• 제목/요약/키워드: cascade effect

검색결과 259건 처리시간 0.027초

Relative Apoptosis-inducing Potential of Homeopathic Condurango 6C and 30C in H460 Lung Cancer Cells In vitro -Apoptosis-induction by homeopathic Condurango in H460 cells-

  • Sikdar, Sourav;Saha, Santu Kumar;Khuda-Bukhsh, Anisur Rahman
    • 대한약침학회지
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    • 제17권1호
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    • pp.59-69
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    • 2014
  • Objectives: In homeopathy, it is claimed that more homeopathically-diluted potencies render more protective/curative effects against any disease condition. Potentized forms of Condurango are used successfully to treat digestive problems, as well as esophageal and stomach cancers. However, the comparative efficacies of Condurango 6C and 30C, one diluted below and one above Avogadro's limit (lacking original drug molecule), respectively, have not been critically analyzed for their cell-killing (apoptosis) efficacy against lung cancer cells in vitro, and signalling cascades have not been studied. Hence, the present study was undertaken. Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted on H460-non-small-cell lung cancer (NSCLC) cells by using a succussed ethyl alcohol vehicle (placebo) as a control. Studies on cellular morphology, cell cycle regulation, generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential (MMP), and DNA-damage were made, and expressions of related signaling markers were studied. The observations were done in a "blinded" manner. Results: Both Condurango 6C and 30C induced apoptosis via cell cycle arrest at subG0/G1 and altered expressions of certain apoptotic markers significantly in H460 cells. The drugs induced oxidative stress through ROS elevation and MMP depolarization at 18-24 hours. These events presumably activated a caspase-3-mediated signalling cascade, as evidenced by reverse transcriptase-polymerase chain reaction (RT-PCR), western blot and immunofluorescence studies at a late phase (48 hours) in which cells were pushed towards apoptosis. Conclusion: Condurango 30C had greater apoptotic effect than Condurango 6C as claimed in the homeopathic doctrine.

소합향원(蘇合香元)이 저산소증 유발 배양 대뇌신경세포에 미치는 영향 (The Effect of Sohaphyang-won's for Delayed Neuronal Death in Hypoxia)

  • 윤경선;정승현;신길조;이원철;문일수;이지훈
    • 대한한방내과학회지
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    • 제24권1호
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    • pp.104-112
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    • 2003
  • Objectives : The purpose of this study is to evaluate the effects of Sohaphyang-won and is to study the mechanism for neuronal death protection in hypoxia with Embryonic day 20(E20) cortical cells of a guinea pig(Sprague Dawley). Methods : E20 cortical cells, used in this investigation were dissociated in Neurobasal media and grown for 14 days in vitro (DIV). On 14 DIV, Sohaphyang-won was added to the culture media for 72 hours. On 17 DIV, cells were given a hypoxic shock and further incubated in normoxia for another three days. On 20 DIV, Sohaphyang-won's effects for neuronal death protection were evaluated by LDH assay and the mechanism was studied by Bcl-2, Bak, Bax, caspase family. Results : This study indicates that Sohaphyang-won's effects for neuronal death protection in hypoxia is confirmed by LDH assay by the method of Embryonic day 20(E20) cortical neuroblast. Conclusions : Sohaphyang-won's mechanism for neuronal death protection in hypoxia restrains inflow of cytochrome C into cellularity caused by Bcl-2 increase and reduces the caspase cascade initiator caspase-10 and the effector caspase-3.

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Effects of Ginsenosides on $pp60^{c-src}$ Kinase, Intracellular Calcium and Cell Proliferation in NIH 373 Cells

  • Hong, Hee-Youn;Yoo, Gyurng-Soo;Choi, Jung-Kap
    • Journal of Ginseng Research
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    • 제22권2호
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    • pp.126-132
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    • 1998
  • In the present study, we examined effects of ginseng saponins (ginsenosides) on pp60c-src protein tyrosine kinase (PTK) activity, intracellular calcium concentration ([$Ca^{2+}$]i), and cell proliferation in NIH3T3 cells. Eight different ginsenosides [ginsenoside-Rb1 (G-$Rb_1$), -$Rb_2$, -Rc, -Rd, -Re, -Rf, -$Rg_1$, -$Rg_2$) and ginseng total saponin (GTS) were used for these experiments. All ginsenosides and GTS tested stimulated the activation of $pp60^{c-src}$ kinase, and especially G-$Rb_1$,-Rd,-$Rg_1$, and -$Rg_1$ showed a higher stimulatory effect than others at 16.7 $\mu\textrm{g}$/ml of ginsenosides with a 18 hr-incubation, increasing the activity by 4.5, 3.5, 3.5, and 3.0-fold, respectively, over that of untreated control. In addition, both G-Rd and -$Rg_2$)Rg2 increased ($Ca^{2+}$), to 202 and 334 nM, respectively, about 2-3-fold above the basal level within 7min at 250 $\mu\textrm{g}$/yml of ginsenosides. The increases of ($Ca^{2+}$), were eliminated by Pretreatment of EGTA, an extracellular calcium chelator, suggtasting that they result from an influx of calcium ion from extracellular medium rather than an efflux from intracellular calcium store, endoplasmic reticulum (ER). All ginsenosides studied enhanced cell proliferation to 1.2-1.4-fold over that of untreated control at 5~250 $\mu\textrm{g}$/ml of concentrations. Interestingly the promotion of cell proliferation by ginsenosides corresponded with the activation of c-src kinase, which is an early step in the mitogenic signaling cascade. Taken together, we suggest that some ginsenosides may lead to cellProliferation via the activation of cellular signal transduction Pathway involving $pp60^{c-src}$ kinase.

