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

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In vitro metabolism of a new protective agent, KR-31543 in human liver microsomes

  • Ji, Hye-Young;Kim, Sook-Jin;Lee, Hong-Il;Lee, Seung-Seok;Lee, Dong-Ha;Lim, Hong;Lee, Hye-Suk
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.286.2-287
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    • 2003
  • The purpose of this paper was to identify the metabolic pathway of a new neuroprotective agent, KR-31543 for ischemia-reperfusion damage in human liver microsomes and characterize cytochrome P450 (CYP) enzymes involved in the in vitro metabolism of KR-31543 generates two metabolites in human liver microsomes : M1, N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine and M2, hydroxy-KR-31543. (omitted)

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Evaluation of Hydration Effect on Human Skin by $^1H$ MRS at 14.1T

  • Choi Chi-Bong;Hong Sung-Tak;Choe Bo-Young;Woo Dong-Chul;Yoon Seong-Ik;Cho Ji-Hyun;Lee Chul-Hyun;Cheong Chae-Joon;Park Sang-Yong;Oh Chil-Hwan
    • Journal of the Korean Magnetic Resonance Society
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    • v.10 no.1
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    • pp.105-114
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    • 2006
  • Purpose: We achieved high resolution MR imaging and spectra of human skin in vitro with using a 14.1 T MRI/MRS system, and evaluated the hydration effect of various cosmetic products by measuring the skin's. moisture concentration. Materials and Methods: We used the Bruker 14.1 T MRI/MRS system with a vertical standard bore that was equipped with a DMX spectrometer gradient system (200 G/cm at a maximum 40 A), RF resonators (2, 5 and 10 mm) and Para Vision software. Spin echo and fast spin echo pulse sequences were employed for obtaining the high resolution MR images. The 3D-localized point resolved spectroscopy (PRESS) method was used to acquire the MR spectra. Results: The high resolution MR images and spectra of human skin in vitro were successfully obtained on a 14.1 T system. The water concentration of human skin after applying a moisturizer was higher than that before applying a moisturizer. Conclusions: The present study demonstrated that the high-resolution MR images and spectra of human skin from a high field NMR instrument could be applicable to evaluating the hydration state of the stratum corneum.

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Effect of Lectin Isolated from Serrognathus platymelus castanicolor Larvae on the Various Cytokine Expressions (넓적사슴벌레(Serrognathus platymelus castanicolor) 유충으로부터 분리한 렉틴의 사이토카인 발현)

  • Jo, Su-Hyun;Kim, Se-Jin;Chung, See-Ryun;Jeune, Kyung-Hee
    • Korean Journal of Pharmacognosy
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    • v.37 no.4 s.147
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    • pp.221-228
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    • 2006
  • A lectin was purified from Serrognathus platymelus castanicolor larvae and named as SPL. The purification was carried out by ion-exchange chromatography on DEAE Sephadex A-50 and gel filtration chromatography on Sephadex G-200. The purity of the protein was verified by polyacrylamide gel electrophoresis and the purified lectin agglutinated erythrocytes of rabbit and human A, B, O, AB. SPL was tested it's ability to enhance the expressions of cytokines, $IL-1\alpha$, IL-2, IL-6, $TNF\alpha$ and $IFN\gamma$ by human peripheral blood mononuclear cells (PBMC) obtained from healthy donors. mRNA analyses were performed by RT-PCR at the moment of 1, 4, 8, 24, 48, 72 and 96 h after stimulation of PBMC with purified SPL. The patterns of IL-2 band were slightly expressed from 24 h and the strongest band was appeared at 96 h. The expressions of $IL-1\alpha$ and IL-6 mRNA were strong from 1 to 8 h and those of $TNF\alpha$ were from 48 to 96 h. The mRNA encoding $IFN\gamma$ were not detected. The addition of SPL for macrophage cultures induced production of nitric oxide (NO) by cells in a dose-dependent manner. NO release was partially inhibited by $TNF\alpha$ antibodies. These results suggest that SPL has the ability to enhance cytokine expressions in PBMC and to induce the NO release by TNFa in macrophage cultures from PBMC cultures.

