• Title/Summary/Keyword: Stress Mechanism

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Endoplasmic Reticulum Stress Activates Hepatic Macrophages through PERK-hnRNPA1 Signaling

  • Ari Kwon;Yun Seok Kim;Jiyoon Kim;Ja Hyun Koo
    • Biomolecules & Therapeutics
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    • v.32 no.3
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    • pp.341-348
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    • 2024
  • Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.

Human Embryonic Stem Cells Experience a Typical Apoptotic Process upon Oxidative Stress

  • Lee, Gun-Soup;Lee, Young-Jae;Kim, Eun-Young;Park, Se-Pill;Lim, Jin-Ho
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.97-97
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    • 2003
  • Embryonic stem (ES) cells, derived from preimplantation embryos, are able to differentiate into various types of cells consisting the whole body, or pluripotency. In addition to the plasticity, ES cells are expected to be different from terminally differentiated cells in very many ways, such as patterns of gene expressions, ability and response of the cells in confronting environmental stimulations, metabolism, and growth rate. As a model system to differentiate these two types of cells, human ES (hES, MB03) cells and terminally differentiated cells (HeLa), we examined the ability of these two types of cells in confronting a severe oxidative insult, that is $H_2 O_2$. Ratio of dying cells as determined by the relative amount of dye neutral red entrapped within the cells after the exposures. Cell death rates were not significantly different when either MB03 or HeLa were exposed up to 0.4 mM $H_2 O_2$. However, relative amount of dye entrapped within the cells sharply decreased down to 0.12% in HeLa cells when the cells were exposed to 0.8 mM $H_2 O_2$, while it was approximately 54% in MB03. Pretreatment of cells with BSO (GSH chelator) and measurement of GSH content results suggest that cellular GSH is the major defensive mechanism of hES cells. Induction of apoptosis in hES cell was confirmed by DNA laddering, induction of Bax, and chromatin condensation. In summary, hES cells 1) are extremely resistant to oxidative stress, 2) utilize GSH as a major defensive mechanism. and 3) experience apoptosis upon exposure to oxidative stress.

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A Study on Physically small Surface Fatigue Crack Growth Behavior in 7075-T651 Aluminum Alloy (7075-T651 AI 합금에 있어서 물리적 미소 표면 피로균열 성장거동에 관한 연구)

  • Sin, Yong-Seung;Seo, Seong-Won;Yu, Heon-Il
    • Journal of the Korean Society for Precision Engineering
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    • v.9 no.1
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    • pp.106-117
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    • 1992
  • In this study, the propagation behaviour and the closure phenomena of physically small surface cracks were investigated by the techinque of the Kikukawa-unloading elastic compliance method using a back face strain gage. The surface cracks initiated and propagated from notched specimens under constant amplitude bending load. The crack shape (aspect ratio) with approximately semi-circular at the early stage was changed to semi-elliptical as the cracks grew larger. The crack depth (a) could be expressed uniquenly by the crack length (c). The dependence of the crack propagation rate on the stress ratio R was strongly related in the lower ${\Delta}K$ range. The deceleration of the surface crack propagation rate was prominent in lower R during the crack length was small. When the propagation rate was rearranged with the effective stress intensity factor range ${\Delta}$K_{eff} the dependence of the crack propagation rate on the stress ratio R was found to be diminshed. These were caused by the crack closure phenomena that was most prominent at the lower propagation rate. The mechanism of crack closure phenomena was dominated by the plasticity-induced mechanism.

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Sonchus asper extract inhibits LPS-induced oxidative stress and pro-inflammatory cytokine production in RAW264.7 macrophages

  • Wang, Lan;Xu, Ming Lu;Liu, Jie;Wang, You;Hu, Jian He;Wang, Myeong-Hyeon
    • Nutrition Research and Practice
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    • v.9 no.6
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    • pp.579-585
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    • 2015
  • BACKGROUND/OBJECTIVES: Sonchus asper is used extensively as an herbal anti-inflammatory for treatment of bronchitis, asthma, wounds, burns, and cough; however, further investigation is needed in order to understand the underlying mechanism. To determine its mechanism of action, we examined the effects of an ethyl acetate fraction (EAF) of S. asper on nitric oxide (NO) production and prostaglandin-E2 levels in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. MATERIALS/METHODS: An in vitro culture of RAW264.7 macrophages was treated with LPS to induce inflammation. RESULTS: Treatment with EAF resulted in significant suppression of oxidative stress in RAW264.7 macrophages as demonstrated by increased endogenous superoxide dismutase (SOD) activity and intracellular glutathione levels, decreased generation of reactive oxygen species and lipid peroxidation, and restoration of the mitochondrial membrane potential. To confirm its anti-inflammatory effects, analysis of expression of inducible NO synthase, cyclooxygenase-2, tumor necrosis factor-${\alpha}$, and the anti-inflammatory cytokines IL-$1{\beta}$ and IL-6 was performed using semi-quantitative RT-PCR. EAF treatment resulted in significantly reduced dose-dependent expression of all of these factors, and enhanced expression of the antioxidants MnSOD and heme oxygenase-1. In addition, HPLC fingerprint results suggest that rutin, caffeic acid, and quercetin may be the active ingredients in EAF. CONCLUSIONS: Taken together, findings of this study imply that the anti-inflammatory effect of EAF on LPS-stimulated RAW264.7 cells is mediated by suppression of oxidative stress.

