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Effects of Ginsenosides and Their Metabolites on Voltage-dependent Ca2+ Channel Subtypes

  • Lee, Jun-Ho;Jeong, Sang Min;Kim, Jong-Hoon;Lee, Byung-Hwan;Yoon, In-Soo;Lee, Joon-Hee;Choi, Sun-Hye;Lee, Sang-Mok;Park, Yong-Sun;Lee, Jung-Ha;Kim, Sung Soo;Kim, Hyoung-Chun;Lee, Boo-Yong;Nah, Seung-Yeol
    • Molecules and Cells
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    • v.21 no.1
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    • pp.52-62
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    • 2006
  • In previous reports we demonstrated that ginsenosides, active ingredients of Panax ginseng, affect some subsets of voltage-dependent $Ca^{2+}$ channels in neuronal cells expressed in Xenopus laevis oocytes. However, the major component(s) of ginseng that affect cloned $Ca^{2+}$ channel subtypes such as ${\alpha}_{1C}$(L)-, ${\alpha}_{1B}$(N)-, ${\alpha}_{1A}$(P/Q)-, ${\alpha}_{1E}$(R)- and ${\alpha}_{1G}$(T) have not been identified. Here, we used the two-microelectrode voltage clamp technique to characterize the effects of ginsenosides and ginsenoside metabolites on $Ba^{2+}$ currents ($I_{Ba}$) in Xenopus oocytes expressing five different $Ca^{2+}$ channel subtypes. Exposure to ginseng total saponins (GTS) induced voltage-dependent, dose-dependent and reversible inhibition of the five channel subtypes, with particularly strong inhibition of the ${\alpha}_{1G}$-type. Of the various ginsenosides, $Rb_1$, Rc, Re, Rf, $Rg_1$, $Rg_3$, and $Rh_2$, ginsenoside $Rg_3$ also inhibited all five channel subtypes and ginsenoside $Rh_2$ had most effect on the ${\alpha}_{1C}$- and ${\alpha}_{1E}$-type $Ca^{2+}$ channels. Compound K (CK), a protopanaxadiol ginsenoside metabolite, strongly inhibited only the ${\alpha}_{1G}$-type of $Ca^{2+}$ channel, whereas M4, a protopanaxatriol ginsenoside metabolite, had almost no effect on any of the channels. $Rg_3$, $Rh_2$, and CK shifted the steady-state activation curves but not the inactivation curves in the depolarizing direction in the ${\alpha}_{1B}$- and ${\alpha}_{1A}$-types. These results reveal that $Rg_3$, $Rh_2$ and CK are the major inhibitors of $Ca^{2+}$ channels in Panax ginseng, and that they show some $Ca^{2+}$ channel selectivity.

A Study on Heavy Metal Contamination and Risk Assessment of Seaweed and Seaweed Products (해조류와 해조류가공품의 중금속 오염실태 및 위해성평가)

  • Lee, Ji-Yeon;Lee, Myung-Jin;Jeong, Il-Hyung;Cho, Young-Sun;Sung, Jin-Hee;Baek, Eun-Jin;Lee, Eun-Bin;Kim, Hye-Jin;Yoon, Mi-Hye
    • Journal of Food Hygiene and Safety
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    • v.34 no.5
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    • pp.447-453
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    • 2019
  • In this study, the contamination of 4 types of heavy metals (lead, cadmium, arsenic, and mercury) was monitored in 80 seaweeds and their processed products, and a food safety assessment was also carried out for these heavy metals. Lead, cadmium and arsenic were analyzed by ICP-OES and mercury was analyzed by mercury analyzer. The detection ranges of heavy metals were found as follows: Pb (N.D-0.802 mg/kg), Cd (N.D-0.759 mg/kg), As (0.134-17.296 mg/kg), and Hg (0.0005-0.0331 mg/kg). Pb and Hg showed no significant differences among seaweeds whereas Cd and As were significantly higher in the species hizikia fusiforme (P<0.05). Food safety assessment from seaweed intake was measured by PTWI (Provisional Tolerable Weekly Intake), PTMI (Provisional Tolerable Monthly Intake), and MADL (Maximum Allowable Daily Body Load) as set by JECFA (Joint FAO/WHO Expert Committee on Food Additives). Pb and Hg were 0.197%, 0.036% of PTWI respectively, while Cd was 1.877% of PTMI and As was 0.619% of MADL. Therefore, it was found that heavy metal levels of seaweed were low and was considered to be safe for consumption.