Osteoblast differentiation of human bone marrow stromal cells (hBMSC) according to age for bone tissue engineering (조직공학 재생골을 위한 연구에서 사람 골수 기원 간엽줄기세포의 나이에 따른 조골세포 분화능에 관한 연구)

  • Song, Gin-Ah;Ryoo, Hyun-Mo;Choi, Jin-Young
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.36 no.4
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    • pp.243-249
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    • 2010
  • Tissue engineered bone (TEB) can replace an autogenous bone graft requiring an secondary operation site as well as avoid complications like inflammation or infection from xenogenic or synthetic bone graft. Adult mesenchymal stem cells (MSC) for TEB are considered to have various ranges of differentiation capacity or multipotency by the donor site and age. This study examined the effect of age on proliferation capacity, differentiation capacity and bone morphogenetic protein-2 (BMP-2) responsiveness of human bone marrow stromal cells (hBMSC) according to the age. In addition, to evaluate the effect on enhancement for osteoblast differentiation, the hBMSC were treated with Trichostatin A (TSA) and 5-Azacitidine (5-AZC) which was HDAC inhibitors and methyltransferase inhibitors respectively affecting chromatin remodeling temporarily and reversibly. The young and old group of hBMSC obtained from the iliac crest from total 9 healthy patients, showed similar proliferation capacity. Cell surface markers such as CD34, CD45, CD90 and CD105 showed uniform expression regardless of age. However, the young group showed more prominent transdifferentiation capacity with adipogenic differentiation. The osteoblast differentiation capacity or BMP responsiveness was low and similar between young and old group. TSA and 5-AZC showed potential for enhancing the BMP effect on osteoblast differentiation by increasing the expression level of osteogenic master gene, such as DLX5, ALP. More study will be needed to determine the positive effect of the reversible function of HDAC inhibitors or methyltransferase inhibitors on enhancing the low osteoblast differentiation capacity of hBMSC.

PVDF Nanofiber Scaffold Coated with a Vitronectin Peptide Facilitates the Neural Differentiation of Human Embryonic Stem Cells

  • Jeon, Byeong-Min;Yeon, Gyu-Bum;Goo, Hui-Gwan;Lee, Kyung Eun;Kim, Dae-Sung
    • Development and Reproduction
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    • v.24 no.2
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    • pp.135-147
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    • 2020
  • Polyvinylidene fluoride (PVDF) is a stable and biocompatible material that has been broadly used in biomedical applications. Due to its piezoelectric property, the electrospun nanofiber of PVDF has been used to culture electroactive cells, such as osteocytes and cardiomyocytes. Here, taking advantage of the piezoelectric property of PVDF, we have fabricated a PVDF nanofiber scaffolds using an electrospinning technique for differentiating human embryonic stem cells (hESCs) into neural precursors (NPs). Surface coating with a peptide derived from vitronectin enables hESCs to firmly adhere onto the nanofiber scaffolds and differentiate into NPs under dual-SMAD inhibition. Our nanofiber scaffolds supported the differentiation of hESCs into SOX1-positive NPs more significantly than Matrigel. The NPs generated on the nanofiber scaffolds could give rise to neurons, astrocytes, and oligodendrocyte precursors. Furthermore, comparative transcriptome analysis revealed the variable expressions of 27 genes in the nanofiber scaffold groups, several of which are highly related to the biological processes required for neural differentiation. These results suggest that a PVDF nanofiber scaffold coated with a vitronectin peptide can serve as a highly efficient and defined culture platform for the neural differentiation of hESCs.

Selective Cytotoxicity Platinum (II) Complex Containing Carrier Ligand of cis-1,2-Diaminocyclohexane (Cis-Diaminocyclohexan을 배위자로 하는 배금(II)착체의 선택적 세포독성)

  • 노영수;정세영;정지창
    • Environmental Analysis Health and Toxicology
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    • v.13 no.3_4
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    • pp.87-94
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    • 1998
  • The use of cisplatin is limited by severe side effects such as renal toxicity. Our platinum-base drug discovery is aimed at developing drugs capable of diminishing toxicity and improving antitumor activity. We synthesized new Pt (II) complex analogue [Pt (cis-DACH)(DPPP)]. 2NO$_3$ (PC) containing cis-1,2-diaminocyclohexane as a carrier ligand and 1,3-bis(diphenylphosphino) propane as a leaving group. Furthermore, nitrate was added to improved the solubility. In this study, its structure was determined and its antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma, and in vitro cytotoxicity was determined against primary cultured rabbit kidney proximal tubular and renal cortical cells of human kidney using colorimetric MTT assay. PC demonstrated acceptable antitumor activity against SKOV-3 and NIH-OVCAR-3 human ovarian adenocarcinoma and significant activity as compared with that of cisplatin. The toxicity of PC was found quite less than that of cisplatin using MTT and $^3$H-thymidine uptake tests in rabbit proximal tubular cells and human kidney cortical cells. PC was used for human cortical tissue in 7 weeks hitoculture by the glucose-consumption tests. We determined that the new platinum drug has lower nephrotoxicity than cisplatin. Based on these results, this novel platinum (II) complex compound (PC) represent a valuable lead in the development of a new anticancer chemotherapeutic agent capable of improving antitumor activity and low nephrotoxicity.

