• Title/Summary/Keyword: Resistance Mechanism

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Metformin alleviates chronic obstructive pulmonary disease and cigarette smoke extract-induced glucocorticoid resistance by activating the nuclear factor E2-related factor 2/heme oxygenase-1 signaling pathway

  • Tao, Fulin;Zhou, Yuanyuan;Wang, Mengwen;Wang, Chongyang;Zhu, Wentao;Han, Zhili;Sun, Nianxia;Wang, Dianlei
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.2
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    • pp.95-111
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    • 2022
  • Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

Phytophthora palmivora RPA1, a Homolog of Phytophthora infestans RPA190, is Irrelevant to Metalaxyl Resistance in Phytophthora palmivora Causing Root and Stem Rot of Durian in Thailand

  • Kamonwan Sichai;Patcharin Nianwichai;Nutsuda Taraput;Veeranee Tongsri;Pattavipha Songkumarn
    • The Korean Journal of Mycology
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    • v.52 no.2
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    • pp.73-96
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    • 2024
  • Root and stem rot caused by Phytophthora palmivora is one of the most serious diseases affecting durian production in Thailand where metalaxyl, an effective fungicide against oomycetes, has been used extensively for a long period to control this disease. Although field isolates of P. palmivora resistant to metalaxyl exist in Thailand, a molecular basis for P. palmivora has not yet been elucidated regarding metalaxyl resistance. The current study tested whether P. palmivora RPA1 (the DNA-directed RNA polymerase I subunit gene), a homolog gene of RPA190 associated with metalaxyl resistance in some isolates of Phytophthora infestans, had a role in the resistance mechanism toward metalaxyl. In total, 40 durian-derived isolates of P. palmivora were assessed for metalaxyl sensitivity using a mycelial growth inhibition assay. The effective concentrations for 50% mycelial growth inhibition values for all isolates tested were in the range 0.01-872.88 mg/L. The isolates were clustered into three groups: sensitive (n=23), moderately resistant (n=11), and resistant (n=6) groups. No polymorphism was revealed based on multiple alignment analysis of the amino acid sequences translated from the corresponding DNA sequences in the region of RPA1 of the metalaxyl-sensitive (n=5), moderately resistant (n=2), and resistant isolates (n=6). Furthermore, investigation of the RPA1 expression among these representative isolates (n=3, each group) indicated that RPA1 expression may not be involved in the regulation of P. palmivora resistance to metalaxyl. Based on this line of evidence, there was no detected relationship regarding metalaxyl resistance and P. palmivora RPA1.

Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

  • Mukherjee, Avinaba;Sadhukhan, Gobinda Chandra
    • Journal of Pharmacopuncture
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    • v.19 no.1
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    • pp.7-15
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    • 2016
  • Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the 'apicoplast', which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle's function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug resistance.

Microstructure and Wear Behavior of $SiC_p-reinforced$ Aluminum Matrix Composites Fabricated by Spray Casting Process (분사주조한 $SiC_p$ 입자강화 알루미늄 복합재료의 미세조직과 마멸특성)

  • Park, Chong-Sung;Kim, Myung-Ho
    • Journal of Korea Foundry Society
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    • v.15 no.6
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    • pp.574-587
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    • 1995
  • The $SiC_p-reinforced$ preforms fabricated by spray casting process were hot-extruded and subsequently T6-treated, and the morphology of the silicon phase and the grain size for these preforms and extruded samples were examined by Image Analyzer. Experimental observation revealed that with increase in volume percent of SiC particles, the grain size and silicon phase of the $Al-Si/SiC_p$ composites become finer, the shape of Si phase is changed from blocky to granular type, and aspect ratio of Si phase tend to become unity. Wear-tests with various sliding velocities, show that the wear resistance of spray cast specimen is increased remarkably compare to the permanent mold cast specimen at the sliding velocity range of $1.98{\sim}2.38m/sec$.. Microstructural observations for the worn surfaces of specimens revealed that wear resistance of Al-Si alloys at certain sliding velocities could be improved not only by the fine grain size of aluminum matrix but also the fine size and granular shape of silicon phases. The wear resistance of $SiC_p$ reinforced aluminum composites was found to be sensitive to the volume percentage of the reinforcing particles. The worn surfaces with various sliding velocities, show that change in wear mechanism seems to occur at the sliding velocity of near 2m/sec for all samples, and such a change in mechanism is delayed with increase in $SiC_p$ volume fraction.

