• Title/Summary/Keyword: PD-1/PD-L1

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Pharmacokinetics of 11-Hydroxyaclacinomycin X (ID-6105), a Novel Anthracycline, after i.v. Bolus Multiple Administration in Rats

  • Yoo Bo-Im;Ahan Kwang Bok;Kang Min Hee;Kwon Oh-Seung;Hong Young-Soo;Lee Jung Joon;Lee Hong Sub;Ryu Jung Su;Kim Tae Yong;Moon Dong-Cheul;Song Sukgil;Chung Youn Bok
    • Archives of Pharmacal Research
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    • v.28 no.4
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    • pp.476-482
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    • 2005
  • We investigated the pharmacokinetics of 11-hydroxyaclacinomycin X (ID-6105), a novel anthracycline, after intravenous (i.v.) bolus administration at a multiple dose every 24 h for 5 days in rats. To analyze ID-6105 levels in biological samples, we used an HPLC-based method which was validated in a pharmacokinetic study by suitable criteria. The concentrations of ID-6105 after the multiple administration for 5 days were not significantly different from the results after the single administration. The $t_{1/2\alpha}, t_{l/2\beta}, V_{dss}, and CL_{t}$ after the multiple administration were not significantly different from the values after the single administration. Moreover, the concentrations of ID-6105 1 min at day 1-5 after i.v. bolus multiple administration did not show the significant difference. Of the various tissues, ID-6105 mainly distributed to the kidney, lung, spleen, adrenal gland, and liver after i.v. bolus multiple administration. ID-6105 concentrations in the kidney or lung 2 h after i.v. bolus administration were comparable to the plasma concentration shortly after i.v. bolus administration. However, the ID-6105 concentrations in various tissues 48 h after i.v. bolus administration decreased to low levels. ID-6105 was excreted largely in the bile after i.v. bolus multiple administration at the dose of 3 mg/kg. The amounts of ID-6105 found in the bile by 12 h or in the urine by 48 h after the administration were calculated to be $14.1\% or 4.55\%$ of the initial dose, respectively, indicating that ID-6105 is mostly excreted in the bile. In conclusion, ID-6105 was rapidly cleared from the blood and transferred to tissues, suggesting that ID-6105 might not be accumulated in the blood following i.v. bolus multiple dosages of 3 mg/kg every 24 h for 5 days. By 48 h after i.v. bolus administration, ID-6105 concentrations in various tissues had decreased to very low levels. The majority of ID-6105 appears to be excreted in the bile.

A Study on the correlation between Drinking and MMPI in lunar cycle (달의 주기(週期)에 따른 음주(飮酒)와 인성(人性)과의 연관성(聯關性)에 관(關)한 조사연구(調査硏究))

  • Lee Seok-Jun;Ryu Yeong-Su;Ryu Hui-Yeong
    • Journal of Oriental Neuropsychiatry
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    • v.4 no.1
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    • pp.155-164
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    • 1993
  • In this study the author had attempted to establish a correlation among alcohol use and MMPI and lunar cycle. MMPI was carried on 2, April 1992(the last day of the second lunar month) and 15, June 1992(the fifteenth day of the fifth lunar month). These experiments took male and female students who were in WON KWANG University as subjects. The results of it suggested the followings. 1) Drinkers and normal subjects average of T-score in each scales were in a normal scores. 2) In every scales except L,K,Si scales drinkers showed higher scores than normal subjects. There was a significant difference on L, F, Pd, Pa, Sc, Ma scales. 3) On the fifteenth day of the month, drinkers showed Higher T-Scores than normal subjects in every scales excepts L,K,Si scales. There was a significant difference in Ma scale. 4) On the last day of the month, drinkers showed higher T-scores than normal subjects in every scales except L,K,Mf,Si scales. There was a significant difference on L, F, Pd, Sc, Ma scales. 5) Drinkers showed higher than normal subjects in symptom of neurosis and psychosis. As the results of above, human character changes to some extend according to alcohol use. There is a tendency that repeated drinking of college students prone to change into habitual drinking or alcoholic impairment. So controlled drinking among the college students is highly recommended.

