• The Korean Journal of Physiology and Pharmacology
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• 제16권6호
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• pp.405-411
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• 2012

The spontaneous axon regeneration of damaged neurons is limited after spinal cord injury (SCI). Recently, mesenchymal stem cell (MSC) transplantation was proposed as a potential approach for enhancing nerve regeneration that avoids the ethical issues associated with embryonic stem cell transplantation. As SCI is a complex pathological entity, the treatment of SCI requires a multipronged approach. The purpose of the present study was to investigate the functional recovery and therapeutic potential of human MSCs (hMSCs) and polymer in a spinal cord hemisection injury model. Rats were subjected to hemisection injuries and then divided into three groups. Two groups of rats underwent partial thoracic hemisection injury followed by implantation of either polymer only or polymer with hMSCs. Another hemisection-only group was used as a control. Behavioral, electrophysiological and immunohistochemical studies were performed on all rats. The functional recovery was significantly improved in the polymer with hMSC-transplanted group as compared with control at five weeks after transplantation. The results of electrophysiologic study demonstrated that the latency of somatosensory-evoked potentials (SSEPs) in the polymer with hMSC-transplanted group was significantly shorter than in the hemisection-only control group. In the results of immunohistochemical study, ${\beta}$-gal-positive cells were observed in the injured and adjacent sites after hMSC transplantation. Surviving hMSCs differentiated into various cell types such as neurons, astrocytes and oligodendrocytes. These data suggest that hMSC transplantation with polymer may play an important role in functional recovery and axonal regeneration after SCI, and may be a potential therapeutic strategy for SCI.

• Journal of Ginseng Research
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• 제45권1호
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• pp.66-74
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• 2021

Background: Abnormal chloride (Cl-) transport has a detrimental impact on mucociliary clearance in both cystic fibrosis (CF) and non-CF chronic rhinosinusitis. Ginseng is a medicinal plant noted to have anti-inflammatory and antimicrobial properties. The present study aims to assess the capability of red ginseng aqueous extract (RGAE) to promote transepithelial Cl- secretion in nasal epithelium. Methods: Primary murine nasal septal epithelial (MNSE) [wild-type (WT) and transgenic CFTR-/-], fisher-rat-thyroid (FRT) cells expressing human WT CFTR, and TMEM16A-expressing human embryonic kidney cultures were utilized for the present experiments. Ciliary beat frequency (CBF) and airway surface liquid (ASL) depth measurements were performed using micro-optical coherence tomography (μOCT). Mechanisms underlying transepithelial Cl- transport were determined using pharmacologic manipulation in Ussing chambers and whole-cell patch clamp analysis. Results: RGAE (at 30㎍/mL of ginsenosides) significantly increased Cl- transport [measured as change in short-circuit current (ΔISC = ㎂/㎠)] when compared with control in WT and CFTR-/- MNSE (WT vs control = 49.8±2.6 vs 0.1+/-0.2, CFTR-/- = 33.5±1.5 vs 0.2±0.3, p < 0.0001). In FRT cells, the CFTR-mediated ΔISC attributed to RGAE was small (6.8 ± 2.5 vs control, 0.03 ± 0.01, p < 0.05). In patch clamp, TMEM16A-mediated currents were markedly improved with co-administration of RGAE and uridine 5-triphosphate (8406.3 +/- 807.7 pA) over uridine 5-triphosphate (3524.1 +/- 292.4 pA) or RGAE alone (465.2 +/- 90.7 pA) (p < 0.0001). ASL and CBF were significantly greater with RGAE (6.2+/-0.3 ㎛ vs control, 3.9+/-0.09 ㎛; 10.4+/-0.3 Hz vs control, 7.3 ± 0.2 Hz; p < 0.0001) in MNSE. Conclusion: RGAE augments ASL depth and CBF by stimulating Cl- secretion through CaCC, which suggests therapeutic potential in both CF and non-CF chronic rhinosinusitis.