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Reinforcing Effect and Behaviors of Root-Pile in Heavy-Duty Direct Shear Test (대형직접전단시험에 의한 뿌리말뚝의 거동 및 보강효과)

  • Han, Jung-Geun;Jang, Sin-Nam
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.5 no.3
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    • pp.23-30
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    • 2002
  • In recently, using of steel reinforcements by reinforcing materials of the reinforced earth, micro-pile and root-pile etc,. is wide-spreading in the stabilizing control of cutting and embankment slopes, but the failure mechanism of reinforced earth as well as the effect of insert angles or types of reinforcement and others are not defined clearly. In this study, therefore heavy-duty direct shear tests were exercised on the reinforced soil and the non-reinforced soil, which was executed for research on the interaction of soil-reinforcement and theirs behavior. The hardness and softness and the standard sands were used for modeling of reinforced soil, the material constants for the computer simulation were estimated from the results of CD-Test. The effects of reinforcing and of friction increasing on the softness, area ratio of reinforcements is equal, were the better than them of the hardness, as well the reinforcing effects of shear strength without regard to the area ratio is much the same at $10^{\circ}$, insert angle of reinforced bar, differ from them of the existing study. Then, the results of numerical analysis showed that the behavior of reinforcements displayed bending resistance and shear resistance at $15^{\circ}$ and $30^{\circ}$, respectively. Also, the state of strain transfer was observed and the behavior of resistance mechanism on reinforcements presented almost the same them of landslides stabilizing pile.

Evaluation of Fretting Wear Damage of Electronic Connectors for the Automotive (자동차용 전장 커넥트 프레팅 마모 손상 평가)

  • Jang, SeungGyu;Kim, Deokhyeon;Kim, Jinsang;Choi, SungJong;Cho, HyunDeog
    • Transactions of the Korean Society of Automotive Engineers
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    • v.22 no.3
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    • pp.33-41
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    • 2014
  • Fretting is a kind of surface degradation mechanism observed in mechanical components and structures. When two pieces of materials, pressed together by an external static load, are subjected to a transverse cyclic loading or various vibrations, so that one contacting face is relatively displaced cyclically parallel to the other face, wear of the mating surfaces occurs. These fretting damages may be observed in electrical connectors for automotive components, where there are special environments and various vibration conditions. This study aims to evaluate the usefulness of fretting test equipment that was developed for reliability test of electrical connector. Fretting tests were carried out using tin coated connectors and friction force, contact resistance, contact area and roughness of contact region were investigated. The following results that will be helpful to understand the fretting wear mechanism, increase process the contact resistance and contact area were obtained. (1) In the same frequency and slip amplitude, the friction force, roughness and contact area increased rapidly until about $10^3$ cycles, after which it was slightly changed. (2) In the various frequency and slip amplitude, the contact area increased with slip amplitude and cyclic numbers, but it did not depend on cyclic frequency. (3) The surface roughness of contact region did not depend on the cyclic frequency. From these results, the applicability of the fretting wear test equipment and reliability of connector were discussed.

Mechanism of resistance acquisition and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children

  • Yang, Hyeon-Jong;Song, Dae Jin;Shim, Jung Yeon
    • Clinical and Experimental Pediatrics
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    • v.60 no.6
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    • pp.167-174
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    • 2017
  • Mycoplasma pneumoniae pneumonia (MPP) is one of the most common forms of community-acquired pneumonia in children and adolescents. Outbreaks of MPP occur in 3- to 7-year cycles worldwide; recent epidemics in Korea occurred in 2006-2007, 2011, and 2015-2016. Although MPP is known to be a mild, self-limiting disease with a good response to macrolides, it can also progress into a severe and fulminant disease. Notably, since 2000, the prevalence of macrolide-resistant MPP has rapidly increased, especially in Asian countries, recently reaching up to 80%-90%. Macrolide-resistant Mycoplasma pneumoniae (MRMP) harbors a point mutation in domain V of 23S rRNA with substitutions mainly detected at positions 2063 and 2064 of the sequence. The excessive use of macrolides may contribute to these mutations. MRMP can lead to clinically refractory pneumonia, showing no clinical or radiological response to macrolides, and can progress to severe and complicated pneumonia. Refractory MPP is characterized by an excessive immune response against the pathogen as well as direct injury caused by an increasing bacterial load. A change of antibiotics is recommended to reduce the bacterial load. Tetracyclines or quinolones can be alternatives for treating MRMP. Otherwise, corticosteroid or intravenous immunoglobulin can be added to the treatment regimen as immunomodulators to downregulate an excessive host immune reaction and alleviate immune-mediated pulmonary injury. However, the exact starting time point, dose, or duration of immunomodulators has not been established. This review focuses on the mechanism of resistance acquisition and treatment options for MRMP pneumonia.

