• 제목/요약/키워드: mechanism of resistance

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구조용 집성재 제조용 접착제(Phenol-Resorcinol-Formaldehyde Resin) 유전 가열을 위한 고주파 전기장 세기 추산 (Estimation of Radio Frequency Electric Field Strength for Dielectric Heating of Phenol-Resorcinol-Formaldehyde Resin Used for Manufacturing Glulam)

  • 양상윤;한연중;박용건;엄창득;김세종;김광모;박문재;여환명
    • Journal of the Korean Wood Science and Technology
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    • 제42권3호
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    • pp.339-345
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    • 2014
  • 집성재의 생산성 향상을 위한 고주파 가열 경화기술에 대해 연구하였다. 고주파가 유전체에 가해지면 내부에서 에너지 손실에 의한 발열이 발생한다. 집성재를 구성하는 라미나와 접착제는 유전체이므로 집성재에 고주파를 주사하면 내부에서 발열이 발생한다. 집성재 제조에 이용되는 대부분의 상온 경화형 접착제는 고온에서 빠른 경화가 이루어지므로 고주파 가열 기술을 이용하면 집성재 내부 접착층의 온도를 상승시킴으로써 빠른 경화를 유도할 수 있다. 본 연구에서는 낙엽송재와 phenol-resorcinol-formaldehyde (PRF) 접착제의 유전 특성을 평가하고, 집성재 내부의 접착층의 빠른 경화를 유도하는 고주파 가열 경화 기작을 이론적으로 분석하였다. 연구 결과, 온도상승인자인 PRF 접착제의 상대손실계수가 낙엽송재의 상대손실계수에 비해 높았으나, 온도상승저해인자인 밀도와 비열도 높았다. 그러나 상대손실계수의 비율이 온도상승저해인자의 비율보다 높기 때문에 고주파 가열에 의한 발열량은 접착제에서 더 높을 것으로 예상된다. 이러한 실험 결과를 이용한 이론적 접근을 바탕으로, 접착층이 목표온도까지 상승하기 위한 ISM 영역의 고주파 주파수 별 전기장의 상대 세기를 추정하였다.

Zearalenone regulates key factors of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1-nuclear factor erythroid 2-related factor 2 signaling pathway in duodenum of post-weaning gilts

  • Cheng, Qun;Jiang, Shu zhen;Huang, Li bo;Yang, Wei ren;Yang, Zai bin
    • Animal Bioscience
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    • 제34권8호
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    • pp.1403-1414
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    • 2021
  • Objective: This study explored the mechanism of the Kelch-like erythroid cell-derived protein with CNC homology-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway under conditions of zearalenone (ZEA)-induced oxidative stress in the duodenum of post-weaning gilts. Methods: Forty post-weaning gilts were randomly allocated to four groups and fed diets supplemented with 0, 0.5, 1.0, or 1.5 mg/kg ZEA. Results: The results showed significant reductions in the activity of the antioxidant enzymes total superoxide dismutase and glutathione peroxidase and increases the malondialdehyde content with increasing concentrations of dietary ZEA. Immunohistochemical analysis supported these findings by showing a significantly increased expression of Nrf2 and glutathione peroxidase 1 (GPX1) with increasing concentrations of ZEA. The relative mRNA and protein expression of Nrf2, GPX1 increased linearly (p<0.05) and quadratically (p<0.05), which was consistent with the immunohistochemical results. The relative mRNA expression of Keap1 decreased linearly (p<0.05) and quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet. The relative mRNA expression of modifier subunit of glutamate-cysteine ligase (GCLM) increased quadratically (p<0.05) in all ZEA treatment groups and the relative mRNA expression of quinone oxidoreductase 1 (NQO1) catalytic subunit of glutamate-cysteine ligase decreased linearly (p<0.05) and quadratically (p<0.05) in the ZEA1.0 group and ZEA1.5 group. The relative protein expression of Keap1 and GCLM decreased quadratically (p<0.05) in the duodenum as the ZEA concentration increased in the diet, respectively. The relative protein expression of NQO1 increased linearly (p<0.05) and quadratically (p<0.05) in all ZEA treatment groups in the duodenum. Conclusion: These findings suggest that ZEA regulates the expression of key factors of the Keap1-Nrf2 signaling pathway in the duodenum, which enables resistance to ZEA-induced oxidative stress. Further studies are needed to examine the effects of ZEA induced oxidative stress on other tissues and organs in post-weaning gilts.

