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on both heating and swimming stress. 2. The weight of spleen decreased with statistical significance in the groups administered ascorbic acid, Guibitang and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on heating stress, but in case of swimming stress, the weight of spleen decreased with statistical significance in the groups administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid. The weight of adrenal decreased with statistical significance in the groups administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on heating stress alone. 3. Plasma norepinephrine content decreased with statistical significance not only in the groups administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid but in the group administered ascorbic acid with Guibitang as compared with in the group administered ascorbic acid on heating stress. In case of swimming stress, norepinephrine decreased with statistical significance in the groups administered ascorbic acid, Guibitang and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid. 4. Plasma dopamine content decreased with statistical significance only in the group administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on both heating and swimming stress. 5. Serum total cholesterol content decreased with statistical significance in the groups administered ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on heating stress, but in case of swimming stress, it decreased with statistiscal significance only in the group administered ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid. 6. Serum triglyceride content decreased with statistical significance not only in the groups administered ascorbic acid, Guibitang and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid but in the group administered ascorbic acid with Guibitang as compared with in the group adminstered ascorbic acid on heating stress. In case of swimming stress, triglyceride decrease with statistical significance only in the group administered ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid. 7. Serum glucose content increased with statistical significance in the groups administered Guibitang and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on both heating and swimming stress, particulaly in case of swimming stress, in the group administered ascorbic acid with Guibitang, it increased with statistical significance as compared with in the group administered ascorbic acid. 8. Serum cortisol content decreased with statistical significance only in the group administered ascorbic acid and ascorbic acid with Guibitang as compared with in the group administered non ascorbic acid on heating stress.

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Embryonic Mortality and Pregnancy Rate in Bovine Embryo Transfer (소 수정란 이식에서의 배사멸과 임신율)

  • 김창근
    • Journal of Embryo Transfer
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    • v.6 no.2
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    • pp.1-17
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    • 1991
  • It is widely recognized that the embryonic or fetal loss after breeding is common in the cattle and that it is an important factor affecting reproductive efficiency. The causes of this loss have been subject of extensive researches and the results indicate that the embryonic mortality may he primary factor responsible for low pregnancy rates in non-embryo transfer bovine populations as well as embryo transfer programs. However, it's causes are still not clearly understood. The embryonic mortality or pregnancy rate has been influenced by various embryonic and maternal effects related to genetic and environmental factors. The timing and extent of embryonic mortality vanes greatly according to authors and estimating methods, because it is difficult to make direct measurements. The major important factors that may influence the embryonic losses or pregnancy rates after embryo transfer can be summeirized. 1.When an embryo is transferred to unmated recipients, the contralateral transfer to corpus luteum results in a lower survival rate than ipsilateral deposition. When the embryos are transferred for the production of twin calves, their survivals and twin pregnancies have quite inconsistent according to the transfer methods either to the unmated-synchronized or already mated recipients and more works are needed to accurrately clarify the previous results. 2.Although embryos can be cultured in vitro some hours without the great declines in pregnancy rates, the rates differ markedly among culture times and media but may be improved by co-transfer systems. 3.Embryo developmental stages and quality grades clearly affect the survival rate following freezing and the pregnancy rate after transfer and the selection of embryos without chromosome abnormalities and of high fertile semen may also be considered to increase the pregnancy rates. 4.Many researches have attempted to relate the plasma progesterone levels to pregnancy rates and others have done either direct progesterone supplementation or luteal stimulation by hCG treatment in order to increase the pregnancy rates. However, these effects on pregnancy rates are inconsistent and also contradictory. 5.The asynchrony between donors or embryos and recipients may he a major cause of embryo death and low pregnancy rate and the sensitivity to uterine asynchyony differs in according to the quality and stages of embryos. 6.The extremes of poor or over nutrition during early pregnancy in the recipients are detrimental to the survival of embryos and the good body condition is required to prevent a reduejion of pregnancy rates. The uterine pathogens in embryonic mortality or fertility have been questioned but the infection of C.pyogenes and Campylobacter fetus is still important pathogens. 7.The heat stress during early pregnancy may reduce conceptus weight and possibly increase the embryonic mortality.

