• Title/Summary/Keyword: Well-regulated

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Characteristics of Hematopoitic Growth Factor, G-CSF and Its Clinical Vision (조혈성장인자 G-CSF 특성과 임상적 비젼)

  • Park, Jeong-Hae;Park, Jung-Ae;Kang, Seok-Woo;Goo, Tae-Won;Chung, Kyung-Tae
    • Journal of Life Science
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    • v.21 no.11
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    • pp.1652-1657
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    • 2011
  • The production of blood cells is regulated by more than 20 different growth factors, called hematopoitic growth factors. These factors have been produced in prokaryotic and mammalian systems for their clinical use. Glranulocyte-Colony Stimulating Factor (G-CSF) is an important therapeutic factor for cancer patients as well as patients with congenital conditions. These patients do not have enough neutrophils and have a high risk of infection. Two groups of recombinant G-CSF have been used to specially treat cancer patients after chemotherapy because chemotherapy induces neutropenia, a major side effect of chemotherapy drugs. Here, structural and biological characteristics of G-CSF are presented. In addition, the relationship between chemotherapy and neutropenia, which is a severe reduction of neutrophils in the blood, and clinical application of G-CSF is discussed. Recombinant G-CSFs are grouped in two forms. Non-glycosylated G-CSF, filgrastim, is produced in Escherichia coli and glycosylated G-CSF, lenograstim, is produced in Chinese hamster ovary cells. Differences in structure and biological activity are compared and challenges for biosimilar production are also highlighted.

The Role of Sirtuin-2 in Tubular Forming Activity of Human Umbilical Vein Endothelial Cells (인간 제대혈 유래 혈관내피세포의 혈관 튜브 형성능에 미치는 Sirtuin-2 (SIRT2)의 역활)

  • Jung, Seok Yun;Kim, Chul Min;Kim, Da Yeon;Lee, Dong Hyung;Lee, Kyu Sup;Kwon, Sang-Mo
    • Journal of Life Science
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    • v.23 no.1
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    • pp.131-136
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    • 2013
  • Sirtuin proteins have emerged as important modulators of several age-associated diseases. These include cancer and diabetes, as well as cardiovascular and neurodegenerative diseases. Among the sirtuin family members, SIRT2 mRNA is strongly expressed. To investigate the pathophysiological significance of SIRT2 as a primary regulator of angiogenesis, we focused on the biological role of SIRT2 under hypoxic conditions, examining the gene expression pattern of sirtuin family members in human umbilical vein endothelial cells (HUVECs). SIRT2 was expressed primarily in the cytoplasm, but it was dynamically trans-localized in the nuclear by hypoxia stimuli. Interestingly, both SIRT2 and the pro-angiogenic factor, VEGF, were up- regulated by hypoxia. A Matrigel assay demonstrated that the HUVECs formed a tube-like structure under hypoxia. The SIRT2 inhibitor, AK-1, significantly decreased the tube-forming activity of the HUVECs under either normoxia or hypoxia conditions. These findings suggest that SIRT2 might be a key regulator of angiogenesis.

Anti-inflammatory effect of ethanol extract from Ecklomia cava on gram-positive bacteria(Peptidoglycan)-induced macrophages (그람-양성균(Peptidoglycan)으로 유도한 대식세포에서 감태 에탄올 추출물의 항염증 효과)

  • Kang, Ok-Hwa;Kim, Sung-Bae;Keum, Joon-Ho;Mun, Su-Hyun;Kim, Yong-Sik;An, Byung-Kwan;An, Hyeon-Jin;Kwon, Dong-Yeul
    • Herbal Formula Science
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    • v.19 no.1
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    • pp.195-205
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    • 2011
  • Objectives : Ecklonia cava is brown alga(Laminariaceae) which grows is sea, it has antioxidant, diarrhea and anticoagulant effect. In this study, the effect of ethanol extract of Ecklonia cava (EC) on peptidoglycan(PGN) -induced NO production in RAW 264.7 cells was investigated. Methods : In the present study, IL-6 production was measured using the enzyme-linked immunosorbent assay(ELISA), prostaglandin $\E_2$($\PGE_2$) production was measured using the EIA kit, and inducible NO synthase(iNOS), cyclooxygenase-2(COX-2), and mitogen-activated protein kinase(MAPK) activation, as determined by western blot analysis and reverse transcription -polymerase chain reaction(RT-PCR). Results : EC inhibited PGN-induced NO and IL-6 production. Consistent with these observations, the protein expression of iNOS and COX-2 were inhibited by EC. Moreover, EC suppressed the phosphorylation of extracellular signal-regulated kinase(ERK) 1/2 in PGN-induced RAW 264.7. Conclusions : These results suggest that EC has inhibitory effects on PGN-induced $\PGE_2$, NO, and IL-6 production, as well as the expressions of iNOS and COX-2 in the murine macrophage. These inhibitory effects occur through blockades on the MAPKs phosphorylation.

