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Effects of $(1R,9S)-{\beta}-Hydrastine$ hydrochloride on L-DOPA-Induced Cytotoxicity in PC12 cells

  • Yin, Shou-Yu;Lee, Jae-Joon;Kim, Yu-Mi;Jin, Chun-Mei;Yang, Yoo-Jung;Lee, Myung-Koo
    • Natural Product Sciences
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    • v.10 no.3
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    • pp.124-128
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    • 2004
  • Previously, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride has been found to lower dopamine content in PC12 cells (Kim et al., 20001). In this study, the effects of $(1R,9S)-{\beta}-Hydrastine$ hydrochloride on L-DOPA-induced cytotoxicity in PC12 cells were investigated. Treatment with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at concentrations higher than $500\;{\mu}M$ caused cytotoxicity in PC12 cells. In addition, $(1R,9S)-{\beta}-Hydrastine$ hydrochloride at non-cytotoxic or cytotoxic concentrations significantly enhanced L-DOPA-induced cytotoxicity (L-DOPA concentration, $50\;{\mu}M$). Treatment of PC12 cells with $750\;{\mu}M$ $-1R,9S)-{\beta}-Hydrastine$ hydrochloride and $50\;{\mu}M$ L-DOPA, alone or in combination, also induced cell death via a mechanism which exhibited morphological and biochemical characteristics of apoptosis, including chromatin condensation and membrane blebbing. Exposure of PC12 cells to $(1R,9S)-{\beta}-Hydrastine$ hydrochloride, L-DOPA and $(1R,9S)-{\beta}-Hydrastine$ hydrochloride plus L-DOPA for 48 h resulted in a marked increase in the cell loss and percentage of apoptotic cells compared with exposure for 24 h. These data indicate that $(1R,9S)-{\beta}-Hydrastine$hydrochloride at higher concentration ranges aggravates L-DOPA-induced neurotoxicity cytotoxicity in PC12 cells. Therefore, it is proposed that the long-term L-DOPA therapeutic patients with $(1R,9S)-{\beta}-Hydrastine$ hydrochloride could be checked for the adverse symptoms.

Antioxidant and Anti-wrinkling Effects of Extracts from Vitex trifolia L. (만형자 추출물의 항산화 및 주름개선 효과)

  • Lee, Mi-Kyoung;Kim, Dong-Hee;Park, Tae-Soon;Son, Jun-Ho
    • Journal of Applied Biological Chemistry
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    • v.58 no.2
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    • pp.125-129
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    • 2015
  • In this study, the antioxidant and anti-wrinkling effects of fraction from Vitex trifolia L. were investigated. Among the fractions, ethyl acetate fraction showed the highest antioxidant activities in 1-1-diphenyl-2-picryl-hydrazyl, 2,2'-azino-bis(3-ethylbenzothiazoine-6-sulfonic acid) radical scavenging and elastase inhibition with 76, 89, and 74%, respectively, at a concentration of $1,000{\mu}g/mL$. This fraction, at the concentration of $25{\mu}g/mL$, inhibited 70% fibroblast cell viability and 86% the matrix metalloprotease (MMP)-1. In addition, the results from Western blot assay showed that this fraction ($25{\mu}g/mL$) expressed the MMP-1 protein level by decreasing 50%. The findings suggest that the ethyl acetate fraction from V. trifolia has great potential as a cosmeceutical ingredient with antioxidant and anti-wrinkling effects.

Screening of Insulin-like Substances from Traditional Herbs of Diabetes Prescription in Donguibogam (동의보감 당뇨 처방에 사용되는 한약재에서 인슐린성 물질(Insulin-like substances)의 탐색)

  • Ju, Young-Sung;Ko, Byoung-Seob
    • Applied Biological Chemistry
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    • v.45 no.1
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    • pp.47-52
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    • 2002
  • In order to search for insulin-like substances from the constituted herbs of Sogal prescriptions, we selected 19 traditional herbs, based on a review of the Donguibogam. The effects of the hot-water extract from the selected herbs on the proliferation and the differentiation of 3T3-L1 fibroblasts were tested. The various water-extracts from Pinellia ternata, Magnolia obovata, Rheum palmatum, Acanthopanax sessiliflorun, Atractylodes japonica and Strychnos ignatii inhibited the proliferation of 3T3-L1 fibroblasts, did not influence entirely in differentiation of 3T3-L1 fibroblasts. Treatment of 3T3-L1 fibroblasts with the extract from Ephedra sinica, Trichosanthes kirilowii, Scrophularia buergeriana and Sophora flavescens significantly increased the differentiation of the cells. In conclusion, these may contain such compounds that play a role of insulin-like action.