Comparative Analysis of Fracture Angulation between Parallel Pinning and Plate Fixation Techniques in the Management of 5th Metacarpal Fractures (제 5 수지 중수골 골절에서 평행 핀 또는 플레이트 고정술 이후 골절각 변화에 대한 비교 연구)

  • Lee, Myungchul;Shin, Hyojung;Choi, Hyungon;Kim, Jeenam;Shin, Donghyeok
    • Archives of Hand and Microsurgery
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    • v.23 no.4
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    • pp.230-238
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    • 2018
  • Purpose: Metacarpal fractures are common injuries of the hand. They are treated using closed reduction (CR) or open reduction (OR) techniques. The management strategy depends on fracture site characteristic and fixation methods. In this study, we evaluated pre- and postoperative fracture angulation, when metacarpal fractures bad been treated using two different techniques: CR with parallel transverse pinning and OR with plate fixation. Methods: Forty-six patients undergoing anatomic reduction to treat extra-articular metacarpal fractures were recruited. They were included in one of two therapeutic groups: Group 1, CR with parallel transverse pinning (n=21); Group 2, OR with plate fixation (n=25). Fracture angulation values have been measured on pre- and postoperative radiologic images. Values were compared between pre- and postoperative states, and between corresponding measurements of each group. Results: All extra-articular metacarpal fractures were successfully treated without wound related complications or the limit of joint motion. Both groups demonstrated adequate reduction at immediate postoperative period (postoperative angulation of group 1, $20^{\circ}{\pm}7^{\circ}$; group 2, $19^{\circ}{\pm}5^{\circ}$). During the observation at follow-up period, Group 1 exhibited slight recurrence (follow-up angulation of group 1, $24^{\circ}{\pm}10^{\circ}$). Nonetheless, Group 2 showed adequate reduction state in both immediate postoperative and long-term follow-up periods (follow-up angulation of group 2, $18^{\circ}{\pm}6^{\circ}$). Conclusion: Extra-articular metacarpal fractures were successfully restored without functional complications. CR with parallel transverse pinning method exhibited recurrence after pin removal, which necessitates cautious postoperative exercise and monitoring.

Ginsenosides from the fruits of Panax ginseng and their cytotoxic effects on human cancer cell lines (인삼(Panax ginseng) 열매로부터 분리한 ginsenoside의 동정 및 암세포독성 효과)

  • Gwag, Jung Eun;Lee, Yeong-Geun;Hwang-Bo, Jeon;Kim, Hyoung-Geun;Oh, Seon Min;Lee, Dae Young;Baek, Nam-In
    • Journal of Applied Biological Chemistry
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    • v.61 no.4
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    • pp.371-377
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    • 2018
  • The fruits of Panax ginseng were extracted with 80% aqueous MeOH and the concentrates were partitioned into EtOAc, n-BuOH, and $H_2O$ fractions. The repeated $SiO_2$ and octadecyl $SiO_2$ column chromatographies for the EtOAc fraction led to isolation of five ginsenosides. The chemical structures of these compounds were determined as ginsenoside F1 (1), ginsenoside F2 (2), ginsenoside F3 (3), ginsenoside Ia (4), notoginsenoside Fe (5) based on spectroscopic analyses including nuclear magnetic resonance, MS, and infrared. Compounds 2-5 were isolated for the first time from the fruits of P. ginseng in this study. All isolated compounds were evaluated for cytotoxic activities against human cancer cell lines such as HCT-116, SK-OV-3, human cervix adenocarcinoma (HeLa), HepG2, and SK-MEL-5. Among them compounds 2, 4, and 5 showed significant cytotoxicity on cancer cells. Compound 2 exhibited cytotoxicity on SK-MEL-5, HepG2, and HeLa cells with $IC_{50}$ values of 82.8, 86.8, and $78.3{\mu}M$, respectively. Compound 4 showed cytotoxicity on HCT-116, SK-MEL-5, SK-OV-3, HepG2, and HeLa cells with $IC_{50}$ values of 24.5, 25.4, 26.3, 22.0, and $24.9{\mu}M$, respectively. Compound 5 did on SK-MEL-5 cell with $IC_{50}$ value of $81.7{\mu}M$. The cytotoxicity of ginsenoside 2, 4, and 5 isolated from the fruits of Panax ginseng showed strong inhibition effect against on cancer cells, all of which have a glucopyranosyl moiety on C-3.