Regulation of cellular functions of p53 by ubiquitination (유비퀴틴화에 의한 세포 내 p53의 기능 조절)

  • Jung, Jin-Hyuk;Lee, Joon-Young;Lee, Sun-Mi;Choe, Tae-Boo;An, Sung-Kwan
    • KSBB Journal
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    • v.24 no.3
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    • pp.217-226
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    • 2009
  • p53 undergoes various post-translational modifications, including phosphorylation, ubiquitination, sumoylation, acetylation, methylation, and poly(ADP-ribosyl)ation. Modification of p53 widely affects to various functions of p53. Acetylation and phosphorylation of p53 have been studied for regulating its transcriptional activity which is observed in various stress condition. Otherwise, ubiquitination of p53 by Mdm2 has been well-studied as a canonical ubiquitin-mediated proteasomal degradation pathway. Moreover several investigators have recently reported that ubiquitination of p53 modulates not only its proteasome-dependent degradation by poly-ubiquitination but also its localization and transcriptional activity by mono-ubiquitination which usually does not serve the proteasome dependent degradation. Here we review recent studies on the cellular functions of p53 regulated by post-translational modifications, particularly focusing on mechanisms of ubiquitination.

Effect of Ginsenoside Rb1 on Cell Adhesion, Surface Molecule Expression and Morphological Changes (Ginsenoside Rb1의 세포간 유착, 세포표면 단백질 발현 및 세포형태변화에 미치는 효과)

  • Kim, Byung-Hun;Cho, Jae-Youl
    • Journal of Ginseng Research
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    • v.33 no.4
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    • pp.330-336
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    • 2009
  • Cell-cell adhesion managed by various adhesion molecules is known to be one of important phenomena found in numerous immunological responses or diseases such as immunostimulation, rheumatoid arthritis and allergic diseases. In this study, we examined the regulatory role of ginsenosides (G)-Rb1, reported to display immunostimulatory and anticancer effects, on cell adhesion, the up-regulation of surface adhesion molecules and morphological changes using monocytic U937 and macrophage-like RAW264.7 cells. G-Rb1 significantly up-regulated U937 cell-cell adhesion mediated by both CD29 and CD43. It also enhanced U937 cell-fibronectin adhesion, while CD29 blocking antibody P5D2 strongly suppressed it. In agreement, this compound also significantly increased the surface level of CD29 as well as CD43. Furthermore, this compound differentially modulated CD82 up-regulation and morphological changes triggered by lipopolysaccharide (LPS) and phorbol-12-myristate-13-acetate (PMA). Therefore, these results suggest that G-Rb1 may have differential modulatory function on cell adhesion events, surface molecule expression and morphological changes responsible for immune responses.

Inhibition of Adipocyte Differentiation and Adipogenesis by Supercritical Fluid Extracts and Marc from Cinnamomum verum (초임계 추출 계피오일의 3T3-L1 지방전구세포의 분화 전사인자 억제에 의한 지방대사 조절)

  • Park, Sung-Jin;Lee, In-Seon;Lee, Sam-Pin;Yu, Mi-Hee
    • Journal of Life Science
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    • v.23 no.4
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    • pp.510-517
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    • 2013
  • This study was performed to evaluate the antiobesity effect of supercritical fluid extracts (SFC) and marc methanol extracts (SFM) from Cinnamomum verum in 3T3-L1 preadipocytes. In inducing the differentiation of 3T3-L1 preadipocytes in the presence of an adipogenic cocktail, iso-butylmethylanthine (IBMX), dexamathasone, and insulin, treatment with fraction residue SFC and SFM. SFC significantly reduced the mRNA expression of the transcription factor peroxisome proliferator-activate-dreceptor-${\gamma}$ ($PPAR{\gamma}$), the sterol regulatory-element-binding protein-1c (SREBP1c), and the CCAAT enhancer-binding-protein ${\alpha}$ ($C/EBP{\alpha}$) in a concentration-dependent manner. Moreover, SFC markedly down-regulated acyl-CoA synthetase-1 (ASC1), fatty acid synthesis (FAS), fatty acid transport-1 (FATP1), fatty acid binding protein 4 (FABP4), and perilipin. These findings suggest that SFC may be a potential therapeutic adjunct for obesity by targeting the differentiation of preadipocytes, as well as their functions.

