• Journal of Korean Neurosurgical Society
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• v.67 no.5
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• pp.510-520
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• 2024

Objective : Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta. The treatment of PD aims to alleviate motor symptoms by replacing the reduced endogenous dopamine. Currently, there are no disease-modifying agents for the treatment of PD. Zebrafish (Danio rerio) have emerged as an effective tool for new drug discovery and screening in the age of translational research. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is known to cause a similar loss of dopaminergic neurons in the human midbrain, with corresponding Parkinsonian symptoms. L-type calcium channels (LTCCs) have been implicated in the generation of mitochondrial oxidative stress, which underlies the pathogenesis of PD. Therefore, we investigated the neuro-restorative effect of LTCC inhibition in an MPTP-induced zebrafish PD model and suggested a possible drug candidate that might modify the progression of PD. Methods : All experiments were conducted using a line of transgenic zebrafish, Tg(dat:EGFP), in which green fluorescent protein (GFP) is expressed in dopaminergic neurons. The experimental groups were exposed to 500 μmol MPTP from 1 to 3 days post fertilization (dpf). The drug candidates : levodopa 1 mmol, nifedipine 10 μmol, nimodipine 3.5 μmol, diethylstilbestrol 0.3 μmol, luteolin 100 μmol, and calcitriol 0.25 μmol were exposed from 3 to 5 dpf. Locomotor activity was assessed by automated tracking and dopaminergic neurons were visualized in vivo by confocal microscopy. Results : Levodopa, nimodipine, diethylstilbestrol, and calcitriol had significant positive effects on the restoration of motor behavior, which was damaged by MPTP. Nimodipine and calcitriol have significant positive effects on the restoration of dopaminergic neurons, which were reduced by MPTP. Through locomotor analysis and dopaminergic neuron quantification, we identified the neuro-restorative effects of nimodipine and calcitriol in zebrafish MPTP-induced PD model. Conclusion : The present study identified the neuro-restorative effects of nimodipine and calcitriol in an MPTP-induced zebrafish model of PD. They restored dopaminergic neurons which were damaged due to the effects of MPTP and normalized the locomotor activity. LTCCs have potential pathological roles in neurodevelopmental and neurodegenerative disorders. Zebrafish are highly amenable to high-throughput drug screening and might, therefore, be a useful tool to work towards the identification of disease-modifying treatment for PD. Further studies including zebrafish genetic models to elucidate the mechanism of action of the disease-modifying candidate by investigating Ca2+ influx and mitochondrial function in dopaminergic neurons, are needed to reveal the pathogenesis of PD and develop disease-modifying treatments for PD.

• Journal of the Korean Society of Radiology
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• v.6 no.2
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• pp.93-98
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• 2012

Micro-computed tomography (microCT) is an important tool for preclinical vascular imaging, with micron-level resolution. This non-destructive means of imaging allows for rapid collection of 2D and 3D reconstructions to visualize specimens prior to destructive analysis such as pathological analysis. Objectives. The aim of this study was to suggest a method for ex vivo, postmortem examination of stented arterial segments with microCT. And ex vivo evaluation of stents such as bare metal or drug eluting stents on in-stent restenosis (ISR) in rabbit model was performed. The bare metal stent (BMS) and drug eluting stent (DES, paclitaxel) were implanted in the left or right iliac arteries alternatively in eight New Zealand white rabbits. After 4 weeks of post-implantation, the part of iliac arteries surrounding the stent were removed carefully and processed for microCT. Prior to microCT analysis, a contrast medium was loaded to lumen of stents. All samples were subjected to an X-ray source operating at 50 kV and 200 ${\mu}A$ by using a 3D isotropic resolution. The region of interest was traced and measured by CTAN analytical software. Objects being exposed to radiation had different Hounsfield unit each other with values of approximately 1.2 at stent area, 0.12 ~ 0.17 at a contrast medium and 0 ~ 0.06 at outer area of stent. Based on above, further analyses were performed. As a result, the difference of lengths and volumes between expanded stents, which may relate to injury score in pathological analysis, was not different significantly. Moreover, ISR area of BMS was 1.6 times higher than that of DES, indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. And ISR area of BMS was higher ($1.52{\pm}0.48mm^2$) than that of DES ($0.94{\pm}0.42mm^2$), indicating that paclitaxel has inhibitory effect on cell proliferation and prevent infiltration of restenosis into lumen of stent. Though it was not statistically significant, it showed that the extent of neointema of mid-region of stents was relatively higher than that of anterior and posterior region in parts of BMS as showing cross-sectional 2-D image. suggest that microCT can be utilized as an accessorial tool for pathological analysis.

