• Nutrition Research and Practice
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• v.13 no.5
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• pp.384-392
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• 2019

BACKGROUND/OBJECTIVES: Enteral nutrition formulas with immune-enhancing nutrients, such as n-3 fatty acids, may manage patients' nutritional status and pathophysiological processes. The aim of our study was to investigate natural killer (NK) cell activity alterations and related cytokine changes resulting from feeding with soybean oil-containing enteral nutrition formula (control group) and plant-derived n-3 fatty acid-enriched enteral nutrition formula. SUBJECTS/METHODS: Subjects participated for 14 consecutive days and consumed enteral formula containing canola and flaxseed oil (n3EN, test group) in nonsurgical patients hospitalized for rehabilitation. Blood samples were collected on the first day and 14 days after the consumption of each formula daily, and anthropometric parameters were collected. Hematology and biochemical values were analyzed, and NK cell activities and serum cytokine concentration were measured. A total of sixty subjects were included in the analysis, excluding dropouts. RESULTS: No significant differences were found in biochemical parameters. The n3EN group's NK cell activities at effector:tumor cell ratios of 10:1, 5:1, 2.5:1 and 0.625:1 were significantly higher than those of the control group after two weeks (P < 0.05). However, there were no statistically significant differences in serum cytokine interleukin (IL)-12, $interferon-{\gamma}$, $IL-1{\beta}$, IL-6 and tumor necrosis $factor-{\alpha}$ values between the two groups. CONCLUSIONS: In conclusion, this study elucidates the beneficial effects of plant-derived n-3 fatty acid supplementation in enteral formula on NK cell activity.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.261-266
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• 2018

To determine the clinical utility of an immunoblot test and RT-PCR-hybridization test, 160 samples from patients with a chronic HCV infection were analyzed by two tests. A total of 133 samples out of 150 positive samples were positive by RT-PCR-hybridization. The true positive rate of the immunoblot tests and the concordance rate of the two tests was 88.6% and 89.3%, respectively. Serotyping and genotyping were performed to evaluate the distribution of the HCV subtype in Korean isolates. HCV serotypes 1 and 2, and genotypes 1b and 2a were the most common sources of HCV infections in this group. In 49 cases studied with the serotypes and genotypes, serotypes 1 and 2 were 57.1% and 42.9%, respectively. Genotypes 1b, 1b/2b, 2a, 2a/2c, and 2b were 51.0%, 2.0%, 34.7%, 8.2%, and 4.1%, respectively. This study shows that immunoblot tests are more useful for screening HCV infections. The RT-PCR-hybridization test confirmed the HCV infection in patients with positive immunoblot test results. The serotype test is preferred over the genotype test for monitoring the progression or response to treatment. On the other hand, there were no significant differences in the response to an ${\alpha}$-interferon treatment of HCV infection with serotype type 1 or type 2 in Korea.

• Journal of Ginseng Research
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• v.39 no.1
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• pp.29-37
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• 2015

Background: Panax ginseng (i.e., ginseng) root is extensively used in traditional oriental medicine. It is a modern pharmaceutical reagent for preventing various human diseases such as cancer. Ginsenosidesd-the major active components of ginsengd-exhibit immunomodulatory effects. However, the mechanism and function underlying such effects are not fully elucidated, especially in human monocytes and dendritic cells (DCs). Methods: We investigated the immunomodulatory effect of ginsenosides from Panax ginseng root on $CD14^+$ monocytes purified from human adult peripheral blood mononuclear cells (PBMCs) and on their differentiation into DCs that affect $CD4^+$ T cell activity. Results: After treatment with ginsenoside fractions, monocyte levels of tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-6, and IL-10 increased through phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK), but not p38 mitogen-activated protein kinase (MAPK). After treatment with ginsenoside fractions, TNF-${\alpha}$ production and phosphorylation of ERK1/2 and JNK decreased in lipopolysaccharide (LPS)-sensitized monocytes.We confirmed that DCs derived from $CD14^+$ monocytes in the presence of ginsenoside fractions (Gin-DCs) contained decreased levels of the costimulatory molecules CD80 and CD86. The expression of these costimulatory molecules decreased in LPS-treated DCs exposed to ginsenoside fractions, compared to their expression in LPS-treated DCs in the absence of ginsenoside fractions. Furthermore, LPS-treated Gin-DCs could not induce proliferation and interferon gamma (IFN-${\gamma}$) production by $CD4^+$ T cells with the coculture of Gin-DCs with $CD4^+$ T cells. Conclusion: These results suggest that ginsenoside fractions from the ginseng root suppress cytokine production and maturation of LPS-treated DCs and downregulate $CD4^+$ T cells.

