• Title/Summary/Keyword: viability loss

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Delivery System of Daunorubicin by Red Blood Cells (적혈구를 이용한 Daunorubicin의 배송시스템)

  • Ham, Seong-Ho;Song, Kyung;Ko, Gun-Il;Kim, Jae-Baek;Sohn, Dong-Hwan
    • Journal of Pharmaceutical Investigation
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    • v.24 no.3
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    • pp.131-137
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    • 1994
  • Drug delivery system by the use of red blood cells was established to sustain the release of drugs in the circulatory system by the intravenous injection. The entrapment method by the preswelling technique was re-examined and evaluated for searching the new entrapping conditions without hemolysis. The addition of 4 volume of $0.6{\times}\;hank's$ balanced salt solution (HBSS) into 1 volume of 50% red blood cells suspension did not induce the hemolysis and change the hematocrit level in this experimental condition (within 15 min). Most of daunorubicin could be entrapped into red blood cells within 15 min. While the intracellular adenosine triphosphate (ATP) level followed by the entrapment was reduced to 86% of normal ATP level, the membrane fluidity and the shape factor of red blood cells were not altered. The release rate of daunorubicin from red blood cells was affected by the hemolysis under this condition. To maintain the intracellular ATP in red blood cells, the new reaction buffer was made With the addition of ATP and sodium pyruvate during the entrapment procedure because the hemolysis during the release test would reflect the loss of intracellular ATP that might result in the decrease of the viability in vivo. The addition of ATP raised the intracellular ATP level, which protect the hemolysis during the release test.

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Protective Effect of Korean Red Ginseng against 6-Hydroxydopamine-induced Nitrosative Cell Death via Fortifying Cellular Defense System (6-Hydroxydopamine으로 유도된 질소적 세포 사멸에 대한 고려홍삼 추출물의 보호효과)

  • Lee, Chan;Jang, Jung-Hee;Park, Gyu Hwan
    • YAKHAK HOEJI
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    • v.60 no.2
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    • pp.92-99
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    • 2016
  • Parkinson's disease (PD) is one of the representative neurodegenerative movement disorders with the selective loss of dopaminergic neurons in the substantia nigra. 6-Hydroxydopamine (6-OHDA) is widely used as an experimental model system to mimic PD and has been reported to cause neuronal cell death via oxidative and/or nitrosative stress. Therefore, daily intake of dietary or medicinal plants which fortifies cellular antioxidant capacity can exert neuroprotective effects in PD. In the present study, we have investigated the protective effect of Korean red ginseng (KRG) against 6-OHDA-induced nitrosative death in C6 glioma cells. Treatment of C6 cells with 6-OHDA decreased cell viability and increased expression of inducible nitric oxide synthase, production of nitric oxide as well as peroxynitrite, and formation of nitrotyrosine. 6-OHDA led to apoptotic cell death as determined by decreased Bcl-2/Bax, phosphorylation of JNK, activation of caspase-3, and cleavage of PARP. Conversely, pretreatment of C6 cells with KRG attenuated 6-ODHA-induced cytotoxicity, apoptosis, and nitrosative damages. To further elucidate the molecular mechanism of KRG protection against 6-OHDA-induced nitrosative cell death, we have focused on the cellular self-defense molecules against exogenous noxious stimuli. KRG treatment up-regulated heme oxygenase-1 (HO-1), a key antioxidant enzyme essential for cellular defense against oxidative and/or nitrosative stress via activation of Nrf2. Taken together, these findings suggest KRG may have preventive and/or therapeutic potentials for the management of PD.

The proteasome inhibition enhances apoptosis by P53 expression and the dissipation of mitochondrial transmembrane potential in TRAIL-resistant lung cancer cells (Proteasome 억제에 의한 P53의 발현과 미토콘드리아 막 전압의 소실로 TRAIL에 저항하는 폐암세포의 사멸 강화)