Effects of Alloying Elements on the High Pressure Wear Characteristics of Ductile Cast Iron II - Silicon and Molybdenum (구상흑연주철의 고압하 마멸특성에 미치는 합금원소의 영향 II-Si, Mo)

  • Bang, Woong-Ho;Kang, Choon-Sik;Park, Jae-Hyun;Kweon, Young-Gak
    • Journal of Korea Foundry Society
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    • v.20 no.4
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    • pp.240-246
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    • 2000
  • Surface layer properties such as composition, phase, hardness, and oxide layer condition are very important if the main failure mechanism of metals is wear. Generally, stable and dense oxide layers are known to decrease the wear rate of metals by prohibition of metallic junction occurred between bare metals. Addition of Si above 4 wt% to DCI(Ductile Cast Iron) is reported to enhance the significant oxidation resistance by forming the silicon-rich surface layer which inhibits further oxidation. And addition of up to 2 wt% Mo to high Si ductile iron produces significant increases in high temperature tensile strength, creep strength, thermal fatigue resistance and oxidation resistance. High pressure wear characteristics of unalloyed DCI(Ductile cast Iron), 4.46 wt% Si ductile iron, 4.3 wt% Si-0.52 wt% Mo ductile iron were investigated through unlubricated pin-on-disc wear test. Wear test was carried out at speed of 23m/min, under pressure of 3 MPa and 3.3 MPa. Wear surfaces of each specimen were observed by SEM to determine the wear mechanism under high pressure wear condition. Addition of Si 4.46 wt% severely deteriorated wear property of ductile iron compared to unalloyed DCI. But combined addition of Si 4.3 wt%andMo0.52wt%decreasedthefrictioncoefficient(${\mu}$)ofductileironsandremarkablydelayedthemild-severeweartransition.

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Experimental Study of Strength and Ductility on Masonry Wall Frame and Shear Wall Frame Subjected to Cyclic Lateral Loading (반복-횡력을 받는 조적벽 골조와 전단벽 골조의 내력 및 연성에 관한 실험적 연구)

  • Lee, Ho;Byeon, Sang-Min;Jung, Hwan-Mok;Lee, Taick-Oun
    • Journal of Korean Association for Spatial Structures
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    • v.13 no.2
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    • pp.83-91
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    • 2013
  • The core aim of this dissertation is to empirically scrutinize a strength characteristic of beam-column frame subjected to the cyclic lateral load, a beam-column frame of un-reinforced masonry wall, and a shear wall frame. First and foremost, I embark upon making three prototypes vis-$\grave{a}$-vis this research. By conducting this process, I touch on an analysis of cyclic behavior and a damage characteristic of the beam-column frame, the beam-column frame of un-reinforced masonry wall, and the shear wall frame. What is more, through the previous procedure, the next part delves into the exact stress transfer path and the destructive mechanism to examine how much and how strong the beam-column frame of un-reinforced Masonry Wall does have a resistance capacity against earthquake in all the architecture constructed by the above-mentioned frame, as well as school buildings. In addition to the three prototypes, two more experimental models, a beam-column frame and shear wall frame, are used to compare with the beam-column frame of un-reinforced masonry wall. Lastly, the dissertation will suggest some solutions to improve the resistance capacity against earthquake regarding all constructions built with non bearing wall following having examining precisely all the analysis with regard to not only behavior properties and the damage mechanism of the beam-column frame and the beam-column frame of un-reinforced Masonry Wall but also the resistance capacity against earthquake of non bearing wall and school buildings.

Formation Mechanisms of Sn Oxide Films on Probe Pins Contacted with Pb-Free Solder Bumps (무연솔더 범프 접촉 탐침 핀의 Sn 산화막 형성 기제)

  • Bae, Kyoo-Sik
    • Korean Journal of Materials Research
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    • v.22 no.10
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    • pp.545-551
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    • 2012
  • In semiconductor manufacturing, the circuit integrity of packaged BGA devices is tested by measuring electrical resistance using test sockets. Test sockets have been reported to often fail earlier than the expected life-time due to high contact resistance. This has been attributed to the formation of Sn oxide films on the Au coating layer of the probe pins loaded on the socket. Similar to contact failure, and known as "fretting", this process widely occurs between two conductive surfaces due to the continual rupture and accumulation of oxide films. However, the failure mechanism at the probe pin differs from fretting. In this study, the microstructural processes and formation mechanisms of Sn oxide films developed on the probe pin surface were investigated. Failure analysis was conducted mainly by FIB-FESEM observations, along with EDX, AES, and XRD analyses. Soft and fresh Sn was found to be transferred repeatedly from the solder bump to the Au surface of the probe pins; it was then instantly oxidized to SnO. The $SnO_2$ phase is a more stable natural oxide, but SnO has been proved to grow on Sn thin film at low temperature (< $150^{\circ}C$). Further oxidation to $SnO_2$ is thought to be limited to 30%. The SnO film grew layer by layer up to 571 nm after testing of 50,500 cycles (1 nm/100 cycle). This resulted in the increase of contact resistance and thus of signal delay between the probe pin and the solder bump.