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In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease

  • Rath, Surya Narayan;Jena, Lingaraja;Bhuyan, Rajabrata;Mahanandia, Nimai Charan;Patri, Manorama
    • Genomics & Informatics
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    • v.19 no.1
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    • pp.7.1-7.13
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    • 2021
  • Levodopa (L-DOPA) therapy is normally practised to treat motor pattern associated with Parkinson disease (PD). Additionally, several inhibitory drugs such as Entacapone and Opicapone are also cosupplemented to protect peripheral inactivation of exogenous L-DOPA (~80%) that occurs due to metabolic activity of the enzyme catechol-O-methyltransferase (COMT). Although, both Entacapone and Opicapone have U.S. Food and Drug Administration approval but regular use of these drugs is associated with high risk of side effects. Thus, authors have focused on in silico discovery of phytochemicals and evaluation of their effectiveness against human soluble COMT using virtual screening, molecular docking, drug-like property prediction, generation of pharmacophoric property, and molecular dynamics simulation. Overall, study proposed, nine phytochemicals (withaphysalin D, withaphysalin N, withaferin A, withacnistin, withaphysalin C, withaphysalin O, withanolide B, withasomnine, and withaphysalin F) of plant Withania somnifera have strong binding efficiency against human COMT in comparison to both of the drugs i.e., Opicapone and Entacapone, thus may be used as putative bioenhancer in L-DOPA therapy. The present study needs further experimental validation to be used as an adjuvant in PD treatment.

Quantitative Analysis of Trace Metals in Lithium Molten Salt by ICP-AES (ICP-AES를 이용한 리튬 용융염내의 미량 금속성분원소 정량에 관한 연구)

  • Kim, Do-Yang;Pyo, Hyung-Yeal;Park, Yong-Joon;Park, Yang-Soon;Kim, Won-Ho
    • Analytical Science and Technology
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    • v.13 no.3
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    • pp.309-314
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    • 2000
  • The quantitative analysis of various trace metals including fission products in lithium molten salts has been performed using a inductively coupled plasma atomic emission spectrometer (ICP-AES). The spectral interferences of lithium content, 500, 1,000 and 2,000 mg/L, in the sample solution were investigated using an optimum wavelength for the respective metal species. As a result, the line intensities for Y, Nd, Sr, and La had no influences from the lithium content up to 2,000 mg/L, while Mo, Ba, Ru, Pd, Rh, Zr and Ce showed spectral interferences of 10% to 50%. The group separation of metals from lithium in the molten salts solution was carried out by adding ammonia water into the solution. The recovery of Ru, Y, Rh, Zr, Nd, Ce, La and Eu was found to be over 90%, while Mo, Ba, Pd, and Sr provided low recovery percentages.

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Preparation of Composite Particles via Electroless Nickel Plating on Polystyrene Microspheres and Effect of Plating Conditions (무전해 니켈 도금된 폴리스티렌 복합 입자 제조 및 도금 조건의 영향)

  • Kim, Byung-Chul;Park, Jin-Hong;Lee, Seong-Jae
    • Polymer(Korea)
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    • v.34 no.1
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    • pp.25-31
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    • 2010
  • Polymer core and metal shell composite particles have been prepared by the electroless nickel plating on the surface of monodisperse polystyrene microspheres. Various sizes of polystyrene particles with highly monodisperse state could be synthesized by controlling the dispersion medium in dispersion polymerization. Electroless nickel plating was performed on the polystyrene particle with diameter of $3.4\;{\mu}m$. The morphology of polystyrene/nickel composite particles was investigated to see the effect of the plating conditions, such as the $PdCl_2$ and glycine concentrations and the dropping rate of nickel plating solution, on nickel deposition. With $PdCl_2$ and glycine concentrations at more than 0.4 g/L and 1 M, respectively, more uniform nickel layer and less precipitated nickel aggregates were formed. At the given plating time of 2 h, the same amount of plating solution was introduced by varying the dropping rate. Though the effect of dropping rate on particle morphology was not noticeable, the dropping rate of 0.15 mL/min for 60 min showed rather uniform plating.

