• Title/Summary/Keyword: human-to-human (H2H)

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Effects of an Extract from the Roots of Platycodon Grandiflorum on the Levels of p53 and pRB in NCI-H460 Human Lung Carcinoma Cells (길경 수용액 추출물에 의한 NCI-H460 인체 폐암세포의 p53 및 pRB의 발현에 미치는 영향)

  • Park, Bong-Kyu;Gam, Chul-Woo;Heo, Tae-Yool;Park, Dong-Il
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.20 no.6
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    • pp.1530-1537
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    • 2006
  • Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health benefits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. Platycodi Radix, the root of Platycodon grandiflorum A. DC (Campanulaceae), commonly known as Doraji in Korea (Chinese name, 'Jiegeng', and Japanese name, 'Kikyo') has been used as an expectorant in traditional Oriental medicine. Extracts from the roots of P. grandiflorum have been reported to have wide ranging health bensfits. In Korea, Platycodi Radix is also used as a food and employed as a folk remedy for adult diseases, such as bronchitis, asthma and pulmonary tuberculosis, hyperlipidemia, diabetes, and inflammatory diseases, and as a sedative. Several studies on its chemical and immunopharmacological effects including immunostimulation and antitumor activity have been performed. However, the relevant molecular mechanisms are poorly understood. In the present study, we investigated the effects of an aqueous extract from the roots of P. grandiflorum AEPG) on the cell growth of human lung adenocarcinoma NCI-H460 cells in order to understand its anti-proliferative mechanism. AEPG treatment down-regulated the cyclin D1 expression in both transcriptional and translational levels without alteration of cyclin E. In AEPG-treated cells, the levels of cyclin-dependent kinase (C아) 6 mRNA and protein were significantly inhibited, but the levels of Cdk2 and Cdk4 were slightly inhibited by treatment of AEPG. AEPG treatment induced a marked accumulation of Cdk inhibitors, p16 and p27. However, AEPG treatment did not affect not only retinoblastoma protein (pRB) but also tumor suppressor p53 protein expression. The present results indicated that AEPG-induced inhibition of lung cancer cell proliferation is associated with the blockage of G1 phase progression through induction of Cdk inhibitors such as p16 and p27, and inhibition of cyclin D1 and Cdk6. AEPG exposure, as offered by this study, provides cluse for the mechanism of AEPG action. Taken together, these findings suggest that P. grandiflorum has strong potential for development as an agent for prevention and treatiment against human lung cancer.

Skin Irriation Effect of Glycolic Acid and UVB in Guinea Pig (Guinea pid를 이용한 Glycolic acid 및 UVB의 피부 자극성 평가)

  • 조대현;홍진태
    • Toxicological Research
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    • v.16 no.1
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    • pp.89-94
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    • 2000
  • Alpha-hydroxy acid(AHA) are used in cosmetic products as a pH adjuster, mild exfoliant and humectant-skin conditioner. Cosmetics containing higher concentration (30%) and lower pH (3.0) of AHA can cause side effects if it is applied without the prescription. For providing information on the safety of AHA and on human risk assessments we studied skin irritation effect of glycolic acid, one of the most commonly used AHA in guinea pigs. The skin irritation by glycolic acid was increased in a dose(10% to 70%), acidity (pH 2.5 to 5.5.) and length of exposure dependent manner (for up to 14 days), respectively. The combination treatment with UVB (0.4 or 3.0 J/$cm^2$) increased glycolic acid-induced skin irritation. Histological examination showed that hyperplasia of non-inflammatory cells in the epidermis of skin treated with high dose of glycolic acid (pH 3.0). There results show that glycolic acid increased skin irritation in a dose, length of exposure and pH dependent manner, respectively, in guinea pig, and the combination with UVB increased glycolic acid-induced skin irritation. The cell proliferation of non-inflammatory cell may be involved in high doses of glycolic acid-induced skin irritation. Long-term application of more than 30% of glycolic acid (pH 3.0) may cause skin irritation.