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Cancer Chemoprevention by Tea Polyphenols Through Modulating Signal Transduction Pathways

  • Lin, Jen-Kun
    • Archives of Pharmacal Research
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    • 제25권5호
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    • pp.561-571
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    • 2002
  • The action mechanisms of several chemopreventive agents derived from herbal medicine and edible plants have become attractive issues in cancer research. Tea is the most widely consumed beverage worldwide. Recently, the cancer chemopreventive actions of tea have been intensively investigated. It have been demonstrated that the active principles of tea were attributed to their tea polyphenols. Recently, tremendous progress has been made in elucidating the molecular mechanisms of cancer chemoprevention by tea and tea polyphenols. The suppression of various tumor biomarkers including growth factor receptor tyrosine kinases, cytokine receptor kinases, P13K, phosphatases, ras, raf, MAPK cascades, NㆍFB, IㆍB kinase, PKA, PKB, PKC, c-jun, c-fos, c-myc, cdks, cyclins, and related transducing proteins by tea polyphenols has been studied in our laboratory and others. The IㆍB kinase (IKK) activity in LPS-activated murine macrophages (RAW 264.7 cells) was found to be inhibited by various tea polyphenols including (-) epigallocatechin-3-gallate (EGCG), theaflavin (TF-1), theaflavin-3-gal-late (TF-2) and theaflavin-3,3'-digallate (TF-3). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other tea polyphenols. TF-3 inhibited both IKK1 and IKK2 activity and prevented the degradation of IㆍBㆍand IㆍBㆍin activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 and other tea polyphenols could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. TF-3 and other tea polyphenols blocked phosphorylation of IB from the cytosolic fraction, inhibited NFB activity and inhibited increases in inducible nitric oxide synthase levels in activated macrophage. TF-3 and other tea polyphenols also inhibited strongly the activities of xanthine oxidase, cyclooxygenase, EGF-receptor tyrosine kinase and protein kinase C. These results suggest that TF-3 and other tea polyphenols may exert their cancer chemoprevention through suppressing tumor promotion and inflammation by blocking signal transduction. The mechanisms of this inhibition may be due to the blockade of the mitogenic and differentiating signals through modulating EGFR function, MAPK cascades, NFkB activation as wll as c-myc, c-jun and c-fos expression.

Activation of PKC-$\beta$II-is Required for Vitamin E-Succinate-Induced Apoptosis of U937 Cells

  • Kim, Song-Ja;Park, Jae-Han;Lee, Sun-Ryung;Bang, Ok-Sun;Kang, Shin-Sung
    • Animal cells and systems
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    • 제4권3호
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    • pp.279-285
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    • 2000
  • Vitamin E-succinate (VES) treatment of U937 human monoblasts induced cells to undergo apoptosis. After 96 h of VES treatment at 10 $\mu$/ml, more than 80% of cells appeared apoptotic. Evidence for apoptosis by VES was based on propidium iodide staining for detection of chromatin condensational fragmentation and electrophoretic DNA ladder formation. Western blot analyses showed a transient increase in Fas and p21 protein levels up to 48 h alter the VES treatment. Protein expression and activity of CDK1 and lamin B degradation were remarkably induced by VES, following the cleavage of caspase-3 after 48 h. The VES-induced apoptosis was found to involve activation of PKC as shown by increases in membrane translocation of PKC$\beat$II and PKC activity. Pretreatment of GF109203X (PKC inhibitor) prior to VES treatment almost completely inhibited the induction of apoptosis as assessed by blockage of VES-induced caspase-3 activity and DNA fragmentation. However, GF109203X h8d no effect on the VES-induced nitric oxide synthesis, which was required for monocvtic differentiation in our previous report (J Cell Sci 111, 435, 1998). Taken together, our data suggest that induction of apoptosis by VES in U937 cells occurs through activation of PKC-$\beat$II resulting in the activation of caspase-3 cascade and is independent of nitric oxide.

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팽창률이 일정한 초음속 노즐흐름에 있어서 비평형 응축이 경사충격파에 미치는 영향 (Effects of Nonequilibrium Condensation on an Oblique Shock Wave in a Supersonic Nozzle of Constant Expansion Rate)

  • 강창수;권순범;김병지;홍종우
    • 대한기계학회논문집
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    • 제14권5호
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    • pp.1311-1319
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    • 1990
  • 본 연구에서는 작동유체로서 습증기와 거동이 유사한 습증기를 대기흡입식 간 헐 초음속 풍동을 이용하여, 팽창율이 일정한 노즐을 통하여 팽창시키는 경우에 대하 여 비평형 응축영역내 입치하는 경우에 대하여, 정체점 상태량의 변화에 기인되는 응 축 및 응축형격파가 경사형격파의 형상과 변화에 미치는 영향을 다음의 관점으로부터 연구하였다.