P3H4 promotes renal cell carcinoma progression and suppresses antitumor immunity via regulating GDF15-MMP9-PD-L1 axis

  • Tian, Shuo;Huang, Yan;Lai, Dong;Wang, Hanfeng;Du, Songliang;Shen, Donglai;Chen, Weihao;Xuan, Yundong;Lu, Yongliang;Feng, Huayi;Zhang, Xiangyi;Zhao, Wenlei;Wang, Chenfeng;Wang, Tao;Wu, Shengpan;Huang, Qingbo;Niu, Shaoxi;Wang, Baojun;Ma, Xin;Zhang, Xu
    • Advances in nano research
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    • v.12 no.6
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    • pp.639-652
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    • 2022
  • The prolyl 3-hydroxylase family member 4 (P3H4), is associated with post-translational modification of fibrillar collagens and aberrantly activated in cancer leading to tumor progression. However, its role in clear cell renal cell carcinoma (ccRCC) is still unknown. Here we reported that P3H4 was highly expressed in renal cancer tissues and significantly positive correlated with poor prognosis. Knockdown of P3H4 inhibited the proliferation, migration and metastasis of renal cancer cells in vitro and in vivo, and also, overexpression of it enhanced the oncogenic process. Mechanistically, P3H4 depletion decreased the levels of GDF15-MMP9 axis and repressed its downstream signaling. Further functional studies revealed that inhibition of GDF15 suppressed renal cancer cell growth and GDF15 recombinant human protein (rhGDF15) supplementation effectively rescued the inhibitory effect induced by P3H4 knockdown. Moreover, decreased levels of MMP9 caused by inhibition of P3H4-GDF15 signaling constrained the expression of PD-L1 and suppression of P3H4 accordingly promoted anti-tumor immunity via stimulating the infiltration of CD4+ and CD8+ T cells in syngeneic mice model. Taken together, our findings firstly demonstrated that P3H4 promotes ccRCC progression by activating GDF15-MMP9-PD-L1 axis and targeting P3H4-GDF15-MMP9 signaling pathway can be a novel strategy of controlling ccRCC malignancy.

The Inhibitory Effects of Haeyeol-tang in Expression of Pro-inflammatory Cytokine on LPS-stimulated THP-1 Cells (해열탕(解熱湯)이 LPS로 자극된 대식세포에 있어 염증관련 Cytokine 발현억제에 미치는 효과)

  • Lee, Byeong-Sam;Kim, Hong-yeoul;Kim, Jin-Ju;Jung, Sung-Ki;Rhee, Hyung-Koo;Jung, Hee-Jae
    • The Journal of Internal Korean Medicine
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    • v.29 no.2
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    • pp.334-347
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    • 2008
  • Background and Objective : Haeyeol-tang, composed of Houttuyniae Herba, Lonicerae Flos, Taraxaci Herba, and Scrophulariae Radix, is widely used for alleviating the symptom of various kinds of inflammatory pulmonary disease, including asthma and COPD. We want to know whether Haeyeol-tang has an anti-inflammatory effect by analyzing expression of pro-inflammatory cytokines. Materials and Methods : We differentiated the THP-1 cells into macrophage-like cells by treatment with PMA. Inflammation was induced by treatment with LPS and PMA. We found the safe concentration of Haeyeol-tang by using MTS assay and used PD98059 as a negative control for comparison of anti-inflammatory effect of Haeyeol-tang. Results : The RT-PCR analysis results show that the cell survival rate is over 100% within 1 ng/mL to 1 ug/mL of Haeyeol-tang and begins to decrease under 100% at 10 ug/mL. The gene expression of $IL-1{\beta}$, IL-6, IL-8, IL-10, $TNF-{\alpha}$ and $TGF-{\beta}$ levels were down-regulated when Haeyeol-tang was treated at concentrations between 1 ng/mL an 1 ug/mL on monocyte-derived macrophages. Interestingly, 1 ug/mL Haeyeol-tang-treated samples showed that the transcriptional activities of IL-8, $TNF-{\alpha}$, IL-10 and $TGF-{\beta}$ were more down-regulated than those of PD098059 $(TNF-{\alpha}$ inhibitor). At protein level, the ELISA analysis results showed that there were more remarkable (p<0.001) decreases in expression of $IL-1{\beta}$, IL-6, IL-8 and $TNF-{\alpha}$ on both the 1 ug/mL Haeyeol-tang-treated group and the PD98059-treated group than the LPS-treated group. Conclusion : We conclude that Haeyeol-tang has an anti-inflammatory effect by inhibiting expression of pro-inflammatory cytokines and chemokines at mRNA and protein levels. These results may provide us a promising way to care for general inflammatory diseases as well as inflammatory pulmonary disease, including asthma and COPD, with further clinical study.

