• Title/Summary/Keyword: Protective factor

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Mycobacterium abscessus ᴅ-alanyl-ᴅ-alanine dipeptidase induces the maturation of dendritic cells and promotes Th1-biased immunity

  • Lee, Seung Jun;Jang, Jong-Hwa;Yoon, Gun Young;Kang, Da Rae;Park, Hee Jo;Shin, Sung Jae;Han, Hee Dong;Kang, Tae Heung;Park, Won Sun;Yoon, Young Kyung;Soh, Byoung Yul;Jung, In Duk;Park, Yeong-Min
    • BMB Reports
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    • v.49 no.10
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    • pp.554-559
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    • 2016
  • Mycobacterium abscessus, a member of the group of non-tuberculous mycobacteria, has been identified as an emerging pulmonary pathogen in humans. However, little is known about the protective immune response of antigen-presenting cells, such as dendritic cells (DCs), which guard against M. abscessus infection. The M. abscessus gene MAB1843 encodes ᴅ-alanyl-ᴅ-alanine dipeptidase, which catalyzes the hydrolysis of ᴅ-alanyl-ᴅ-alanine dipeptide. We investigated whether MAB1843 is able to interact with DCs to enhance the effectiveness of the host's immune response. MAB1843 was found to induce DC maturation via toll-like receptor 4 and its downstream signaling pathways, such as the mitogen-activated protein kinase and nuclear factor kappa B pathways. In addition, MAB1843-treated DCs stimulated the proliferation of T cells and promoted Th1 polarization. Our results indicate that MAB1843 could potentially regulate the immune response to M. abscessus, making it important in the development of an effective vaccine against this mycobacterium.

A Population-based Case-control Study on Risk Factors for Gastric Cardia Cancer in Rural Areas of Linzhou

  • Sun, Chang-Qing;Chang, Yu-Bo;Cui, Ling-Ling;Chen, Jia-Jun;Sun, Nan;Zhang, Wei-Jie;Jia, Xiao-Can;Tian, Yuan;Dai, Li-Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.5
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    • pp.2897-2901
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    • 2013
  • Gastric cancer is the second most common cause of cancer-related deaths in the world. Although certain dietary factors and lifestyles have been suggested to be associated with gastric carcinogenesis, there have been few investigations focusing on rural areas. A case-control study was therefore carried out to investigate the risk factors of gastric cardia cancer (GCC) in rural areas of Linzhou. A total of 470 newly diagnosed cases of GCC and 470 healthy controls were included. Face-to-face interviews were conducted, using a uniform questionnaire containing questions on demographics, per capita income, living habits, dietary habits and family history of tumors. The relationship between putative risk factors and GCC was assessed by odds ratios (OR) and their 95% confidence intervals (95%CI) derived from conditional logistic regression model by the COXREG command using SPSS 12.00. Multivariate logistic regression analysis was used to evaluate simultaneously the effects of multiple factors and other potential confounding factors. Multivariate logistic analysis showed that smoking (OR=1.939, 95%CI:1.097-3.426), alcohol drinking (OR=2.360, 95%CI: 1.292-4.311), hot food consumption (OR=2.034, 95%CI: 1.507-2.745), fast eating (OR=1.616, 95%CI: 1.171-2.230), mouldy food (OR=4.564, 95%CI: 2.682-7.767), leftover food (OR=1.881. 95%CI: 1.324-2.671), and family history of tumor (OR=2.831, 95%CI: 1.588-5.050) were risk factors for GCC. High per capita income (OR=0.709, 95%CI: 0.533-0.942), high education level (OR=0.354, 95%CI: 0.163-0.765), consumption of fresh fruits (OR=0.186, 95%CI: 0.111-0.311) and vegetables (OR=0.243, 95%CI: 0.142-0.415), and high BMI (OR=0.367, 95%CI: 0.242-0.557) were protective factors for GCC. Our data indicate that unhealthy lifestyle and dietary habits might be important contributors to GCC in this population.

Effect of Lignin and Hemicellulose on the Mutagenicity of IQ (Lignin과 Hemicellulose의 IQ에 의한 돌연변이 억제에 관한 연구)