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Toxicogenomic Study to Identify Potential New Mechanistic Markers on Direct-Acting Mutagens in Human Hepatocytes (THLE-3)

  • Kim, Youn-Jung;Song, Mi-Kyung;Song, Mee;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.3 no.4
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    • pp.231-237
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    • 2007
  • Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

Effects of Amitriptyline and Imipramine on Superoxide Generation, Myeloperoxidase Release, Leukotriene $B_4$ in Human Neutrophils (Amitriptyline과 Imipramine이 호중구에서의 Superoxide 생성, Myeloperoxidase 유리, Leukotriene $B_4$생성과 칼슘 동원에 나타내는 영향)

  • Shin Yong-Kyoo;Lee Chung-Soo;Lee Kwang-Soo
    • The Korean Journal of Pharmacology
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    • v.31 no.1 s.57
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    • pp.123-133
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    • 1995
  • A number of tricyclic antidepressants appear to have inhibitory action on calmodulin. Although amitriptyline, imipramine and doxepine have been shown to inhibit calcium uptake, oxidative phosphorylation and ATPase activities, effects of amitriptyline, imipramine and doxepine on functional responses of human neutrophils have not been elucidated. In this study, effects amitriptyline, imipramine and doxepine on superoxide and hydrogen peroxide generation, myeloperoxidase release, leukocriene B4 formation and intracellular calcium level were investigated. Superoxide and hydrogen peroxide production in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. EDTA, EGTA, verapamil and bepredil inhibited heat aggregated IgG-induced superoxide production. Chlorpromazine, trifluoperazine, staurosporine and H-7 also inhibited it. PMA-induced superoxide production was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and H-7. Amitriptyline, imipramine, chlorpromazine and trifluoperazine inhibited the myeloperoxidase release by heat aggregated IgG. Productions of $LTB_4$, and 5-HETE in heat aggregated IgG-activated neutrophils were inhibited by amitriptyline, imipramine and doxepine. In neutrophils, elevation of intracellular calcium induced by heat aggregated IgG was inhibited by amitriptyline, imipramine, doxepine, chlorpromazine and EGTA, while verapamil slightly inhibited increase of intracellular calcium and H-7 did not inhibit it. These results suggest that the inhibitory effect of amitriptyline, imipramine and doxepine on respiratory burst, myeloperoxidase release and LTB4 production in heat aggregated IgG-activated neutrophils appears to be ascribed to the inhibition of calcium mobilization, calmodulin and protein kinase C.

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Effectiveness of Intravenous Isoniazid and Ethambutol Administration in Patients with Tuberculosis Meningoencephalitis and HIV Infection

  • Butov, Dmytro;Feshchenko, Yurii;Kuzhko, Mykhailo;Gumenuik, Mykola;Yurko, Kateryna;Grygorova, Alina;Tkachenko, Anton;Nekrasova, Natalia;Tlustova, Tetiana;Kikinchuk, Vasyl;Peshenko, Alexandr;Butova, Tetiana
    • Tuberculosis and Respiratory Diseases
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    • v.83 no.1
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    • pp.96-103
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    • 2020
  • Background: The aim of this study was to investigate the effectiveness of intravenous isoniazid (H) and ethambutol (E) administered in patients with new sputum positive drug-susceptible pulmonary tuberculosis (TB) with tuberculous meningoencephalitis (TM) and human immunodeficiency virus (HIV) co-infection in the intensive phase of treatment. Methods: Fifty-four patients with TB/TM and HIV co-infection were enrolled for this study. Group 1 comprised of 23 patients treated with E and H intravenously, while rifampicin and pyrazinamide were prescribed orally. Group 2 consisted of 31 patients treated with the first-line anti-TB drugs orally. The concentrations of H and E in blood serum were detected using a chromatographic method. Results: A significant improvement in the clinical symptoms and X-ray signs in patients treated intravenously with H and E was observed and compared to group 2. The sputum Mycobacterium tuberculosis positivity was observed during the second month of the treatment in 25.0% of patients from group 1 and 76.1% of the patients from the control group (p=0.003). In addition, nine patients (39.1%) died up to 6 months when H and E were prescribed intravenously compared with 22 (70.9%) in group 2 (p=0.023). Conclusion: In TB/TM with HIV, the intravenous H and E treatment was more effective than oral H and E treatment at 2 months of intensive treatment in sputum conversion as well as in clinical improvement, accompanied by significantly higher mean serum concentrations. In addition, the mortality rate was lower in intravenous H and E treatment compared to oral treatment.

