• Tuberculosis and Respiratory Diseases
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• v.45 no.5
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• pp.962-974
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• 1998

Background: Alteration of p53 tumor suppressor genes is most frequently identified in human neoplasms, including lung carcinoma. It is well known that bcl-2 oncoprotein protects cells from apoptosis. Recent studies have demonstrated that bcl-2 expression is associated with favorable prognosis for patients with non-small cell lung carcinoma. However, the precise biologic role of bcl-2 in the development of these tumors is still obscure. p53 and bcl-2 have important regulatory influence in the apoptotic pathway and thus their relationship is of interest in tumorigenesis, especially lung cancer. Purpose: The author investigated to know the prognostic significance of the expression of p53 and bcl-2 in radically resected non-small cell lung cancer. Method: 84 cases of formalin-fixed paraffin-embedded blocks from resected primary non-small cell lung cancer from 1980 to 1994 at Hanyang University Hospital were available for both clinical follow-up and immunohistochemical staining using monoclonal antibodies for p53 and bcl-2. Results : The histologic classification of the tumor was based on WHO criteria., and the specimens included 45 squamous cell carcinomas(53.6%), 28 adeonocarcinomas(33.3%) and 11 large cell carcinomas(13.1 %). p53 immunoreactivity was noted in 47 cases of 84 cases(56.0%). bcl-2 immunoreactivity was noted in 15 cases of 84 cases(17.9%). The mean survival duration was $64.23{\pm}10.73$ months in bcl-2 positive group and $35.28{\pm}4$. 39 months in bcl-2 negative group. The bcl-2 expression was significantly correlated with survival in radically resected non-small cell lung cancer patients(p=0.03). The mean survival duration was $34.71{\pm}6.12$ months in p53 positive group and $45.35{\pm}6.30$ months in p53 negative group(p=0.21). The p53 expression was not predictive for survival. There was no correlation between combination of the different status of p53 and bcl-2 expression in our study. Conclusions : The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. bcl-2 overexpression is a good prognostic factor in non-small cell lung cancer and p53 expression is not significantly associated with the prognostic factor in non-small cell lung cancer.

• Journal of Life Science
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• v.34 no.2
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• pp.113-121
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• 2024

Endoplasmic reticulum (ER) stress responses are markedly induced during toxic responses caused by various chemical substances, including difenoconazole, but no research has been conducted on 1,2,3-trichloropropane (TCP), a chemical that is generally used in agriculture and industry, which induces hepatotoxicity. Therefore, in this study, the changes in indicators for hepatotoxicity, apoptosis, and ER stress were analyzed in TCP-treated Sprague Dawley (SD) rats to study the regulatory mechanism of ER stress during the hepatotoxicity. The TCP-treated group decreased in body weight and dietary intake compared to the vehicle-treated group, and necrosis and vacuolation increased significantly in liver histology. In addition, the expression of apoptosis-related factors, including Bax/Bcl-2 and cleaved caspase (Cas)-3/Cas-3 increased significantly in the TCP-treated group compared to the vehicle-treated group. In the analysis of ER stress response indicators, the expression of C/EBP homologous protein (CHOP), phospho-eukaryotic translation initiation factor 2 alpha subunit (eIF2α), and phospho-inositol-requiring enzyme 1α (IRE1α) increased only in the TCP100-treated group and decreased in the TCP200-treated group. However, the transcriptions of growth arrest and DNA damage-34 (GADD34) increased in the TCP200-treated group, while Spliced X-box binding protein-1 (XBP1s) and unspliced XBP1(XBP1u) decreased in the same group. These results suggest that the ER stress response is successfully triggered during the hepatotoxicity induced by TCP treatment through the alternative regulation of the unfolded-protein response (UPR) pathway.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.12
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• pp.1701-1707
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• 2016