Dislocation-oxide interaction in Y2O3 embedded Fe: A molecular dynamics simulation study

  • Azeem, M. Mustafa;Wang, Qingyu;Li, Zhongyu;Zhang, Yue
    • Nuclear Engineering and Technology
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    • v.52 no.2
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    • pp.337-343
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    • 2020
  • Oxide dispersed strengthened (ODS) steel is an important candidate for Gen-IV reactors. Oxide embedded in Fe can help to trap irradiation defects and enhances the strength of steel. It was observed in this study that the size of oxide has a profound impact on the depinning mechanism. For smaller sizes, the oxide acts as a void; thus, letting the dislocation bypass without any shear. On the other hand, oxides larger than 2 nm generate new dislocation segments around themselves. The depinning is similar to that of Orowan mechanism and the strengthening effect is likely to be greater for larger oxides. It was found that higher shear deformation rates produce more fine-tuned stress-strain curve. Both molecular dynamics (MD) simulations and BKS (Bacon-Knocks-Scattergood) model display similar characteristics whereby establishing an inverse relation between the depinning stress and the obstacle distance. It was found that (110)oxide || (111)Fe (oriented oxide) also had similar characteristics as that of (100)oxide || (111)Fe but resulted in an increased depinning stress thereby providing greater resistance to dislocation bypass. Our simulation results concluded that critical depinning stress depends significantly on the size and orientation of the oxide.

The Study about the Fatigue Strength Improvement Mechanism by the Processing of Fillet Welded Joint (필렛용접이음부의 후처리에 따른 피로강도 향상 메커니즘의 연구)

  • Lim, Cheong Kweon;Park, Moon Ho;Chang, Chun Ho
    • Journal of Korean Society of Steel Construction
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    • v.11 no.3 s.40
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    • pp.319-327
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    • 1999
  • This study makes mechanism of the fatigue strength improvement by the processing of weld toe clear for the vertical cross rib specimens which was made fillet weld joint, also it proposes to the appropriate later processing. As a result of tension fatigue test, the fatigue strength improvement could have been seen in later processed specimens than as-weld specimens. Especially fatigue crack initial life $N_c$ increased in specimens which processed grinder after hammer-peening. Also, fatigue crack propagation life $N_p$ improved more in hammer-peening specimens than as-weld or TIG specimens. It thinks that $N_c$ is because of the geometrical shape of weld toe, i.e. the relaxation of the stress concentration and also that $N_p$ is because the big compression residual stress which was introduced in the surface by hammer-peening is restraining the propagation of fatigue crack.

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Molecular cloning of metal-responsive transcription factor-1 (MTF-1) and transcriptional responses to metal and heat stresses in Pacific abalone, Haliotis discus hannai

  • Lee, Sang Yoon;Nam, Yoon Kwon
    • Fisheries and Aquatic Sciences
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    • v.20 no.7
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    • pp.9.1-9.13
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    • 2017
  • Background: Metal-responsive transcription factor-1 (MTF-1) is a key transcriptional regulator playing crucial roles in metal homeostasis and cellular adaptation to diverse oxidative stresses. In order to understand cellular pathways associated with metal regulation and stress responses in Pacific abalone (Haliotis discus hannai), this study was aimed to isolate the genetic determinant of abalone MTF-1 and to examine its expression characteristics under basal and experimentally stimulated conditions. Results: The abalone MTF-1 shared conserved features in zinc-finger DNA binding domain with its orthologs; however, it represented a non-conservative shape in presumed transactivation domain region with the lack of typical motifs for nuclear export signal (NES) and Cys-cluster. Abalone MTF-1 promoter exhibited various transcription factor binding motifs that would be potentially related with metal regulation, stress responses, and development. The highest messenger RNA (mRNA) expression level of MTF-1 was observed in the testes, and MTF-1 transcripts were detected during the entire period of embryonic and early ontogenic developments. Abalone MTF-1 was found to be Cd inducible and highly modulated by heat shock treatment. Conclusion: Abalone MTF-1 possesses a non-consensus structure of activation domains and represents distinct features for its activation mechanism in response to metal overload and heat stress. The activation mechanism of abalone MTF-1 might include both indirect zinc sensing and direct de novo synthesis of transcripts. Taken together, results from this study could be a useful basis for future researches on stress physiology of this abalone species, particularly with regard to heavy metal detoxification and thermal adaptation.

