• Journal of Gastric Cancer
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• 제3권2호
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• pp.80-83
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• 2003

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. Fasassociated death domain (FADD) protein, an adaptor protein of death receptors, is a critical regulatory component of the extrinsic cell- death pathway that exerts its pro-apoptotic effect upon binding with death receptors. Expression of the FADD protein has not been reported in stomach cancer. The aim of this study was to explore the expression status of the FADD protein in stomach cancers. Materials and Methods: In the current study, we analyzed the expression of the FADD protein in 60 advanced stomach cancer by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the FADD protein in 23 ($38\%$) of the 60 cancers. Normal gastric mucosal cells showed expression of the FADD protein. Conclusion: Taken together, these results indicate that decreased expression of the FADD protein is a frequent event in stomach cancers and suggest that to avoid apoptosis, stomach cancer cells in vivo may need loss of FADD expression, which might contribute to tumor development.

• Journal of Gastric Cancer
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• 제3권2호
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• pp.75-79
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• 2003

Purpose: Evidence exists that dysregulation of apoptosis is involved in the pathogenesis of cancer development. The Bcl-$x_{L}$/Bcl-2-associated death promoter (BAD), a member of the Bcl-2 family, is a critical regulatory component of the intrinsic cell-death pathway that exerts its pro-apoptotic effect upon heterodimerization with anti-apoptotic proteins Bcl-2 and Bcl-$X_{L}$. Expression of the BAD protein has been reported in several cancer types, but not in stomach cancer. The aim of this study was to explore the expression status of the BAD protein in gastric carcinomas. Materials and Methods: In the current study, we analyzed the expression of the BAD protein in 60 advanced gastric adenocarcinomas by using immunohistochemistry and a tissue microarray approach. Results: Immunopositivity (defined as $\geq\30\%$) was observed for the BAD protein in 57 ($95\%$) of the 60 cancers. Normal gastric mucosal cells showed weaker expressions of the BAD protein than gastric carcinomas. Conclusion: Taken together, these results suggest that stomach cancer cells in vivo may need BAD protein expression for apoptosis. Also, the higher expression of the BAD protein in stomach cancer cells than in normal gastric mucosal cells suggests that apoptosis might be easily triggered in susceptible stomach cancer cells, thereby producing selective pressure to make more apoptosis-resistant cells during tumor development.

• Reproductive and Developmental Biology
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• 제42권2호
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• pp.7-12
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• 2018

In this review, we have tried to summarize the evidence and molecular characterization indicating that $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of $20{\alpha}$-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine $20{\alpha}$-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The $20{\alpha}$-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the $20{\alpha}$-HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.

• Tribology and Lubricants
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• 제30권6호
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• pp.337-342
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• 2014

The reduction of drag torque is an important research issue in terms of improving transmission efficiency. Drag torque in a wet clutch occurs because of the viscous drag generated by the transmission fluid in a narrow gap (clearance) between the friction plate and a separate plate. The objective of this paper is to observe the effects of the friction plate area and the clearance on the drag torque using finite element simulation. The two-phase flow of air and oil fluid is considered and modeled for the simulation. The simulation analysis reveals that as the rotational speed increases, the drag torque generally increases to a critical point and then decreases sharply at a high speed regime. The clearance between the two plates plays an important role in controlling drag torque peak. An increase in the clearance causes a decrease in shear stress; thus, the drag torque also decreases according to Newton's law of viscosity. An observation of the effect of the area of contact between transmission fluid and friction plate shows that the drag torque increases with the contact area. The flow vectors inside the flow channel present clear evidence that the velocity of the fluid flows is faster with a larger friction plate, that is, in the case of a larger contact area. Therefore, the optimum size of the friction plate should be determined carefully, considering both the clutch performance and drag reduction. It is expected that the results from this study can be very useful as a database for clutch design and to predict the drag torque for the initial design with respect to various clutch parameters.

• 대한한방내과학회지
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• 제27권3호
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• pp.603-616
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• 2006

The water extract of Gamiyaengshinhwan (GYH), has been used in vitro tests for its beneficial effects on neuronal survival and neuroprotective functions, particularly in connection with CT105-related dementias and Alzheimer's disease(AD). CT105 derived from proteolytic processing of the $\beta$-amyloid precursor protein (APP), including the amyloid-$\beta$ peptide ($A{\beta}$), plays a critical role in the pathogenesis of Alzheimer's dementia. We determined that transfected overexpressing APP695 and $A{\beta}$ CT105 have a profound attenuation in the Increase in CT105 expressing neuro2A cells from GYH. Experimental evidence indicates that GYH protects against neuronal damage from cells, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing CT105-associated neuronal degeneration, we demonstrated that GYH inhibits formation of amyloid-$\beta$ fragment ($A{\beta}$ CT105). which are the characteristic, and possibly causative, features of AD. The decreased CT105 $A{\beta}$ in the presence of GYH was observed in the conditioned medium of this CT105-secreting cell line under in vitro. In the cells, GYH significantly attenuated mitochondrion-initiated apoptosis and decreased the activity of Bax, a key enzyme in the apoptosis cell-signaling cascade. These results suggest that neuronal damage in AD might be due to two factors: a direct CT05 toxicity and the apoptosis initiated by the mitochondria. Multiple cellular and molecular neuroprotective mechanisms, including attenuation of apoptosis and direct inhibition of CT105 aggregation, underlie the neuroprotective effects of GYH.