Dyeing Properties and Color of Silk Fabrics Dyed with Safflower Yellow Dye (홍화 황색소 견섬유에 대한 염색성과 색상)

  • Shin, Youn-Sook;Son, Kyung-Hee;Yoo, Dong-Il
    • Journal of the Korean Society of Clothing and Textiles
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    • v.32 no.6
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    • pp.928-934
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    • 2008
  • The objective of this study is to investigate the dyeing properties of safflower yellow dye on silk for the standardization of dyeing process and color reproducibility. Yellow colorants were water-extracted from safflower petals, concentrated, and freeze-dried to obtain colorants powder. The effects of dye concentration, dyeing temperature, and pH of dye bath were studied in terms of dye uptake and shade. Fastness to dry cleaning and light was evaluated. Dye uptake increased with raising temperature and brighter and more vivid yellow shade was obtained when dyed at $30^{\circ}C$. As colorants concentration increased, dye uptake increased progressively and the shade got darker and deeper. Maximum color strength was obtained at pH 3.5. It was speculated that the adsorption of colorants seemed to occur mainly by hydrogen bonding and physical force at pH 5.5 and by ionic bonding as well as hydrogen bonding below isoelectric point(pH 3.8-4.0). The results of reproducibility test showed acceptable color difference in the range of $1.11{\sim}2.01$. Washing fastness was fairly good as 4/5 rating, while light fastness was 2/3 rating.

HY253, a Novel Decahydrofluorene Analog, Induces Apoptosis via Intrinsic Pathway and Cell Cycle Arrest in Liver Cancer HepG2 Cells

  • Choi, Ko-woon;Suh, Hyewon;Jang, Seunghun;Kim, Dongsik;Lee, Chul-Hoon
    • Journal of Microbiology and Biotechnology
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    • v.25 no.3
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    • pp.413-417
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    • 2015
  • Recently, we isolated HY253, a novel decahydrofluorene analog with a molecular structure of 7,8a-divinyl-2,4a,4b,5,6,7,8,8a,9,9a-decahydro-1H-fluorene-2,4a,4b,9a-tetraol from the roots of Aralia continentalis, which is known as Dokwhal (獨活), a traditional medicinal herb. Moreover, we previously reported its cytotoxic activity on cancer cell proliferation in human lung cancer A549 and cervical cancer HeLa cells. The current study aimed to evaluate its detailed molecular mechanisms in cell cycle arrest and apoptotic induction in human hepatocellular carcinoma HepG2 cells. Flow cytometric analysis of HepG2 cells treated with $60{\mu}M$ HY253 revealed appreciable cell cycle arrest at the G1 phase via inhibition of Rb phosphorylation and down-regulation of cyclin D1. Furthermore, using western blots, we found that up-regulation of cyclin-dependent kinase inhibitors, such as p21CIP1 and p27KIP1, was associated with this G1 phase arrest. Moreover, TUNEL assay and immunoblottings revealed apoptotic induction in HepG2 cells treated with $60{\mu}M$ HY253 for 24 h, which is associated with cytochrome c release from mitochondria, via down-regulation of anti-apoptotic Bcl-2 protein, which in turn resulted in activation of caspase-9 and -3, and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP). Accordingly, we suggest that HY253 may be a potent chemotherapeutic hit compound for treating human liver cancer cells via up-regulation and activation of the p53 gene.

Characterization of MACS Isolated Cells from Differentiated Human ES Cells (인간 배아줄기세포로부터 분화된 세포에서 MACS 방법을 이용하여 분리한 세포의 특성에 대한 연구)