Intergranular Corrosion Mechanism of Slightly-sensitized and UNSM-treated 316L Stainless Steel

  • Lee, J.H.;Kim, K.T.;Pyoun, Y.S.;Kim, Y.S.
    • Corrosion Science and Technology
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    • v.15 no.5
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    • pp.226-236
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    • 2016
  • 316L stainless steels have been widely used in many engineering fields, because of their high corrosion resistance and good mechanical properties. However, welding or aging treatment may induce intergranular corrosion and stress corrosion cracking etc. Since these types of corrosion are closely related to the formation of chromium carbide in grain boundaries, the alloys are controlled by methods such as the lowering of carbon content, solution heat treatment. This work focused on the intergranular corrosion mechanism of slightly-sensitized and Ultrasonic Nano-crystal Surface Modification (UNSM)-treated 316L stainless steel. Samples were sensitized for 1, 5, and 48 hours at $650^{\circ}C$ in $N_2$ gas atmosphere. Subsequently UNSM treatments were carried out on the surface of the samples. The results were discussed on the basis of the sensitization by chromium carbide and carbon segregation, the residual stress and grain refinement. Even though chromium carbide was not precipitated, the intergranular corrosion rate of 316L stainless steel was drastically increased with aging time, and it was confirmed that the increased intergranular corrosion rate of slightly-sensitized (not carbide formed) 316L stainless steel was due to the carbon segregation along the grain boundaries. However, UNSM treatment improved the intergranular corrosion resistance of aged stainless steels, and its improvement was due to the reduction of carbon segregation and the grain refinement of the outer surface, including the introduction of compressive residual stress.

Psychological Wellbeing across the Family Life Cycle based on Bioecological Family Welfare Model (생태학적 가족복지모형을 적용한 가족생활주기에 따른 심리적 복지)

  • Jeon, Hyo-Jeong
    • Journal of the Korean Home Economics Association
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    • v.45 no.5
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    • pp.121-133
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    • 2007
  • The purpose of this study was to investigate the psychological wellbeing as applied to the bioecological family life welfare model, concerning individual attributes, family backgrounds, and family processes across the family life cycles. Based on Bronfenbrenner's bioecological perspective, the "bioecological family welfare model", which includes person (individual attributes), context (family background), process (mechanism - family process), and time (the family life cycles), was applied as a research paradigm for this study. The sample for the questionnaire study comprised for 900 families, considering the family life cycle in Busan and the Kyungnam area. The families were categorized into 6 family life cycles based on Duvall and Hill's family life cycle. For the final analysis, 628 families were used. According to the path analysis results, the length of commitment before marriage and self-esteem had significant effects on the stress coping ability. Several individual attributes and family backgrounds such as age, length of marriage, family life cycle, self-esteem and stress coping ability had significant effects on marital adjustment. The family life cycle and age were significant variables on family function. The significant variables on psychological wellbeing were monthly income, length of commitment before marriage, stress coping ability and marital adjustment. The regression model showed that the variables of the individual attributes, context and family process accounted for 51% of the psychological wellbeing. The results show that the suggested research model was significant and effective to explain the mechanism of psychological wellbeing. Individual attributes and family context have an impact on stress coping, marital adjustment, and family function, which in turn affect psychological wellbeing.

Effect of cohesion of infill materials on the performance of geocell-reinforced cohesive soil subgrade

  • Yang Zhao;Zheng Lu;Jie Liu;Lei Ye;Weizhang Xu;Hailin Yao
    • Geomechanics and Engineering
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    • v.33 no.3
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    • pp.301-315
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    • 2023
  • Adopting cohesive soil as geocell-pocket infill materials is not fully accepted by researchers in the field of road engineering. The cohesion that may inhibit the lateral limitation of geocells is a common vital idea that exists within every researcher. However, the influence of infill materials' cohesion on geocell-reinforced performance is still not thoroughly determined. The mechanism behind this still needs to be studied in depth. This study initially discussed the relationship between subgrade bearing capacity, geocells' contribution to reinforced performance, and infill materials' cohesion (IMC). A law was proposed that adopting the soil with high cohesion as infill materials benefited the subgrade bearing capacity, but this was attributed to the superior mechanical properties of infill materials rather than geocells' contribution. Moreover, the vertical and lateral deformation of subgrade, coupling shear stress and confining stress of geocells, and deformation of geocells were deeply studied to analyze the mechanism that high cohesion can inhibit the geocells' contribution. The results indicate that the infill materials with high cohesion result in the total displacement of the subgrade toward to deeper depth, not the lateral direction. These responses decrease the vertical coupling shear stress, confining stress, and normal displacement of geocell walls, which weaken the lateral limitation of geocells.