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Increased Genotoxicity of N'-methyl-N'-nitroguanidine by Oxidative Stress (산화적 스트레스에 의한 N'-methyl-N'-nitroguanidine의 유전독성증가)

  • Kang, Jin-Seok;Jung, Ki-Kyung;Suh, Soo-Kyung;Kim, Joo-Hwan;Lee, Hwa-Ok;Jung, Hai-Kwan;Kim, Seung-Hee;Park, Sue-Nie
    • Environmental Analysis Health and Toxicology
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    • v.22 no.4
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    • pp.357-366
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    • 2007
  • To investigate the possible enhancement of genotoxicity in stress environment, we examined the of effect of genotoxic material in oxidative stress-induced condition using human tell line. Human lymphoblast cell line, TK6 was treated with hydrogen peroxide ($H_2O_2$) for induction of oxidative stress, and treated with N'-methyl-N'-nitroguanidine (MNNG), af a genetoxic material. We carried out MTS assay to set treatment doses. TK6 was treated with $H_2O_2$ at 6.75 (low dote) or $13.5\;{\mu}M$ (high dose) for 2 h, and treated with MNNG af 0.117 (low dose), 0.234 (middle dose), $0.468\;{\mu}M$ (high dose) for 2 h. As results, a treatment of MNNG induced DNA dam age as dose dependently. And TK6 treated with $H_2O_2$ at low as well as high dose followed by MNNG treatment showed higher DNA damage compared to MNNG alone treated groups. Malondialdehyde, as a marker of lipid peroxidation was increased in $H_2O_2$ and MNNG treated groups. Real-time RT-PCR analyses for expression of several antioxidative enzymes showed that catalase mRNA and glutathione peroxidase 1 mRNA expression were decreased in $H_2O_2$ and MNNG treated groups. Taken together, we conclude that genotoxicity induced by MNNG is enhanced in a condition of oxidative stress induced by $H_2O_2$ and it suggests that it should be associated with induction of lipid peroxidation and decrease of antioxidant enzymes.

Comparison of Nitric Oxide, Hydrogen Peroxide, and Cytokine Production in RAW 264.7 Cells by Bifidobacterium and Other Intestinal Bacteria

  • Om, Ae-Son;Park, So-Young;Hwang, In-Kyeong;Ji, Geun-Eog
    • Journal of Microbiology and Biotechnology
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    • v.9 no.1
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    • pp.98-105
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    • 1999
  • Intestinal bacteria comprise one-third of the contents of the large intestine in humans. Their interactions with the gastrointestinal immune system induce characteristic immunological responses which stimulate or suppress the host's defense system. RAW 264.7 murine cell line was used as a macrophage model to assess the effects of the exposure to the isolated human intestinal bacteria, Bacteroides, Bifidobacterium, Eubacterium, Streptococcus, and E. coli, on NO (nitric oxide), $H_2O_2$(hydrogen peroxide), and cytokines IL (interleukin)-6 and TNF (tumor necrosis factor)-a production. RAW 264.7 cells were cultured in the presence of heat-killed bacteria for 24 h at concentrations of 0-$50\mu$g/ml. Our results showed that Bacteroides and E. coli stimulated IL-6, TNF-$\alpha$, NO, and $H_2O_2$production at high levels even at $1\mu$g/ml, whereas Bifidobacterium, Eubacterium, and Streptococcus showed a low level of stimulation at $1\mu$g/ml, and a gradual increase as the cell concentration increased up to $50\mu$g/ml. This result suggests that gram-negative Bacteroides and E. coli are better able to stimulate macrophage than gram-positive Bifidobacterium, Streptococcus, and Eubacterium. The in vitro approaches employed here should be useful in further characterization of the effects of intestinal bacteria on gastrointestinal and systemic immunity.