  • 성미경
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.1
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    • pp.67-71
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    • 1997
  • Different concentrations of lignin and hemicellulose were preincubated with 0.01$\mu\textrm{g}$ of 2-amino-3-methylimidazo[4, 5-f]quinoline(IQ) at simulated gastrointestinal pH condition s. The Ames Salmonella assay using Salmonella typhimurim TA98 was performed to detect any changes in the mutagenicity of IQ in the presence of lignin or hemicellulose. IQ revealed very weak or no mutagenicity when it was preincubated at pH 2.1. However, there was a dose-dependent inhibition of IQ mutagenicity in tile presence of lignin or hemicellulose at pH 5.4 and 6.6. The antimutagenic activities of fibers were not different from each other. Also, at lower concentrations of fibers, pH 5.4 was more effective in suppressing IQ mutagenicity, while 300$\mu\textrm{g}$ of lignin or hemicellulose significantly reduced the mutagenicity of IQ regardless of pH conditions. These results suggest that at gastrointestinal pH conditions, both soluble and insoluble fibers inhibit mutagenicity of IQ by adsorption. Therefore, a possible mechanism for Protective effect of fibers against cancer is due to their adsorption to mutagens in the gastrointestinal tract, and pH seems to be an important factor in the regulation of interactions between the fiber and mutagens.

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Meta-analysis of Associations between ATM Asp1853Asn and TP53 Arg72Pro Polymorphisms and Adverse Effects of Cancer Radiotherapy

  • Su, Meng;Yin, Zhi-Hua;Wu, Wei;Li, Xue-Lian;Zhou, Bao-Sen
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10675-10681
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    • 2015
  • Background: The ataxia telangiectasia mutated (ATM) protein and p53 play key roles in sensing and repairing radiation-induced DNA double strand breaks (DSBs). Accumulating epidemiological evidence indicates that functional genetic variants in ATM and TP53 genes may have an impact on the risk of radiotherapy-induced side effects. Here we performed a meta-analysis to investigate the potential interaction between ATM Asp1853Asn and TP53 polymorphisms and risk of radiotherapy-induced adverse effects quantitatively. Materials and Methods: Relevant articles were retrieved from PubMed, ISI Web of Science and the China National Knowledge Infrastructure (CNKI) databases. Eligible studies were selected according to specific inclusion and exclusion criteria. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled to estimate the association between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and risk of radiotherapy adverse effects. All analyses were performed using the Stata software. Results: A total of twenty articles were included in the present analysis. In the overall analysis, no significant associations between ATM Asp1853Asn and TP53 Arg72Pro polymorphisms and the risk of radiotherapy adverse effects were found. We conducted subgroup analysis stratified by type of cancer, region and time of appearance of side effects subsequently. No significant association between ATM Asp1853Asn and risk of radiotherapy adverse effects was found in any subgroup analysis. For TP53 Arg72Pro, variant C allele was associated with decreased radiotherapy adverse effects risk among Asian cancer patients in the stratified analysis by region (OR=0.71, 95%CI: 0.54-0.93, p=0.012). No significant results were found in the subgroup analysis of tumor type and time of appearance of side effects. Conclusions: The TP53 Arg72Pro C allele might be a protective factor of radiotherapy-induced adverse effects among cancer patients from Asia. Further studies that take into consideration treatment-related factors and patient lifestyle including environmental exposures are warranted.

Effect of Soy Isoflavones on the Expression of $TGF-{\beta}1$ and Its Receptors in Cultured Human Breast Cancer Cell Lines

  • Kim Young-Hwa;Jin Kyong-Suk;Lee Yong-Woo
    • Biomedical Science Letters
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    • v.11 no.2
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    • pp.175-183
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    • 2005
  • The two major isoflavones in soy, genistein and daidzein, are well known to prevent hormone-dependent cancers by their anti estrogenic activity. The exact molecular mechanisms for the protective action are, however, not provided yet. It has been reported that genistein and daidzein have a potential anticancer activity through their antiproliferative effect in many hormone-dependent cancer cell lines. Transforming growth $factor-\beta1(TGF-\beta1)$ has also been found to have cell growth inhibitory effect, especially in mammary epithelial cells. This knowledge led to a hypothetical mechanism that the soy isoflavones-induced growth inhibitory effect can be derived from the regulation of $TGF-\beta1$ and $TGF-\beta$ receptors. In order to test this hypothesis, the effects of the soy isoflavones at various concentrations and periods on the expression of $TGF-\beta1$and $TGF-\beta$ receptors were investigated by using Northern blot analysis in human breast carcinoma epithelial cell lines, an estrogen receptor positive cell line (MCF-7) and an estrogen receptor negative cell line (MDA-MB-231). As a result, only genistein has shown a profound dose-dependent effect on $TGF-\beta1$ expression in the $ER^+$ cell line within the range of doses tested, and the expression levels are correspondent to their inhibitory activities of cell growth. Moreover, daidzein showed down-regulated $TGF-\beta1$ expression at a low dose, the cell growth proliferation was promoted at the same condition. Therefore, antiproliferative activity of the soy isoflavones can be mediated by $TGF-\beta1$ expression, and the effects are mainly, if not all, occurred by ER dependent pathway. The expression of $TGF-\beta$ receptors was induced at a lower dose than the one for $TGF-{\beta}1$ induction regardless of the presence of ER, and the expression patterns are similar to those of the cell growth inhibition. These results indicated that the regulation of $TGF-\beta$ receptor expression as well, prior to $TGF-\beta1$ expression, may be involved in the antiproliferative activity of soy isoflavones. Little or no expression of $TGF-\beta$ receptors was found in the MCF-7 and MDA-MB-231 cells, suggesting refractory properties of the cells to growth inhibitory effect of the $TGF-\beta$. The soy isoflavones can seemingly restore the sensitivity of growth inhibitory responses to $TGF-\beta1$ by re-inducing $TGF-\beta$ receptors expression. In conclusions, our findings presented in this study show that the antitumorigenic activity of the soy isoflavones could be mediated by not only $TGF-\beta1$induction but $TGF-\beta$ receptor restoration. Thus, soy isoflavones could be good model molecules to develop new nonsteroidal antiestrogenic chemopreventive agents, associated with, regulation of $TGF-\beta$ and its receptors.

