• Title/Summary/Keyword: Critical pathways

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WNT Signaling in Lung Repair and Regeneration

  • Raslan, Ahmed A.;Yoon, Jeong Kyo
    • Molecules and Cells
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    • v.43 no.9
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    • pp.774-783
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    • 2020
  • The lung has a vital function in gas exchange between the blood and the external atmosphere. It also has a critical role in the immune defense against external pathogens and environmental factors. While the lung is classified as a relatively quiescent organ with little homeostatic turnover, it shows robust regenerative capacity in response to injury, mediated by the resident stem/progenitor cells. During regeneration, regionally distinct epithelial cell populations with specific functions are generated from several different types of stem/progenitor cells localized within four histologically distinguished regions: trachea, bronchi, bronchioles, and alveoli. WNT signaling is one of the key signaling pathways involved in regulating many types of stem/progenitor cells in various organs. In addition to its developmental role in the embryonic and fetal lung, WNT signaling is critical for lung homeostasis and regeneration. In this minireview, we summarize and discuss recent advances in the understanding of the role of WNT signaling in lung regeneration with an emphasis on stem/progenitor cells.

Can antioxidants be effective therapeutics for type 2 diabetes?

  • Park, Soyoung;Park, So-Young
    • Journal of Yeungnam Medical Science
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    • v.38 no.2
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    • pp.83-94
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    • 2021
  • The global obesity epidemic and the growing elderly population largely contribute to the increasing incidence of type 2 diabetes. Insulin resistance acts as a critical link between the present obesity pandemic and type 2 diabetes. Naturally occurring reactive oxygen species (ROS) regulate intracellular signaling and are kept in balance by the antioxidant system. However, the imbalance between ROS production and antioxidant capacity causes ROS accumulation and induces oxidative stress. Oxidative stress interrupts insulin-mediated intracellular signaling pathways, as supported by studies involving genetic modification of antioxidant enzymes in experimental rodents. In addition, a close association between oxidative stress and insulin resistance has been reported in numerous human studies. However, the controversial results with the use of antioxidants in type 2 diabetes raise the question of whether oxidative stress plays a critical role in insulin resistance. In this review article, we discuss the relevance of oxidative stress to insulin resistance based on genetically modified animal models and human trials.

Development and Application of Critical Pathway for Nasal Bone Fracture Patients (코뼈골절 환자에서 표준진료지침의 개발과 적용)

  • Hwang, Kun;Shin, Jung Yae;Lee, Hye Kyung;Lee, Hwan Jun
    • Quality Improvement in Health Care
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    • v.10 no.2
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    • pp.154-163
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    • 2003
  • Purpose: The aim of this study is to develop and apply the critical pathway to the nasal bone fracture patients and to elucidate its effect. Methods: Critical pathway (CP) sheet and questionnaire were developed by a team approach. Critical pathway were applied to 30 nasal bone fracture patients (CP group) from June 2001 to November 2001. Length of hospitalization, cost for hospitalization and bed turnover rate of CP group were compared to those of the 30 patients who had same disease entities and treated by conventional regimen (control group). Results: Length of hospitalization in the CP group (4.20 day) were significantly shorter than that of control group (6.21 day). Mean cost for hospitalization of the CP group (492,106 won) were significantly lower than that of control group (678,376 won). Bed turnover rate in CP group (2.5) were higher than that of control group. The patients satisfaction for the medical personnel, explanation regarding operation procedure, therapeutic operation fee, and length of hospitalization were all affirmative. Conclusion: Critical pathway that we developed for nasal bone fracture definitely improved the quality of treatment and lowered cost of medical service. Furthermore, other critical pathways should be developed for another facial trauma patients.

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Alkylglyceronephosphate Synthase (AGPS) Alters Lipid Signaling Pathways and Supports Chemotherapy Resistance of Glioma and Hepatic Carcinoma Cell Lines

  • Zhu, Yu;Liu, Xing-Jun;Yang, Ping;Zhao, Meng;Lv, Li-Xia;Zhang, Guo-Dong;Wang, Qin;Zhang, Ling
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.7
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    • pp.3219-3226
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    • 2014
  • Chemotherapy continues to be a mainstay of cancer treatment, although drug resistance is a major obstacle. Lipid metabolism plays a critical role in cancer pathology, with elevated ether lipid levels. Recently, alkylglyceronephosphate synthase (AGPS), an enzyme that catalyzes the critical step in ether lipid synthesis, was shown to be up-regulated in multiple types of cancer cells and primary tumors. Here, we demonstrated that silencing of AGPS in chemotherapy resistance glioma U87MG/DDP and hepatic carcinoma HepG2/ADM cell lines resulted in reduced cell proliferation, increased drug sensitivity, cell cycle arrest and cell apoptosis through reducing the intracellular concentration of lysophosphatidic acid (LPA), lysophosphatidic acid-ether (LPAe) and prostaglandin E2 (PGE2), resulting in reduction of LPA receptor and EP receptors mediated PI3K/AKT signaling pathways and the expression of several multi-drug resistance genes, like MDR1, MRP1 and ABCG2. ${\beta}$-catenin, caspase-3/8, Bcl-2 and survivin were also found to be involved. In summary, our studies indicate that AGPS plays a role in cancer chemotherapy resistance by mediating signaling lipid metabolism in cancer cells.