터빈 블레이드 말단과 슈라우드 사이의 간극변화에 따른 슈라우드에서의 열/물질전달 특성 (Heat/Mass Transfer Characteristics on Shroud with Turbine Blade Tip Clearances)

  • 이동호;최종현;조형희
    • 대한기계학회논문집B
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    • 제25권3호
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    • pp.414-421
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    • 2001
  • The present study is conducted to investigate the local heat/mass transfer characteristics on the shroud with blade tip clearances. The relative motion between blade and shroud has little influence on the overall heat transfer characteristics, except some local effects. Therefore, the relative motion between the blade and shroud is neglected in this study. A naphthalene sublimation method is employed to determine the detailed local heat/mass transfer coefficients on the surface of the shroud. The tip clearance is changed from 0.66% to 2.85% of the blade chord length. The flow enters the gap between the blade tip and shroud at the pressure side due to the pressure difference. Therefore, the heat/mass transfer characteristics on the shroud are changed significantly from those with endwall. At first, high heat/mass transfer occurs along the profile of blade at the pressure side due to the entrance effect and acceleration of the gap flow. Then, the heat/mass transfer coefficients on the shroud increase along the suction side of the blade because tip leakage vortices are generated and interact with the main flow. The results show that the heat/mass transfer characteristics are changed largely with the gap distance between the tip of turbine blade and the shroud.

가미녕신환(加味寧神丸)이 CT105로 유도된 Neuro2A 세포주에서의 항치매 효과(效果) (Study on the Inhibitory Effect of Anti-Alzheimer in CT105-induced Neuro 2A Cell Lines by Gamiyaungshinhwan Water Extract)

  • 방재선;윤현덕;신오철;신유정;박치상
    • 대한한방내과학회지
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    • 제27권3호
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    • pp.603-616
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    • 2006
  • The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

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충동터빈과 반동터빈 캐스케이드에서의 팁 간극 손실에 대한 비교 연구 (Comparative Study of Tip Clearance Loss in Impulse and Reaction Turbine Cascades)

  • 박경욱;정은환;송성진
    • 한국추진공학회:학술대회논문집
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    • 한국추진공학회 2008년도 제31회 추계학술대회논문집
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    • pp.145-148
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    • 2008
  • 현재 항우연에서 개발 중인 우주발사체 터보펌프에 사용되는 터빈은 단단 충동터빈을 적용하고 있다. 우주발사체의 안정성을 위해 팁 간극을 비교적 많이 허용하고 있는데, 효율적인 면에서는 반동터빈 보다 다소 뒤지지만, 높은 출력비를 가지는 충동터빈이 팁 간극이 커질 때 어떤 효율경향을 나타내는지 알아보는 일은 의미 있는 일이다. 실험은 아음속 조건에서 실험하였고, 팁 간극을 각각 코드기준 1%$\sim$20%일 경우 충동과 반동 각각의 경우에 대하여 하류 전압손실을 측정하였다. 측정결과 팁 간극이 10%보다 더 커지면, 충동터빈이 오히려 전압손실량이 반동터빈보다 더 작아진다. 이것은 팁 간극이 비교적 큰 조건에서 충동터빈이 반동터빈보다 효율이나 출력비 면에서 더 나은 성능을 나타냄을 의미한다.

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미역 추출물과 알긴산의 근육손실 억제 효능 (Undaria pinnatifida Extracts and Alginic Acid Attenuated Muscle Atrophy in TNF-α Induced Myoblast Cells through MAFbx Signaling Cascade)

  • 최상윤;김미나;이현희;허진영
    • 생명과학회지
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    • 제31권2호
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    • pp.137-143
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    • 2021
  • 근육 위축증은 근섬유의 손상으로 인한 근육세포의 감소에 의해 일어나며 심장질환, 당뇨, 각종 노인성 만성질환을 일으킨다고 알려져 있다. 본 연구는 미역 추출물 및 이의 성분인 알긴산의 근육세포보호, 근육감소억제 및 근육재생효과를 확인하고자 하였다. 미역 추출물 및 알긴산을 분화된 C2C12 myoblast 세포에 처리한 결과 TNF-α에 의한 근육섬유의 감소가 억제하였고murf1과 MaFbx의 발현량도 감소하였다. 또한, 마우스에 미역 추출물 및 알긴산을 10주간 급여한 결과 cardiotoxin에 의한 다리부종이 감소하였으며 근육단백질인 MyHC와 PGC-1α의 발현량이 증가 하였다. 따라서 미역 추출물 및 알긴산은 근감소 억제 및 근육재생 효과를 나타내어 기능성소재의 활용 가능성을 확인하였다.