The present study investigated the anti-obesity effect of pine cone (PC, Pinus koraiensis) supercritical extract in high-fat diet (HFD)-induced obese mice. Male C57BL/6J mice were treated with HFD, HFD+catechin, and HFD+PC [two different doses, 20 mg/kg body weight (b.w.) and 100 mg/kg b.w.] in each AIN93G supplement for 8 weeks. Treatment of HFD mice with both low and high doses of PC significantly reduced body weight gain compared to HFD mice. Liver weight of mice was reduced in both the low and high dose PC-supplemented groups (24.19% and 19.83%, respectively). Total adipose tissue weight of mice was reduced in both the low and high dose PC-supplemented groups (45.54% and 62.66%, respectively). Serum total cholesterol, triglyceride, LDL cholesterol, and HDL cholesterol were reduced in the low and high dose PC-supplemented groups, and ratios of HDL cholesterol to LDL cholesterol increased by 94.55% in the high dose PC-supplemented group. Serum leptin was significantly reduced in the low and high dose PC-supplemented groups (28.14% and 62.72%, respectively). These results were supported by genetic expression of protein and enzymes related to lipid metabolism assessed by real-time PCR. There was significant reduction of lipid regulatory transcription factors such as $PPAR-{\gamma}$, C/EBP, and SREBP and lipid enzymes such as fatty acid synthesis and lipoprotein lipase in the low and high dose PC-supplemented groups. However, there was no statistical difference between low and high dose PC treatments. These results suggest that pine cone supercritical extract supplementation is able to regulate serum lipid profiles by reducing total cholesterol, triglyceride, and LDL cholesterol levels, followed by regulation of expression of lipid metabolic factors, resulting in reduction of weight gain in HFD-induced obese mice.

• Journal of Life Science
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• v.25 no.9
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• pp.961-969
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• 2015

Epigallocatechin gallate (EGCG), the main catechin in green tea, has been shown to have some beneficial effects against various human diseases, including diabetes, neurodegenerative disorders, cancer, cardiovascular disease and obesity. To investigate the mechanism of the suppressive effects of EGCG on inflammatory response in macrophages, alterations on the levels of nitric oxide (NO) regulatory factors and inflammatory cytokines were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells. No significant toxicity was detected in RAW264.7 cells treated with 100–400 μM EGCG. Moreover, the optimal concentration of LPS was determined to be 1 μg/ml based on the results of cell viability assay, NO assay and IL-6 enzyme-linked immunsorbent assay (ELISA). Furthermore, NO levels decreased significantly by 68.2% in the 400 μM EGCG/LPS treated group, while the level of inducible nitric oxide synthase (iNOS) expression decreased by 12-17% in the 200 and 400 μM EGCG/LPS treated group. A significant decrease in transcription of pro-inflammatory cytokines (TNF- α and IL-1β) and anti-inflammatory cytokine (IL-10) was also detected in the EGCG/LPS treated group. However, IL-6 transcript and protein was maintained at a constant level when in the LPS treated group relative to the EGCG/LPS treated group. Overall, these results suggest that the differential regulation of inflammatory cytokines is an important factor influencing the suppressive effects of EGCG against LPS-activated inflammatory response in RAW264.7 cells.

• Asia-Pacific Journal of Business Venturing and Entrepreneurship
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• v.5 no.4
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• pp.1-34
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• 2010

Recently, failure rates of Kosdaq IPO firms are increasing and their survival rates tend to be very low, and when these firms do fail, often times backed by a number of governmental financial supports, they may inflict severe financial damage to investors, let alone economy as a whole. To ensure investors' confidence in Kosdaq and foster promising and healthy businesses, it is necessary to precisely assess their intrinsic values and survivability. This study investigates what contributed to the failure of IPO firms and analyzed how these elements are factored into corresponding firms' stock returns. Failure risks are assessed at the time of IPO. This paper considers factors reflecting IPO characteristics, a firm's underwriter prestige, auditor's quality, IPO offer price, firm's age, and IPO proceeds. The study further went on to examine how, if at all, these failure risks involved during IPO led to post-IPO stock prices. Sample firms used in this study include 98 Kosdaq firms that have failed and 569 healthy firms that are classified into the same business categories, and Logit models are used in estimate the probability of failure. Empirical results indicate that auditor's quality, IPO offer price, firm's age, and IPO proceeds shown significant relevance to failure risks at the time of IPO. Of other variables, firm's size and ROA, previously deemed significantly related to failure risks, in fact do not show significant relevance to those risks, whereas financial leverage does. This illustrates the efficacy of a model that appropriately reflects the attributes of IPO firms. Also, even though R&D expenditures were believed to be value relevant by previous studies, this study reveals that R&D is not a significant factor related to failure risks. In examing the relation between failure risks and stock prices, this study finds that failure risks are negatively related to 1 or 2 year size-adjusted abnormal returns after IPO. The results of this study may provide useful knowledge for government regulatory officials in contemplating pertinent policy and for credit analysts in their proper evaluation of a firm's credit standing.