• Clinical and Experimental Reproductive Medicine
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• v.24 no.3
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• pp.281-292
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• 1997

The objective of this study was to compare retrospectively the survival and pregnancy rates(PR) of cryopresered-thawed embryos obtained from intracytoplasmic sperm injection (ICSI) or conventional in vitro fertilization (IVF). Ninety-six cycles of cryopresered-thawed embryo transfer (ET) were performed in 79 patients from June, 1996 to September, 1997 and grouped as followings: 20 cycles (16 patients) inseminated by ICSI (ICSI Group) and 76 cycles (63 patients) by conventional IVF (IVF Group). Slow-freezing and rapid-thawing protocol was used with 1.5M propanediol (PROH) and 0.1M sucrose as cryoprotectant. All embryos were frozen-thawed at the two pronuclear (2 PN) stage excluding four cycles in which the early cleavage stage embryos were frozen, and allowed to cleave in vitro for one day before ET. The duration from freezing to thawing was comparable in both groups ($mean{\pm}SD$, $112.1{\pm}80.0$ vs. $124.8{\pm}140.1$ days). The age of female ($31.2{\pm}3.4$ vs. $32.6{\pm}3.3$ years) and the endometrial thickness prior to progesterone injection ($9.4{\pm}2.0$ vs. $9.3{\pm}1.8$ mm) were also comparable in both groups. There was no significant difference in the outcomes of cryopreserved-thawed ET between two groups: survival rate ($85.2{\pm}16.1%$ vs. $82.2{\pm}19.7%$), cleavage rate ($96.9{\pm}6.7%$ vs. $94.7{\pm}13.0%$), cumulative embryo score (CES, $54.5{\pm}31.1$ vs. $49.0{\pm}20.0$), preclinical loss rate (5.0% vs. 5.3%), clinical miscarriage rate (0% vs 29.4%), clinical PR per transfer (35.0% vs. 22.4%), implantation rate (9.9% vs. 5.6%), and multifetal PR (42.9% vs. 17.6%). In conclusion, human embryos resulting from ICSI can be cryopreserved-thawed and transferred successfully, and the survival rate and PR are comparable to conventional IVF.

• Journal of health informatics and statistics
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• v.41 no.1
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• pp.49-56
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• 2016

Objectives: Carotid intima-media thickness (CIMT) and the presence of carotid artery plaque are widely used as preclinical markers of atherosclerosis. Due to operator dependency in measuring CIMT, it is important to evaluate the reliability of measuring CIMT and plaque between centers in a multicenter study. The purpose of this study is to evaluate the inter-rater reliability of CIMT and plaque presence among three clinical centers of the Cardiovascular and Metabolic Disease Etiology Research Center (CMERC). Methods: Twenty people without known cardiovascular disease (age 37-64) were enrolled during 2014-2015, and their left and right carotid arteries were examined repeatedly with ultrasonography for CIMT measurements at three clinical centers according to a predetermined protocol. Maximum and mean values of CIMT at distal common carotid artery were recorded. Plaque presence at a carotid artery was checked by an operator. The reliability of CIMT and carotid plaque presence was assessed using an intraclass correlation coefficient (ICC) and kappa statistics, respectively. Results: Calculated ICC was 0.647 (95% CI: 0.487-0.779) for maximum CIMT, and 0.758 (95% CI: 0.632- 0.854) for mean CIMT. In Bland Altman plot, most observed values were distributed within mean difference ${\pm}1.96$ SD ranges. Kappa statistics of plaque presence between two centers were 0.304 (center 1 and 2), 0.507 (center 1 and 3), and 0.606 (center 2 and 3), respectively, while Fleiss kappa for overall agreement was 0.445. Conclusions: The inter-rater reliability of CIMT measurements among three clinical centers turned out to be high, and the agreement of measuring carotid plaque presence was fair.

• Journal of Nutrition and Health
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• v.41 no.5
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• pp.391-401
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• 2008

Probiotics have emerged as a potential treatment modality for numerous gastrointestinal disorders, including IBD. However, few probiotics have undergone appropriate preclinical screening in vivo. Kefir is considered a probiotic, benefiting the host through its effects in the intestinal tract. Despite numerous studies examining the action of probiotics on the host organism, few have analyzed the effects on intestinal environment. We assessed the protective effect of kefir for three weeks before inducing colitis with 2% dextran sodium sulfate for five days. The DSS loads were similar in all DSS treatment group. The results of the experiment are as follows. Food intake and FER of experimental groups were not significantly different each other, but water consumption tended to be higher in all DSS treatment groups as compared with the normal control. And visual inspection of feces revealed mild diarrhea in rat given 2% DSS. The anti-inflammatory activity of kefir was determined by myeloperoxidase activity during the DSS treatment, and there was no significant difference in any group. The levels of thiobarbituric acid reactive substances (TBARS) as a colonic lipid peroxidation were significantly lower in the kefir intake groups than in rats treated with 2% DSS alone. The DNA % in tail and tail moment values as a DNA damage level of the blood lymphocytes in kefir intake groups tended to be lower than 2% DSS treatment alone, especially tail lengths were significantly diminished. According to the colonic histopathological assay, there were a severe inflammation of lamina propria and submucosa and mild edema in mucosa and sub mucosa in DSS alone treated group. We found a slight regenerative change in kefir treatment groups. In our experiments, this means that ulcerative colitis related to oxidative injury might be prevented by kefir as a probiotic. Further studies of the potential benefits of kefir as a probiotic in inflammatory condition are encouraged.