  • Seol, Jae-Won;Park, Sang-Youel
    • Korean Journal of Veterinary Research
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    • v.49 no.1
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    • pp.1-8
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    • 2009
  • The ubiquitin-proteasome mediated protein degradation pathway plays an important role in regulating both cell proliferation and cell death. Proteasome inhibitors are well known to induce apoptosis in various human cancer cell lines. We investigated the effect of combined treatment with proteasome inhibitor and TRAIL, and a possible mechanism of the enhancing apoptosis by the both treatment, on TRAIL-resistant non-small cell lung cancer. A549 cells were exposed to the N-Acetyl-Leu-Leu-Norleu-al (ALLN) as a proteasome inhibitor and then treated with recombinant TRAIL protein. In A549 cells under proteasome inhibition conditions by pretreatment with ALLN, TRAIL treatment significantly decreased cell viability compared to that ALLN and TRAIL alone treatment. Also, the both treatment induced cell damage through DNA fragmentation and p53 expression. In addition, the combined treatment of both markedly increased caspase-8 activation, especially the exposure for 2 h, and Bax expression and induced the dissipation of mitochondrial transmembrane potential in A549 cells. Taken together, these findings showed that proteasome inhibition by ALLN enhanced TRAIL-induced apoptosis via DNA degradation by activated P53 and mitochondrial transmembrane potential loss by caspase-8 activation and bax expression. Therefore, our results suggest that proteasome inhibitor may be used a very effectively chemotherapeutic agent for the tumor treatment, especially TRAIL-resistant tumor cell.

An Analog of the Antimicrobial Peptide CopA5 Inhibits Lipopolysaccharide-Induced Macrophage Activation

  • Yoon, I Na;Hong, Ji;Zhang, Peng;Hwang, Jae Sam;Kim, Ho
    • Journal of Microbiology and Biotechnology
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    • v.27 no.2
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    • pp.350-356
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    • 2017
  • We previously reported that the CopA3 peptide (LLCIALRKK, ${\small{D}}-form$) originally isolated from the Korean dung beetle has antimicrobial and immunosuppressive effects. However, the high cost of producing the synthetic peptide, especially the ${\small{D}}-form$, has limited the development of CopA3 for therapeutic purposes. Here, we investigated whether the CopA3 deletion derivative, CopA5, which is composed of only five amino acids (LLCIA) and has the ${\small{L}}-form$ structure, could inhibit the lipopolysaccharide (LPS)-induced activation of macrophages. Peritoneal exudate macrophages (PEM) were isolated from mice and exposed to LPS in the presence or absence of CopA5, and biomarkers of macrophage activation were measured. Our results revealed that LPS-induced nitric oxide (NO) production, tumor necrosis factor $(TNF)-{\alpha}$ secretion, and phagocytic activity of PEM were significantly inhibited by CopA5 treatment. Similar to CopA3, the structurally modified CopA5 peptide had no cell toxicity (as assessed by measurement of cell viability loss and apoptosis) in PEM. Moreover, the LPS-induced upregulation of the activating phosphorylation of signal transducer and activator of transcription 1 (STAT1) was markedly inhibited by CopA5 treatment. These results suggest that, similar to CopA3, CopA5 inhibits macrophage activation by inhibiting STAT1 phosphorylation and blocking the release of NO and $TNF-{\alpha}$. CopA5 may therefore prove therapeutically useful in the realm of immune suppression.

Antioxidant Effects of Scutellaria baicalensis Georgi Against Hydrogen Peroxide-induced DNA Damage and Apoptosis in HaCaT Human Skin Keratinocytes

  • Lee, Seung Young;Jin, Hyun Mi;Ryu, Byung-Gon;Jung, Ji Young;Kang, Hye Kyeong;Choi, Hee Won;Choi, Kyung Min;Jeong, Jin Woo
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.04a
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    • pp.68-68
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    • 2018
  • In this study, we investigated whether S. baicalensis rhizome ethanol extract (SBRE) has antioxidant capacities against oxidative stress induced cellular damage in the HaCaT keratinocytes. Our results revealed that treatment with SBRE prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased the HaCaT cell viability. SBRE also effectively attenuated $H_2O_2$ induced comet tail formation, and inhibited the $H_2O_2$ induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V positive cells. In addition, SBRE exhibited scavenging activity against intracellular ROS generation and restored the mitochondria membrane potential loss induced by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with SBRE. Furthermore, SBRE increased the levels of HO-1 associated with the induction of Nrf2. Therefore, we believed that SBRE may potentially serve as an agent for the treatment and prevention of neurodegenerative diseases caused by oxidative stress.

