• Title/Summary/Keyword: p53 activation

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Comparative study of antioxidant and anti-neuroinflammatory activity of leaf extracts of three different species of Bamboos in different extraction solvents containing caffeic acid, p-coumaric acid and tricin (왕대, 조릿대, 오죽의 추출 용매에 따른 항산화, 신경염증제어 활성 및 지표성분 caffeic acid, p-coumaric acid, tricin의 함량 비교)

  • Kim, Yon-Suk;Cho, Duk-Yeon;Kim, Mikyung;Choi, Dong-Kug
    • Korean Journal of Food Science and Technology
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    • v.53 no.3
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    • pp.296-303
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    • 2021
  • The antioxidant and anti-neuroinflammatory activities of water, 30, 70, and 100% ethanol extracts of leaves of three different species of bamboo (Phyllostachys nigra, P. bambusoides, and Sasa borealis) were investigated. The levels of total polyphenol and flavonoid were measured, and antioxidant activity was evaluated using various antioxidant assays (DPPH, ABTS, and FRAP). Lipopolysaccharide (LPS)-induced BV2 microglial cell activation was used to evaluate the anti-neuroinflammatory properties of the bamboo leaf extracts. Treatment with both aqueous and ethanolic extracts showed no cytotoxicity in BV-2 microglial cells. Pre-treatment of BV-2 cells with bamboo leaf extracts significantly inhibited LPS-induced excessive production of nitric oxide in a dose-dependent manner. Moreover, phytochemical analysis based on the extraction solvent showed that caffeic acid, p-coumaric acid, and tricin are the principal constituents of all three bamboo leaf extracts. Therefore, our findings suggest that bamboo leaf extract contains potent antioxidants and anti-neuroinflammatory compounds that can be used as potential therapeutic agents for the treat neuroinflammatory diseases.

Apoptotic Cell Death by Methanol Extract of Phellinus linteus-Barley Corn in Human Leukemic U937 Cells through Induction of p21 and Bax, and Activation of Caspase-3 (상황보리 추출물에 의한 p21 및 Bax 발현 증가와 caspase 활성화를 통한 U937 인체백혈병 세포의 apoptosis 유발)

  • Park, Cheol;Kim, Hyun-Joog;Chung, Kyung-Tae;Yoon, Tae-Kyung;Choi, Byung-Tae;Lee, Yong-Tae;Park, Dong-Il;Choi, Yung-Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.21 no.5
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    • pp.1226-1232
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    • 2007
  • Phellinus linteus is a well-known Oriental medicinal fungus that has various biological activities, including immunomodulatory and anti-tumor activities, the mechanisms of which are poorly understood. In the present study, we investigated the anti-proliferative activity of the methanol extract of P. linteus-Barley corn (MEPLB) in human lekemic U937 cells. It was found that exposure of U937 cells to MEPLB resulted morphological change and growth inhibition in a dose-dependent manner as measured by trypan blue count and MTT assay. Upon treatment with MEPLB, U937 cells developed many of the hallmark features of apoptosis, including condensation of chromatin and an increase in the sub-G1 population suggesting that the anti-proliferative effect of MEPLB is associated with the induction of apoptosis. The anti-proliferative and apoptotic effects of MEPLB were connected with a marked induction of the pro-apoptotic Bax and cyclin-dependent kinase (Cdk) inhibitor p21 in a p53-independent manner. Additionally, MEPLB treatment significantly induced the caspase-3 activity in U937 cells. Taken together, the present results suggest that apoptotic signals evoked by MEPLB in human leukemic U937 cells may converge caspase-3 activation through an up-regulation of Bax rather than a down-regulation of Bcl-2 or Bel-xL.

What is the Appropriate Kettlebell Mass for a Kettlebell Swing? (케틀벨 스윙 시 적당한 케틀벨의 무게는 얼마일까?)