• Development and Reproduction
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• v.12 no.1
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• pp.19-30
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• 2008

Proper development of fertilized oocyte to blastocyst is a key step in mammalian development to implantation. During development of preimplantation embryos, the mammalian embryo needs supply the energy substrate for keep viability. Usually mammalian oocyte get substrate especially energy substrate from oviduct and uterus, because it does not store much substrate into cytoplasm during oogenesis. Carbohydrates are known as a main energy substrate for preimplantation stage embryos. Glucose, lactate and pyruvate are essential component in preimplantation embryo culture media and there are stage specific preferences to them. Glucose transporter and $H^+$-monocarboxylate cotransporter are a main mediator for carbohydrate transport and those expression levels are primarily under the control of intrinsic or extrinsic factors like insulin and glucose. Other organic substances, amino acids, lipids and nucleotides are used as energy substance and cellular regulation factor. Though since 1960s, successful development of fertilized embryo to blastocyst has been accomplished with chemically defined medium for example BWW and give rise to normal offspring in mammals, the role of metabolites and the regulation of intermediary metabolism are still poorly understood. Glucose may permit expression of metabolic enzymes and transporters in compacting morula, capable of generating the energy required for blastocyst formation. In addition, it has been suggested that the cytokines can modulate the metabolic rate of carbohydrate in embryos and regulate the preimplantation embryonic development through control the metabolic rate. Recently we showed that lactate can be used as a mediator for preimplantation embryonic development. Those observations indicate that metabolites of carbohydrate are required by the early embryo, not only as an energy source, but also as a key substrate for other regulatory and biosynthetic pathways. In addition metabolites of carbohydrate may involve in cellular activity during development of preimplantation embryos. It is suggested that through these regulation and with other regulation mechanisms, embryo and uterus can prepare the embryo implantation and further development, properly.

• Journal of Microbiology and Biotechnology
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• v.25 no.10
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• pp.1751-1760
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• 2015

Mucin2 (MUC2), an important regulatory factor in the immune system, plays an important role in the host defense system against bacterial translocation. Probiotics known to regulate MUC2 gene expression have been widely studied, but the interactions among probiotic, pathogens, and mucin gene are still not fully understood. The aim of this study was to investigate the role of MUC2 in blocking effects of probiotics on meningitic E. coli-induced pathogenicities. In this study, live combined probiotic tablets containing living Bifidobacterium, Lactobacillus bulgaricus, and Streptococcus thermophilus were used. MUC2 expression was knocked down in Caco-2 cells by RNA interference. 5-Aza-2'-deoxycytidine (5-Aza-CdR), which enhances mucin-promoted probiotic effects through inducing production of Sadenosyl-L-methionine (SAMe), was used to up-regulate MUC2 expression in Caco-2 cells. The adhesion to and invasion of meningitic E. coli were detected by competition assays. Our studies showed that probiotic agents could block E. coli-caused intestinal colonization, bacteremia, and meningitis in a neonatal sepsis and meningitis rat model. MUC2 gene expression in the neonatal rats given probiotic agents was obviously higher than that of the infected and uninfected control groups without probiotic treatment. The prohibitive effects of probiotic agents on MUC2-knockdown Caco-2 cells infected with E44 were significantly reduced compared with nontransfected Caco-2 cells. Moreover, the results also showed that 5-Aza-CdR, a drug enhancing the production of SAMe that is a protective agent of probiotics, was able to significantly suppress adhesion and invasion of E44 to Caco-2 cells by upregulation of MUC2 expression. Taken together, our data suggest that probiotic agents can efficiently block meningitic E. coli-induced pathogenicities in a manner dependent on MUC2.