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Effect of Cymbidium Root Extracts on Oxidative Stress-induced Myoblasts Damage (산화스트레스에 의해 유도된 근세포 손상에서 심비디움 뿌리추출물의 효과)

  • Kim, Wan Joong;Kim, Han-Sung;Opitz, Joerg;Kabayama, Kazuya;Kim, Tack-Joong
    • Journal of Life Science
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    • v.24 no.9
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    • pp.1019-1024
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    • 2014
  • Skeletal muscle atrophy can be defined as a decrease in or a disease of the muscle tissue, or as a disorder of the nerves that control the muscle, through injury or lack of use. This condition is associated with reactive oxygen species (ROS), resulting in various muscular disorders. Exposure to ROS induces muscle atrophy through several biological factors, such as SOD1 and HSP70. We found that cymbidium root extract reduced the $H_2O_2$-induced viability loss in C2C12 myoblasts and inhibited apoptosis. In addition, we showed that the cymbidium root extract increased the expression of HSP70 and decreased the expression of SOD1 in the $H_2O_2$-induced C2C12 myoblasts. These results suggest that cymbidium root extract might have therapeutic value in reducing ROS-induced muscle atrophy.

Reflection on Kinetic Models to the Chlorine Disinfection for Drinking Water Production

  • Lee, Yoon-Jin;Nam, Sang-ho
    • Journal of Microbiology
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    • v.40 no.2
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    • pp.119-124
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    • 2002
  • Experiments for the characterization of inactivation were performed in a series of batch processes with the total coliform used as a general indicator organism based on the chlorine residuals as a disinfectant. The water samples were taken from the outlet of a settling basin in a conventional surface water treat- ment system that is provided with the raw water drawn from the mid-stream of the Han River, The inactivation of total coliform was experimentally analysed for the dose of disinfectants contact time, filtration and mixing intensity. The curves obtained from a series of batch processes were shaped with a general tailing-off and biphasic mode of inactivation, i.e. a sharp loss of bacterial viability within 15 min followed by an extended phase. In order to observe the effect of carry-over suspended solids on chlorine consumption and disinfection efficiency, the water samples were filtered, prior to inoculation with coliforms, with membranes of both 2.5$\mu$m and 11.0 $\mu$m pore size, and with a sand tilter of 1.0 mm in effective size and of 1.4 in uniformity coefficient. As far as the disinfection efficiency is concerned, there were no significant differences. The parameters estimated by the models of Chick-Wat-son, Hom and Selleck from our experimental data obtained within 120 min are: log(N/N$\_$0/)=-0.16CT with n=1, leg(N/N$\_$0/)=-0.71C$\^$0.87/ with n 1 for the Chick-Watson model, log (N/N$\_$0/)=-1.87C$\^$0.47/ T$\^$0.36/ for the Hom model, log (MHo)=-2.13log (1+CT/0.11) for the Selleck model. It is notable that among the models reviewed with regard to the experimental data obtained, the Selleck model appeared to most closely resemble the total coliform survival curve.

Protective Effect of Borneolum on ER Stress-induced Damage in C6 Glial Cells (ER Stress에 의해 유발된 C6 Glial Cells의 손상에 대한 용뇌(龍腦)의 보호효과)

  • Jeon, In-Cheol;Bang, Chang-Ho;Moon, Byung-Soon;Lee, In
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.6
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    • pp.1368-1378
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    • 2009
  • Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER response is characterized by changes in specific proteins, induction of ER chaperones and degradation of misfolded proteins. Also, the pathogenesis of several diseases like Alzheimer's disease, neuronal degenerative diseases, and diabetes reveal the role of ER stress as one of the causative mechanisms. Borneolum has been used for neuronal disease in oriental medicine. In the present study, the protective effect of borneolum on thapsigargin-induced apoptosis in rat C6 glial cells. Treatment with C6 glial cells with 5 uM thapsigargin caused the loss of cell viability, and morphological change, which was associated with the elevation of intracellular $Ca^{++}$ level, the increase in Grp78 and CHOP and cleavage of pro-caspase 12 Furthermore, thapsigargin induced Grp98, XBP1, and ATF4 protein expression in C6 glial cells. Borneolum reduced thapsigargin-induced apoptosis through ER pathways. In the ER pathway, borneolum attenuated thapsigargin-induced elevations in Grp78, CHOP, ATF4, and XBP1 as well as reductions in pro-caspase 12 levels. Also, our data showed that borneolum protected thapsigargin-induced cytotoxicity in astrocytes from rat (P3) brain. Taken together, our data suggest that borneolum is neuroprotective against thapsigargin-induced ER stress in C6 glial cells and astrocytes. Accordingly, borneolum may be therapeutically useful for the treatment of thapsigargin-induced apoptosis in central nervous system.