  • Kim, Bo Kyeong;Thau, Dao Van;Yoon, Sukhoon
    • Korean Journal of Applied Biomechanics
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    • v.31 no.4
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    • pp.308-313
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    • 2021
  • Objective: The purpose of this study was to investigate the effect of different kettlebell mass (30%, 40%, and 50% of the body mass) on kinematics and kinetic variables of kettlebell swing. Method: Total of 16 healthy male who had at least 1 year of kettlebell training experience were participated in this study (age: 31.69 ± 3.46 yrd., height: 173.38 ± 4.84 cm, body mass: 74.53 ± 6.45 kg). In this study, a 13-segments whole-body model (upper trunk, lower trunk, pelvis, both side of forearm, upperarm, thigh, and shank) was used and 26 reflective markers were attached to the body to identify the segments during the movement. A 3-dimensional motion analysis with 8 infrared cameras and 4 channeled EMG was performed to find the effect of kettlebell mass on its swing. To verify the kettlebell mass effect, a one-way ANOVA with a repeated measure was used and the statistical significance level was set at 𝛼=.05. Results: Firstly, in all lower extremity joints and thoracic vertebrae, a statistically significant change in angle was shown according to an increase in kettlebell mass during kettlebell swing (p<.05). Secondly, in both the up-swing and down-swing phases, the knee joint and ankle joint ROM showed a statistically significant increase as the kettlebell mass increased (p<.05) but no statistically significant difference was found in the hip joint and thoracic spine (p>.05). Lastly, the hamstrings muscle activity was statistically significantly increased as the kettlebell mass increased during up-swing phases (p<.05). Also, as the kettlebell mass increased in P4 of the down swing phase, the gluteus maximus showed a statistically significantly increased muscle activation, whereas the rectus femoris showed a statistically significantly decreased muscle activation (p <.05). Conclusion: As a result of this study, hip extension decreased and knee extension increased at 40% and 50% of body mass, and the spine also failed to maintain neutrality and increased flexion. Also, when kettlebell swings are performed with 50% of body mass, synergistic muscle dominance appears over 30% and 40% of body mass, which is judged to have a risk of potential injury. Therefore, it is thought that for beginners who start kettlebell exercise, swing practice should be performed with 30% of body mass. In addition, even in the case of experienced seniors, as the weight increases, the potential injury risk may increase, so it is thought that caution should be exercised when performing swings with 40% and 50% of body mass. In conclusion, it is thought that increasing the weight after sufficiently training with 30% of the weight of all subjects performing kettlebell swing is a way to maximize the exercise effect as well as prevent injury.

Kinetics and Mechanism for Substitution of cis-[Co$(NH_3)_4$Cl($H_2O$)]$^{2+}$ and GlyOR (R = $C_2H_5$, $CH_3$, H) in Acidic Solution (Ⅰ) (산성용액내에서 cis-[Co$(NH_3)_4$Cl($H_2O$)]$^{2+}$ 와 GlyOR (R = $C_2H_5$, $CH_3$, H)과의 치환반응에 대한 속도론적 연구(Ⅰ))

  • Lee, Il Bong;Mun, Jin Hui;Park, Byeong Gak
    • Journal of the Korean Chemical Society
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    • v.38 no.10
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    • pp.719-725
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    • 1994
  • Kinetic studies were carried out for substitution reaction of $cis-[Co(NH_3)_4Cl(OH_2)]^{2+}(\mu$ = 0.75) with GlyOR (R = $C_2H_5$, $CH_3$, H) in pH 5 buffer solution at $20^{\circ}C$ by UV/Vis-spectrophotometry. We obtained cis-[Co$(NH_3)_4$Cl(glyOR)]$^{2+}$ as product. The reaction turns out to be first order for Co(III) and GlyOR, respectively. The rate constants are obtained as 9.21, 11.66 and 15.33 l${\cdot}\;mol^{-1}{\cdot}sec^{-1}$ for GlyOEt, GlyOMt and GlyOH, respectively. The activation parameters $E_a,\;{\Delta}H^{\neq}\;and\;{\Delta}S^{\neq}$ for GlyOEt were obtained as 65.77, 63.35 kJ/mol and -53.51(e.u.), respectively and were obtained as 70.91, 68.50 kJ/mol and -38.42(e.u.) for GlyOMt. In case of GlyOH, respectable values of 79.72, 77.30 kJ/mol and -26.59(e.u.) were obtained. On the basis of kinetic data and the observed activation parameters, we propose that the proper mechanism involves $S_N$2 step.