• Korean Journal of Oriental Medicine
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• v.11 no.1
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• pp.83-95
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• 2005

Arriving in the '90s, the worldwide trend of longing for naturalism and popularity of complementary and alternative medicine in America has caused traditional Oriental Medicine and medicinal plants markets to develop rapidly. And China has been pursuing the globalization policy of Chinese medicine by the initiation of the society of traditional Chinese medicine. Under this situation, it is a time for us to think about in a serious manner whether existing organization and system of Oriental medicine and the department of Oriental medicine at the schools in Korea reflects reality or whether we should turn it to some different direction. The purpose of this research is to compare the educational systems in relation to the traditional medicine between Korea and China, and to seek and look into its implication, and also to make a contribution to further developments and changes of direction for Oriental medicine education in Korea. 1. I investigated carefully the educational system of the colleges of traditional Chinese medicine, and results from this survey revealed that the academic institutions for the medicinal training in China consists of varied systems, such as 7-year program for medicinal training linking with master degree course, 6-year program, 5-year program (more than 90%), 4-year program, and so on, so then China has been raising the specialists in their traditional medicine arena through those varied academic programs. Such an educational system as the department of Chinese medicine in order to educate and produce specialists or pharmacists specializing in traditional Chinese medicine is operated only by Beijing University of Chinese Medicine in terms of 7-year academic program for medicinal major that linked with master degree course, and the rest of schools run 5-year program or 4-year program (more than 90%). And other human resources required for cultivation of medicinal plants and manufacturing herbal medicines are mostly trained at 3-year course colleges or 2-year course vocational schools. 2. In connection with traditional Chinese medicine, there are a variety of departments in the schools in China other than Chinese Medicine and Pharmacology: i.e. Acupuncture, Moxibustion and Tuina, Preclinical Medicine, Pharmaceuticals, Materials of Medicine, Phrenology and Law, Languages and Literature, etc. Therefore, these programs constitute multi academic system and also an appropriate educational base that fits in varied needs of market. Particularly, the university having 7-year program emphasize, English proficiency so that it can be considered that this academic program is a specialized course in order to achieve globalization of Chinese medicine. 3. In Korea, there are only 11 Oriental medicine schools with 6-year program which have been established by the private foundations and 3 departments of Oriental medicine at 4-year university. Therefore, we need to establish varied departments related to branches of our traditional medicine like China. 4. It is necessary to establish varied new departments related to Oriental Medicine that will be able to take a professional role in the course of pursuing the strategic goals such as scientification, globalization, standardization of Oriental Medicine, also that will meet needs of the world alternative and complementary medicine and herbal medicine markets. In order to achieve such strategic goals, we need to organize an academic system that will be different from existing systems and programs, also we are required to research further on the educational and training programs.

• Journal of Life Science
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• v.17 no.5 s.85
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• pp.678-686
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• 2007

Human mesenchymal stem cells(hMSC), that have been reported to be present in bone marrow, adipose tissues, dermis, muscles and peripheral blood, have the potential to differentiate along different lineages including those forming bone, cartilage, fat, muscle and neuron. Therefore, hMSC are attractive candidates for cell and gene therapy. The optimal conditions for hMSC expansion require medium supplemented with fetal bovine serum(FBS). Some forms of cell therapy will involve multiple doses, raising a concern over immunological reactions caused by medium-derived FBS proteins. Previously, we have shown that hADSC can be cultured in human serum(HS) during their isolation and expansion, and that they maintain their proliferative capacity and ability for multilineage differentiation and promote engraftment of peripheral blood-derived CD34 cells mobilized from bone marrow in NOD/SCID mice. In this study we determined whether hADSC grown in HS maintain surface markers expression similar with cells grown in FBS during culture expansion and compared gene expression profile by Affymetrix microarray. Flow cytometry analysis showed that HLA-DR, CD117, CD29 and CD44 expression in HS-cultured hADSC during culture expansion were similar with that in FBS-cultured cells. However, the gene expression profile in HS-cultured hADSC was significantly different from that in FBS-cultured cells. Therefore, these data indicated that HS-cultured hADSC should be used in vivo animal study of hADSC transplantation for direct extrapolation of preclinical data into clinical application.