Effects of the Hot Water Extract Mixtures from Achyranthes bidentata Blume and Panax ginseng on Osteoclast and Osteoblast Differentiation (우슬과 인삼 열수추출 혼합물의 파골세포와 조골세포 분화 효과)

  • Kim, Jin Seong;Lee, Sang Won;Kim, Young Ock;Bang, Man Seok;Oh, Chung Hun;Kim, Chul Tae
    • Korean Journal of Medicinal Crop Science
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    • v.23 no.2
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    • pp.117-124
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    • 2015
  • Osteoporosis induces a bone mineral density loss due to imbalance of bone homeostasis that is achieved by osteoclasts (which are involved in bone resorption) and osteoblasts (which are involved in bone formation). Thus, this study was performed to evaluate the effects of hot water extract of the Achyranthes bidentata Blume (ABB) and Panax ginseng (Gin) on osteoclast and osteoblast differentiation. In this study, there was no cytotoxicity by ABB, 50 and $100{\mu}g/ml$ of Gin significantly decreased cell viability of RANKL-induced osteoclast in RAW264.7 cell (p < 0.01). But, it was $50{\mu}g/ml$ of ABB and Gin mixtures increased due to protective action of ABB. Furthermore, Gin contained groups (Gin, ABB and Gin mixtures) were inhibitory effects on osteoclast differentiation and bone resorption, and increased in osteoblast differentiation activity. Gin clearly inhibited RANKL-induced osteoclast differentiation by decreased calcitonin and TRAP (p < 0.01). Also, these extracts significantly increased calcium accumulation formation of osteoblastic differentiation reagents-induced osteoblast in MC3T3-E1 cell (p < 0.05). These results suggest that ABB and Gin mixtures may be a potential as drug for the treatment of osteoporosis.

Cell Viability and Hair Growth Effect on 3T3-L1 Cells of Ethanol Extract from Calendula officinalis L. Flower, Phellinus linteus Fruit Body and Houttuynia cordata Thunb. Whole Plant (금잔화, 상황, 어성초 에탄올 추출물의 세포독성 평가 및 3T3-L1 세포에 대한 육모 효과)

  • Jin, Seong Woo;Koh, Young Woo;Yun, Kyeong Won;Kim, Kyung Je;Je, Hae Shin;Im, Seung Bin;Kim, Kwang Sang;Kim, Min Sook;Yu, Byung Jo;Seo, Kyoung Sun
    • Korean Journal of Medicinal Crop Science
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    • v.25 no.6
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    • pp.404-410
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    • 2017
  • Background: Hair loss related syndromes are increasing due to environmental pollution and stress. Hair care products are mainly prepared by mixing chemicals and natural extracts, such as those obtained from medicinal plants. The purpose of this study was to investigate the effects of 70% ethanol extracts from the flowers of Calendula officinalis, fruit body of Phellinus linteus, and the whole plant of Houttuynia cordata on the growth of CCD-986 cells, hair follicle dermal papilla cells (HFDPC), and 3T3-L1 cells. Methods and Results: All sample extracts at all concentrations, except for that from P. linteus fruit body at $500{\mu}g/m{\ell}$, were cytotoxic to CCD-986 cells. However, none of the sample extracts were cytotoxic to HFDPC. The lipid differentiation of 3T3-L1 cells regulates hair regeneration via secretion of platelet derived growth factor. The 70% ethanol extract of H. cordata whole plant promoted hair growth. Adipogenesis rate significantly increased in a treatment concentration-dependent manner. Conclusions: These results suggest that 70% ethanol extracts of C. officinalis flower, P. linteus fruit body and H. cordata could be used for the development of hair care products.