Conditioned Media of RAW 264.7 Cells Stimulated with Phellinus linteus Extract Regulates the Epithelial-mesenchymal Transition in Prostate Cancer Cells (상황버섯에 의해 활성화된 RAW 264.7 대식세포주 배양액의 인간 전립선암 세포주의 epithelial-mesenchymal transition 조절)

  • Kang, Taewoo;An, Hyun-Hee;Park, Sul-Gi;Yu, Sun-Nyoung;Hwang, You-Lim;Kim, Ji-Won;Ahn, Soon-Cheol
    • Journal of Life Science
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    • v.29 no.8
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    • pp.904-915
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    • 2019
  • Prostate cancer (PCa) is one of the most metastatic tumor. Although hormone therapy or surgical castration is mostly conducted to treat PCa, it has a lot of side effects. Recently, many researchers have been exploring the tumor microenvironment to remedy these circumstances. Immune cells, especially macrophages, are an important composition of the tumor microenvironment. Under normal conditions, macrophages exhibit mild tumoricidal activity against tumors. However, once activated by interferon gamma or lipopolysaccharides, macrophages can kill cancer cells directly or indirectly by secreting cytokines and chemokines. In this study, murine macrophage RAW 264.7 cells were treated with Phellinus linteus extract. To analyze their pro-inflammatory phenotype, we were used several assays such as a real-time polymerase chain reaction, an enzyme-linked immunosorbent and nitric oxide assay. Prostate cancer cells were treated with the RAW 264.7-conditioned media, which was identified as a pro-inflammatory nature, for 48 h, and the expression of epithelial-mesenchymal transition (EMT)-related genes was determined. Not only N-cadherin, Snail, Twist, Slug, and Cadherin 11, which are mechenchymal-related proteins, were decrease, but epithelial marker of E-cadherin was increased. In addition, the mRNA level of vimentin, ccl2, and vegfa were decreased, as the EMT is closely related to the migration and invasion of cancer cells. In conclusion, the RAW 264.7-conditioned media stimulated with P. linteus extract inhibited migration and invasion and regulated the EMT pathway in human prostate cancer cells.

The Effect of Therapeutic Listening on Occupational Performance, Auditory Problem Behavior, and Attention in Children With Sensory Modulation Disorder (감각조절 장애 아동에게 치료적 듣기가 작업수행, 청각행동문제, 주의집중에 미치는 영향)

  • Park, Mi-Young;Kim, Hee;Cha, Tae-Hyun;Kim, Soo-Kyung
    • The Journal of Korean Academy of Sensory Integration
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    • v.18 no.3
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    • pp.14-26
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    • 2020
  • Objective : The purpose of this study was to investigate the effect of therapeutic listening on task performance, auditory behavior problems, and attention in children with sensory modulation disorder. Methods : Sixteen children aged four to seven years who were classified as children with sensory modulation disorder were randomly assigned to either the experimental group (n = 8) or the control group (n = 8). From July 1 to October 18, 2017, both groups participated in sensory integration programs, while therapeutic listening training was administered only to the experimental group. Sensory integration therapy was conducted in two sessions per week for six weeks (12 sessions); each session consisted of 40 minutes of therapy and 10 minutes of parent education. Therapeutic listening was conducted in three thirty-minute sessions per week for six weeks (18 sessions). We used the Canadian Occupation Performance Measure (COPM) to evaluate changes in the participants' occupational performance between pre- and post-intervention. We used Fisher's Auditory Problems Checklist (FAPC) to observe changes in behavioral problems related to hearing. The Child Attention Scale for Teacher (CAST) was used to evaluate changes in attention. Results : No significant differences pre- and post-intervention between the two groups were observed. The participants' auditory behavioral problems improved significantly in the experimental group, but no significant difference was found between the two groups. There was no significant difference in attention between the two groups, but there was a significant difference between the two groups in the "adaptability" and "emotion" domains (p < .05). Conclusion : The results suggest that therapeutic listening training has a positive effect on reducing problematic behaviors related to hearing and improving the occupational performance of children with sensory modulation disorder. This study provides a basis for improving the sensory processing ability of children with sensory modulation disorder by applying listening training in the clinical field and at home.

