• Title/Summary/Keyword: Cell toxicity

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Decitabine in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes, Which Combined with Complex Karyotype Respectively

  • Gao, Su;Li, Zheng;Fu, Jian-Hong;Hu, Xiao-Hui;Xu, Yang;Jin, Zheng-Ming;Tang, Xiao-Wen;Han, Yue;Chen, Su-Ning;Sun, Ai-Ning;Wu, De-Pei;Qiu, Hui-Ying
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6627-6632
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    • 2015
  • Background: We conducted a study exploring the clinical safety and efficacy of decitabine in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), combined with a complex karyotype. Materials and Methods: From April 2009 to September 2013, a total of 35 patients with AML/MDS combined with a complex karyotype diagnosed in the First Affiliated Hospital of Soochow University were included for retrospective analysis. All patients were treated with decitabine alone ($20mg/m^2$ daily for 5 days) or combination AAG chemotherapy (Acla 20mg qod*4d, Ara-C $10mg/m^2$ q12h*7d, G-CSF $300{\mu}g$ qd, the dose of G-CSF adjusted to the amount in blood routinely). Results: In 35 patients, 15 exhibited a complete response (CR), and 6 a partial response (PR), the overall response rate (CR+PR) being 60% (21 of 35). Median disease-free survival was 18 months and overall survival was 14 months. In the 15 MDS patients with a complex karyotype, the CR rate was 53.3% (8 of 15); in 20 AML patients with complex karyotype, the overall response rate was 65% (13 of 20). The response rate of decitabine alone (22 cases) was 56.5% (13 of 22), while in the combination chemotherapy group (13 cases), the effective rate was 61.5% (8 of 13)(P>0.05). There are 15 patients with chromosome 7 aberration, after treatment with decitabine, 7 CR, 3 PR, overall response rate was 66.7% (10 of 15). Of 18 patients with 3 to 5 kinds of chromosomal abnormalities, 66.7% demonstrated a response; of 17 with more than 5 chromosomal abnormalities, 52.9% had a response. In the total of 35 patients, with one course (23 patients) and ${\geq}$two courses (12 patients), the overall response rate was 40.9% and 92.3% (P<0.05). Grade III to IV hematological toxicity was observed in 27 cases (75%). Grade III to IV infections were clinically documented in 7 (20%). Grades I to II non-hematological toxicity were infections (18 patients), haematuria (2 patients), and bleeding (3 patients). With follow-up until September 2013, 7 patients were surviving, 18 had died and 10 were lost to follow-up. In the 6 cases who underwent allogeneic hematopoietic stem cell transplantation (HSCT) all were still relapse-free survivors. Conclusions: Decitabine alone or combination with AAG can improve outcome of AML/MDS with a complex karyotype, there being no significant difference decitabine in inducing remission rates in patients with different karyotype. Increasing the number of courses can improve efficiency. This approach with fewer treatment side effects in patients with a better tolerance should be employed in order to create an improved subsequent chance for HSCT.

Effects of Momordica Charantia L. Water Extracts on the Rat Liver and Kidney with Acute Toxicated by Lead (여주 추출물이 급성 납 중독된 흰쥐의 간과 콩팥에 미치는 효과)

  • Lee, Hyun-Hwa;Cheong, Min-Ju;Huh, Jin;Song, Seon-Young;Boo, Hee-Ock
    • Applied Microscopy
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    • v.39 no.4
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    • pp.355-363
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    • 2009
  • The purpose of this study was to demonstrate the effect of Momordica Charantia L. water extracts, one of the natural chelator, on the biochemical and enzyme activity changes in the rats liver and kidney caused by lead acetate. Rat approximately 250 g in weight were grouped into the control, lead acetate treated, and the Momordica Charantia L. boiling water extracts treated after lead acetate groups. Lead acetate (1,000 ppm) and Momordica Charantia L. water extracts (5%, 10%) were delivered drinking water. Serum AST, ALT and BUN were measured, histological alteration of liver and kidney were examined by light microscopy. Momordica Charantia L. extract group was decreased serum AST, ALT and BUN level induced by lead. Optical observations of liver tissue, lead group were observed necrosis of hepatic cells and infiltration of inflammatory cells, but Momordica Charantia L. extract group was observed only slight infiltration of inflammatory cells around the central vein. Optical observations of kidney tissue, lead acetate induced atrophy and necrosis of glomerulus and infiltration of inflammatory cell around renal tubule. For the group treated with Momordica charantia L. extract, the glomerulus was similar to the control, some around the renal tubule was observed infiltration of inflammatory cells. In conclusion, Momordica Charantia L. water extract may protect the lead-induced toxicity on liver and kidney.

