• Journal of the Korean Society of Food Science and Nutrition
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• v.40 no.10
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• pp.1404-1410
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• 2011

Biological compounds (caffeic acid, rosemarinic acid, and chlorogenic acid) from mulberry leaf extracts were administered to mice in order to confirm their stability. All male and female mice survived upon a 4,000 mg/g dose in an acute toxicity test, and they also survived after injection of 2,000 mg/kg for 13 weeks repeatedly. Therefore, the level of toxicity was not high. In a comparison of the control and test groups, there were no significant differences upon naked eye inspection, and the weights of stomachs infected by Helicobacter pylori were not significantly different. Regarding the effects on immune cells, NO of macrophages decreased more than that of control when medicine was administered. The spleens of the female mice group proliferated slightly in LPS and Con A within 48 hr, whereas the other test group showed a similar level and the cell toxicity of natural killing cells decreased. Therefore, we concluded that caffeic acid, rosemarinic acid, and chlorogenic acid from mulberry leaf extracts are not harmful for the treatment of infected patients the development as a healthy functional food.

• YAKHAK HOEJI
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• v.48 no.6
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• pp.335-344
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• 2004

Interleukin-2 (IL-2), a glycoprotein mainly secreted by CD4+ T helper Iymphocytes, has been developed to use recombinant cytokine to augment the immune response against cancer since IL-2 not only stimulates T Iymphocytes but also enhances natural killer (NK) cell activity. In order to evaluate the immunological safety of recombinant mouse IL-2 (rmIL-2) in cancer therapy, renal cell carcinoma was established in the flank by s.c. injection of renca cell line. Tumor-bearing BALB/c mice were treated with I.p. injections with $2{\times}10^5$ Lu rmIL-2. Even though the tumor size was diminished, there were not significant recovery of body and relative lymphoid organ weights including thymic atrophy in rmIL-2 immunotherapy. Distribution ratios of T cell subsets in thymus were analysed using flow cytometry. Without regard to dosage of rmIL-2, the ratio of CD3+CD4-CD8- T cells was increased in accordance with survival of solid tumor but that of CD4+CD8+ T cells was decreased dramatically. Emergence of autoantibodies (ANA, anti-dsDNA, and anti-histone) in blood was measured after rmIL-2 treatment. The results showed that the levels of ANA and anti-dsDNA did not significantly changed, but the level of anti-histone was increased significantly owing to rmIL-2 therapy. These results indicate rmIL-2 immunotherapy is to induce the autoimmune potential, and the anti-histone measurement as a biomarker of autoimmunity is useful in cancer immunotherapy.

• IMMUNE NETWORK
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• v.9 no.6
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• pp.236-242
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• 2009

Background: Melanoma is the most fatal form of skin cancer due to its rapid metastasis. Recently, several studies reported that selenium can induce apoptosis in melanoma cells. However, the precise mechanism remains to be elucidated. In this study, we investigated the effect of selenium on cell proliferation in murine melanoma and on tumor growth and metastasis in C57BL/6 mice. Methods: Cell proliferation was measured by MTT assay in selenium-treated melanoma cells. Cell cycle distribution was analysized by staining DNA with propidum iodide (PI). mRNA and protein expression related to cell cycle arrest was measured by reverse transcription PCR and western blot. Tumor growth and metastasis was measured by in vivo model. Results: Selenium was suppressed the proliferation of melanoma cells in a dose dependent manner. The growth inhibition of melanoma by selenium was associated with an arrest of cell cycle distribution at G0/G1 stage. The mRNA and protein level of CDK2/CDK4 was suppressed by treatment with selenium in a time-dependent manner. In vivo, tumor growth was not suppressed by selenium; however tumor metastasis was suppressed by selenium in mouse model. Conclusion: These results suggest that selenium might be a potent agent to inhibit proliferative activity of melanoma cells.

• Korean Journal of Pharmacognosy
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• v.18 no.2
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• pp.118-126
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• 1987

Natural Killer cells are considerd to play an important role in antitumor immune surveilance mechanism. In this study, 21 putative anticancer drugs selected from reference were assessed by evaluating the effect on rat Natural Killer cell activity (NKCA). All 21 herb drugs were extracted in boiling water, lyophilized, autoclaved, and then used for experiment. Culture supernatant of concanavalin-A (Con-A)-stimulated rat spleen cells as a source of lymphokine was also used as a control of comparison. Rat spleen cells were used as effector and NKCA was measured in 4hr $^{51}Cr-release$ assay against Yac-1 mouse lymphoma cell line. In order to determine the optimal conditions for NKCA augmentation, effector cells were treated with 3 different concentrations of each drug for 24, or 48 hrs before testing of NKCA, In optimal conditions determined from previous results, the effect of herb drugs on NKCA were assessed in 3 to 5experiments. NKCA was significantly enhanced by treatment with 4 herb drugs(Ponciri Fructus, Houttuyniae Herba, Aurantii Pericarpium, Nepetae Herba). Culture supernatant of Con-A-stimulated spleen cells also augmented the rat NKCA more significantly. The results show that 4 of the herb medicines supposed to display anticancer effect may have activity as a biological response modifier through augmentation of NKCA.

