• Journal of Microbiology and Biotechnology
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• v.24 no.9
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• pp.1269-1279
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• 2014

Xanthomonas oryzae pv. oryzae (Xoo) strains are plant pathogenic bacteria that can cause serious blight of rice, and their virulence towards plant host is complex, making it difficult to be elucidated. Caenorhabditis elegans has been used as a powerful model organism to simplify the host and pathogen system. However, whether the C. elegans is feasible for studying plant pathogens such as Xoo has not been explored. In the present work, we report that Xoo strains PXO99 and JXOIII reduce the lifespan of worms not through acute toxicity, but in an infectious manner; pathogens proliferate and persist in the intestinal lumen to cause marked anterior intestine distension. In addition, Xoo triggers (i) the p38 MAPK signal pathway to upregulate its downstream C17H12.8 expression, and (ii) the DAF-2/DAF-16 pathway to upregulate its downstream gene expressions of mtl-1 and sod-3 under the condition of daf-2 mutation. Our findings suggest that C. elegans can be used as a model to evaluate the virulence of Xoo phytopathogens to host.

• IMMUNE NETWORK
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• v.12 no.3
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• pp.126-128
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• 2012

We report on a case of severe hepatotoxicity in a 52-year-old male with multiple myeloma (MM) who had received bortezomib therapy. At patient presentation, liver enzymes were normal, but started to markedly increase 3 days after the patient's second dose of bortezomib was administered, when free kappa light chains were noticeably reduced in the serum. After discontinuation of bortezomib, liver enzymes recovered gradually to baseline. Then, the patient was started on a thalidomide-containing regimen, which he was able to tolerate well. The patient achieved complete remission prior to autologous stem cell transplantation (ASCT). The patient underwent ASCT without occurrence of further liver toxicity.

• Archives of Pharmacal Research
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• v.28 no.1
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• pp.100-105
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• 2005

Mancozeb (MCZ) is known to have detrimental effects on the reproductive system, but the toxicity of MCZ on immune responses has not been systematically investigated. We investigated the effects of MCZ exposure on the activities of murine peritoneal macrophages through evaluation of MCZ-induced alteration of nitric oxide (NO) production and tumor necrosis $factor-{\alpha}(TNF-\alpha)$ synthesis. Macrophages were examined ex vivo from mice orally treated with various doses of MCZ for 5 consecutive days per week for 4 weeks (subacute exposure, 250, 1000, 1500 mg/kg/day) followed by culture for 2 $(TNF-{\alpha})$ or 3 days (NO) in the presence of LPS plus $IFN-{\gamma}$. Macrophages from naive mice were also cultured with various concentrations of MCZ (0.05, 0.25, 0.5, 1 and 2 ${\mu}g//mIL$ in the presence of LPS plus $IFN-{\gamma}$ for 2 $(TNF-{\alpha})$ or 3 days (NO) in vitro. NO production was decreased with the in vitro exposure to all concentrations of MCZ. However, the amount of NO production by peritoneal macrophages from MCZ-subacutely exposed mice was increased in comparision with that of control group. In vitro, MCZ suppressed $(TNF-\alpha)$ secretion with significant reduction at 2 ${\mu}g/mL$ MCZ. Conversely, $(TNF-{\alpha})$ release was enhanced ex vivo. This study provides the substantial evidence on MCZ-induced alternation in macrophage activity. In order to clearly understand the contrasting effect of MCZ on peritoneal macrophage activity, it is necessary to further investigate the influence of major metabolite of MCZ (ETU) exposure on the NO production and $(TNF-{\alpha})$ synthesis.

• THE JOURNAL OF KOREAN ORIENTAL ONCOLOGY
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• v.6 no.1
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• pp.19-28
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• 2000

In this experiment, we examined the the effect of Laetrile Oil to the immune system and tried to disclose the anti-cancer mechanism of this. The result is listed as below. 1. After per-os, sub-cutaneous and into the peritoneal injection of Laetrile Oil to the SPF mice, the LD50 is above 5000mg/kg at even group. 2. Mean survival days of mice treated with laetril oil, after S-180 cells transplantation into the peritoneal cavity decreases 1.5 days(-6.8%) compared with the Mean survival days of the control group(22days.) 3. Effects of laetril oil on natural killer cell activity at Effector/Target Cell Ratio with 100:1, 50:1, 10:1 into methotrexate-pretreated mice is like this.: Compared with $29.22\pm12.7\%$ Cytotoxicity of the control group, sample group's Cytotoxicity had $38.83{\pm}12.5%$ of meaningful acrease. At 100:1 Effecr/Target Cell Ratio. At 50:1 Effector/Target Cell Ratio, control group has $20.02{\pm}9.6%$ Cytotoxiciy and sample group had $31.53{\pm}13.4%$ Cytotoxicity. At 25:1 Effector/Target Cell Ratio control group has $13.60{\pm}6.6%$ Cytotoxicity and sample group had $20.81{\pm}9.8%$ Cytotoxicity According to the above results, the Laetrile Oil represents nontotoxic to a SPF mice. non-effective to transplantable Sarcoma 180 tumors, and activaion in NK cell activity.