해독금화산(解毒金花散)의 Methicillin-Resistant Staphylococcus aureus에 대한 항균효과 (Antibacterial Effect of Haedokgeumhwa-san against Methicillin-Resistant Staphylococcus aureus)

  • 이하일;이수경;권영미;송용선
    • 한방재활의학과학회지
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    • 제25권2호
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    • pp.1-13
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    • 2015
  • Objectives Methicillin-Resistant Staphylococcus aureus (MRSA) is a human pathogen and a major cause of hospital-acquired infections. New antibacterial agents that have not been compromised by bacterial resistance are needed to treat MRSA-related infections. In this study, we investigated the antimicrobial activity ofethanol extract of Haedokgeumhwa-san (HGH) which prescription is composed of korean medicine against MRSA. Methods The antibacterial activity of HGH extract was evaluated against MRSA strains by using the Disc diffusion method, broth microdilution method (minimal inhibitory concentration; MIC), checkerboard dilution test, and time-kill test; its mechanism of action was investigated by bacteriolysis, detergent or ATPase inhibitors. The checkerboard dilution test was used to examined synergistic effect of ampicillin, oxacillin, ciprofloxacin, vancomycin, gentamicin and norfloxacin in combination with HGH ethanol extract. A time-kill assay was performed a survival curve which was obtained by plotting viable colony counts depending on time on bacterial growth. Results The minimum inhibitory concentration (MIC) of ethanol extract (HGH) ranged from 1,000 to $2,000{\mu}g/mL$ against all the tested bacterial strains, respectively. We are able to confirm that HGH extract has potentially strong antibacterial activity. In the checkerboard dilution test, fractional inhibitory concentration index of HGH in combination with antibiotics indicated synergy or partial synergism against S. aureus. A time-kill study showed that the growth of the tested bacteria was considerably inhibited after 8 hr of treatment with the combination of HGH with selected antibiotics. For measurement of cell membrane permeability, HGH $250{\sim}1,000{\mu}g/mL$ along with concentration of Triton X-100 (TX) and Tris-(hydroxymethyl) aminomethane (Tris) were used. In the other hand, N,N-dicyclohexylcarbodimide (DCCD) and Sodium azide ($NaN_3$) was used as an inhibitor of ATPase. TX, Tris, DCCD and $NaN_3$ cooperation against S. aureus showed synergistic action. Accordingly, antimicrobial activity of HGH was affected by cell membrane and inhibitor of ATPase. Conclusions These results suggest that Haedokgeumhwa-san extract has antibacterial activity, and that HGH extract offers a potential as a natural antibiotic against MRSA.

3-Deoxysappanchalcone Inhibits Cell Growth of Gefitinib-Resistant Lung Cancer Cells by Simultaneous Targeting of EGFR and MET Kinases