The Study on the Lower Limb Surface Changes Caused by the Limb Movements (Part 1) (동작에 따른 하지피부면의 변화에 관한 연구 (제일보) - 탈관절과 슬관절 굴신을 중심으로 -)

  • 박영득
    • Journal of the Korean Home Economics Association
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    • v.20 no.4
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    • pp.1-12
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    • 1982
  • This study was to investigate the changes of shape of the lower limb surface, the rate of the measurement of expansion and contraction and correlation coefficient between variables caused by hip joint and knee joint movements. The results of the investigation are as follows; 1. According to the development figure of shell when the leg was raised $45^{\circ}$forward($M_{2}$), total length of F.L shortened while B.L lengthened. This result is contarary to $M_{3}$raising the leg $15^{\circ}$ backward. In both $M_{2}$, $M_{3}$movements, the rate of expansion and contraction to the course direction was insignificant. When hip joint was bent $15^{\circ}$ with knee joint $120^{\circ}$bent ($M_{4}$) and hip joint was bent $30^{\circ}$ with knee joint $90^{\circ}$ bent($M_{5}$), upper section of back hip expanded while the front hip section contracted slightly. In the Movement of sitting on the chair($M_{6}$), abdomen, front hip section and upper thight section contracted to the wale direction remarkably while the back hip section expanded conspicuously. 2. According to the rate of expansion and contraction of skin (surface) by the somatometry. In $M_{2}$, C.F.L. upper and middle thight girth contracted and B.L, C.L, L.L expanded. This fact is contarary to M3. In M4, M5, C.F.L showed remarkable contraction and C.B.L expanded remarkably. In $M_{6}$, C.B.L contracted most of all the items measured and knee girth, F.L, L.L, C.B.L, hip girth expanded conspicuously. 3. According to the correlation coefficient between variables. In various movements, the correlation among girth items commonly showed a high or middle grade, the correlation among length items also commonly showed a low grade and that girth and length items showed a very low grade commonly. Waist girth, hip grith, F.L, B.L, L.L items showed that there were significant correlation.

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Prioritizing Human Use Antibiotics for Environmental Health Management and Estimating Their Environmental Concentrations in Korean Waterway (인체용 항생제의 우선관리대상 선정과 물환경 중 오염농도 추정)

  • Kim, Myung-Hyun;Park, Jeong-Im;Kim, Young-Hee;Choi, Kyung-Ho
    • Journal of Environmental Health Sciences
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    • v.32 no.5 s.92
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    • pp.462-468
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    • 2006
  • Antibiotics are manufactured and used for specific physiological functions, hence they may exert adverse ecological consequences when they are in contact with nontarget organisms. In the last decade, many reports have been made on the occurrences of various antibiotic compounds in surface water, and their potential impact to the environment has become an increasing concern. This study was conducted to prioritize antibiotic substances with potential environment risk in Korea. Human use antibiotics with an EIC (Expected Introduction Concentration) value greater than $1{\mu}g/l$, US FDA's action limit criteria, were selected. In order to calculate a worst-case EIC for each substance, annual production volume (in kg) of each antibiotic substance was derived using the Korea Pharmaceutical Manufacturers Association (KPMA)'s monetary database. Sixteen substances were preliminarily selected. The EICs of the 16 antibiotic substances were refined with the excretion rate of the parent substances. Ten antibiotic substances were identified to have EIC-corrected greater than $1{\mu}g/l$, which include Amoxicillin ($15.8{\mu}g/l$), Cefaclor ($10.1{\mu}/l$), Roxithromycin ($4.2{\mu}g/l$), Cephradine ($4.5{\mu}g/l$), Cefatrizine ($2.6{\mu}g/l$), Cefadroxil ($3.3{\mu}g/l$), Aztreonam ($2.3{\mu}g/l$), Ceftazidime ($2.8{\mu}g/l$), Ribostamycin ($1.3{\mu}g/l$), and Ceftezole ($1.3{\mu}g/l$). Additional risk assessments for these antibiotic substances are suggested.

Improvement of polymerase chain reaction methods for rapid detection of Listeria monocytogenes in raw milk (원유로부터 Listeria monocytogenes의 신속검색을 위한 종합효소 연쇄반응법의 개선)

