• Title/Summary/Keyword: Resistance inhibition

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Inhibition of p90RSK activation sensitizes triple-negative breast cancer cells to cisplatin by inhibiting proliferation, migration and EMT

  • Jin, Yujin;Huynh, Diem Thi Ngoc;Kang, Keon Wook;Myung, Chang-Seon;Heo, Kyung-Sun
    • BMB Reports
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    • v.52 no.12
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    • pp.706-711
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    • 2019
  • Cisplatin (Cis-DDP) is one of the most widely used anti-cancer drugs. It is applicable to many types of cancer, including lung, bladder, and breast cancer. However, its use is now limited because of drug resistance. p90 ribosomal S6 kinase (p90RSK) is one of the downstream effectors in the extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathway and high expression of p90RSK is observed in human breast cancer tissues. Therefore, we investigated the role of p90RSK in the Cis-DDP resistance-related signaling pathway and epithelial-mesenchymal transition (EMT) in breast cancer cells. First, we discovered that MDA-MB-231 cells exhibited more Cis-DDP resistance than other breast cancer cells, including MCF-7 and BT549 cells. Cis-DDP increased p90RSK activation, whereas the inactivation of p90RSK using a small interfering RNA (siRNA) or dominant-negative kinase mutant plasmid overexpression significantly reduced Cis-DDP-induced cell proliferation and migration via the inhibition of matrix metallopeptidase (MMP)2 and MMP9 in MDA-MB-231 cells. In addition, p90RSK activation was involved in EMT via the upregulation of mRNA expression, including that of Snail, Twist, ZEB1, N-cadherin, and vimentin. We also investigated NF-κB, the upstream regulator of EMT markers, and discovered that Cis-DDP treatment led to NF-κB translocation in the nucleus as well as its promoter activity. Our results suggest that targeting p90RSK would be a good strategy to increase Cis-DDP sensitivity in triple-negative breast cancers.

Sensitivity of the Pyrenophora teres Population in Algeria to Quinone outside Inhibitors, Succinate Dehydrogenase Inhibitors and Demethylation Inhibitors

  • Lammari, Hamama-Imene;Rehfus, Alexandra;Stammler, Gerd;Benslimane, Hamida
    • The Plant Pathology Journal
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    • v.36 no.3
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    • pp.218-230
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    • 2020
  • Net blotch of barley caused by Pyrenophora teres (Died.) Drechsler, is one of the most destructive diseases on barley in Algeria. It occurs in two forms: P. teres f. teres and P. teres f. maculata. A total of 212 isolates, obtained from 58 fields sampled in several barley growing areas, were assessed for fungicide sensitivity by target gene analysis. F129L and G137R mitochondrial cytochrome b substitution associated with quinone outside inhibitors (QoIs) resistance, and succinate dehydrogenase inhibitors (SDHIs) related mutations (B-H277, C-N75S, C-G79R, C-H134R, and C-S135R), were analyzed by pyrosequencing. In vitro sensitivity of 45 isolates, towards six fungicides belonging to three chemical groups (QoI, demethylase inhibitor, and SDHI) was tested by microtiter technique. Additionally, sensitivity towards three fungicides (azoxystrobin, fluxapyroxad, and epoxiconazole) was assessed in planta under glasshouse conditions. All tested isolates were QoI-sensitive and SDHI-sensitive, no mutation that confers resistance was identified. EC50 values showed that pyraclostrobin and azoxystrobin are the most efficient fungicides in vitro, whereas fluxapyroxad displayed the best disease inhibition in planta (81% inhibition at 1/9 of the full dose). The EC50 values recorded for each form of net blotch showed no significant difference in efficiency of QoI treatments and propiconazole on each form. However, in the case of fluxapyroxad, epoxiconazole and tebuconazole treatments, analysis showed significant differences in their efficiency. To our knowledge, this study is the first investigation related to mutations associated to QoI and SDHI fungicide resistance in Algerian P. teres population, as well as it is the first evaluation of the sensitivity of P. teres population towards these six fungicides.