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Effect of Thermal Aging on the Intermetallic compound Growth kinetics in the Cu pillar bump (Cu pillar 범프 내의 금속간화합물 성장거동에 미치는 시효처리의 영향)

  • Lim, Gi-Tae;Lee, Jang-Hee;Kim, Byoung-Joon;Lee, Ki-Wook;Lee, Min-Jae;Joo, Young-Chang;Park, Young-Bae
    • Journal of the Microelectronics and Packaging Society
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    • v.14 no.4
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    • pp.15-20
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    • 2007
  • Growth kinetics of intermetallic compound (IMC) at various interface in Cu pillar bump during aging have been studied by thermal aging at 120, 150 and $165^{\circ}C$ for 300h. In result, $Cu_6Sn_5\;and\;Cu_3Sn$ were observed in the Cu pillar/SnPb interface and IMC growth followed parabolic law with increasing aging temperatures and time. Also, growth kinetics of IMC layer was faster for higher aging temperature with time. Kirkendall void formed at interface between Cu pillar and $Cu_3Sn$ as well as within the $Cu_3Sn$ layer and propagated with increasing time. $(Cu,Ni)_6Sn_5$ formed at interface between SnPb and Ni(P) after reflow and thickness change of $(Cu,Ni)_6Sn_5$ didn't observe with aging time. The apparent activation energies for growth of total $(Cu_6Sn_5+Cu_3Sn),\;Cu_6Sn_5\;and\;Cu_3Sn$ intermetallics from measurement of the IMC thickness with thermal aging temperature and time were 1.53, 1.84 and 0.81 eV, respectively.

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Organotin Compounds Act as Inhibitor of Transcriptional Activation with Human Estrogen Receptor

  • Cho, Eun-Min;Lee, Haeng-Seog;Moon, Jeong-Suk;Kim, Im-Soon;Sim, Sang-Hyo;Ohta, Akinori
    • Journal of Microbiology and Biotechnology
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    • v.22 no.3
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    • pp.378-384
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    • 2012
  • In aquatic invertebrates, particularly marine gastropods, organotin compounds induce irreversible sexual abnormality in females, which is termed imposex, at very low concentrations. Organotin compounds are agonists for nuclear receptors such as RXRs and $PPAR{\gamma}$. However, the imposex phenomenon has not been reported to act as an antagonist on estrogen receptors in other species, including vertebrates and invertebrates. In order to gain insights into the antagonistic activity of organotin compounds on estrogen receptors (ERs), we examined the inhibitive effect of these compounds on estradiol-dependent ${\beta}$-galactosidase activity using the yeast two-hybrid detection system consisting of a combination of the human estrogen receptor ($hER{\beta}$) ligand-binding domain and the co-activator steroid receptor co-activator-1 (SRC1). Tributyltin-hydroxide (TBT-OH) and triphenyltin-chlorine (TPT-Cl) exhibited an inhibitive effect on $E_2$-dependent transcriptional activity, similar to antagonistic chemicals such as 4-hydroxytamoxifen (OHT) or ICI 182,780, at a very low concentration of $10^{-14}$ M TBT or $10^{-10}$ M TPT, respectively. The yeast growth and transcriptional activity with transcriptional factor GAL4 did not exhibit any effect at the tested concentration of TBT or TPT. Moreover, the yeast two-hybrid system using the interaction between p53 and the T antigen of SV40 large did not describe any effect at the tested concentration of OHT or ICI 182,780. However, the interaction between p53 and T antigen was inhibited at a TBT or TPT concentration of $10^{-9}$ M, respectively. These results indicate that TBT and TPT act as inhibitors of ER-dependent reporter gene transcriptional activation and of the interaction between $hER{\beta}$ LBD and the co-activator SRC1 in the yeast two-hybrid system. Consequently, our data could partly explain the occurrence of organotin compound-induced imposex on the endocrine system of mammals, including humans.