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A Case of Primary Mediastinal Germ Cell Tumor Associated with Klinefelter's Syndrome (Klinefelter 증후군에 병발된 원발성 종격동 생식세포종 1예)

  • Kim, Yong-Jo;Kwun, Gyo-Seon;Lee, Young Wo;Kim, Kyung-Tae;Park, Yeon-Hee;Ryoo, Baek-Yeol;Kim, Tae You;Im, Young-Hyuck;Lee, Choon-Taek;Kang, Yoon-Koo;Cho, Kyung Ja;Lee, Jhin-Oh;Kang, Tae-Woong
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.6
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    • pp.1035-1041
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    • 1996
  • Klinefelter's syndrome is characterized by small testes, azoospermia, gynecomastia, and elevated levels of plasma gonadotropins in men with two or more X chromosomes. Previous investigators reponed that patients with Klinefelter's syndrome are predisposed to the development of a non-seminomatous germ cell tumor in the mediastinum. It is suggested that this linkage may be due to the hormonal imbalance in Klinefelter's syndrome and consequently, the formation of dysgenetic germ cell and/or abnomal migration of germ cell We report here a case of Klinefelter's syndrome in a 24-years-old man who was presented with anterior mediastinal mass. The clinical and laborarotory fmdings were compatible with Klinefelter's syndrome and he was found to have 47 XXY karyotype. Pathological findings for mediastinal mass revealed mixed germ cell tumor composed of mature cystic teraloma and endodermal sinus rumor. He was treated with cis platin containing chemotherapy and followed up in partial remission.

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Effects of Ginseng Feeding on the Recovery of Posthemorrhagic Anemia and Erythrokinetics in Rabbits (인삼이 사혈성빈혈 회복 및 Erythrokinetics에 미치는 영향)

  • Park, Yong-Duck;Lee, In-Sook;Kim, Myung-Sun
    • The Korean Journal of Physiology
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    • v.15 no.1
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    • pp.9-18
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    • 1981
  • For centuries, ginseng has been used for the therapeutic purpose in oriental herb medicine. Several studies have been conducted in the past to evaluate the effect of ginseng on erythropoiesis. However the results were controversial. We therefore attempted in the present studies to evaluate the effect of ginseng on the erythropoietic activity. In one series of experiments, the recovery pattern of peripheral blood(red cell count, hemoglobin content, hematocrit and reticulocyte count) was studied in posthemorrhagic anemic rabbits. After animals were maintained with normal(control group) or 1 gm% ginseng (experimental group) diet for 2 weeks, hemorrhagic anemia was induced by withdrawing blood equivalent to 25% of the total blood volume and then changes in peripheral blood were followed for following 30 days. In other series of experiments, we studied effect of ginseng on erythrokinetics using $^{59}Fe$. $^{59}Fe(10{\sim}40\;{\mu}Ci/animal)$ was injected intravenously after animals were fed with normal (control group) or 1 gm% ginseng(experimental group) diet for 2 weeks. And radioactivities in the blood compartments were measured at appropriate intervals for 15 days. Front these various erythrokinetic parameters were estimated. Results are summarized as follows: 1) Reticulocyte count was higher in the experimental group than in the control group after 2 weeks of administration of experimental diet. During the posthemorrhagic period, the reticulocyte count increased in both the control and experimental groups, but the increase appeared much earlier in the experimental group. 2) The posthemorrhagic recoveries of hematocrit, hemoglobin content and red cell count appeared to be faster in the experimental group as compaired with the control group. 3) The half life$(T_{1/2})$ of $^{59}Fe$ in the plasma was significantly(P<0.05) shorter in the experimental group(82.6 min, N=8) than in the control group(121 min, N=6). Plasma iron turnover (PIT) of the experimental group (1.78 mg/dl/24 hr.) was approximately 4 times greater than that of the control group(0.45 mg/dl/24 hr.). 4) The maximum red cell utilization(RC-U) was 82.1% in the experimental group ana 74.5% in the control group. Red cell iron turnover(RIT) of the experimental group(1.62 mg/dl/24 hr.) was slightly higher than that of the control group(0.35 mg/dl/24 hr). 5) Erythron turnover was significantly(p<0.05) greater in the experimental group(1.27 mg/dl/24 hr.) than in the control group(0.24 mg/dl/24 hr.). Marrow transit time of the experimental group(2.05 days) tended to he faster than that of the control group(2.84 days). These results suggest that the gingseng improves the recovery of posthemorrhagic anemia and stimulates the erythropoiesis in rabbits.