Inhibition Effect on Pathogenic Microbes and Antimicrobial Resistance of Probiotics (Probiotics의 병원성 미생물에 대한 억제효과와 항균제 내성)

  • Kim, Jae Soo;Yuk, Young Sam;Kim, Ga Yeon
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.3
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    • pp.294-300
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    • 2019
  • To investigate the inhibition effect on pathogenic microbes and the antimicrobial resistance of probiotics, a total of 140 probiotics were isolated from 35 kinds of Korean commercially available Kimchi. Of those, L. plantarum was identified from 53 strains (37.9%), E. faecium from 27 strains (19.3%), and L. rhamnosus from 7 strains (5.0%) using 16S rRNA gene sequencing. Sixty nine strains (49.3%) showed overall antimicrobial activity against pathogenic microbes, namely S. Typhi, S. Enteritidis, E. coli O157:H7, S. flexneri, NAG Vibrio, Listeria monocytogenesis, Y. enterocolitica, S. aureus, S. pyogenes, G. vaginalis, C. albicans, and P. acne. The proportions of L. plantarum, E. faecium, and L. rhamnosus strains to pathogenic microbes were 75.5%, 40.7%, and 28.6%, respectively. In addition, a resistance test with 18 antimicrobial agents using a disk diffusion assay revealed a resistance incidence of 98.6% for nalidixic acid, 83.6% for streptomycin, 75.7% for gentamicin 73.6% for vancomycin, 72.1% for norfloxacin, and 67.9% for ciprofloxacin. In conclusion, L. plantarum, L. sakei, and E. faecium strains with various antimicrobial activities and broad antibiotic resistance are useful for treating diarrhea in long-term inpatients and for the alternative use for treating Candida species female vaginitis.

Real-Time PCR Detection of 16S rRNA Novel Mutations Associated with Helicobacter pylori Tetracycline Resistance in Iran

  • Dadashzadeh, Kianoosh;Milani, Morteza;Rahmati, Mohammad;Akbarzadeh, Abolfazl
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.20
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    • pp.8883-8886
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    • 2014
  • Background: Tetracycline is an antibiotic widely used for the treatment of Helicobacter pylori infection, but its effectiveness is decreasing due to increasing bacterial resistance. The aim of this study was to investigate the occurrence of 16S rRNA mutations associated with resistance or reduced susceptibility to tetracycline ofHelicobacter pylori by real-time PCR (RT-PCR) assays from culture. Materials and Methods: Tetracycline susceptibility and minimal inhibition concentration (MIC) was determined by the Epsilometer test (Etest) method. A LightCycler assay developed to detect these mutations was applied to DNA extracted from culture. The 16S rRNA of these isolates was sequenced and resistance-associated mutations were identified. From 104 isolates of H. pylori examined, 11 showed resistance to tetracycline. Results: LightCycler assay was applied to DNA extracted from 11 tetracycline-susceptible and 11 tetracycline resistance H. pylori isolates. In our study the sequencing of the H. pylori wild types in 16 s rRNA gene were AGA 926-928 with MIC (0.016 to $0.5{\mu}g/ml$), while the sequencing and MIC for resistant were GGA and AGC, (0.75 to $1.5{\mu}g/ml$), respectively. Also we found a novel mutation in 2 strains with $84^{\circ}C$ as their melting temperatures and exhibition of an A939C mutation. Conclusions: We conclude that real-time PCR is an excellent method for determination of H. pylori tetracycline resistance related mutations that could be used directly on biopsy specimens.

Different Mechanisms of Induced Systemic Resistance and Systemic Acquired Resistance Against Colletotrichum orbiculare on the Leaves of Cucumber Plants