Cultural and Physiological Conditions for T-2 Toxin Production by Fusarium sp. (Fusarium 균주의 배양 조건 및 생리적 조건에 따른 T-2 toxin의 생성 조건)

  • 홍성희;양규환
    • Korean Journal of Microbiology
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    • v.36 no.2
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    • pp.91-96
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    • 2000
  • The cultural and physiological conditions for the T-2 toxin [4,15-diacetoxy-8-(3-mety1butyloxy)-12,13- epoxy-trichothec-9-en-3-01, $C_{24}H_{30}O_9$] production by Fusarium spp. were studied. Thin layer chromatography (TLC) assay and the microbiological assay uslng Rhodotomla rubra were used to quantitate tbe T- 2 toxin. Among the four strains of Fusarium spp., F tn'cinctum NRRL 3299 was best for T-2 toxin production. In solid culture, white com grit medium was best for T-2 toxm production. Temperature played a critical role in the production of T-2 toxin. T-2 toxin production was favored by long duration of low-temperature incubation. The growth and toxin production were relatively high on galactose, fructose, glucose, and sucrose media, when each was used as a sole carbon source, and relatively low on sorbitol, glycerol, and lactose media. For nitrogen sources, $NH_4^(+) and NO_3^{-}were used well as a sole nitrogen source, but $NO_2^-$ was not used. Initial pH and speed of shaker also affected the production of T-2 toxin. From temperature shifting experiment, it is clear that T-2 toxin metabolic pathway is regulated by temperature-dependent enzyme depression or enzyme induction system.

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The Comparative Law Research On The Mandatory Control About Illegal Foreign Workers in China (중국의 불법체류 외국인근로자에 대한 법적 규제에 관한 비교법적 연구)

  • Noh, Jae-Chul
    • The Journal of the Korea Contents Association
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    • v.14 no.9
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    • pp.236-246
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    • 2014
  • Most countries have been promoted the legislative policy for the legal employment, causing a social conflicts by illegal immigrants in any countries. Despite the efforts to alleviate the illegal aliens, there are not nearly enough successful cases, and encounter a social problem about illegal stay worker. China is no exception. At present, the issue of China's foreign illegal employment is expected to be a social problem in the present and the future. However, the legislative policy against immigration control law and illegal foreign employment in China is very neglectful. There is a lack of adjusting rule of law on illegal foreign workers in China, and the remedy is also insufficient. It is necessary to secure a legal right for the protection of the Rights of illegal foreign workers based on the international norms. For this purpose, the illegal foreign workers related law should be enacted, and based on this, administration should be strengthened. The trend of major countries of illegal aliens is centered around an employer hiring strictly regulated. There is a need to have a strengthen regulation on the employer rather than the foreign workers in China. To this end, employer who hire illegal foreign workers should be required to receive considerable disadvantages such as penalties and fines, prison sentences, as well as various kinds of burdens and repatriation costs. It is necessary to run the voluntary repatriation(Freiwillige $R\ddot{u}ckehr$) program of illegal immigrants, and there is a need to take action for illegal immigrants who voluntary return home within a certain period are exempt from penalty. In conclusion, China must push ahead with a direction of positive policy in related ministries rather than sit on its hands on the wrong choice or a confusion of an employer and foreign workers with a policy on illegal foreign residents in limbo.