  • Jin-Young Lee;Seung-On Lee;Ah-Won Kwak;Seon-Bin Chae;Seung-Sik Cho;Goo Yoon;Ki-Taek Kim;Yung Hyun Choi;Mee-Hyun Lee;Sang Hoon Joo;Jin Woo Park;Jung-Hyun Shim
    • Biomolecules & Therapeutics
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    • 제31권4호
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    • pp.446-455
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    • 2023
  • The mechanistic functions of 3-deoxysappanchalcone (3-DSC), a chalcone compound known to have many pharmacological effects on lung cancer, have not yet been elucidated. In this study, we identified the comprehensive anti-cancer mechanism of 3-DSC, which targets EGFR and MET kinase in drug-resistant lung cancer cells. 3-DSC directly targets both EGFR and MET, thereby inhibiting the growth of drug-resistant lung cancer cells. Mechanistically, 3-DSC induced cell cycle arrest by modulating cell cycle regulatory proteins, including cyclin B1, cdc2, and p27. In addition, concomitant EGFR downstream signaling proteins such as MET, AKT, and ERK were affected by 3-DSC and contributed to the inhibition of cancer cell growth. Furthermore, our results show that 3-DSC increased redox homeostasis disruption, ER stress, mitochondrial depolarization, and caspase activation in gefitinib-resistant lung cancer cells, thereby abrogating cancer cell growth. 3-DSC induced apoptotic cell death which is regulated by Mcl-1, Bax, Apaf-1, and PARP in gefitinib-resistant lung cancer cells. 3-DSC also initiated the activation of caspases, and the pan-caspase inhibitor, Z-VAD-FMK, abrogated 3-DSC induced-apoptosis in lung cancer cells. These data imply that 3-DSC mainly increased mitochondria-associated intrinsic apoptosis in lung cancer cells to reduce lung cancer cell growth. Overall, 3-DSC inhibited the growth of drug-resistant lung cancer cells by simultaneously targeting EGFR and MET, which exerted anti-cancer effects through cell cycle arrest, mitochondrial homeostasis collapse, and increased ROS generation, eventually triggering anti-cancer mechanisms. 3-DSC could potentially be used as an effective anti-cancer strategy to overcome EGFR and MET target drug-resistant lung cancer.

전립선 암세포주 DU145의 세포고사 유도를 통한 신선초 (Angelica keiskei) 메틸렌 클로라이드 추출물의 항암효과 (Antitumor Activity of Methylene Chloride Fraction from Angelica Keiskei Through Induction of Apoptosis in Human Prostate Carcinoma DU145 Cells)

  • 강윤묵;김성무;김현중;박경란;심범상;김성훈;최승훈;안규석;안광석
    • 대한암한의학회지
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    • 제15권1호
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    • pp.19-27
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    • 2010
  • The roots and leaves of Angelica keiskei (AK) have been used for the treatment of various diseases including coronary heartdisease, hypertension, and cancer in the Korean folk medicine. However, the mechanism by which methylenechloride fraction (MF) from AK exerts anti-tumorigenic activity in human prostate cancer cells has not been fully understood. In the present study, we report the MF exerted the highest cytotoxicity against prostate cancer DU145 cells compared with other fractions. Especially, MF caused the accumulation of sub-G1 DNA contents of cell cycle and increased annexin V-positive apoptotic bodies and DNA fragmentation. MF down-regulated several proliferative (Cyclin D1) and anti-apoptotic (Bcl-xl, Bcl-2, IAP-1/2, and survivin)gene products in these cells. Hence, MF induced apoptosis through the caspase-3 activation in DU145 cells. We further confirmed that caspase-3 plays an importance role in MF-induced apoptosis in DU145 cells by using caspase-3 inhibitor. Additionally, we observed that MF potentiated Dox-induced apoptosis in DU145 cells. Taken together, our data demonstrate the evidence that MF induces apoptosis depend on caspase-3 activation of and overcomes resistance to chemotherapy in human prostate cancer cells.

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Glomus 내생균근균(內生菌根菌) 접종(接種)이 수분(水分) 스트레스에 노출(露出)된 참싸리의 건조저항성(乾燥抵抗性) 및 생리적(生理的) 변화(變化)에 미치는 영향(影響) (Effects of Endomycorrhizal Glomus Inoculation on Drought Resistance and Physiological Changes of Lespedeza cyrtobotrya Seedlings Exposed to Water Stress)