• Biomolecules & Therapeutics
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• 제25권2호
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• pp.140-148
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• 2017

Hyperlipidemia, which is closely associated with a fatty diet and aging, is commonly observed in the western and aged society. Therefore, a novel therapeutic approach for this disease is critical, and an immunological view has been suggested as a novel strategy, because hyperlipidemia is closely associated with inflammation and immune dysfunction. In this study, the effects of an aqueous extract of Rubus occidentalis (RO) in obese mice were investigated using immunological indexes. The mice were fed a high-fat diet (HFD) to induce hyperlipidemia, which was confirmed by biochemical analysis and examination of the mouse physiology. Two different doses of RO and rosuvastatin, a cholesterol synthesis inhibitor used as a control, were orally administered. Disturbances in immune cellularity as well as lymphocyte proliferation and cytokine production were significantly normalized by oral administration of RO, which also decreased the elevated serum tumor necrosis factor $(TNF)-{\alpha}$ level and total cholesterol. The specific immune-related actions of RO comprised considerable improvement in cytotoxic T cell killing functions and regulation of antibody production to within the normal range. The immunological evidence confirms the significant cholesterol-lowering effect of RO, suggesting its potential as a novel therapeutic agent for hyperlipidemia and associated immune decline.

• 한국수자원학회:학술대회논문집
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• 한국수자원학회 2019년도 학술발표회
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• pp.149-149
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• 2019

Gross Primary production (GPP) and evapotranspiration (ET) are the two critical components of carbon and water cycle respectively, linking the terrestrial surface and ecosystem with the atmosphere. The ratio between GPP to ET is called ecosystem water use efficiency (EWUE) and its quantification at the forest site helps to understand the impact of climate change due to large scale anthropogenic activities such as deforestation and irrigation. This study was conducted at the FLUXNET forest site CN-Qia (2003-2005) using Community land model (CLM 5.0). We simulated carbon and water fluxes including GPP, ecosystem respiration (ER), and ET using climatic variables as forcing dataset for 30 years (1981-2010). Model results were validated with the FLUXNET tower observations. The correlation showed better performance with values of 0.65, 0.77, and 0.63 for GPP, ER, and ET, respectively. The model underestimated the results with minimum bias of -0.04, -1.67, and -0.40 for GPP, ER, and ET, respectively. Effect of climate 'CLIM' and '$CO_2$' were analyzed based on EWUE and its trend was evaluated in the study period. The positive trend of EWUE was observed in the whole period from 1981-2010, and the trend showed further increase when simulated with rising $CO_2$. The time period were divided into two parts, from 1981-2000 and from 2001 to 2010, to identify the warming effect on EWUE. The first period showed the similar increasing trend of EWUE, but the second period showed slightly decreasing trend. This might be associated with the increase in ET in the wet temperate forest site due to increase in climate warming. Water use efficiency defined by transpiration (TR) (TWUE), and inherent-TR based WUE (IT-WUE) were also discussed. This research provides the evidence to climate warming and emphasized the importance of long term planning for management of water resources and evaporative demand in irrigation, deforestation and other anthropogenic activities.

• Archives of Pharmacal Research
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• 제27권7호
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• pp.757-762
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• 2004