• 생명과학회지
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• 제19권4호
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• pp.549-552
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• 2009

유전자의 융합으로 인한 돌연변이는 염색체 재배열, 트랜스 스플라이싱, 유전자간 스플라이싱으로 인하여 야기된다고 알려져 있다. 우리는 두 개의 서로 다른 유전자의 pre-mRNA의 융합으로 인하여 만들어지는 트랜스 스플라이싱의 전사 산물에 관심을 가져, 인간의 태아 줄기 세포에서 이러한 돌연변이 양상을 분석하였다. 배아줄기세포의 mRNA에서 트랜스 스플라이싱 전사체 70개를 탐지해 내고, 이들의 융합되는 패턴에 따라 5'UTR-5'UTR, 5'UTR-3'UTR, 3'UTR-3'UTR, 5'UTR- CDS, 3'UTR-CDS, CDS-CDS의 6개의 유형으로 분류하여 분석하였다. 두 유전자의 융합되는 영역은 UTR영역보다 CDS에서 풍부하였는데, 이러한 이유는 많은 인트론 수로 인해 야기되는 것으로 추정된다. 융합되는 유전자의 염색체상의 위치분석 결과, 17번과 19번 염색체가 융합유전자의 활성화를 나타내었다. 이러한 연구결과는 향후 융합유전자와 인간의 질병 연구에 크게 기여할 것으로 사료된다.

• Clinical and Experimental Reproductive Medicine
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• 제44권2호
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• pp.90-95
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• 2017

Objective: We investigated whether the insemination method (in vitro fertilization [IVF] or intracytoplasmic sperm injection [ICSI]) affected morphokinetic events and abnormal cleavage events in embryonic development. Methods: A total of 1,830 normal fertilized embryos were obtained from 272 IVF and ICSI cycles that underwent ovum retrieval culture using a time-lapse system (Embryoscope) from June 2013 to March 2015. All embryos were investigated by a detailed time-lapse analysis that measured the developmental events in the hours after IVF or ICSI insemination. Results: No significant differences were observed between the two groups regarding clinical outcomes (p>0.05). ICSI-derived embryos showed significantly faster morphokinetics than those derived from conventional IVF, from the time to pronuclear fading to the time to 6 cells (p<0.05). However, no significant differences were found from the time to 7 cells to the time to expanded blastocyst (p>0.05). There were no differences in abnormal cleavage events between the two groups (p>0.05); they showed the same rates of direct cleavage from 1 to 3 cells, 2 multinucleated cells, 2 uneven cells, and reverse cleavage. Conclusion: The morphokinetics of embryo development was found to vary between IVF- and ICSI-fertilized oocytes, at least until the 6-cell stage. However, these differences did not affect the clinical outcomes of the embryo. Additionally, no significant differences in abnormal cleavage events were found according to the fertilization method.

• 한국약용작물학회지
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• 제14권6호
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• pp.317-321
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• 2006

This study was performed to compare effect of anticancer activities on Rhodiola sachalinensis by ultrasonifi-cation process and solvent. Compared the yield to the water extracts (WE), wafer extracts with ultrasonification (WEU) at60, loot and ethyl alcohol extracts (EE), ethyl alcohol extracts with ultrasonification (EEU) at 60 ${\circ}$C from Rhodiola sachalinensis. Experimental studies were progressed through the anticancer activities such as cell cytotoxicity, inhibition activities of cell growth. The cell cytotoxicity using human embryonic kidney cell (HEK293) was showed cytotoxicity of below 26.26%by extracts of Rhodiola sachalinensis in 1.0 mg/ml concentration, The anticancer activities were increased in over 70% by extracts of Rhodiola sachalinensis in A549, AGS, Hep3B and MCF-7 cells. From the results, the extract Rhodiola sachalinensis were showed useful anticancer activities.