  • 김효진;이경준;한심희
    • 한국환경복원기술학회지
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    • 제5권2호
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    • pp.53-62
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    • 2002
  • The objectives of this study were to understand the tolerance mechanism of woody plants to water stress and tolerance changes in relation to mycorrhizal formation. Lespedeza cyrtobotrya Miq. commonly used for erosion control in slopes were raised from seeds and transplanted to 120 plastic pots. Sixty pots received the top soil of a Fraxinus americana forest, while remaining 60 pots received the autoclaved top soil. The forest soil contained 1,200 spores per 100g of arbuscular endomycorrhizal fungus, mostly Glomus sp. The plants were raised outside with regular supply of water and mineral nutrients. Two kinds of water deficit treatment and a control were started at the middle of July : cyclic water deficit treatment with 3 cycles of sequential water stress at the point of xylem water potential of about -0.6, -0.6, and -1.7 MPa and recovery, and non-cyclic water deficit treatment with single water stress at about -1.5 MPa. The non-stressed plants received plenty of water throughout the period. In late August the plants were harvested for measurements of dry weight, N, P, carbohydrate contents, net photosynthesis and superoxide dismutase(SOD) activities. Both cyclic and non-cyclic water deficit treatments reduced dry weight by 60% and 40%, respectively, and reduced nitrogen absorption, while increased SOD activities. Water-stressed plants also showed increased carbohydrate contents in the leaves and lowered stomatal conductance. Mycorrhizal inoculation resulted in an average of 40% infection of roots and 2-3 times increase in P absorption in water-stressed as well as non-stressed plants. Mycorrhizal formation also increased shoot-root ratio. The results that SOD activities of water-stressed plants with mycorrhizal infection were significantly lower than those of non-mycorrhizal plants suggest the possibility of improvement of water-stressed condition by mycorrhizal formation. It was concluded that endomycorrhizal formation increased tolerance of Lespedeza cyrtobotrya seedlings to water stress.

Plumbagin에 의한 헬리코박터 파이로리균의 성장 및 병원성 인자 발현 억제효과 (Plumbagin Inhibits Expression of Virulence Factors and Growth of Helicobacter pylori)

  • 이민호;우현준;박민;문철;엄용빈;김사현;김종배
    • 한국미생물·생명공학회지
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    • 제44권2호
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    • pp.218-226
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    • 2016
  • 헬리코박터 파이로리균은 인간의 위에 감염하여 위염, 위궤양, 심지어 위암을 포함한 다양한 위장 질환의 발생시키는 원인으로 알려져 있다. 이러한 헬리코박터균의 제균을 위해 항생제 치료법이 이용되고 있지만 이러한 항생제들에 대한 헬리코박터균의 내성 증가가 전세계적인 문제로 대두되고 있다. 보고들에 따르면, 천연물질인 plumbagin은 항균 및 항암 효과를 가지고 있는 것으로 알려져있다. 따라서 본 연구에서는 헬리코박터 표준균주(ATCC 49503)에 plumbagin을 처리한 후 항균효과를 확인하였으며, 세균의 성장 및 병원성과 관련된 다양한 물질들의 발현에 미치는 영향을 immunoblotting 및 RT-PCR 방법을 이용하여 조사하였다. plumbagin의 헬리코박터균 억제효과를 확인하기 위해 한천희석법과 액체배지희석법을 이용해 최소억제농도를 도출하였다. 위와 같은 Plumbagin에 의한 헬리코박터균의 억제기전을 이해하기 위하여 헬리코박터균에 plumbagin을 처리한 후 세균 의 증식과 관련된 물질들을 대상으로 RT-PCR을 수행한 결과 RNA polymerase subunit α (rpoA)의 mRNA 발현이 감소한 것을 확인하였다. 또한, 헬리코박터균에 plumbagin을 처리한 후 주요 병원성인자들의 발현을 조사한 결과 CagA와 VacA 독소들의 mRNA 및 단백질양이 감소한 것을 확인하였으며, 유레아제(ureA)와 부착단백(alpA)의 발현도 plumbagin 처리에 의해 감소한 것을확인하였다. 위와 같은 결과들을 토대로, plumbagin은 본 연구에서 밝힌 기전들을 통해 헬리코박터균의 성장, 감염 및 발병을 억제하는 것으로 사료된다.

Ceriporia lacerata 균사체 배양물이 3T3-L1 세포에서 인슐린 신호 전달에 미치는 영향 (Effect of Submerged Culture of Ceriporia lacerata Mycelium on Insulin Signaling Pathway in 3T3-L1 Cell)