Evaluation of antioxidant properties and oxidative stability of oregano seed solvent fraction (추출용매에 따른 오레가노 종자 분획물의 항산화 및 유지산화안정성 평가)

  • Lee, Hyun-Jong;Kim, Min-Ah;Hong, Sungsil;Kim, Mi-Ja
    • Korean Journal of Food Science and Technology
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    • v.53 no.1
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    • pp.12-18
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    • 2021
  • The in vitro antioxidant activity of oregano seed fractions, fractionizing with 80% ethanol, n-hexane, ethyl acetate, n-butanol, and water, was evaluated, and their effects on edible oils were determined in corn oil at 180℃. The ethyl acetate fraction had the highest radical-scavenging activity. The ferric reducing antioxidant power activity and total phenol content of the ethyl acetate fraction were determined as 6,130 µmol ascorbic acid equivalents/g extract and 770 µmol tannic acid equivalents/g extract, respectively, which were significantly higher than those of the other fractions (p<0.05). Primary and secondary oxidation products in corn oil added with the ethyl acetate fraction of oregano seed significantly decreased by 1.5 and 1.26 times, respectively, compared with those in the control groups. The major volatile ingredients in the ethyl acetate fraction of oregano seeds were determined to be carvacrol, thymoquinone, and 3-cyclopentylcyl-cyclopentan-1-one. Ethyl acetate is a suitable solvent for extracting antioxidant compounds from oregano seeds and can be used as a natural antioxidant.

Multi-Institute, Single Group, Prospective Observational Study to Evaluate the Efficacy of Mucomyst® in Relieving Symptoms of Globus Pharyngeus Refractory to Proton Pump Inhibitor (양성자펌프억제제에 반응하지 않는 인두이물감 환자에서 "뮤코미스트Mucomyst®" 객담제거 및 상기도 염증치료를 통한 증상개선효과 평가 다기관, 단일군, 전향적 관찰 연구)

  • Park, Hannah;Park, Il-Seok;Lee, Sang Hyuk;Lee, Seung-Won;Lee, Sang Joon;Lee, Byung-Joo;Cheon, Yong-Il;Park, Jun-Ook;Oh, Kyoung Ho;Shin, Yoo Seob
    • Journal of the Korean Society of Laryngology, Phoniatrics and Logopedics
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    • v.33 no.1
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    • pp.20-25
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    • 2022
  • Background and Objectives Globus pharyngeus is one of the most common symptoms of patients visiting otorhinolaryngology out-patient clinic, and usually long-lasting, difficult to treat, and frequently recurrent. Mucomyst®, N-acetyl cysteine is an inhalation agent mainly used for mucolysis and reducing inflammation in airway via antioxidative effect. The purpose of this study was to evaluate the efficacy of inhaled Mucomyst® treatment in patients with globus pharyngeus refractory to proton pump inhibitor (PPI). Materials and Method We prospectively evaluated the efficacy of Mucomyst® in relieving symptoms of globus pharyngeus refractory to PPI in nine medical centers. Three hundred and three patients enrolled and finally 229 patients finished the inhaled Mucomyst® therapy for 8 weeks. We analyzed the change of Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Visual Analogue Scale (VAS) for globus, and Globus Pharyngeus Symptom Scale (GPS) after use of Mucomyst® for 4 and 8 weeks. Results The GPS, RSI, RFS, and VAS score significantly decreased serially in patients who finished 8 week-inhalation treatment. The GPS improvement gap was significantly correlated with initial GPS (p<0.001) in multiple regression analysis. Conclusion Inhaled Mucomyst® therapy was effective for the reduction of both subjective and objective findings in refractory globus patients. This study might suggest new treatment option for patients with globus. However, further thorough studies would be needed to assess the real effect of inhaled Mucomyst® treatment as a standard treatment for globus.