• Nutrition Research and Practice
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• 제8권4호
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• pp.377-385
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• 2014

BACKGROUND/OBJECTIVES: Abundant consumption of seaweeds in the diet is epidemiologically linked to the reduction in risk of developing cancer. In larger cases, however, identification of particular seaweeds that are accountable for these effects is still lacking, hindering the recognition of competent dietary-based chemo preventive approaches. The aim of this research was to establish the antiproliferative potency and angiosuppressive mode of action of Stoechospermum marginatum seaweed methanolic extract using various experimental models. MATERIALS/METHODS: Among the 15 seaweeds screened for antiproliferative activity against Ehrlich ascites tumor (EAT) cell line, Stoechospermum marginatum extract (SME) was found to be the most promising. Therefore, it was further investigated for its anti-proliferative activity in-vitro against choriocarcinoma (BeWo) and non-transformed Human embryonic kidney (HEK 293) cells, and for its anti-migratory/tube formation activity against HUVEC cells in-vitro. Subsequently, the angiosuppressive activity of S. marginatum was established by inhibition of angiogenesis in in-vivo (peritoneal angiogenesis and chorioallantoic membrane assay) and ex-vivo (rat cornea assay) models. RESULTS: Most brown seaweed extracts inhibited the proliferation of EAT cells, while green and red seaweed extracts were much less effective. According to the results, SME selectively inhibited proliferation of BeWo cells in-vitro in a dose-dependent manner, but had a lesser effect on HEK 293 cells. SME also suppressed the migration and tube formation of HUVEC cells in-vitro. In addition, SME was able to suppress VEGF-induced angiogenesis in the chorio allantoic membrane, rat cornea, and tumor induced angiogenesis in the peritoneum of EAT bearing mice. A decrease in the microvessel density count and CD31 antigen staining of treated mice peritoneum provided further evidence of its angiosuppressive activity. CONCLUSIONS: Altogether, the data underline that VEGF mediated angiogenesis is the target for the angiosuppressive action of SME and could potentially be useful in cancer prevention or treatment involving stimulated angiogenesis.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.311-319
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• 2020

Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a newly emerging viral disease with fatal outcomes. However, no MERS-CoV-specific treatment is commercially available. Given the absence of previous structure-based drug discovery studies targeting MERS-CoV fusion proteins, this set of compounds is considered the first generation of MERS-CoV small molecule fusion inhibitors. After a virtual screening campaign of 1.56 million compounds followed by cell-cell fusion assay and MERS-CoV plaques inhibition assay, three new compounds were identified. Compound numbers 22, 73, and 74 showed IC₅₀ values of 12.6, 21.8, and 11.12 µM, respectively, and were most effective at the onset of spike-receptor interactions. The compounds exhibited safe profiles against Human embryonic kidney cells 293 at a concentration of 20 µM with no observed toxicity in Vero cells at 10 µM. The experimental results are accompanied with predicted favorable pharmacokinetic descriptors and drug-likeness parameters. In conclusion, this study provides the first generation of MERS-CoV fusion inhibitors with potencies in the low micromolar range.

• 한국표면공학회:학술대회논문집
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• 한국표면공학회 2018년도 춘계학술대회 논문집
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• pp.23-23
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• 2018

In this study, new titanium alloys were prepared by adding elements such as tantalum (Ta), zirconium (Zr) and the like to complement the biological, chemical and mechanical properties of titanium alloys. The Ti-40Ta-xZr ternary alloy was formed on the basis of Ti-40Ta alloy with the contents of Zr in the contents of 0, 3, 7 and 15 wt. %. Plasma electrolytic oxidation (PEO), which combines high-voltage sparks and electrochemical oxidation, is a novel method to form ceramic coatings on light metals such as Ti and its alloys. These oxide film produced by the electrochemical surface treatment is a thick and uniform porous form. It is also composed of hydroxyapatite and calcium phosphate-based phases, so it has the characteristics of bone inorganic, non-toxic and very high bioactivity and biocompatibility. Ti-40Ta-xZr alloys were homogenized in an Ar atmosphere at $1050^{\circ}C$ for 1 hour and then quenched in ice water. The electrochemical oxide film was applied by using a power supply of 280 V for 3 minutes in 0.15 M calcium acetate monohydrate ($Ca(CH_3COO)_2{\cdot}H_2O$) and 0.02 M calcium glycerophosphate ($C_3H_7CaO_6P$) electrolyte. A small amount of 0.0075M zinc acetate and magnesium acetate were added to the electrolyte to enhance the bioactivity. The mechanical properties of the coated surface of Ti-40Ta-xZr alloys were evaluated by Vickers hardness, roughness test, and elastic modulus using nano-indentation, and the surface wettability was evaluated by measuring the contact angle of the coated surface. In addition, cell activation and differentiation were examined by cell culture of HEK 293 (Human embryonic kidney 293) cell proliferation. Surface properties of the alloys were analyzed by scanning electron microscopy(FE-SEM), EDS, and X-ray diffraction analysis (XRD).