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Stereospecific Synthesis of Methyl-6-deoxy-$\beta$-L-idopyranoside (Methyl-6-deoxy-$\beta$-L-idopyranoside의 합성)

  • 민신홍;박복구;옥광대
    • YAKHAK HOEJI
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    • v.30 no.6
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    • pp.352-355
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    • 1986
  • Methyl-6-deoxy-$\beta$-L-idopyranoside was prepared in good yield by treatment of methyl 2,3,4-tri-O-benzyl-6-deoxy-$\alpha$-D-xylo-hex-5-enopyranoside with H$_2$ on pd, followed by reaction of Na/NH$_3$ at $-50^{\circ}C$. The ratio of L-idopyranoside and D-glucopyranoside was 7 to 1 in 80.7%. It was confirmed that L-idopyranoside was 1C conformation as being expected.

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A Sensitive, Efficient, and Cost-Effective Method to Determine Rotigotine in Rat Plasma Using Liquid-Liquid Extraction (LLE) and LC-MRM

  • Kim, Ji Seong;Jang, Yong Jin;Kim, Jin Hee;Kim, Jin Hwan;Seo, Jae Hee;Park, Il-Ho;Kang, Myung Joo;Choi, Yong Seok
    • Mass Spectrometry Letters
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    • v.13 no.4
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    • pp.146-151
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    • 2022
  • Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson's disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH-DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over previous methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00-115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the development of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

A Study on the Washability and Washing Conditions of the Industrial Alkaline Laundry Detergent Suitable for Water Discharge Standards and Detergent Regulations (수질 배출기준 및 세제 안전기준에 적합한 산업용 알칼리 세탁세제의 세척성과 세탁조건 연구)

  • Song, Hyunjoo;Song, Sunhye
    • Textile Coloration and Finishing
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    • v.33 no.4
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    • pp.250-257
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    • 2021
  • Laundry industry has traditionally been considered an industry that generates large amounts of wastewater and Volatile Organic Compounds(VOCs). This is still the case until now. Household laundry detergents are produced and distributed within the safety regulations on the amount of harmful substances detected. While industrial laundry detergents are often distributed without safety regulations, and even laundry workers manufacture and use them on their own. This contaminates water and air and also threatens the safety of workers. This study is a basic study for distributing eco-friendly detergents(EFD-A) developed through previous studies to the laundry industry. Safety, washability and wastewater quality of EFD-A are evaluated. Three existing commercial detergents(PD1, PD2, LD4) are also evaluated to compare with EFD-A. The safety of detergents is confirmed by the content of optical brightener, VOCs, and arsenic. Washability is evaluated by the difference in reflectance of washed and unwashed artificial soiled fabrics according to detergent concentration, washing temperature, and washing time. TOC is used as the index of assessing the wastewater quality. The results are as follows; EFD-A doesn't contain the optical brighteners, VOCs, and arsenic. The optimal washing conditions for EFD-A are 3 g/L concentration, 40 ℃ washing temperature, and 30 min washing time. The soil removal efficiency is about 71 %, which was similar to or somewhat superior to that of PD1, PD2, and LD4. TOC is 63.5 %, which is about 15 % lower than the discharge limit. Through this study, the developed detergent EFD-A can be used as a safe and eco-friendly detergent for the human body and the environment.