  • Cho, Jae Won;Lim, Chun Kyu;Shin, Mi Ra;Bang, Kyoung Hee;Koong, Mi Kyoung;Jun, Jin Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.33 no.3
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    • pp.171-178
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    • 2006
  • Objective: Human embryonic stem (ES) cells have a great potential in regenerative medicine and tissue engineering. The human ES cells could be differentiated into specific cell types by treatments of growth factors and alterations of gene expressions. However, the efficacy of guided differentiation and isolation of specific cells are still low. In this study, we characterized isolated cells from differentiated human ES cells by magnetic activated cell sorting (MACS) system using specific antibodies to cell surface markers. Methods: The undifferentiated hES cells (Miz-hESC4) were sub-cultured by mechanical isolation of colonies and embryoid bodies were spontaneously differentiated with DMEM containing 10% FBS for 2 weeks. The differentiated cells were isolated to positive and negative cells with MACS system using CD34, human epithelial antigen (HEA) and human fibroblast (HFB) antibodies, respectively. Observation of morphological changes and analysis of marker genes expression were performed during further culture of MACS isolated cells for 4 weeks. Results: Morphology of the CD34 positive cells was firstly round, and then it was changed to small polygonal shape after further culture. The HEA positive cells showed large polygonal, and the HFB positive spindle shape. In RT-PCR analysis of marker genes, the CD34 and HFB positive cells expressed endodermal and mesodermal genes, and HEA positive cells expressed ectodermal genes such as NESTIN and NF68KD. The marker genes expression pattern of CD34 positive cells changed during the extension of culture time. Conclusion: Our results showed the possibility of successful isolation of specific cells by MACS system from undirected differentiated human ES cells. Thus, MACS system and marker antibodies for specific cell types might be useful for guided differentiation and isolation of specific cells from human ES cells.

Evaluation of physical property and cytotoxicity of resin infiltrant based on a triethylene glycol dimethacrylate (TEGDMA)

  • Min, Ji-Hyun;Roh, Ji-Yeon;Kim, Ki-Rim
    • Journal of Korean society of Dental Hygiene
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    • v.19 no.2
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    • pp.173-181
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    • 2019
  • Objectives: The resin infiltration technique is a promising alternative therapy for arresting the early dental caries. However, there are very few reports on the safety and biocompatibility of this technique. We evaluated various properties of resin infiltrant (RI) based on a triethylene glycol dimethacrylate (TEGDMA).The water sorption (Wsp) and water solubility (Wsl) was assessed. Additionally, the cytotoxicity of RI against both animal and human fibroblast cell lines was investigated. Methods: The RI of the $Icon^{(R)}$, the first product developed for resin infiltration, is mainly composed of TEGDMA in the resin matrix. The Wsp and Wsl for the RI were measured in accordance with ISO 4049 specifications. Fourier-transform infrared spectroscopy (FTIR) was used for analyzing the polymerization before and after curing of RI. The cytotoxicity of RI against the mouse fibroblasts (L929) and human gingival fibroblasts (hTERT-hNOF) was evaluated using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and the data were analyzed using one-way analysis of variance. Results: Wsp and Wsl of the RI specimens were $53.37{\mu}g/mm^3$ and $10.6{\mu}g/mm^3$, respectively. FTIR analysis revealed a slightly higher degree of curing with longer irradiation time. The degree of conversion for RI was high (80.9%) after 40 seconds of light curing. There was a significant decrease in the viability of L929 and hTERT-hNOF cells at RI extraction solution concentrations above 50%, respectively, compared to that in the negative control (p< 0.05). Conclusions: Even though the RI exhibited positive effect on the early prevention of dental caries, the clinicians should also consider the toxicity of RI on periodontal tissues.

Study on Refractive Index and Thickness of Human Stem Cells by Using Imaging Ellipsometry (영상 타원법을 이용한 인간 줄기세포의 굴절률과 두께 분포 연구)

  • Choi, Joong-Kyu;Shim, Woo-Young;Lee, Gwang;Kim, Sang-Youl;Park, Sang-Uk;CheGal, Won;Cho, Hyun-Mo;Cho, Yong-Jai
    • Korean Journal of Optics and Photonics
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    • v.20 no.1
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    • pp.53-56
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    • 2009
  • We applied an ellipsometric technique to get quantitative information about the thickness and refractive index of human Mesenchymal Stem Cells (hMSCs). The images of ellipsometric constants $\Delta$, $\Psi$ for the nucleus region and for the cell body region of hMSCs were obtained by using an Imaging Ellipsomter (IE) for their in vitro state. A numerical inversion method was applied to deduce the refractive index and the thickness of hMSCs from the measured $\Delta$, $\Psi$. Thus the images of the refractive index and those of the thickness of hMSCs for the nucleus region and for the cell body region are reported.