  • Yi, Chul-hyun;Son, Won-geun;Kang, Ho-jo
    • Korean Journal of Veterinary Research
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    • v.36 no.1
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    • pp.119-129
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    • 1996
  • The present study was conducted to rapidly detect Listeria monocytogenes in raw milk. Specificity and sensitivity of polymerase chain reaction(PCR) technique, and direct PCR were examinded in raw milk, also were compared the calssical culture methods with PCR technique. This method used a pair of primers based on a unique region in the 16S rRNA sequence of L nomocytogenes. In the PCR specificity tests, each of the 10 strains of L monocytogenes tested gave a single 70-bp band. But the other six Listera spp tested gave negative results. Results of the sensitivity tests showed that as few as 2 CFU of L monocytogenes in pure cultures could be detected with 16S rRNA-based primers, L-1 and L-2. In different PCR cycles, a PCR product was detected with $10^3$ cells of L monocytogenes from 25 cycles to 50 cycles and the concentration of PCR products was cycle-dependent. Raw milk samopes added L monocytogenes cells gave negative results. However, these samplers gave a single 70-bp band by pretreatment of pronase, and PCR products were detected with $10^1$ cells of L monocytogenes. To detemine the most sensitive culture protocol to use in conjunction with the PCR assay, raw milk samples were inoculated with L monocytogenes at concentrations ranging from 1 to $5.7{\times}10^4CFU/ml$. PCR assays from Listeria enrichment broth(LEB) containing raw milk samples added L monocytogene EGD could dtect 10 cells in pronase-pretreated samples without incubation, and 1 cell of L monocytogenes in both 12 hr and 24 hr incubation, respectively. Isolation raw of PCR assays was similar to that of classical culture methods, but required time for detection of L monocytogenes could remarkably be reduced compare to culture methods.

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A Novel Linking Schiff-Base Type Ligand (L: py-CH=N-C6H4-N=CH-py) and Its Zinc Coordination Polymers:Preparation of L, 2-Pyridin-3-yl-1H-benzoimidazol, trans-[Zn(H2O)4L2].(NO3)2.(MeOH)2[Zn(NO3)(H2O)2(L)].(NO3).(H2O)2 and [Zn(L)(OBC)(H2O)] (OBC = 4,4'-Oxybis(benzoate))

  • Kim, Han-Na;Lee, Hee-K.;Lee, Soon-W.
    • Bulletin of the Korean Chemical Society
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    • v.26 no.6
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    • pp.892-898
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    • 2005
  • A long, bis(monodentate), linking Schiff-base ligand L (py-CH=N-$C_6H_4$-N=CH-py) was prepared from 1,4-phenylenediamine and 3-pyridinecarboxaldehyde by the Schiff-base condensation. Ligand L has two terminal pyridyl groups capable of coordinating to metals through their nitrogen atoms. In contrast, the same reaction between 1,2-phenylenediamine and 3-pyridinecarboxaldehyde produced a mixture of imidazol isomers (2-pyridin-3-yl-1H-benzoimidazole), which are connected to one another by the N-H…N hydrogen bonding to form a tetramer. From Zn($NO_3)_2{\cdot}6H_2O$ and ligand L under various conditions, one discrete molecule, trans- [Zn($H_2O)_4L_2]{\cdot}(NO_3)_2{\cdot}(MeOH)_2$, and two 1-D zinc polymers, [Zn$(NO_3)(H_2O)_2(L)]{\cdot}(NO_3){\cdot}(H_2O)_2$ and [Zn(L) (OBC)($H_2O$)], were prepared. In ligand L, the N$\ldots$N separation between the terminal pyridyl groups is 13.994 $\AA$, with their nitrogen atoms at the meta positions (3,3’) in a trans manner. The corresponding N$\ldots$N separations in its compounds range from 13.853 to 14.754 $\AA$.

Effect of GA3 and Thidiazuron on Seedlessness and Fruit Quality of 'Kyoho' Grapes (GA3와 Thidiazuron 처리가 '거봉' 포도의 무핵화와 과실품질에 미치는 영향)

  • Lee, ByulHaNa;Kwon, YongHee;Park, YoSup;Park, Hee-Seung
    • Horticultural Science & Technology
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    • v.31 no.2
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    • pp.135-140
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    • 2013
  • This experiment was conducted to find the effects of a $GA_3$ and thidiazuron (TDZ) on seedless rate, harvest time, fruit cracking and fruit quality in 'Kyoho' grapes over two years from 2008 to 2009. In 2008, fruit clusters were dip treated with $GA_3$ $25.0mg{\cdot}L^{-1}$ twice at full bloom (FB) and 14 days after full bloom (DAFB) in a combination with TDZ 0 or $2.5mg{\cdot}L^{-1}$. Berry seedless rate and berry enlargement were slightly improved only when TDZ was added to the second $GA_3$ treatment at 14 DAFB, compared to $GA_3$ + TDZ treatments at both FB and 14 DAFB. However, berry cracking rate was significantly increased by any plant growth regulator (PGR) treatments compared to non treatment. In 2009, $GA_3$ at $12.5mg{\cdot}L^{-1}$ and $25.0mg{\cdot}L^{-1}$ was dip treated twice at FB and 14 DAFB while TDZ $2.5mg{\cdot}L^{-1}$ was treated only at 14 DAFB. Berry cracking rate was depended on the concentration of $GA_3$ applied. The higher concentration at $25.0mg{\cdot}L^{-1}$ significantly increased berry cracking rate while the lower concentration at $12.5mg{\cdot}L^{-1}$ had no effect. Also, the addition of TDZ to $GA_3$ $25.0mg{\cdot}L^{-1}$ at 14 DAFB, substantially decreased the cracking rate to the level of untreated control. Although all PGR treatments advanced fruit maturity, the most significant advance occurred when TDZ was added to $GA_3$ $12.5mg{\cdot}L^{-1}$ only at the second dip. Considering the overall aspects related to fruit maturity and quality, we concluded that the double applications of $12.5mg{\cdot}L^{-1}$ $GA_3$ at FB and 14 DAFB with addition of $2.5mg{\cdot}L^{-1}$ TDZ only at 14 DAFB was appropriate to produce about 400-500 g size of seedless 'Kyoho' grape cluster having 35-40 berries.