• Microbiology and Biotechnology Letters
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• v.49 no.1
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• pp.75-87
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• 2021

Type I Interferons (IFNα) are known for their role as biological anticancer agents owing to their cell-apoptosis inducing properties. Development of an appropriate, cost-effective host expression system is crucial for meeting the increasing demand for proteins. Therefore, this study aims to develop codon-optimized IFNα-2b in L. lactis NZ3900. These cells express extracellular protein using the NICE system and Usp₄₅ signal peptide. To validate the mature form of the expressed protein, the recombinant IFNα-2b was screened in a human colorectal cancer cell line using the cytotoxicity assay. The IFNα-2b was successfully cloned into the pNZ8148 vector, thereby generating recombinant L. lactis pNZ8148-SP_Usp45-IFNα-2b. The computational analysis of codon-optimized IFNα-2b revealed no mutation and amino acid changes; additionally, the codon-optimized IFNα-2b showed 100% similarity with native human IFNα-2b, in the BLAST analysis. The partial size exclusion chromatography (SEC) of extracellular protein yielded a 19 kDa protein, which was further confirmed by its positive binding to anti-IFNα-2b in the western blot analysis. The crude protein and SEC-purified partial fraction showed IC₅₀ values of 33.22 ㎍/ml and 127.2 ㎍/ml, respectively, which indicated better activity than the metabolites of L. lactis NZ3900 (231.8 ㎍/ml). These values were also comparable with those of the regular anticancer drug tamoxifen (105.5 ㎍/ml). These results demonstrated L. lactis as a promising host system that functions by utilizing the pNZ8148 NICE system. Meanwhile, codon-optimized usage of the inserted gene increased the optimal protein expression levels, which could be beneficial for its large-scale production. Taken together, the recombinant L. lactis IFNα-2b is a potential alternative treatment for colorectal cancer. Furthermore, its activity was analyzed in the WiDr cell line, to assess its colorectal anticancer activities in vivo.

• Food Science and Preservation
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• v.31 no.2
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• pp.307-314
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• 2024

Broussonetia kazinoki twig extract (BKT) is recognized for its antioxidant and anti-cancer effects and natural whitening properties. So, it is used as a raw material for cosmetics. B. kazinoki twig is also an edible raw material. B. kazinoki has been used in Asia for paper production and oriental medicine, has anti-diabetic effects, and contains various flavonoids and alkaloids. In this study, to evaluate the efficacy of BKT on allergic skin inflammatory responses, we investigated its effects on factors related to skin inflammation in HaCaT keratinocytes and allergic responses in RBL-2H3 cells. There was no cytotoxicity of the 70% ethanol extract against HaCaT and RBL-2H3 cells. In HaCaT cells, stimulation with tumor necrosis factor-alpha (TNF-𝛼) and interferon-gamma (IFN-𝛾) increased the production of several chemokines, including thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC), and regulated on activation, normal T cell expressed and secreted (RANTES). However, it was observed that this elevation was notably mitigated in a concentration-dependent manner upon treatment with BKT. Furthermore, BKT treatment demonstrated a significant reduction of 𝛽-hexosaminidase and inflammatory cytokines TNF-𝛼 and IL-4 in IgE-sensitized RBL-2H3 cells. Thus, it is expected that BKT can be used as a natural cosmetic and food ingredient that effectively suppresses allergic inflammatory reactions.

• Tuberculosis and Respiratory Diseases
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• v.41 no.2
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• pp.87-96
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• 1994