Physicochemical Properties of Protaetia brevitarsis sinulensis Larvae Reared with Feed Including Noni and Nipa Palm (노니와 해죽순 급이가 흰점박이꽃무지 유충에 미치는 물리화학적 특성)

  • Kim, Sam Woong;Je, Kyeong Min;Kim, Dul Nam;Kim, Tae Wan;Bang, Kyu Ho;Chi, Won-Jae;Bang, Woo Young;Kim, Jang Hyeon;Yang, Chul Woong;Kim, Il-Suk
    • Journal of Life Science
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    • v.32 no.10
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    • pp.784-791
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    • 2022
  • This study observed changes in the body composition of Protaetia brevitarsis sinulensis larvae when reared with feed that included noni and nipa palm. Compared to the control group, the death rate and product yield of the treatment group were improved after the larval fasting process. The brightness of the larval powder of the treatment group increased, but the redness decreased. The crude fat content of the treated group was slightly increased according to the assays of the general components, but the mineral content was significantly increased. The total structural amino acids of the treatment group decreased, but the total free amino acids increased. The structural amino acids generally tended to decrease in the treatment group. However, the free amino acids showed no specific differences. Among the free amino acids, tryptophan, phosphoserine, and methylhistidine were highly increased in the treatment group, whereas threonine, methionine, and asparagine showed the opposite results. Among the polyunsaturated fatty acids, eicosapentaenoic acid (C20:5n3) of omega-3 was increased in the treatment group, but the omega-6 series was decreased. Since minerals, total free amino acids, and omega-3 fatty acids in the treatment group were increased compared to the control group, we suggest that noni and nipa palm can potentially be applied to the production of functionally improved substances as additional sources of feed for Protaetia brevitarsis sinulensis larvae.

Evaluation and Verification of the Attenuation Rate of Lead Sheets by Tube Voltage for Reference to Radiation Shielding Facilities (방사선 방어시설 구축 시 활용 가능한 관전압별 납 시트 차폐율 성능평가 및 실측 검증)

  • Ki-Yoon Lee;Kyung-Hwan Jung;Dong-Hee Han;Jang-Oh Kim;Man-Seok Han;Jong-Won Gil;Cheol-Ha Baek
    • Journal of the Korean Society of Radiology
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    • v.17 no.4
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    • pp.489-495
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    • 2023
  • Radiation shielding facilities are constructed in locations where diagnostic radiation generators are installed, with the aim of preventing exposure for patients and radiation workers. The purpose of this study is seek to compare and validate the trend of attenuation thickness of lead, the primary material in these radiation shielding facilities, at different maximum tube voltages by Monte Carlo simulations and measurement. We employed the Monte Carlo N-Particle 6 simulation code. Within this simulation, we set a lead shielding arrangement, where the distance between the source and the lead sheet was set at 100 cm and the field of view was set at 10 × 10 cm2. Additionally, we varied the tube voltages to encompass 80, 100, 120, and 140 kVp. We calculated energy spectra for each respective tube voltage and applied them in the simulations. Lead thicknesses corresponding to attenuation rates of 50, 70, 90, and 95% were determined for tube voltages of 80, 100, 120, and 140 kVp. For 80 kVp, the calculated thicknesses for these attenuation rates were 0.03, 0.08, 0.21, and 0.33 mm, respectively. For 100 kVp, the values were 0.05, 0.12, 0.30, and 0.50 mm. Similarly, for 120 kVp, they were 0.06, 0.14, 0.38, and 0.56 mm. Lastly, at 140 kVp, the corresponding thicknesses were 0.08, 0.16, 0.42, and 0.61 mm. Measurements were conducted to validate the calculated lead thicknesses. The radiation generator employed was the GE Healthcare Discovery XR 656, and the dosimeter used was the IBA MagicMax. The experimental results showed that at 80 kVp, the attenuation rates for different thicknesses were 43.56, 70.33, 89.85, and 93.05%, respectively. Similarly, at 100 kVp, the rates were 52.49, 72.26, 86.31, and 92.17%. For 120 kVp, the attenuation rates were 48.26, 71.18, 87.30, and 91.56%. Lastly, at 140 kVp, they were measured 50.45, 68.75, 89.95, and 91.65%. Upon comparing the simulation and experimental results, it was confirmed that the differences between the two values were within an average of approximately 3%. These research findings serve to validate the reliability of Monte Carlo simulations and could be employed as fundamental data for future radiation shielding facility construction.