The protective adaptive response to electrophiles and reactive oxygen species is mediated by the induction of phase II detoxifying genes including glutathione S-transferases (GSTs). NF-E2-related factor-2 (Nrf2) phosphorylation by protein kinase C (PKC) is a critical event for its nuclear translocation in response to oxidative stress. Previously, we have shown that peroxynitrite plays a role in activation of Nrf2 and Nrf2 binding to the antioxidant response element (ARE) via the pathway of phosphatidylinositol 3-kinase (PI3-kinase) and that nitric oxide synthase in hepatocytes is required for GSTA2 induction. In view of the importance of PKC and Pl3-kinase in Nrf2-mediated GST induction, we investigated the role of these kinases in peroxynitrite formation for GSTA2 induction by oxidative stress and determined the relationship between PKC and PI3-kinase. Although PKC activation by phorbol 12-myristate-13-acetate (PMA) did not increase the extents of constitutive and inducible GSTA2 expression, either PKC depletion by PMA or PKC inhibition by staurosporine significantly inhibited GSTA2 induction by tert-butylhydroquinone (t-SHa) a prooxidant chemical. Therefore, the basal PKC activity is req- uisite for GSTA2 induction. 3-Morpholinosydnonimine (SIN-1), which decomposes and yields peroxynitrite, induced GSTA2, which was not inhibited by PKC depletion, but slightly enhanced by PKC activation, suggesting that PKC promotes peroxynitrite formation for Nrf2-mediated GSTA2 induction. Treatment of cells with S-nitroso-N-acetyl-penicillamine (SNAP), an exogenous NO donor, in combination with t-BHQ may produce peroxynitrite. GSTA2 induction by SNAP ＋ t-BHQ was not decreased by PKC depletion, but rather enhanced by PKC activation, showing that the activity of PKC might be required for peroxynitrite formation. LY294002 a P13-kinase inhibitor blocked GSTA2 induction by t-BHQ, which was reversed by PMA-induced PKC activation. These results provide evidence that PKC may playa role in formation of peroxynitrite that activates Nrf2 for GSTA2 induction and that PKC may serve an activator for GSTA2 induction downstream of PI3-kinase.

• Molecules and Cells
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• 제44권10호
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• pp.710-722
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• 2021

Hypoxia, or low oxygen tension, is a hallmark of the tumor microenvironment. The hypoxia-inducible factor-1α (HIF-1α) subunit plays a critical role in the adaptive cellular response of hypoxic tumor cells to low oxygen tension by activating gene-expression programs that control cancer cell metabolism, angiogenesis, and therapy resistance. Phosphorylation is involved in the stabilization and regulation of HIF-1α transcriptional activity. HIF-1α is activated by several factors, including the mitogen-activated protein kinase (MAPK) superfamily. MAPK phosphatase 3 (MKP-3) is a cytoplasmic dual-specificity phosphatase specific for extracellular signal-regulated kinase 1/2 (Erk1/2). Recent evidence indicates that hypoxia increases the endogenous levels of both MKP-3 mRNA and protein. However, its role in the response of cells to hypoxia is poorly understood. Herein, we demonstrated that small-interfering RNA (siRNA)-mediated knockdown of MKP-3 enhanced HIF-1α (not HIF-2α) levels. Conversely, MKP-3 overexpression suppressed HIF-1α (not HIF-2α) levels, as well as the expression levels of hypoxia-responsive genes (LDHA, CA9, GLUT-1, and VEGF), in hypoxic colon cancer cells. These findings indicated that MKP-3, induced by HIF-1α in hypoxia, negatively regulates HIF-1α protein levels and hypoxia-responsive genes. However, we also found that long-term hypoxia (>12 h) induced proteasomal degradation of MKP-3 in a lactic acid-dependent manner. Taken together, MKP-3 expression is modulated by the hypoxic conditions prevailing in colon cancer, and plays a role in cellular adaptation to tumor hypoxia and tumor progression. Thus, MKP-3 may serve as a potential therapeutic target for colon cancer treatment.

• Journal of Trauma and Injury
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• 제34권3호
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• pp.162-169
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• 2021

Purpose: For severe lung injuries or acute respiratory distress syndrome that occurs during critical care due to trauma, extracorporeal membrane oxygenation (ECMO) may be used as a salvage treatment. This study aimed to describe the experiences at a single center with the use of ECMO in trauma patients. Methods: We enrolled a total of 25 trauma patients who were treated with ECMO between January 2015 and December 2019 at a regional trauma center. We analyzed and compared patients' characteristics between survivors and non-survivors through a medical chart review. We also compared the characteristics of patients between direct and indirect lung injury groups. Results: The mean age of the 25 patients was 45.9±19.5 years, and 19 patients (76.0%) were male. The mean Injury Severity Score was 26.1±10.1. Ten patients (40.0%) had an Abbreviated Injury Scale (AIS) 3 score of 4, and six patients (24.0%) had an AIS 3 score of 5. There were 19 cases (76.6%) of direct lung injury. The mortality rate was 60.0% (n=15). Sixteen patients (64.0%) received a loading dose of heparin for the initiation of ECMO. There was no significant difference in heparin use between the survivors and non-survivors (70% in survivors vs. 60% in non-survivors, p=0.691). When comparing the direct and indirect lung injury groups, there were no significant differences in variables other than age and ECMO onset time. Conclusions: If more evidence is gathered, risk factors and indications will be identified and we expect that more trauma patients will receive appropriate treatment with ECMO.