Incipient motion criteria of uniform gravel bed under falling spheres in open channel flow

  • Khe, Sok An;Park, Sang Deog;Jeon, Woo Sung
    • Proceedings of the Korea Water Resources Association Conference
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    • 2018.05a
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    • pp.149-149
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    • 2018
  • Prediction on initial motion of sediment is crucial to evaluate sediment transport and channel stability. The condition of incipient movement of sediment is characterized by bed shear stress, which is generated from force of moving water against the bed of the channel, and by critical shear stress, which depends on force resisting motion of sediment due to the submerged weight of the grains. When the bed shear stress exceeds the critical shear stress, sediment particles begin rolling and sliding at isolated and random locations. In Mountain River, debris flow frequently occurs due to heavy rainfall and can lead some natural stones from mountain slope into the bed river. This phenomenon could add additional forces to sediment transport system in the bed of river and also affect or change direction and magnitude of sediment movement. In this paper, evaluations on incipient motion of uniform coarse gravel under falling spheres impacts using small scale flume channel were conducted. The drag force of falling spheres due to water flow and length movement of falling spheres were investigated. The experiments were carried out in flume channel made by glass wall and steel floor with 12 m long, 0.6 m wide, and 0.6 m deep. The bed slopes were selected with the range from 0.7% to 1.5%. The thickness of granular layer was at least 3 times of diameter of granular particle to meet grain placement condition. The sphere diameters were chosen to be 4cm, 6 cm, 8 cm, 10 cm. The spheres were fallen in to the bed channel for critical condition and under critical condition of motion particle. Based on the experimental results, the Shields curve of particles Reynold number and dimensionless critical shear stress were plotted. The relationship between with drag force and the length movement of spheres were plotted. The pathways of the bed material Under the impact of spheres falling were analyzed.

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Genetic Regulation of Cellular Responses and Signal Targeting Pathways Invoked by an Environmental Stress (환경 스트레스에 의한 세포 내 신호의 이동 경로와 유전적 조절)

  • Kim, Il-Sup;Kim, Hyun-Young;Kang, Hong-Gyu;Yoon, Ho-Sung
    • Korean Journal of Environmental Biology
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    • v.26 no.4
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    • pp.377-384
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    • 2008
  • A cell is the product of a long period of evolution and can be represented as an optimized system (homeostasis). Stimuli from the outside environment are received by sensory apparatus on the surface of the cell and transferred through complicated pathways and eventually regulate gene expression. These signals affect cell physiology, growth, and development, and the interaction among genes in the signal transduction pathway is a critical part of the regulation. In this study, the interactions of deletion mutants and overexpression of the extracopies of the genes were used to understand their relationships to each other. Also, green fluorescent protein (GFP reporter gene) was fused to the regulatory genes to elucidate their interactions. Cooverexpression of the two genes in extracopy plasmids suggested that patS acts at the downstream of hetR in the regulatory network. The experiments using gfp fusion in different genetic background cells also indicated the epistasis relationships between the two genes. A model describing the regulatory network that controls cell development is presented.

p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Regulated Kinase Regulate Nitric Oxide Production and Inflammatory Cytokine Expression in Raw Cells

  • Choi, Cheol-Hee;Kim, Sang-Hyun
    • IMMUNE NETWORK
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    • v.5 no.1
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    • pp.30-35
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    • 2005
  • Background: p38 and extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) signaling are thought to have critical role in lipopolysaccharide (LPS)-induced immune response but the molecular mechanism underlying the induction of these signaling are not clear. Methods: Specific inhibitors for p38, SB203580, and for ERK, PD98059 were used. Cells were stimulated by LPS with or without specific MAPK inhibitors. Results: LPS activated inducible nitric oxide synthase (iNOS), subsequent NO productions, and pro-inflammatory cytokine gene expressions (TNF-${\alpha}$, IL-$1{\beta}$, IL-6, and IL-12). Treatment of both SB203580 and PD98059 decreased LPS-induced NO productions. Concomitant decreases in the expression of iNOS mRNA and protein were detected. SB203580 and PD98059 decreased LPS-induced gene expression of IL-$1{\beta}$ and IL-6. SB203580 increased LPS-induced expression of TNF-${\alpha}$ and IL-12, and reactive oxygen species production, but PD98059 had no effect. Conclusion: These results indicate that both p38 and ERK pathways are involved in LPS-stimulated NO synthesis, and expression of IL-$1{\beta}$ and IL-6. p38 signaling pathways are involved in LPS-induced TNF-${\alpha}$ and IL-12, and reactive oxygen species plays an important role in these signaling in macrophage.