Plant Regeneration via Multiple Shoots Formation from Sucker Explants of Rubus fruticosus L. (블랙베리(Rubus fruticosus L.)의 맹아절편체로부터 다경유도를 통한 식물체 재분화)

  • Shin Jeong-Sun;Sim Ock-Kyeong;Lee Jong-Chon;Cho Han-Jik;Kim Ee-Yup;Lee Kang-Seop
    • Korean Journal of Plant Resources
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    • v.18 no.3
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    • pp.456-461
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    • 2005
  • This study was carried out to induce plant regeneration via shoot formation from sucker explants of Rubus fruticosus L. To induce adventitious shoots, sucker explants were sterilized in $1.2\%$ NaOCl solution, and cultured on the MS solid medium supplemented with kinetin (0.5, 1.0, 3.0 mg/L) and BA (0.5, 1.0, 3.0 mg/L), respectively. As above, to induce adventitious shoots, sucker explants were cultured on the MS solid medium supplemented with IBA (0, 0.1, 1.0 mg/L) and BA (0, 0.1, 1.0, 2.0 mg/L). After 4 weeks of culture, the highest frquency $(100\%)$ of shoot formation from sucker explants was obtained from the medium with 1.0 mg/L BA. The highest shoot number per explant from in vitro shoot explants was 5.3. After 10 weeks of culture, the number of shoot per explant was increased. The highest frequency $(85\%)$ of root formation was obtained at 0.5 mg/L glycine medium, when the explant with shoot were cultured on the MS medium containing glycine at various concentrations from 0 to 2.0 mg/L. The survival rate of the plantlets after transfer to plastic pots containing sand, soil, and vermiculite (1:1:1, vol.) was $95\%$. The results indicate that micropropagation procedure can be applied for an efficient mass propagation of Rubus fruticosus.

A Novel Anti-PD-L1 Antibody Exhibits Antitumor Effects on Multiple Myeloma in Murine Models via Antibody-Dependent Cellular Cytotoxicity

  • Ahn, Jae-Hee;Lee, Byung-Hyun;Kim, Seong-Eun;Kwon, Bo-Eun;Jeong, Hyunjin;Choi, Jong Rip;Kim, Min Jung;Park, Yong;Kim, Byung Soo;Kim, Dae Hee;Ko, Hyun-Jeong
    • Biomolecules & Therapeutics
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    • v.29 no.2
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    • pp.166-174
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    • 2021
  • Multiple myeloma is a malignant cancer of plasma cells. Despite recent progress with immunomodulatory drugs and proteasome inhibitors, it remains an incurable disease that requires other strategies to overcome its recurrence and non-response. Based on the high expression levels of programmed death-ligand 1 (PD-L1) in human multiple myeloma isolated from bone marrow and the murine myeloma cell lines, NS-1 and MOPC-315, we propose PD-L1 molecule as a target of anti-multiple myeloma therapy. We developed a novel anti-PD-L1 antibody containing a murine immunoglobulin G subclass 2a (IgG2a) fragment crystallizable (Fc) domain that can induce antibody-dependent cellular cytotoxicity. The newly developed anti-PD-L1 antibody showed significant antitumor effects against multiple myeloma in mice subcutaneously, intraperitoneally, or intravenously inoculated with NS-1 and MOPC-315 cells. The anti-PD-L1 effects on multiple myeloma may be related to a decrease in the immunosuppressive myeloid-derived suppressor cells (MDSCs), but there were no changes in the splenic MDSCs after combined treatment with lenalidomide and the anti-PD-L1 antibody. Interestingly, the newly developed anti-PD-L1 antibody can induce antibody-dependent cellular cytotoxicity in the myeloma cells, which differs from the existing anti-PD-L1 antibodies. Collectively, we have developed a new anti-PD-L1 antibody that binds to mouse and human PD-L1 and demonstrated the antitumor effects of the antibody in several syngeneic murine myeloma models. Thus, PD-L1 is a promising target to treat multiple myeloma, and the novel anti-PD-L1 antibody may be an effective anti-myeloma drug via antibody-dependent cellular cytotoxicity effects.