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Overview of UV-B Effects on Marine Algae (자외선이 해조류에 미치는 영향에 관한 고찰)

  • 한태준
    • Korean Journal of Environmental Biology
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    • v.17 no.1
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    • pp.1-9
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    • 1999
  • Numerous observations revealed strong evidence of increased middle ultraviolet radiation or UV-B (280 ~ 320 nm) at the earth's surface resulting from stratospheric ozone depletion. UV is the waveband of electromagnetic radiation which is strongly absorbed by nucleic acids and proteins, thus causing damage to living systems. It has been recorded in the East Sea, Korea that solar UV-B impinging on the ocean surface penetrates seawater to significant depths. Recent researches showed that exposure to UV-B for as short as 2h at the ambient level (2.0 Wm$^{-2}$) decreased macroalgal growth and photosynthesis and destroyed photosynthetic pigments. These may suggest that UV-B could be an important environmental factor to determine algal survival and distribution. Some adaptive mechanisms to protect macroalgae from UV-damage have been found, which include photoreactivation and formation of UV-absorbing pigments. Post-illumination of visible light mitigated UV-induced damage in laminarian young sporophytes with blue the most effective waveband. The existence of UV-B absorbing pigments has been recognized in the green alga, Ulva pertusa and the red alga, Pachymeniopsis sp., which is likely to exert protective function for photosynthetic pigments inside the thalli from UV-damage. Further studies are however needed to confirm that these mechanisms are of general occurrence in seaweeds. Macroalgae together with phytoplankton are the primary producers to incorporate about 100 Gt of carbons per year, and provide half of the total biomass on the earth. UV-driven reduction in macroalgal biomass, if any, would therefore cause deleterious effects on marine ecosystem. The ultimate impacts of increasing UV-B flux due to ozone destruction are still unknown, but the impression from UV studies made so far seems to highlight the importance of setting up long-term monitoring system for us to be able to predict and detect the onset of large -scale deterioration in aquatic ecosystem.

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Spermidine Protects against Oxidative Stress in Inflammation Models Using Macrophages and Zebrafish

  • Jeong, Jin-Woo;Cha, Hee-Jae;Han, Min Ho;Hwang, Su Jung;Lee, Dae-Sung;Yoo, Jong Su;Choi, Il-Whan;Kim, Suhkmann;Kim, Heui-Soo;Kim, Gi-Young;Hong, Su Hyun;Park, Cheol;Lee, Hyo-Jong;Choi, Yung Hyun
    • Biomolecules & Therapeutics
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    • v.26 no.2
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    • pp.146-156
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    • 2018
  • Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.

Protective Effects of Capsosiphon fulvescens and Pheophorbide a on Streptozotocin-induced Oxidative Stress in Testicular (Streptozotocin에 의한 산화 스트레스로부터 매생이 추출물의 정소 조직 보호 효과)

  • Son, Won-rak;Nam, Mi-Hyun;Han, Ah-Ram;Pyo, Min-Cheol;Kim, Se-Wook;Jung, Hye-Lim;Lee, Hwa;Kim, Ji-Yeon;Lee, Kwang-Won
    • Journal of Food Hygiene and Safety
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    • v.30 no.2
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    • pp.202-209
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    • 2015
  • We investigated the effect of Capsosiphon fulvescens (CFE) and pheophorbide a (PhA) contained in CFE on oxidative stress regarded as a factor for diabetic complication. Streptozotocin (STZ), known as an oxidative stress inducer, was intraperitoneal injected for causing diabetes. After 7 days, CFE (4 and 20 mg/kg body weight) and PhA (0.2 mg/kg body weight) were treated once a day for 9 weeks. After the sacrifice, testis tissues were collected for the experiments. We confirmed that the treatment with CFE and PhA in diabetic animals not only decreased level of lipid peroxidation and serum nitric oxide compared with the diabetes group, but also the activities of glutathione peroxidase and glutathione-S-transferase were restored remarkably. Furthermore the activity of antioxidant enzymes, catalase and superoxide dismutase, were significantly recovered. With these results, our study suggest that CFE containing PhA may prevent seminal glands damages induced by oxidative stress in diabetic condition.