• The Journal of Korea CHUNA Manual Medicine
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• v.1 no.1
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• pp.83-90
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• 2000

Oryeong-San, Pangpungtongseong-San, Rangkyeoksanwha-Tang, Sipeemikwanjoong -Tang and Taeumjoui-Tang are not only examined using the code which are related to overweight in the QRIS but are also investigated the level of Free Radical using the Free Radical Measurement after steeping those 5 prescriptions in water. The results are as follows: 1. We indicated in the study of QRIS that 5 kinds of medicines which used most frequently In the treatment of the obesity appeared to affect the Immune system, spleen, kidneys, pancreas, the fatigue toxicity, TSH, and the metabolic disability but did not influence high on the contents of overweight and those of fatty cell, as well. in addition, there were no significant differences between the prescriptions as regards testosterone and progesterone. 2. In the Free Radical Measurement, Rangkyeoksanwha-Tang evaluated significantly high level of Free Radical, whereas others appear to have the similar level of Free Radical. These findings suggest that the treatment of the obesity affects particular body parts with respect to the control of overweight, although those medicines are not related directly to the areas(such as fatty cell Code), it is possible that they influence on the cure for the obesity. Furthermore, they indicate that with soaking prescription, Free Radical is not produced as much as we expected.

• Molecular & Cellular Toxicology
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• v.5 no.1
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Bulletin of the Korean Chemical Society
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• v.35 no.8
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• pp.2494-2504
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• 2014

P38 mitogen activated protein (MAP) kinase is an important anti-inflammatory drug target, which can be activated by responding to various stimuli such as stress and immune response. Based on the conformation of the conserved DFG loop (in or out), binding inhibitors are termed as type-I and II. Type-I inhibitors are ATP competitive, whereas type-II inhibitors bind in DFG-out conformation of allosteric pocket. It remains unclear that how these allosteric inhibitors stabilize the DFG-out conformation and interact. Organosilicon compounds provide unusual opportunity to enhance potency and diversity of drug molecules due to their low toxicity. However, very few examples have been reported to utilize this property. In this regard, we performed docking of an inhibitor (BIRB) and its silicon analog (Si-BIRB) in an allosteric binding pocket of p38. Further, molecular dynamics (MD) simulations were performed to study the dynamic behavior of the simulated complexes. The difference in the biological activity and mechanism of action of the simulated inhibitors could be explained based on the molecular mechanics/generalized Born surface area (MM/GBSA) binding free energy per residue decomposition. MM/GBSA showed that biological activities were related with calculated binding free energy of inhibitors. Analyses of the per-residue decomposed energy indicated that van der Waals and non-polar interactions were predominant in the ligand-protein interactions. Further, crucial residues identified for hydrogen bond, salt bridge and hydrophobic interactions were Tyr35, Lys53, Glu71, Leu74, Leu75, Ile84, Met109, Leu167, Asp168 and Phe169. Our results indicate that stronger hydrophobic interaction of Si-BIRB with the binding site residues could be responsible for its greater binding affinity compared with BIRB.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.1
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• pp.16-22
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• 2016

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

• Herbal Formula Science
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• v.17 no.2
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• pp.73-83
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• 2009

Objective : In vitro proapoptotic effect of Hangbaek-Tang (HBT) has been documented by one of us. In the present study, we aimed to demonstrate in vivo effect of HBT on tumor growth. Methods : In vitro selective cytotoxicity of HBT was examined by enumeration of viable cell numbers using BC3A mouse leukemic cells and normal spleen cells. In vivo effect of HBT (25 and 50 mg/mouse) on tumor growth was assayed using BC3A cells innoculated subcutaneously in the flank. Annexin-V apoptosis assay and PI staining was performed to determine the effective serum factor in HBT-treated mice. Leukocyte recruitment into peritoneum were analyzed by microscopy with a stained cytosmear of peritoneal lavage fluid. Results : HBT exhibited in vitro selective cytotoxicity to leukemic cells and did not show any toxicity on immune organs. In vivo i.p. administration of HBT induced significant reduction in tumor growth but not complete regression. Sera obtained from HBT-treated mice strongly inhibited BC3A cell growth in vitro and were revealed to markedly enhance apoptosis and accompanying cell death, when compared to those from PBS-treated mice. Abundant extravasation of leukocytes, especially neutrophils, into peritoneum was observed in HBT-treated mice. Conclusions : HBT causes leukemic, BC3A cell death in vivo via apoptosis as well as in vitro, for which functional involvement of leukocytes is suggested.

• Toxicological Research
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• v.31 no.1
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• pp.49-59
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• 2015

Eye is a highly vascularised organ. There are chances that a foreign substance can enter the systemic circulation through the eye and cause oxidative stress and evoke immune response. Here the eyes of rabbits were exposed, for a period of 7 days, to 5 known ocular irritants: Cetyl pyridinium chloride (CPC), sodium salicylate (SS), imidazole (IMI), acetaminophen (ACT) and nicotinamide (NIC). The eyes were scored according to the draize scoring. Blood collected from the treated rabbit were analyzed for haematological and biochemical parameters. After sacrifice, histological analysis of the eye and analysis of pro-inflammatory biomarkers ($IL-1{\alpha}$, $IL-1{\beta}$, IL-8 and $TNF-{\alpha}$) in the cornea using ELISA was carried out. Spleen was collected and the proliferation capacities of spleenocytes were analyzed. Liver and brain were collected and assessed for oxidative stress. The eye irritation potential of the chemicals was evident from the redness and swelling of the conjunctiva and cornea. Histopathological analysis and ELISA assay showed signs of inflammation in the eye. However, the haematological and biochemical parameters showed no change. Spleenocyte proliferations showed only slight alterations which were not significant. Also oxidative stress in the brain and liver were negligible. In conclusion, chemicals which cause ocular irritation and inflammation did not show any systemic side-effects in the present scenario.