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Induction of an Experimental PKU-Like Condition in Infant Rats During the First Two Weeks After Birth (신생(新生)쥐의 생후(生後) 2주간(週間)에 있어서 Phenylketonuria 적(的) 조건(條件)의 실험적(實驗的) 유도(誘導))

  • Kim, Haeng-Ja;Longenecker, John B.
    • Journal of Nutrition and Health
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    • v.14 no.2
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    • pp.59-70
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    • 1981
  • The objective of this study is to induce the primary characteristics of phenylketonuria in infant rats during the first 2 weeks after birth. The critical biochemical parameter in the development of phenylketonuria is the elevation of plasma phenylalanine while tyrosine is maintained at a relatively low level. A PKU-like condition was induced in infant rats during the first 2 weeks after birth using a modification of our previously published procedure for the development of a temporary (1 to 3 days) PKU-like condition. Phenylalanine was administered by stomach intubation every 6 hours (starting at 6:00 a.m.) at a dose level of 400mg per kg body weight (after birth-day 2 thru 5) and 500mg per kg body weight (day 6 thru 14). Amethopterin was given at 0.00625 or 0.0125mg per kg body weight (day 3 thru 14) and p-chlorophenylalanine at 50 mg per kg body weight (day 5 thru 14) at 9:00 a.m. and 9:00 p.m. At the times measured (6,10 and 14 days) plasma phenylalanine/tyrosine (P/T) ratios were elevated from a normal value of the or less to values ranging from 6 to 15. During the second week after birth a staggering gait, abnormal stance and decreased social behavior were also observed. None of these PKU-like characteristics were apparent in the three control groups receiving (a) no phenylalanine or inhibitors, (b) phenylalanine alone, or (c) inhibitors alone. The establishment of these primary biochemical characteristics of phenylketonuria by stomach intubation of phenylalanine and a combination of low dose levels of enzyme inhibitors to infant rats provides an experimental system which should he valuable for extensive biochemical, histological and behavioral studies in phenylketonuria.

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FLOW CYTOMETRIC ANALYSIS OF LYMPHOCYTE AND CYCLING CELL DISTRIBUTION IN PERIAPICAL LESIONS (유세포 분석기를 이용한 치근단 병소의 임파구 조성 및 CYCLING CELL 분포에 관한 연구)

  • Oh, Tae-Seok;Lim, Sung-Sam
    • Restorative Dentistry and Endodontics
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    • v.18 no.2
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    • pp.317-340
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    • 1993
  • This study was designed 1) to compare the distributions of periapical inflammatory cells and 2) to identify lymphocytes and compare the lymphocyte distribution with T lymphocyte subpopulation and then 3) to examine the distribution of cycling cell in human dental periapical lesions. From each of the twenty-five human dental periapical lesions observed one small portion was fixed, embeded in paraffin, sectioned serially and stained with HE. The periapical inflammatory cells were counted to obtain the relative concentration of lymphocyte, plasma cell, macrophage and neutrophil. The large part of each lesion was analysed using Flow cytometer and monoclonal antibodies to obtain the relative concentration of T lymphocyte, B lymphocyte, T'helper cell and T suppressor/cytotoxic cell. In addition to that, seven human dental periapical lesions were examined with DNA analysis to observe the distribution of cycling cell. Following results were obtained: 1. 24 cases of the 32 periapical lesions examined were diagnosed as periapical granuloma and the remaining 8 cases as periapical cyst. Lymphocytes comprised 42.1% of total inflammatory cells in periapical granuloma and 41.8% in periapical cyst. Corresponding percentages for macrophages were 33.8% and 30.3%; for plasma cells, 15.9% and 19.0%; for neutrophils, 8.2% and 8.8%. 2. All of the periapical lesions examined had T lymphocyte, B lymphocyte, T helper cell, T suppressor/cytotoxic cell. And in all cases, T lymphocytes were observed predominantly more than B lymphocytes. 3. In 2 cases of the control group only T lymphocytes were found, and in the remaining 2 cases T lymphocytes were observed predominantly. 4. T helper cells were observed predominantly more than T suppressor/cytotoxic cells in all cases of perapical granulomas. 5. T suppressor/cytotoxic cells were observed predominantly more than T helper cells in 4 cases of periapical cysts (total 5 cases were examined) and only in one case T helper cells were more than T suppressor/cytotoxic cells. 6. In control group, T helper cells were predominant in 2 cases and T helper cells were equivalent to T suppressor/cytotoxic cells in one case. In remaining one case T suppressor/cytotoxic cells were predominant. 7. As the result of DNA analysis, the average proliferating indices of the various groups examined were measured as follows: in the control group 5.45%, in periapical granuloma 6.64%, in periapical cyst 10.1%. The highest index was observed in periapical cyst.

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