Antioxidant and Anti-inflammation Activity of Red Cabbage Extract (적양배추 추출물의 항산화 및 항염증 활성)

  • Ha, Hyun-Joo;Lee, Chun-Bok
    • Culinary science and hospitality research
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    • v.20 no.2
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    • pp.16-26
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    • 2014
  • This study investigated the anti-inflammatory and antioxidnat effects of red cabbage extracts on RAW264.7 cells. Cell toxicity was determined by MTT assay. We evaluated the anti-inflammatory effects of red cabbage extracts by measuring nitric oxide (NO), inducible NOS (iNOS) production, and cyclooxygenase-2 (COX-2) expression by Western blotting. Ethanolic and water extracts (0.25, 0.5, and 1.0 mg/mL) significantly suppressed LPS-stimulated production of NO. Two kinds of extracts reduced the expression of iNOS and COX-2 proteins. The present results show that red cabbage extract has potent anti-inflammatory effects on RAW264.7 cells. In addition, two kinds of extracts as well as various antioxidant activities such as 2,2'-azino-bis-(3-ethylbenzo thiazoline-6-sulfonic acid)(ABTS) radical scavenging activity, ferric reducing antioxidant power(FRAP). The total polyphenol and flavonoid contents of the ethanolic and water extracts from red cabbage were $18.699{\pm}0.87$ and $11.174{\pm}4.86$ mg GAE/g extract, respectively, and $7.782{\pm}2.23$ and $15.608{\pm}3.54$ mg CE/g extract. The ABTS radical scavenging activities of the ethanolic and water extracts and BHT were $0.269{\pm}0.12$, $0.212{\pm}0.22$ and $1.235{\pm}0.07mM$ Trolox equivalent/mg extract, respectively. The FRAP values of the extracts were similar to those of BHT, which were used as a positive control. Therefore, red cabbage extract is considered as a good food material of functional foods for prevention against various diseases.

Eye Irritation Test of Lens Washing Agents as ReNuTM (렌즈 보존액 ReNuTM에 대한 안점막자극시험)

  • Jang, Woo-Yeong;Lee, Jeong-Yeong;Joo, Kyung-Bok
    • Journal of Korean Ophthalmic Optics Society
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    • v.10 no.4
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    • pp.293-304
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    • 2005
  • As the eye irritant test of lens washing agent, ReNu$^{TM}$ was analysed using Draize methods (1959) according to KFDA Guidelines. In addition, to test the potential toxicity of test articles the ratio of inflammatory cells and non-inflammatory epitheloid cells were also observed using smear cytology methods against ocular discharge. At test, the histopathological changes on the cornea, iris, retina and sclera were also observed in all animals. Slight irritancy of the cornea and conjunctiva were observed at 1, 2 and 3 days after dropping in non-washing group. The Mean Index of Ocular Irritation(MIOI) of these points are detected as 4.17, 3.00 and 1.33, respectively. In washing group, slight irritancy of the cornea and conjunctiva were observed at 1 and 2 days after dropping with MIOI as 0.67 and 1.33, respectively. Therefore, ReNu$^{TM}$ was considered as non-irritating materials because the MIOI is detected below 5.00 throughout the whole experimental periods in both washing and non-washing groups. The Index of Acute Ocular Irritation(IAOI) is also detected as 4.17(1 day after dropping). Except of the somewhat increase trend of the inflammatory cell ratios in ocular discharge at 1 day after dropping of non-washing group, but significances are not detected, on the other hand, no meaningful changes on smear cytology of ocular discharges are observed in this study. In addition, no abnormal histopathological changes on the cornea, iris, retina and sclera were also not detected in ReNu$^{TM}$ dropping group compared to that of non-treated control eyes.