Apoptotic Response of Human Oral Squamous Carcinoma Cells to Etoposide (Etoposide에 대한 사람구강편평상피암종세포의 세포자멸사 반응)

  • Kim, Gyoo-Cheon;Lee, Kyoung-Duk;Park, Jae-Hyun;Kim, Duk-Han;Park, Jeong-Kil;Park, June-Sang;Park, Bong-Soo
    • Journal of Oral Medicine and Pain
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    • v.30 no.2
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    • pp.231-238
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    • 2005
  • Anti-cancer drugs have been shown to target diverse cellular functions in mediation cell death in chemosensitive tumors. Most antineoplastic drugs used in chemotherapy of leukemias and solid tumors induce apoptosis in drug-sensitive target cells. However, the precise molecular requirements that are central for drug-induced cell death are largely unknown. Etoposide is used for the treatment of lung and testicular cancer. This study was performed to examine whether etoposide promote apoptosis in human oral squamous carcinoma cells (OSC9) as well as in lung and testicular cancer. Etoposide had a significant dose- and time-dependent inhibitory effect on the viability of OSC9 cells. TUNEL assay showed the positive reaction on condensed nuclei. Hoechst stain demonstrated that etoposide induced a change in nuclear morphology. The expression of p53 was increased at 48 hour, suggesting that the nuclear of OSC9 cell was damaged, thereby inducing apoptosis. Etoposide treatment induced caspase-3 cleavage and activation. Intact PARP protein 116-kDa and 85-kDa cleaved product were observed. The activated caspase-3 led cleavage of the PARP. These results demonstrate that etoposide-induced apoptosis in OSC9 cells is associated with caspase-3 activation.

Correction: Ethanolic Extract of Marsdenia condurango Ameliorates Benzo[a]pyrene-induced Lung Cancer of Rats -Condurango Ameliorates BaP-induced Lung Cancer in Rats-

  • Sikdar, Sourav;Mukherjee, Avinaba;Khuda-Bukhsh, Anisur Rahman
    • Journal of Pharmacopuncture
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    • v.18 no.2
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    • pp.86-87
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    • 2015
  • Objectives: Condurango is widely used in various systems of complementary and alternative medicine (CAM) against oesophageal and stomach ailments including certain types of cancer. However, until now no systematic study has been conducted to verify its efficacy and dose with proper experimental support. Therefore, we examined if ethanolic extract of Condurango could ameliorate benzo[a]pyrene (BaP)-induced lung cancer in rats in vivo to validate its use as a traditional medicine. Methods: After one month of scheduled BaP feeding (50 mg/kg body-weight), lung cancer developed after four months. BaP-intoxicated rats were then treated with Condurango (0.06 mL) twice daily starting at the end of the four months for an additional one, two and three months, respectively. Effects of Condurango were evaluated by analyzing lung histology, reactive oxygen species (ROS) and antioxidant biomarkers, DNA-fragmentation, RT-PCR (Reverese Transcriptase-Polymerase Chain Reaction), ELISA (Enzyme linked immunosorbent assay) and western blot of several apoptotic signalling markers and comparing the results against those obtained for controls. Results: A histological study revealed gradual progress in lung tissue-repair activity in Condurango-fed cancer-bearing rats, showing gradual tissue recovery after three months of drug administration. Condurango has the capacity to generate ROS, which may contribute to a reduction in anti-oxidative activity and to an induction of oxidative stress-mediated cancer-cell death. Condurango-activated pro-apoptotic genes (Bax, caspase-3, caspase-9, p53, cytochrome-c, apaf-1, ICAD and PARP) and down-regulated antiapoptotic-Bcl-2 expression were noted both at mRNA and protein levels. Studies on caspase-3 activation and PARP cleavage by western blot analysis revealed that Condurango induced apoptosis through a caspase-3-dependent pathway. Conclusions: The anticancer efficacy of an ethanolic extract of Condurango for treating BaP-induced lung cancer in rats lends support for its use in various traditional systems of medicine.