• Journal of Life Science
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• v.31 no.11
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• pp.1028-1036
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• 2021

Firefly luciferase (FLuc) can function as an efficient marker in the gene and viral therapies. Nonetheless, its clinical translation has been unaccomplished with the concerns on its exogenous nature and the similarity with human fatty acyl-CoA synthetase. In this study, we aimed to show safety of FLuc by conducting a set of preclinical experiments and a human use. Initially, FLuc permeability across the plasma membrane was investigated by delivering the FLuc-carrying viral vector, OTS-412, or the FLuc recombinant protein. After in vitro infection of OTS-412 into different cancer cell lines, FLuc activity was detected only in the cell lysates, but not in culture media. In addition, recombinant FLuc protein further showed the impermeability against the plasma membrane. Similar result was also observed in the in vivo experiment. After being injected into the VX2 tumor-bearing rabbit, the FLuc exclusively resided within the tumor tissue without being detected in the blood plasma or other organs. Human cancer cell lines originated from various organs were lysed and treated to the FLuc, and none of the human substrates was reactive against the FLuc. As a final step, FLuc recombinant protein was intravenously injected into a human. The luciferase was degraded with the half-life of 20 to 30 minutes in blood, and was untraceable from 1.5 hr after the injection. In addition, the blood plasma was nonresponsive against the fatty acids. Hematological analysis was also comparable between the pre- and post-injection. Altogether, our study collectively demonstrates the safety of the firefly luciferase.

• Journal of Life Science
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• v.28 no.7
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• pp.819-826
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• 2018

Orostachys japonicus (OJ) is a medicinal herb with immunoregulatory, anti-aging, anti-oxidative, and many other therapeutic properties. The purpose of this study was to elucidate the anti-cancer property of cultivated OJ. SW480 cell viability was significantly reduced by cumulative exposure to OJ extract. We also observed inhibitory effects of OJ after 72 hr through the growth and migration of SW480 cells using scratch assay. SW480 cells in OJ-free medium began to move into the scratch site at 24 hr; however, cells in medium containing OJ did not migrate into the scratch site until 48 hr. Male C57BL/6 mice (4 weeks old) were orally administered OJ extract for 31 days before injection of SW480 cells. At 7, 14, and 28 days after subcutaneous injection of SW480 cells, tumor weight and volume were analyzed. The body weight of the OJ-treated group was continuously increased during administration of the OJ extract relative to the control group. Injection of SW480 cells caused a reduction in body weight in all groups; however, the OJ-treated group exhibited a significant increase in body weight after 14 days. Tumor weight and volume were lower in the OJ-treated group than in the control group after 28 days. Although these results suggest that OJ suppresses the proliferation and migration of human colon cancer cells, additional studies are required to provide preclinical evidence before launching clinical trials evaluating OJ as an anti-cancer biohealth product.

• Journal of Food Hygiene and Safety
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• v.25 no.4
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• pp.410-417
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• 2010

Various functional foods, marketing health and functional effects, have been distributed in the market. These products, being in forms of foods, tablets, and capsules, are likely to be mistaken as drugs. In addition, non-experts may sell these as foods, or use these for therapy. Efforts for creating health food regulations or building regulatory system for improving the current status of functional foods have been made, but these have not been communicated to consumers yet. As a result, problems of circulating functional foods for therapy or adding illegal medical to such products have persisted, which has become worse by internet media. The cause of this problem can be categorized into (1) product itself and (2) its use, but in either case, one possible cause is lack of communications with consumers. Potential problems that can be caused by functional foods include illegal substances, hazardous substances, allergic reactions, considerations when administered to patients, drug interactions, ingredients with purity or concentrations too low to be detected, products with metabolic activations, health risks from over- or under-dose of vitamin and minerals, and products with alkaloids. (Journal of Health Science, 56, Supplement (2010)). The reason why side effects related to functional foods have been increasing is that under-qualified functional food companies are exaggerating the functionality for marketing purposes. KFDA has been informing consumers, through its web pages, to address the above mentioned issues related to functional foods, but there still is room for improvement, to promote proper use of functional foods and avoid drug interactions. Specifically, to address these issues, institutionalizing to collect information on approved products and their side effects, settling reevaluation systems, and standardizing preclinical tests and clinical tests are becoming urgent. Also to provide crucial information, unified database systems, seamlessly aggregating heterogeneous data in different domains, with user interfaces enabling effective one-stop search, are crucial.