  • Jeun, Yong-Chull;Park, Kyung-Seok;Kim, Choong-Hoe
    • Mycobiology
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    • v.29 no.1
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    • pp.19-26
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    • 2001
  • Defense mechanisms against anthracnose disease caused by Colletotrichum orbiculare on the leaf surface of cucumber plants after pre-treatment with plant growth promoting rhizobacteria(PGPR), amino salicylic acid(ASA) or C. orbiculare were compared using a fluorescence microscope. Induced systemic resistance was mediated by the pre-inoculation in the root system with PGPR strain Bacillus amylolquefaciens EXTN-1 that showed direct antifungal activity to C. gloeosporioides and C. orbiculare. Also, systemic acquired resistance was triggered by the pre-treatments on the bottom leaves with amino salicylic acid or conidial suspension of C. orbiculare. The protection values on the leaves expressing SAR were higher compared to those expressing ISR. After pre-inoculation with PGPR strains no change of the plants was found in phenotype, while necrosis or hypersensitive reaction(HR) was observed on the leaves of plants pre-treated with ASA or the pathogen. After challenge inoculation, inhibition of fungal growth was observed on the leaves expressing both ISR and SAR. HR was frequently observed at the penetration sites of both resistance-expressing leaves. Appressorium formation was dramatically reduced on the leaves of plants pre-treated with ASA, whereas EXTN-1 did not suppress the appressorium formation. ASA also more strongly inhibited the conidial germination than EXTN-1. Conversely, EXTN-1 significantly increased the frequency of callose formation at the penetration sites, but ASA did not. The defense mechanisms induced by C. orbiculare were similar to those by ASA. Based on these results it is suggested that resistance mechanisms on the leaf surface was different between on the cucumber leaves expressing ISR and SAR, resulting in the different protection values.

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Sensitization to Doxorubicin by Inhibition of the Nrf2-Antioxidant System (Doxorubicin 매개 세포독성에 대한 Nrf2 경로의 역할)

  • Cho, Jeong-Min;Park, Hyun-M;Kwak, Mi-Kyoung
    • YAKHAK HOEJI
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    • v.52 no.1
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    • pp.67-72
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    • 2008
  • The use of doxorubicin, which is one of the most effective anticancer agents, is often limited by occurrence of acquired resistance in tumor cells. GSH has been shown to be involved in the development of this drug resistance. Transcription factor Nrf2 governs the expression of GSH synthesizing glutamylcysteine ligase (GCL), as well as multiple phase 2 detoxifying enzymes. Here we show that Nrf2 is one of factors determining doxorubicin sensitivity. Nrf2-deficient fibroblasts (murine embryonic fibroblasts, MEF) were more susceptible to doxorubicin mediated cell death than wild-type cells. Doxorubicin treatment elevated levels of Nrf2-regulated genes including NAD(P)H: quinone oxidoreductase (Nqo1) and GCL in wild-type fibroblasts, while no induction was observed in Nrf2-deficient cells. Doxorubicin resistance in human ovarian SK-OV cells was reversed by treatment with L-buthionine-sulfoxamine (BSO), which is depleting intracellular GSH. Finally, transfection of SK-OV cells with Nrf2 siRNA resulted in exacerbated cytotoxicity following doxorubicin treatment compared to scrambled RNA control. These results indicate that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to anticancer agents.

Capsular serogrouping and antimicrobial drug susceptibility of Pasteurella multocida isolated from Youngnam swine herds (영남지방 돼지에서 분리한 Pasteurella multocida의 협막혈청형 및 항균제 감수성 조사)

  • Cho, Gil-jae;Kim, Bong-hwan;Tak, Ryun-bin
    • Korean Journal of Veterinary Research
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    • v.29 no.4
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    • pp.487-492
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    • 1989
  • The capsular serogroupes and drug susceptibility of 111 isolates of Pasteurella multocida from pigs with atrophic rhinitis and pneumonic lesions were investigated. Of the 111 P multocida isolates, 42 were from lung lesions, 47 from nasal turbinate lesions and the remaining 22 from the nasal swabs. P multocida isolates were typed for capsular serogroupes A by hyaluronidase inhibition of capsule and D by acriflavine auto-agglutination. Most isolates(64.9%) were type A, 23.4% were type D and the remaining 11.7% were untypable. Resistance to triple sulfa(97.3%) was most frequent, followed by resistance to tiamulin(71.2%), tylosin(56.8%), streptomycin(36.9%), and neomycin(36.0%). The majority of the organisms were susceptible in order of prevalence to baytril(100%), ampicillin(98.2%), linsmycin(97.3%), colistin(97.3%), cephalothin(94.6%), gentamicin(93.7%), amikacin(92.3%), tetracycline(91.9%), trimethoprim/sulfamethoxazole(91.0%), and kanamycin(90.1%). No differences in drug resistance in relation to capsular serogroupes of P multocida and the origin of lesions were noted. A high prevalence of multiple drug resistance was observed and the most common resistant patterns were Sss, Tm, Ty(12.6%) and Sm, Sss, Tm, Ty(8.1%) patterns.