Meeting the meat: delineating the molecular machinery of muscle development

  • Jan, Arif Tasleem;Lee, Eun Ju;Ahmad, Sarafraz;Choi, Inho
    • Journal of Animal Science and Technology
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    • v.58 no.5
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    • pp.18.1-18.10
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    • 2016
  • Muscle, studied mostly with respect to meat production, represents one of the largest protein reservoirs of the body. As gene expression profiling holds credibility to deal with the increasing demand of food from animal sources, excessive loss due to myopathies and other muscular dystrophies was found detrimental as it aggravates diseases that result in increased morbidity and mortality. Holding key point towards improving the developmental program of muscle in meat producing animals, elucidating the underlying mechanisms of the associated pathways in livestock animals is believed to open up new avenues towards enhancing the lean tissue deposition. To this end, identification of vital candidate genes having no known function in myogenesis, is believed to increase the current understanding of the physiological processes going on in the skeletal muscle tissue. Taking consequences of gene expression changes into account, knowledge of the pathways associated with their activation and as such up-regulation seems critical for the overall muscle homeostasis. Having important implications on livestock production, a thorough understanding of postnatal muscle development seems a timely step to fulfil the growing need of ever increasing populations of the world.

Environmental Distribution and Fate of Perfluorinated Compounds (PFCs) as Emerging POPs: Physico-Chemical Properties, Emission, Contamination Level, Inter-phase Distribution and Long-Range Transport (잠재적 POPs로서의 과불소화화합물의 환경 내 분포 및 거동: 물성, 환경 내 농도수준, 상 분배 및 장거리이동을 중심으로)

  • Kim, Seung-Kyu
    • Environmental Analysis Health and Toxicology
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    • v.23 no.3
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    • pp.143-164
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    • 2008
  • Concern about perfluorinated compounds (PFCs) is growing nationally as well as globally. PFCs could be considered emerging POPs due to their environmentally persistent, bioaccumulative, and potentially harmful properties. Moreover. perfluoroalkylates (PFAs) such as PFOS and PFOA are reported to experience long-range transport (LRT) to the Arctic in spite of their low volatility and strong solubility. The possible pathways contributing to LRT have been proposed but are still in debate in combination with unclear source definition and uncertain physico-chemical properties. The environmental fate of PFCs is more complicated because of the presence of precursors that are degraded to PFAs and are extremely different from their daughters, PFAs. in physico-chemical properties. To what extent and through what pathways are human and wildlife exposed is determined by the environmental fate and distribution of PFCs. To define uncertainties in fate and distribution thus is critical to prevent erroneous policy and/or determination related with exposure and risk reduction. This article aimed to review controversy and/or uncertain issues for the environmental fate and distribution of PFCs and to prospect research topics necessary to dissolve uncertainties.

A Ferroxidase, Cfo1, Regulates Diverse Environmental Stress Responses of Cryptococcus neoformans through the HOG Pathway

  • Lee, Kyung-Tae;Lee, Jang-Won;Lee, Dohyun;Jung, Won-Hee;Bahn, Yong-Sun
    • Mycobiology
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    • v.42 no.2
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    • pp.152-157
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    • 2014
  • The iron uptake and utilization pathways play a critical role in allowing human pathogens, including Cryptococcus neoformans, the causative agent of fatal meningoencephalitis, to survive within the mammalian body by competing with the host for iron. Here we show that the iron regulon is also required for diverse environmental stress responses and that in C. neoformans, it is regulated by the high-osmolarity glycerol response (HOG) pathway. Between CFO1 and CFO2, two ferroxidase genes in the iron regulon, CFO1 but not CFO2 was induced during oxidative and osmotic stress. Interestingly, we found that the HOG pathway repressed basal expression of both CFO1 and CFO2. Furthermore, when the HOG pathway was blocked, CFO2 also responded to oxidative and osmotic stress and the response of CFO1 was increased. We also established that CFO1 plays a major role in responding and adapting to diverse environmental stresses, including oxidative and genotoxic damage, osmotic fluctuations, heavy metal stress, and stress induced by cell membrane destabilizers. Therefore, our findings indicate that in C. neoformans, the iron uptake and utilization pathways are not only required for iron acquisition and survival, but also play a significant role in the environmental stress response through crosstalk with the HOG pathway.