Background : Since tumor necrosis factor was discovered in 1975, TNF has been well known about its cytotoxic effect on tumor cells in vivo and in vitro. According to the recent improvement of molecular biological techinques, it is possible that exogenous TNF gene is transferred to tumor cells and is expressed in theirs. By virtue of TNF gene transfer, we have expected that TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells in vivo without systemic side effect. The expected mechanisms in which antitumor effects of TNF expressed in TNF-gene-transferred tumor cells are working would be as followings. In the first mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill tumor cells around(like homicide). In the second mechanism, TNF expressed in TNF-gene-transferred tumor cells would kill themselves(like suicide). In the third mechanism, TNF expressed in TNF-gene-transferred tumor cells would recruit immune effector cells and kill tumor cells indirectly. In the last mechanism, TNF expressed in TNF-gene-transferred tumor cells would augment cytokine such as interferon-$\gamma$ to kill tumor cells. Among these four mechanisms of antitumor effect, only the second mechanism has not been established yet. Therefore, to elucidate the second mechanism, We performed this study. Method : We transferred TNF-$\alpha$ gene to NCI-H2058, a human mesothelioma cell line and WEHI164, a murine fibrosarcoma cell line by using retroviral vector(pLT12SNTNF). And, We determined by using MTT assay whether TNF expressed in TNF-gene-transferred tumor cell lines would kill themselves like suicide or not. Then, if TNF-gene-transferred tumor cell lines would not suicide themselves, I would know more about the TNF sensitivity of TNF-gene-transferred tumor cell lines to exogenous TNF also by MTT assay. Result : NCI-H2058 and WEHI164 which were sensitive to TNF, became far less sensitive to endogenous and exogenous TNF after being transferred TNF-$\alpha$ gene to. Conclusion : TNF-gene-transfer to NCI-H2058 and WEHI164 gave them resistance to TNF.

• Asian-Australasian Journal of Animal Sciences
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• v.21 no.12
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• pp.1753-1759
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• 2008

Forty weanling piglets ($5.6{\pm}0.5kg$ and 26 to 30 d of age) were used in a 28-d experiment to determine the effects of ${\beta}$-glucan from Paenibacillus polymyxa and L-theanine on growth performance. Piglets were randomly allotted to four groups (n = 10, 2 animals per pen) provided with the basal feed (control), ${\beta}$-glucan 400 mg/kg feed, L-theanine 80 mg/kg feed or ${\beta}$-glucan plus l-theanine (combination of the above-mentioned concentrations). Body weight and feed consumption were recorded during four weeks. Subsequently, the immunomodulatory effects of ${\beta}$-glucan and L-theanine were investigated for lipopolysaccharide (LPS)-induced cytokine production in vitro and in vivo on day 28. Although there were no significant differences in the growth performances among the treatment groups, ${\beta}$-glucan plus L-theanine had 5.6% greater ADG (p = 0.074) on day 21 to 28. ${\beta}$-Glucan alone or plus L-theanine increased interleukin (IL)-10 levels and decreased interferon (IFN)-$\gamma$ and tumor necrosis factor (TNF)-${\alpha}$ levels in cultured medium by LPS treatment (p<0.05). Plasma IL-10 levels were also increased in the piglets fed with ${\beta}$-glucan alone or plus L-theanine after LPS challenge ($25{\mu}g/kg$, i.p.), whereas plasma IFN-$\gamma$ and TNF-${\alpha}$ levels were decreased (p<0.05). The levels of IFN$\gamma$ in piglets fed with ${\beta}$-glucan plus L-theanine showed the greatest inhibition after LPS challenges. In conclusion, treatment of ${\beta}$-glucan alone or plus L-theanine might lessen inflammatory responses against Gram-negative bacterial infection via the inhibition of pro-inflammatory cytokine production and enhancement of anti-inflammatory cytokine production. Further studies are needed to determine an optimal concentration of ${\beta}$-glucan and L-theanine for improved growth performance.

• Herbal Formula Science
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• v.20 no.2
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• pp.13-28
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• 2012

Objectives : The present study aimed to investigate the pharmacological activity of water and ethanol (EtOH) extracts from Socheongnyong-tang (SCNT) on inflammation and its related disease. Methods : The cells were treated with nontoxic concentrations of water and EtOH extract from SCNT in BEAS-2B, HaCaT, RAW 264.7 and 3T3-L1 cells. These cells were stimulated by tumor necrosis facter (TNF)-${\alpha}$, TNF-${\alpha}$/interferon (IFN)-${\gamma}$, and lipopolysaccharide (LPS), respectively. 3T3-L1 cells were differentiated by insulin. After incubation, supernatant were collected and biological indicator measured by enzyme-linked immunosorbent assay. Results : Our results indicate that the water and EtOH extract of SCNT significantly inhibited the production of regulated on activation normal T-cell expression and secreted (RANTES) by treatment of TNF-${\alpha}$ in BEAS-2B cell, and significantly reduced the production of RANTES and macrophage-derived chemokine increased by treatment of TNF-${\alpha}$/IFN-${\gamma}$ in HaCaT cell. Moreover, those extracts significantly decreased the activity of nitric oxide and prostaglandin $E_2$ in LPS-induced RAW 264.7, and significantly inhibited the increased activity of glycerol-3-phosphate dehydrogenase and expression of leptin induced by differentiation in 3T3-L1 cell. Conclusions : These results indicate that both water and EtOH extract of SCNT has powerful effects on inflammation and its related disease. Therefore, SCNT can be developed as a potential pharmacological agent related various diseases. Although the significant effects were observed in both SCNT water and EtOH extract, the EtOH extract was more effective on most experiments than its water extract. Taken together, these findings indicate that the SCNT EtOH extract may have more potential pharmacological agent.