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Surface Treatment of 304L Stainless Steel for Improving The Pitting Corrosion Resistance by Inhibitor

  • Hue Nguyen Viet;Kwon Sik Chol
    • Journal of the Korean institute of surface engineering
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    • v.36 no.3
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    • pp.277-283
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    • 2003
  • Electrochemical techniques were used to study the surface treatment for improving the pitting corrosion resistance of 304L stainless steel by inhibitors in chloride medium. Sodium molybdate (in concentration range : 0.005-80 g/l) , sodium nitrite (in concentration range : 0.001-50 g/l) and their mixture were used for this study. It was found that, molybdate and nitrite were good passivators for 304L stainless steel, but molybdate was not able to prohibit the pitting ; nitrite prevented pitting corrosion of 304L stainless steel only at the concentration more than 25 g/l. The relationship between pitting potentials and concentrations of inhibitors in the logarithm expression obeyed the linear function. It was found that the surface treatment by mixture of two inhibitors enables stainless steel to have increased the corrosion resistance , the pitting corrosion of 304L stainless steel was completely prohibited by the mixtures of molybdate and nitrite in ratio min, with $m\;\geq\;3\;and\;n\;\geq\;10$. The interesting cases on electrochemical measurement of threshold of inhibitors concentration combination for optimum surface treatment were described.

Posttreatment Effects of Castor Bean Oil and Heating in Treated Jabon Wood on Boron Leaching, Dimensional Stability, and Decay Fungi Inhibition

  • PRIADI, Trisna;LESTARI, Marini Dwi;CAHYONO, Tekat Dwi
    • Journal of the Korean Wood Science and Technology
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    • v.49 no.6
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    • pp.602-615
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    • 2021
  • Red jabon wood is a potential fast-growing species for veneer, furniture, and many other wood products, but its durability is very low. The purpose of this study was to investigate the effects of castor bean oil and heating on boron leaching, dimensional stability, and resistance to decay fungi in treated jabon wood. Red jabon wood was preserved with boron solutions containing 5% boron (boric acid, borax, or borax-boric acid). Following that, castor bean oil impregnation and heating were used as posttreatments. Furthermore, all the wood samples were tested in terms of leaching, dimensional stability, and resistance against Schizophyllum commune and Fomitopsis palustris fungi. This study discovered that boron compounds, castor bean oil, and heating treatments influenced the leaching, dimensional stability, and resistance of red jabon wood to decay fungi. The double impregnation of boric acid or borax and castor bean oil, followed by heating at 160℃, significantly reduced water absorption and leaching while increasing the dimensional stability and resistance of red jabon wood against the two tested decay fungi.

Effect of ArsA, Arsenite-Specific ATPase, on Inhibition of Cell Division in Escherichia coli

  • Lee, Sung-Jae;Lee, Soo-Chan;Choi, Seung-Ho;Chung, Mi-Kyung;Rhie, Ho-Gun;Lee, Ho-Sa
    • Journal of Microbiology and Biotechnology
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    • v.11 no.5
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    • pp.825-830
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    • 2001
  • Escherichia coli, which harbored the ars operon from a plasmid pMH12 of Klebsiella oxytoca D12, showed filamentation due to the expression of ars genes in the presence of arsenite. The continued DNA replication in the absence of cell division was revealed, since nucleoids abound with DAPI appeared to be arranged in chains. In contrast to overexpression of arsA, its frame-shift mutant and knock-out mutant lost filamentation in the presence of arsenite, which suggested that ars-induced division block was dependent on expression of arsA. ArsA-induced division inhibition was not a consequence of an inhibition of DNA replication, and the inability of arsenite to induce an SOS response indicated that arsA-mediated division inhibition was dependent on the expression of the gene product encoded by the minB operon. ArsA is a peripheral membrane protein with an ATP-binding domain, which is homologous to MinD that requires ATP-dependent efflux. These results suggested that ArsA could possibly recruit MinC to the membrane and modulate cytoplasmic FtsZ to block assembly at the middle of the cell.

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