• Korean Journal of Poultry Science
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• v.44 no.1
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• pp.1-9
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• 2017

The objective of the present study was to determine the expression of genes associated with lipopolysaccharide (LPS)-induced stressor in two breeds of chickens: the Korean native chicken (KNC) and the White Leghorn chicken (WLH). Forty chickens per breed, aged 40 weeks, were randomly allotted to the control (CON, administered the saline vehicle) and LPS-injected stress groups. Samples were collected at 0 and 48 h post-LPS injection, and total RNA was extracted from the chicken livers for RNA microarray and quantitative real-time polymerase chain reaction (qRT-PCR) analyses. In response to LPS, 1,044 and 1,193 genes were upregulated, and 1,000 and 1,072 genes were downregulated in the KNC and WLH, respectively, using a ${\geq}2$-fold cutoff change. A functional network analysis revealed that stress-related genes were downregulated in both KNC and WLH after LPS infection. The results obtained from the qRT-PCR analysis of mRNA expression of heat shock 90 (HSP90), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), activating transcription factor 4 (ATF4), sterol regulatory element-binding protein 1 (SREBP1), and X-box binding protein 1 (XBP1) were confirmed by the results of the microarray analysis. There was a significant difference in the expression of stress-associated genes between the control and LPS-injected KNC and WLH groups. The qRT-PCR analysis revealed that the stress-related $HSP90{\alpha}$ and HMGCR genes were downregulated in both LPS-injected KNC and WLH groups. However, the HSP70 and $HSP90{\beta}$ genes were upregulated only in the LPS-injected KNC group. The results suggest that the mRNA expression of stress-related genes is differentially affected by LPS stimulation, and some of the responses varied with the chicken breed. A better understanding of the LPS-induced infective stressors in chicken using the qRT-PCR and RNA microarray analyses may contribute to improving animal welfare and husbandry practices.

• Journal of Life Science
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• v.17 no.8 s.88
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• pp.1090-1099
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• 2007

Myristicin, l-allyl-3,4-methylenedioxy-5-methoxybenzene, was one of the major essential oils of nutmeg. However, its anti-allergic effect in the Th1/Th2 immune response was poorly understood. Recently, it was shown that T-bet and GATA-3 was master Th1 and Th2 regulatory transcription factors. In this study, we have attempted to determine whether myristicin regulates Th1/Th2 cytokine production, T-bet and GATA-3 gene expression in ovalbumin (OVA)-induced asthma model mice. Myristicin reduced levels of IL-4, Th2 cytokine production in OVA-sensitized and challenged mice. In the other side, it increased $IFN-{\gamma}$, Th1 cytokine production in myristicin administrated mice. We also examined to ascertain whether myristicin could influence eosinophil peroxidase (EPO) activity. After being sensitized and challenged with ovalbumin (OVA) showed typical asthmatic reactions. These reactions included an increase in the number of eosinophils in bronchoalveolar lavage fluid, an increase in inflammatory cell infiltration into the lung tissue around blood vessels and airways, and the development of airway hyper-responsiveness (AHR). The administration of myristicin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, these findings provide new insight into the immunopharmacological role of myristicin in terms of its effects in a murine model of asthma.

• Journal of Life Science
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• v.27 no.2
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• pp.155-163
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• 2017

Mori Folium, the leaf of Morus alba, is a traditional medicinal herb that shows various pharmacological activities such as antiinflammatory, antidiabetic, antimelanogenesis, antioxidant, antibacterial, antiallergic, and immunomodulatory activities. However, the mechanisms of their inhibitory effects on adipocyte differentiation and adipogenesis remain poorly understood. In the present study, we investigated the inhibition of adipocyte differentiation and adipogenesis by ethanol extracts of Mori Folium (EEMF) in 3T3-L1 preadipocytes. Treatment with EEMF suppressed the terminal differentiation of 3T3-L1 preadipocytes in a dose-dependent manner, as confirmed by a decrease in the lipid droplet number and lipid content through Oil Red O staining. EEMF significantly reduced the accumulation of cellular triglyceride, which is associated with a significant inhibition of pro-adipogenic transcription factors, including sterol regulatory element-binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor-${\gamma}$ ($PPAR{\gamma}$), and CCAAT/enhancer-binding proteins ${\alpha}$ ($C/EBP{\alpha}$) and ${\beta}$ ($C/EBP{\beta}$). In addition, EEMF potentially downregulated the expression of adipocyte-specific genes, including adipocyte fatty acid binding protein (aP2) and leptin. Furthermore, EEMF treatment effectively increased the phosphorylation of the AMP-activated protein kinase (AMPK) and acetyl CoA carboxylase (ACC); however, treatment with a potent inhibitor of AMPK, compound C, significantly restored the EEMF-induced inhibition of pro-adipogenic transcription factors and adipocyte-specific genes. These results together indicate that EEMF has preeminent effects on the inhibition of adipogenesis through the AMPK signaling pathway, and further studies will be needed to identify the active compounds in Mori Folium.