• Journal of Microbiology and Biotechnology
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• v.27 no.6
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• pp.1071-1077
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• 2017

A rise in the occurrence of allergic diseases is attributed to the dysregulated balance of type 1/type 2 immunity, where type 2 T-helper (Th2) cells predominate over type 1 T-helper (Th1) cells, leading to an abnormally increased production of IgE in response to unharmful antigens. Kimchi, a traditional Korean fermented food, is a rich source of beneficial lactic acid bacteria. In this study, we investigated the ability of Enterococcus faecium FC-K derived from kimchi to induce type I immunity in the presence of Th2 polarizing conditions in vitro and in vivo. Stimulation of mouse peritoneal macrophages with E. faecium FC-K induced the production of tumor necrosis factor alpha, interleukin (IL)-6, and IL-12. Under the in vitro Th2 conditions in which splenic T cells were activated in the presence of IL-4, E. faecium FC-K enhanced the ability of T cells to produce interferon $(IFN)-{\gamma}$. Using the ovalbumin (OVA)-induced allergy model, male BALB/c mice receiving E. faecium FC-K reduced the serum level of total IgE, but not that of OVA-specific IgE. Furthermore, the population of activated splenic B cells during OVA immunization was decreased in E. faecium FC-K-treated mice, accounting for a reduction of total IgE in the serum. Restimulating splenocytes from OVA-immunized mice with OVA ex vivo resulted in an increased production of $IFN-{\gamma}$, with no effect on IL-4, in E. faecium FC-K-treated mice. These observations provide the evidence that E. faecium FC-K can be a beneficial probiotic strain that can modulate the Th2-mediated pathologic response.

• Journal of Korean Medical Science
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• v.33 no.52
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• pp.336.1-336.12
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• 2018

Background: We aimed to investigate mucosal immunity related to forkhead box P3 ($FOXP3^+$) regulatory T (Treg) cells, T helper 17 (Th17) cells and cytokines in pediatric inflammatory bowel disease (IBD). Methods: Mucosal tissues from terminal ileum and colon and serum samples were collected from twelve children with IBD and seven control children. Immunohistochemical staining was done using anti-human FOXP3 and anti-$ROR{\gamma}t$ antibodies. Serum levels of cytokines were analyzed using a multiplex assay covering interleukin $(IL)-1{\beta}$, IL-4, IL-6, IL-10, IL-17A/F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, interferon $(IFN)-{\gamma}$, soluble CD40L, and tumor necrosis factor-${\alpha}$. Results: $FOXP3^+$ Treg cells in the lamina propria (LP) of terminal ileum of patients with Crohn's disease were significantly (P < 0.05) higher than those in the healthy controls. $ROR{\gamma}t^+$ T cells of terminal ileum tended to be higher in Crohn's disease than those in the control. In the multiplex assay, serum concentrations (pg/mL) of IL-4 ($9.6{\pm}1.5$ vs. $12.7{\pm}3.0$), IL-21 ($14.9{\pm}1.5$ vs. $26.4{\pm}9.1$), IL-33 ($14.3{\pm}0.9$ vs. $19.1{\pm}5.3$), and $IFN-{\gamma}$ ($15.2{\pm}5.9$ vs. $50.2{\pm}42.4$) were significantly lower in Crohn's disease than those in the control group. However, serum concentration of IL-6 ($119.1{\pm}79.6$ vs. $52.9{\pm}39.1$) was higher in Crohn's disease than that in the control. Serum concentrations of IL-17A ($64.2{\pm}17.2$ vs. $28.3{\pm}10.0$) and IL-22 ($37.5{\pm}8.8$ vs. $27.2{\pm}3.7$) were significantly higher in ulcerative colitis than those in Crohn's disease. Conclusion: Mucosal immunity analysis showed increased $FOXP3^+$ T reg cells in the LP with Crohn's disease while Th17 cell polarizing and signature cytokines were decreased in the serum samples of Crohn's disease but increased in ulcerative colitis.