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Biological Activity and Manufacturing of Yanggeng with Yangha Flower Buds (양하 꽃대의 생리활성 및 양갱 제조)

  • Kim, Min-Ju;Kim, Ae-Jung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.8
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    • pp.1180-1185
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    • 2015
  • This study was performed to investigate the biological activity of yangha flower buds as well as to manufacture of yanggeng prepared with various levels (0 g, 3 g, 6 g, 9 g, and 12 g) of yangha flower buds. DPPH and ABTS scavenging activities of yangha flower buds were 96% and 57% compared to levels of vitamin C, respectively. In the oxygen radical antioxidant capacity assay, antioxidant activity increased dose dependently up to $500{\mu}g/mL$ of yangha flower buds. There was no toxicity up to $1,000{\mu}g/mL$ in vascular smooth muscle cells, and yanggeng significantly reduced migration and proliferation by platelet-derived growth factor-BB-stimulated rat aortic smooth muscle cell migration and proliferation. In the sensory evaluation, the optimal sample was YY9, which was prepared with 9 g of yangha flower buds. It can be concluded that yangha flower buds show antioxidant and vascular protective activities. The optimal sample (YY9) is expected to contribute as a new functional food.

Therapeutic Strategy for the Prevention of Pseudorabies Virus Infection in C57BL/6 Mice by 3D8 scFv with Intrinsic Nuclease Activity

  • Lee, Gunsup;Cho, SeungChan;Hoang, Phuong Mai;Kim, Dongjun;Lee, Yongjun;Kil, Eui-Joon;Byun, Sung-June;Lee, Taek-Kyun;Kim, Dae-Hyun;Kim, Sunghan;Lee, Sukchan
    • Molecules and Cells
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    • v.38 no.9
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    • pp.773-780
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    • 2015
  • 3D8 single chain variable fragment (scFv) is a recombinant monoclonal antibody with nuclease activity that was originally isolated from autoimmune-prone MRL mice. In a previous study, we analyzed the nuclease activity of 3D8 scFv and determined that a HeLa cell line expressing 3D8 scFv conferred resistance to herpes simplex virus type 1 (HSV-1) and pseudorabies virus (PRV). In this study, we demonstrate that 3D8 scFv could be delivered to target tissues and cells where it exerted a therapeutic effect against PRV. PRV was inoculated via intramuscular injection, and 3D8 scFv was injected intraperitoneally. The observed therapeutic effect of 3D8 scFv against PRV was also supported by results from quantitative reverse transcription polymerase chain reaction, southern hybridization, and immunohistochemical assays. Intraperitoneal injection of 5 and $10{\mu}g$ 3D8 scFv resulted in no detectable toxicity. The survival rate in C57BL/6 mice was 9% after intramuscular injection of 10 $LD_{50}$ PRV. In contrast, the 3D8 scFv-injected C57BL/6 mice showed survival rates of 57% ($5{\mu}g$) and 47% ($10{\mu}g$). The results indicate that 3D8 scFv could be utilized as an effective antiviral agent in several animal models.