Protective Effects of EGCG on UVB-Induced Damage in Living Skin Equivalents

  • Kim, So-Young;Kim, Dong-Seok;Kwon, Sun-Bang;Park, Eun-Sang;Huh, Chang-Hun;Youn, Sang-Woong;Kim, Suk-Wha;Park, Kyoung-Chan
    • Archives of Pharmacal Research
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    • v.28 no.7
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    • pp.784-790
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    • 2005
  • In this study, we evaluate the effects of (-)-epigallocatechin-3-gallate (EGCG) on ultraviolet B(UVB)-irradiated living skin equivalents (LSEs). Histologically, UVB irradiation induced thinning of the LSE epidermis, whereas EGCG treatment led to thickening of the epidermis. Moreover, EGCG treatment protected LSEs against damage and breakdown caused by UVB exposure. Immunohistochemically, UVB-exposed LSEs expressed p53, Fas, and 8-hydroxy-deoxyguanosine (8-OHdG), all of which are associated with apoptosis. However, EGCG treatment reduced the levels of UVB-induced apoptotic markers in the LSEs. In order to determine the signaling pathways induced by UVB, Western blot analysis was performed for both c-Jun $NH_2$-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), which are associated with UVB-induced oxidative stress. UVB activated JNK in the epidermis and dermis of the LSEs, and EGCG treatment reduced the UVB-induced phosphorylation of JNK. In addition, p38 MAPK was also found to have increased in the UVB-exposed LSEs. Also, EGCG reduced levels of the phosphorylation of UVB-induced p38 MAPK. In conclusion, pretreatment with EGCG protects against UVB irradiation via the suppression of JNK and p38 MAPK activation. Our results suggest that EGCG may be useful in the prevention of UVB-induced human skin damage, and LSEs may constitute a potential substitute for animal and human studies.

Inhibitory effects of Sargassum horneri extract against endoplasmic reticulum stress in HepG2 cells (괭생이 모자반 추출물의 소포체 스트레스 억제 효능)

  • Park, Sora;Thomas, Shalom Sara;Cha, Youn-Soo;Kim, Kyung-Ah
    • Journal of Nutrition and Health
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    • v.53 no.6
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    • pp.583-595
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    • 2020
  • Purpose: This study examined the effects of Sargassum horneri extracts on palmitic acid (PA)-induced endoplasmic reticulum (ER) stress in HepG2 cells. Methods: HepG2 cells were treated with varying concentrations of S. horneri extract or PA, and the cell viability was measured by water soluble tetrazolium salts analysis. The effective induction of ER stress and the effects of S. horneri were investigated through an examination of the ER stress-related genes, such as activating transcription factor 4 (ATF4), X-box binding protein (XBP1s), C/EBP homologous protein (CHOP), and 78-kDa glucose-regulated protein (GRP78) by quantitative reverse transcription polymerase chain reaction. The expression and activation levels of unfolded protein response (UPR) associated proteins, such as inositol-requiring enzyme-1α (IRE1α), eukaryotic translation initiation factor 2 alpha submit (eIF2α), and CHOP were examined by western blot analysis. Results: The treatment with PA increased the expression of UPR associated genes significantly and induced ER stress in a 12-hour treatment. Subsequent treatment with S. horneri reduced mRNA expression of ATF4, GRP78, and XBP1s. In addition, the protein levels of phosphate (p)-IRE1α, p-elF2α, and CHOP were also reduced by a treatment with S. horneri. An analysis of sirtuin (SIRT) mRNA expression in the S. horneri and PA-treated HepG2 cells showed that S. horneri increased the levels of SIRT2, SIRT6, and SIRT7, which indicates a possible role in reducing the expression of ER stress-related genes. Conclusion: These data indicate that S. horneri can exert an inhibitory effect on ER stress caused by PA and highlight its potential as an agent for managing various ER stress-related diseases.