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Gene Profile of Mesenchymal Stem Cell Induced by SAC or Hydrogen Peroxide (H2O2) (마늘성분 SAC 및 Hydrogen Peroxide에 의한 줄기세포의 유전자 발현 윤곽)

  • Park, Ran-Sook
    • The Korean Journal of Food And Nutrition
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    • v.25 no.4
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    • pp.863-870
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    • 2012
  • Though hydrogen peroxide ($H_2O_2$) causes a deleterious effect to cells with its reactive oxygen species resulting in cell death, S-allyl cysteine (SAC, a bioactive organosulfur compound of aged garlic extract) has been known to have a cytoprotective effect. Few reported profiles of gene expression of $H_2O_2$ and SAC treated human cord blood derived mesenchymal stem cells (MSC). This study revealed changes in the profile of twenty-one genes grouped by oxidative stress, antioxidant, cell death, anti-apoptosis and anti-aging by quantitative real time PCR. A concentration of $100{\mu}M$ of SAC or $50{\mu}M$ of $H_2O_2$ was applied to MSC which show moderate growth and apoptosis pattern. $H_2O_2$ treatment enhanced expression of eleven genes out of twenty-one genes compared with that of control group, on the contrary SAC suppressed expression of eighteen genes out of twenty-one genes except C ros oncogene. SAC decreased expression of oxidative stress genes such as SOD1, CAT and GPX. These results seemed consistent with reports which elucidated over-expression of NF-${\kappa}$B by $H_2O_2$, and suppression of it by SAC. This study will confer basic information for further experiments regarding the effects of SAC on gene levels.

Effects of Helicobacter pylori Antigen on Producton of Transforming growth factor-$\beta$1 and Nitric oxide in Human Fibroblast (사람성유아세포의 Transforming growth factor-$\beta$1과 Nitric oxide 생성에 미치는 Helicobacter pylori 항원의 효과)

  • 박무인;박선자;구자영;김광혁
    • Journal of Life Science
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    • v.11 no.2
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    • pp.181-189
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    • 2001
  • Cytokines are hormone-like proteins which mediate and regulast inflammatory and immune responses. Transforming growth factor -$\beta$1(TGF-$\beta$) plays an important role in the control of the immune response and wound healing, and in the development o various tissues and organs, Nitric oxide(NO) is major messenger molecule regulating immune function and blood vessel dilation and serving as a neurotransmitter in the brain and peripheral nervous system. Also, NO is to be a potent mutagen that cause mutation in the p53 tumor suppressor gene in early phases of human gastric carcinogenesis. The purpose of this study was to investigate the effect of Helicobacter phlori lystes, lipopolysaccharide (LPS), and Staphylococcus enterotoxin B(SEB) on production of TGF-$\beta$1 and NO by human fibroblasts. Primary cultured human fibroblasts were incubated with H. pylori lysates(Hp), LPs, SEB, Hp+LPS, Hp+SEB, Hp+LPS+SEB. Cultured supernatants that were collected at 24, 48 and 72 hr were assessed for TGF-$\beta$1 by enzyme-linked immunosorbent assay and NO production by quantification of nitrite ion. TGF-$\beta$1 production in fibroblasts exposed with Hp, LPS or SEB for 48 hrs was enhanced, but for 72 hrs inhibited. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB was lowered in comparison with single exposure of Hp in cases of 24 and 48 hrs incubation, but for 72 hrs decreased in Hp vaculoating toxin(+), increased in Hp vacuolating toxin(-). No production in fibroblasts increaed at all doses of LPS. But its production by exposure of SEB increased or decreased according to dose and incubation time. Also, NO production by Hp vacuolating toxin(+) increased at all doses, but its production by Hp vacuolating toxin(-) decreased. Its production by doble exposure such as Hp+LPS, Hp+SEB, Hp+LPS+SEB decreased in comparison with single exposure Hp Therefore, quantities pf TGB-$\beta$1 and NO released by human fibroblasts shows differences according to kinds of stimulants. Also, in care stimulated with same kinds of stimulants, its productions exhibit quantitative differences according to exposure times. These results suggest that the decreased of TGF-$\beta$1 in fibroblasts by mixed exposure with Hp producing vacuolating toxin and bacterial toxins such as LPS and SEB may effect negatively in healing of host tissue and increased of NO by infection oh H. pylori may related to the increased susceptibility for human gastric carcinogenesis.

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