A Study on the Effect and Mechanism of Gamikyejakjimogawusul-tang Herbal Acupuncture on Induced Rheumatoid Arthritis model of DBA/1 mice (계작지모가우슬탕(桂芍知母加牛膝湯) 약침이 류마티스 관절염 생쥐에 미치는 영향)

  • Jung, Soon Hyun;Cho, Chong kwan;Kim, So Yun;Kim, Young Il
    • Journal of Haehwa Medicine
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    • v.24 no.2
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    • pp.35-57
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    • 2016
  • Objectives : The purpose of this study is to prove the effect and mechanism of Gamikyejakjimogawusul-tang(GKHA) herbal acupuncture on induced rheumatoid arthritis model of DBA/1 mice. Methods : We check effect of GKHA extract on the AST, ALT, Creatinine, BUN of serum and cell viability of GK extract in RAW 264.7 cells to test the stability of this study. In vitro, we measure total phenol contents, total flavonoid contents, DPPH free radical scavenging activity, ABTS cation radical scavenging activity of Gamikyejakjimogawusul-tang, effect of GK extract on ROS(Reactive Ooxygen Species) production to estimate a anti-oxidant capacity, and we also measure effect of GK extract on NO (Nitric Oxid), IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF production in RAW 264.7 cells to estimate a anti-inflammatory efficacy. In vivo, we compare a rheumatoid arthritis manifestation between control and experimental group and estimate a AI. Then we check effect of GKHA on the level of WBC, neutrophil, lympocyte, monocyte in the blood to see the effect of immune cells in blood. In addition we measure effect of GKHA on the level of hs-CRP, IgM, IgG, IL-$1{\beta}$, IL-6, IL-17, IL-21, TNF-${\alpha}$, MCP-1, GM-CSF in serum. We observe effects of GKHA on imaging of cartilage degeneration using micro CT-arthrography in paw hind. And we calculate effects of GKHA that reduced BV ratio, BS/BV ratio using 3D Micro-CT. Lastly we observe effects of GKHA histopathologic examination analysis. Results : 1. The toxicity on liver and kidney was disregardable and the cytotoxicity against RAW 264.7 cells was also disregardable. 1. Total phenol contents and total flavonoid contents in GK extract were in high level. 2. DPPH free radical scavenging activity and ABTS cation radical scavenging activity were increased according to concentration of GK extract 3. ROS production was significantly decreased in GK extract (at 10, $100{\mu}g/ml$). 4. NO, IL-6, TNF-${\alpha}$, MCP-1 production were significantly decreased in GK extract(at 10, $100{\mu}g/ml$). IL-17, GM-CSF production were significantly decreased in GK extract(at 1, 10, $100{\mu}g/ml$). IL-$1{\beta}$, IL-21 production were also decreased but there was no statistical significance. 5. 25x observation after H&E and M-T staining, infiltration of immune cells and subsidence of the cartilage and damage to the synovial cells were decreased. Conclusions : This study showed that GKHA extract had anti-oxidant capacity, anti-inflammatory efficacy. GKHA extract also had inhibiting effect on the process of rheumatoid arthritis and can protect joint and cartilage. So we expect that GKHA extract can be a meaningful treatment to rheumatoid arthritis patients.

Development of bio-fusion materials with skin penetrating property derived from Aurelia aurita (경피 침투율이 높은 보름달 물해파리 유래 바이오 융합 소재 개발)

  • Kim, Hyoung Sik;Seo, Hyo Hyun;Lee, Seo-Hui;Lim, Hyun Jung;Shin, Jeong Won;Kim, Seop Ri;Moh, Sang Hyun;Kim, Kwang-Hwan
    • Journal of the Korea Convergence Society
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    • v.8 no.1
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    • pp.35-42
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    • 2017
  • Previously, we reported LVH peptiede derived from Aurelia aurita as cosmecetuticals with anti-winkle activity. In this study, we synthesized pal-LVH using palmitic acid to enhance skin permeability of LVH and examined the effects as cosmeceuticals of pal-LVH. To evaluate these effects, we performed cell toxicity, wound healing, and patch test for skin irritation with LVH and pal-LVH and compared these results for their effects. As a result. pal-LVH was not showed in cytotoxicity and allergenic effect like as LVH. Besides, pal-LVH had almost same excellent anti-ageing properties in high concentration and anti-winkle effect in low concentrationwas as LVH. These results suggested synthesis of palimitic acid and LVH did not affect any functions as cosmeceuticals with increasing skin permeability. Therefore, pal-LVH can be adaptable as new cosmecetuticals with anti-winkle and anti-ageing materials and applied in the development of medicine through various convergence study.