• 한방비만학회지
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• 제18권1호
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• pp.10-18
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• 2018

Objectives: Metabolic syndrome is correlated with increased cardiovascular risk and characterized by several factors, including visceral obesity, hypertension, insulin resistance, and dyslipidemia. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential (TRP) melastatin 7 (TRPM7) channels have been associated with the development of cardiovascular diseases. The purpose of this study was to investigate the effects of Dangkwisoo-san, ginger and curcumin on TRPM7 channel. Methods: Human embryonic kidney (HEK) 293 cells stably transfected with the TRPM7 expression vectors were maintained in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum (FBS), 1% penicillin/streptomycin, $5{\mu}g/mL$ blasticidin, and 0.4 mg/mL zeocin in a humidified 20% $O_2$/10% $CO_2$ atmosphere at $37^{\circ}C$. Whole-cell patch clamp recordings were obtained using an Axopatch 700B amplifier and pClamp v.10.4 software, and signals were digitalized at 5 kHz using Digidata 1422A. Results: Dangkwisoo-san extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward TRPM7 whole-cell currents at dose dependent manner and the half maximal inhibitory concentration $(IC)_{50}$ of Dangkwisoo-san was $218.3{\mu}g/mL$. Also, ginger extract (100, 200, 300, 400, and $500{\mu}g/mL$) inhibited the outward and inward of TRPM7 whole-cell currents in a dose dependent manner and the $IC_{50}$ of ginger was $877.2{\mu}g/mL$. However, curcumin had no effects on TRPM7 whole-cell currents. Conclusions: These results suggest that both Dangkwisoo-san and ginger have good roles to inhibit the TRPM7 channel, suggesting that Dangkwisoo-san and ginger are considered one of the candidate agents for the treatment of metabolic syndrome such as cardiovascular disease.

• 한방비만학회지
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• 제18권2호
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• pp.57-63
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• 2018

Objectives: Metabolic syndrome is defined by a cluster of major cardiovascular risk factors: obesity, insulin resistance, dyslipidemia, and arterial hypertension. Several members of a large family of nonselective cation entry channels, e.g., transient receptor potential vanilloid 4 (TRPV4) channels have been associated with the development of dyslipidemia and hypertension. The purpose of this study was to investigate the effects of Leejung-tang (Lizhong-tang), Rikkunshito, and Bojungikgi-tang (Buzhongyiqi-tang) on TRPV4 channel. Methods: Human embryonic kidney 293 cells stably transfected with the TRPV4 expression vectors were maintained in Dulbecco's modified Eagle's medium supplemented with 10% fetal bovine serum, 1% penicillin/streptomycin, $5{\mu}g/mL$ blasticidin, and 0.4 mg/mL zeocin in a humidified 20% $O_2/10%$ $CO_2$ atmosphere at $37^{\circ}C$. Whole-cell patch clamp recordings were obtained using an Axopatch 700B amplifier and pClamp v.10.4 software (Molecular Devices, San Jose, CA, USA), and signals were digitalized at 5 kHz using Digidata 1422A. Results: Leejung-tang and Rikkunshito (10, 30 and 50 mg/mL) had no effects on the TRPV4 whole-cell currents at dose dependent manner. However, Bojungikgi-tang (10, 30, and 50 mg/mL) inhibited the TRPV4 whole-cell currents in a dose dependent manner and the half maximal inhibitory concentration (IC50) of Bojungikgi-tang was 18.2 mg/mL. Conclusions: These results suggest that Bojungikgi-tang plays an important roles to inhibit the TRPV4 channel, suggesting that Bojungikgi-tang is considered one of the candidate agents for the treatment of metabolic syndrome such as dyslipidemia and hypertension.