Magnetic Parameters as Indicators of Late-Quaternary Environments on Fort Riley Kansas (암석 자기 변수들을 이용한 제4기 고환경 복원-Fort Riley 캔사스)

  • Park, kyeong
    • The Korean Journal of Quaternary Research
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    • v.11 no.1
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    • pp.57-68
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    • 1997
  • Climatic change of the late-Quaternary period has been record-ed in the loess deposits of the central Great plains and the record of such change is extractable using a number of approaches and parameters. The stratigraphy of loess deposits which have been investigated on Fort Riley exhibits the same sequence of loess units and intercalated buried soils as is found elsewhere in the re-gion but adds detail unique to the reservation Upland late-Qua-ternary composite stratigraphy preserved on the reservation con-sists of the basal Sangamon soil of the Last interglacial(c. 120-110ka), Gilman Canyon Formation(c. >40 -20ka), Peoria loess(c. 20 -10ka) Brady soil(c. 11 -10ka) Bignell loess(c. 9-\ulcornerka). and mod-ern surface soil. Application of magnetic analyses has provided proxy data sets that represent a time series of climatically regulated pedogenesis/weathering and botanical composition. magetic data have yielded an impression of the variation in climate from Sangamon time to the late Holocene through a reconstruction of the history of pedogenesis/weathering. Sangamon soil formation dominated the reservation durin the Last interglacial as indicated by magnetic parameters. During Gil-man Canyon time loess influx was usually sufficiently slow as to permit pedogenesis which appears to have been at a maximum twice during that time. Warm season grasses were important dur-ing soil formation but diminished in importance during the peri-ods of more rapid loess fall which were cooler and perhaps wet-ter. Peoria loess fall a function of the deterioration of climate during the last Glacial Maximum thinly blanketed the reservation with thickest accumulations occurring to the north-west(Bala Cemetery site)proximal to the source region. Long-term surface stability did not apparently occur within Peoria time but short-term stability may be indicaed by the presence of thin weathering zones(incipient soils) in the Peoria loess. Re-gional landscape stability prevailed during the environmental shift at the Pleistocene/Holocene transition resulting in forma-tion of the well expressed Brady soil. One or more weak soils developed in the Bignell loess as it ac-cumulated. A notable feature of the Bignell loess is the appear-ance of the Altithermal dry period: the loess experienced little weathering and was dominated by warm season grasses until the latter of the Holocene.

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Dieckol Attenuates Microglia-mediated Neuronal Cell Death via ERK, Akt and NADPH Oxidase-mediated Pathways

  • Cui, Yanji;Park, Jee-Yun;Wu, Jinji;Lee, Ji Hyung;Yang, Yoon-Sil;Kang, Moon-Seok;Jung, Sung-Cherl;Park, Joo Min;Yoo, Eun-Sook;Kim, Seong-Ho;Ahn Jo, Sangmee;Suk, Kyoungho;Eun, Su-Yong
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.3
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    • pp.219-228
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    • 2015
  • Excessive microglial activation and subsequent neuroinflammation lead to synaptic loss and dysfunction as well as neuronal cell death, which are involved in the pathogenesis and progression of several neurodegenerative diseases. Thus, the regulation of microglial activation has been evaluated as effective therapeutic strategies. Although dieckol (DEK), one of the phlorotannins isolated from marine brown alga Ecklonia cava, has been previously reported to inhibit microglial activation, the molecular mechanism is still unclear. Therefore, we investigated here molecular mechanism of DEK via extracellular signal-regulated kinase (ERK), Akt and nicotinamide adenine dinuclelotide phosphate (NADPH) oxidase-mediated pathways. In addition, the neuroprotective mechanism of DEK was investigated in microglia-mediated neurotoxicity models such as neuron-microglia co-culture and microglial conditioned media system. Our results demonstrated that treatment of anti-oxidant DEK potently suppressed phosphorylation of ERK in lipopolysaccharide (LPS, $1{\mu}g/ml$)-stimulated BV-2 microglia. In addition, DEK markedly attenuated Akt phosphorylation and increased expression of $gp91^{phox}$, which is the catalytic component of NADPH oxidase complex responsible for microglial reactive oxygen species (ROS) generation. Finally, DEK significantly attenuated neuronal cell death that is induced by treatment of microglial conditioned media containing neurotoxic secretary molecules. These neuroprotective effects of DEK were also confirmed in a neuron-microglia co-culture system using enhanced green fluorescent protein (EGFP)-transfected B35 neuroblastoma cell line. Taken together, these results suggest that DEK suppresses excessive microglial activation and microglia-mediated neuronal cell death via downregulation of ERK, Akt and NADPH oxidase-mediated pathways.