Soluble Prokaryotic Expression and Purification of Bioactive Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand

  • Do, Bich Hang;Nguyen, Minh Tan;Song, Jung-A;Park, Sangsu;Yoo, Jiwon;Jang, Jaepyeong;Lee, Sunju;So, Seoungjun;Yoon, Yejin;Kim, Inki;Lee, Kyungjin;Jang, Yeon Jin;Choe, Han
    • Journal of Microbiology and Biotechnology
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    • v.27 no.12
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    • pp.2156-2164
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    • 2017
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is considered as an antitumor agent owing to its ability to induce apoptosis of cancer cells without imparting toxicity toward most normal cells. TRAIL is produced in poor yield because of its insoluble expression in the cytoplasm of E. coli. In this study, we achieved soluble expression of TRAIL by fusing maltose-binding protein (MBP), b'a' domain of protein disulfide isomerase (PDIb'a'), or protein disulfide isomerase at the N-terminus of TRAIL. The TRAIL was purified using subsequent immobilized metal affinity chromatography and amylose-binding chromatography, with the tag removal using tobacco etch virus protease. Approximately 4.5 mg of pure TRAIL was produced from 125 ml flask culture with a purification yield of 71.6%. The endotoxin level of the final product was $0.4EU/{\mu}g$, as measured by the Limulus amebocyte lysate endotoxin assay. The purified TRAIL was validated and shown to cause apoptosis of HeLa cells with an $EC_{50}$ and Hill coefficient of $0.6{{\pm}}0.03nM$ and $2.41{\pm}0.15$, respectively. The high level of apoptosis in HeLa cells following administration of purified TRAIL indicates the significance and novelty of this method for producing high-grade and high-yield TRAIL.

The Possible Mechanisms Involved in Citrinin Elimination by Cryptococcus podzolicus Y3 and the Effects of Extrinsic Factors on the Degradation of Citrinin

  • Zhang, Xiaoyun;Lin, Zhen;Apaliya, Maurice Tibiru;Gu, Xiangyu;Zheng, Xiangfeng;Zhao, Lina;Abdelhai, Mandour Haydar;Zhang, Hongyin;Hu, Weicheng
    • Journal of Microbiology and Biotechnology
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    • v.27 no.12
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    • pp.2119-2128
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    • 2017
  • Citrinin (CIT) is a toxic secondary metabolite produced by fungi belonging to the Penicillium, Aspergillus, and Monascus spp. This toxin has been detected in many agricultural products. In this study, a strain Y3 with the ability to eliminate CIT was screened and identified as Cryptococcus podzolicus, based on the sequence analysis of the internal transcribed spacer region. Neither uptake of CIT by cells nor adsorption by cell wall was involved in CIT elimination by Cryptococcus podzolicus Y3. The extracellular metabolites of Cryptococcus podzolicus Y3 stimulated by CIT or not showed no degradation for CIT. It indicated that CIT elimination was attributed to the degradation of intracellular enzyme(s). The degradation of CIT by C. podzolicus Y3 was dependent on the type of media, yeast concentration, temperature, pH, and initial concentration of CIT. Most of the CIT was degraded by C. podzolicus Y3 in NYDB medium at 42 h but not in PDB medium. The degradation rate of CIT was the highest (94%) when the concentration of C. podzolicus Y3 was $1{\times}10^8cells/ml$. The quantity of CIT degradation was highest at $28^{\circ}C$, and there was no degradation observed at 3$5^{\circ}C$. The study also showed that acidic condition (pH 4.0) was the most favorable for CIT degradation by C. podzolicus Y3. The degradation rate of CIT increased to 98% as the concentration of CIT was increased to $20{\mu}g/ml$. The toxicity of CIT degradation product(s) toward HEK293 was much lower than that of CIT.