Effects of Mycelial Extract of Phellinus linteus on Ethanol-Induced Liver Injury in Rats (알코올성 간 손상에 대한 상황버섯 배양균사체 추출물의 효능)

  • Choi, Byung-Tae;Choi, Yung-Hyun;Gil, Young-Gi
    • Journal of Life Science
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    • v.16 no.6
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    • pp.978-983
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    • 2006
  • We investigated the anti-inflammatory effects of mycelial culture extract from Phellinus linteus (MCPL) for suppression in the process of ethanol-induced inflammation in rat liver. Levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly increased in the serum of ethanol-treated rats compared to normal. However, the level of ALT was arrested markedly in ethanol-treated rats with MCPL compared to ethanol alone treated control ones. Severe histopathological changes of liver such as cloudy swelling, inflammatory cells infiltration, Kupffer cell reaction and focal necrosis were demonstrated in the rats challenged with ethanol compared with normal. Fewer scores of these changes were observed in MCPL-treated rat with recovered glycogen in centrolobular region of hepatic lobule. The Western analysis showed that the expression of inflammatory proteins such as cyclooxygenase (COX)-1, COX-2, inducible nitric oxide synthase (iNOS), tumor necrosis factor $(TNF)-{\alpha}$ were increased in the ethanol-treated rat. But decline of COX-2 and iNOS expression were observed in MCPL-treated rat. Immunohistochemical analysis showed that the expression of COX-2 and $TNF-{\alpha}$ tended to increase in ethanol-treated rat, but decrease of these reactions were induced by MCPL treatment. These results suggest that MCPL may act as a protective agent for alcohol-induced liver injury through a regulating inflammation-related proteins.

The Anti-Fibrogenic Effect of a Pharmaceutical Composition of[5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione] (Oltipraz) and Dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB)

  • Kang, Keon-Wook;Kim, Yoon-Gyoon;Kim, Choon-Won;Kim, Sang-Geon
    • Archives of Pharmacal Research
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    • v.25 no.5
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    • pp.655-663
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    • 2002
  • Liver fibrosis is a prepathological state wherein damaged liver tissues in chronic liver diseases, such as hepatitis, are not repaired to normal tissues, but converted to fibrous tissue. 5-(2-Pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz), a cancer chemopreventive agent, is effective against a wide variety of chemical carcinogens. Recently, we reported that oltipraz inhibits liver fibrogenesis (Kang et al., 2002). In the present study, the effects of oltipraz in combination with dimethyl-4,4'-dimethoxy-5,6,5',6'-dimethylene dioxybiphenyl-2,2'-dicarboxylate (DDb) on dimethylnitrosamine (DMN)-induced liver fibrogenesis were assessed in rats. Oltipraz (30 mg/kg body weight, po, 3 times per week for 4 weeks) was found to inhibit the increases in plasma ALT, AST and bilirubin by DMN, whereas DDB (30 mg/kg body weight, po, 3 times per week for 4 weeks) attenuated the increases in the plasma ALT and bilirubin. The lowered plasma protein and albumin contents in DMN-treated rats were completely restored by oltipraz, but not by DDB. DDB decreases liver cell injury and inflammation through inhibition of nuclear factor-kB. DMN increased the accumulation of liver collagen, as indicated by the increase in the 4-hydroxyproline content in liver homogenates, which was reduced by treatment with oltipraz, but not by DDB. Given the differential effect between oltipraz and DDB, the potential enhancement of antifibrotic efficacy by the drugs was assessed in the animal model. Despite the minimal effect of DDB on DMN-induced fibrogenesis, DDB (5-25 mg/kg), administered together with oltipraz (25-5 mg/kg), showed an additive protective effect against hepatotoxicity and fibrosis induced by DMN, which was shown by the blood chemistry parameters and histopathological analysis. The adequate composition ratio of oltipraz to DDB was 5:1. These results provide information on the pharmaceutical composition, comprising of oltipraz and DDB as the active components, for the treatment and/or prevention of liver fibrosis and cirrhosis.