• Journal of Life Science
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• v.28 no.10
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• pp.1127-1131
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• 2018

Cortisol, a steroid hormone, functions within metabolism, immune response, and stress. Intense or prolonged physical exercise increases cortisol levels to enhance the gluconeogenesis pathway and stabilize blood glucose level. However, cortisol also exerts a negative impact on muscle function and creates a stressful environment in skeletal muscle cells. The present study investigated the function of cortisol as a stress hormone. To examine the effect of the exercise-induced hormone cortisol on skeletal muscles, C2C12 cells were cultured and treated with cortisol at different concentrations. As a result, we found that the morphology of C2C12 changed remarkably with 5 ug/ml cortisol treatment. Western blot analysis was conducted to learn whether ER-stress and autophagy were induced. We found that the expression ratio of LC3I/LC3II decreased and BiP expression increased after cortisol treatment. In addition, immunocytochemistry analysis with IER3 antibody clearly showed that apoptosis is induced after 12-hour cortisol treatment. These results indicate that cortisol treatment could induce apoptosis, ER-stress, and autophagy in muscle cells. This study would provide valuable information in the study of the effects of exercise on skeletal muscle cells and the development of additives to reduce cortisol stress.

• Journal of Physiology & Pathology in Korean Medicine
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• v.20 no.1
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• pp.37-42
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• 2006

Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants such as lipopolysaccharide (LPS) leads to the production of significant amounts of MMP-9. Here, we show that LPS-induced MMP-9 production and activation was inhibited by the water extract from the fruit of Chaenomeles sinensis (CS), the root of Polygonum cuspidatum (PC), but increased by the extract from Boswellia carterii (BC). To investigate the mechanism by which those extracts inhibits MMP-9 activation, we examined the level of MMP-9 mRNA expression. We observed a significant change in the MMP-9 expression between LPS alone and LPS plus Chaenomeles sinensis and Polygonum cuspidatum extracts-treated cells. In addition, LPS significantly up-regulated MMP-9 promoter activity in Raw 264.7 cells, which was attenuated by the CS and PS extracts. However, water extracts from Boswellia carterii increased MMP-9 expression and MMP-9 promoter activity which were induced by LPS treatment in Raw 264.7 cells. These data suggest that water extracts from Chaenomeles sinensis and Polygonum cuspidatum can modulate anti-inflammatory immune response, which may be in part associated with the regulation of MMP-9 production and/or activation through the regulation of MMP-9 expression in mouse macrophage cells.

• Applied Microscopy
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• v.38 no.1
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• pp.11-19
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• 2008

To examine the effect of the electrolyzed alkaline reduced water (ERW) on animal immunity, by employing Echinostoma hortense that is a parasite in the small intestine, the immune response of C57BL/6 was examined. To C57BL/6 mice, Echinostoma hortense metacercaria 15 per animal was in oculate dorsally, the worm was collected after 2 weeks, and the change of goblet cells and mast cells in the mucosa of small intestine was examined, and by using a protein chip, the change of cytokines in the serum was compared and observed. As a result, average 8.3 worms were collected from the C57BL/6 mice infected with E. hortense, and in the group fed with the ERW, average 10 worms were collected. In regard to the examination of the change of goblet cells, in the experimental group infected with E. hortense and fed with the ERW, average 4.3 worms per villus were detected, hence, it was found that the expression of goblet cells was low (p<0.001). Regarding the examination of the change of mast cells, similarly, in the group infected with E. hortense and fed with the ERW, average 11 worms per villus were detected, and it appears to be less than control group (p<0.001). Regarding the expression of cytokines in mouse serum, in comparison of the experiment group infected with E. hortense and control group, in the expression of the Th1 cytokines IL-6, IL-$1{\beta}$, IFN-${\gamma}$, TNF-${\alpha}$, and IL-2, and the Th2 cytokines IL-4, IL-5, IL-10, and IL-13, a significant difference was not detected. In our study, it was found that in the infection of E. hortense, the ERW mediates its effect on the number of goblet cells and mast cells in the intestinal mucosa, and simultaneously, the worm expulsion was delayed, and thus the conclusion that the ERW mediated its effect on the intestinal immunity of mice was obtained.

• Journal of Veterinary Science
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• v.24 no.4
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• pp.52.1-52.13
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• 2023

Background: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. Objectives: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. Methods: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Results: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b⁺CD206⁺ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E₂ (PGE₂) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. Conclusions: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE₂ pathway.

• Journal of Life Science
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• v.29 no.4
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• pp.484-491
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• 2019

Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

• Microbiology and Biotechnology Letters
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• v.44 no.2
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• pp.201-207
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• 2016

The aim of this study was to investigate the potential of lactic acid bacteria (LAB) strains as probiotics. Two strains were isolated from healthy chicken cecum and their acid and bile tolerance, residual organic acids, antibacterial activity against pathogenic bacteria, and immunomodulation activity were measured. Identification of the isolated strains was performed using the API 50CHL system and phylogenetic analysis using 16S rDNA sequencing. The isolates were determined to be Lactobacillus sakei strains. The acid tolerance of strains L2 and L8 was high enough that 75% of the inoculum survived in pH 2 for 2 h. The bile tolerance of both strains was observed at a 1% Oxgall concentration in MRS broth. The production of organic acids (lactic acid and acetic acid) and pH changes during growth were monitored and the maximum concentrations were obtained after 48 h of incubation. Culture supernatants of the two LAB strains showed strong antibacterial activity against pathogenic bacteria. The heat-killed LAB cells also induced high levels of immune cell proliferation compared with the control, and stimulated IL-6 and TNF-α production in mouse macrophages. Therefore, L. sakei strains L2 and L8 can be considered suitable probiotic bacteria.