  • 신은지;김지은;;박용만;윤성균;장병철;이삼빈;김병천
    • 생명과학회지
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    • 제26권3호
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    • pp.325-330
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    • 2016
  • 본 연구에서는 선행 연구에서 항당뇨 효능이 확인된 Ceriporia lacerata 균사체 배양물 건조물(CL01)을 3T3-L1 세포에 인슐린과 병용 혹은 단독 처리하여 CL01이 세포 단계에서 인슐린 신호 전달에 미치는 영향을 분석하였다. 분화된 3T3-L1 세포에서 포도당 흡수 정도를 측정한 결과, 인슐린과 CL01을 병용 처리한 군에서 농도 의존적으로 유의적으로 포도당 흡수 정도가 증가하였고, 인슐린 부재 상태에서 CL01을 처리하였을 때는 포도당 흡수 작용이 거의 일어나지 않았음을 확인하였다. 또한 분화된 세포에서 인슐린 신호 전달 관련 단백질 및 mRNA 발현을 측정한 결과, IRβ, Akt, PI3K, AMPK 단백질의 인산화가 진행되었고, GLUT4 mRNA 발현이 증가하였음을 알 수 있었다. 이들 결과를 통해 CL01이 당 대사 및 인슐린 신호 전달에 관여하는 유관 단백질 및 유전자 발현에 영향을 미치며 이에 따라 세포 내로 포도당 흡수를 증가시키는 것을 확인하였다.

Proteasome Inhibitor-Induced IκB/NF-κB Activation is Mediated by Nrf2-Dependent Light Chain 3B Induction in Lung Cancer Cells

  • Lee, Kyoung-Hee;Lee, Jungsil;Woo, Jisu;Lee, Chang-Hoon;Yoo, Chul-Gyu
    • Molecules and Cells
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    • 제41권12호
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    • pp.1008-1015
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    • 2018
  • $I{\kappa}B$, a cytoplasmic inhibitor of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces $I{\kappa}B{\alpha}$ degradation via an alternative pathway, lysosome, which results in $NF-{\kappa}B$ activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced $I{\kappa}B{\alpha}$ degradation is necessary. Here, we demonstrated that PI up-regulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for $I{\kappa}B{\alpha}$ degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced $I{\kappa}B{\alpha}$ degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent $I{\kappa}B{\alpha}$ degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the $I{\kappa}B$/$NF-{\kappa}B$ pathway, which attenuates the anti-tumor efficacy of PIs.

$pep^{27}$ and lytA in Vancomycin-Tolerant Pneumococci

  • Olivares, Alma;Trejo, Jose Olivares;Arellano-Galindo, Jose;Zuniga, Gerardo;Escalona, Gerardo;Vigueras, Juan Carlos;Marin, Paula;Xicohtencatl, Juan;Valencia, Pedro;Velazquez-Guadarrama, Norma
    • Journal of Microbiology and Biotechnology
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    • 제21권12호
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    • pp.1345-1351
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    • 2011
  • Vancomycin therapy failure due to the emergence of tolerance in pneumococci is increasing. The molecular mechanism of tolerance is not clear, but lytA and $pep^{27}$ are known to be involved. Our aim was to evaluate the expression of both genes in vancomycin-tolerant Streptococcus pneumoniae (VTSP) strains. Eleven VTSP strains from a total of 309 clinical isolates of S. pneumoniae from 1997 to 2006 were classified according to the criteria of Liu and Tomasz. All VTSP strains were evaluated for susceptibility according to CLSI criteria, serotype by the Quellung test, and clonality by PFGE. The expressions of lytA and $pep^{27}$ were analyzed in different growth phases by RT-PCR with and without vancomycin. Eighty-two percent of VTSP strains showed resistance to penicillin, and 100% were sensitive to vancomycin and cefotaxime. The most frequent serotypes of VTSP strains were 23F (4/11) and 6B (3/11). Clonal relationship was observed in only two strains. No significant changes were observed in $pep^{27}$ expression in the three phases of growth in VTSP strains with and without vancomycin. Interestingly, $pep^{27}$ expression in the stationary phase in the non-tolerant reference strain R6 was significantly higher. However, no significant differences in lytA expression were observed between VTSP and R6 strains during the phases of growth analyzed. The absence of changes in $pep^{27}$ expression in VTSP strains in the stationary phase may be related to their ability to tolerate high antibiotic concentrations, and thus, they survive and remain in the host under the antibiotic selective pressure reflected in therapeutic failure.