• Journal of Microbiology and Biotechnology
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• v.34 no.4
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• pp.880-890
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• 2024

The immunomodulatory effects of Euglena gracilis (Euglena) and its bioactive component, β-1,3-glucan (paramylon), have been clarified through various studies. However, the detailed mechanisms of the immune regulation remain to be elucidated. This study was designed not only to investigate the immunomodulatory effects but also to determine the genetic mechanisms of Euglena and β-glucan in cyclophosphamide (CCP)-induced immunosuppressed mice. The animals were orally administered saline, Euglena (800 mg/kg B.W.) or β-glucan (400 mg/kg B.W.) for 19 days, and CCP (80 mg/kg B.W.) was subsequently administered to induce immunosuppression in the mice. The mice exhibited significant decreases in body weight, organ weight, and the spleen index. However, there were significant improvements in the spleen weight and the spleen index in CCP-induced mice after the oral administration of Euglena and β-glucan. Transcriptome analysis of the splenocytes revealed immune-related differentially expressed genes (DEGs) regulated in the Euglena- and β-glucantreated groups. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that pathways related with interleukin (IL)-17 and cAMP play significant roles in regulating T cells, B cells, and inflammatory cytokines. Additionally, Ptgs2, a major inflammatory factor, was exclusively expressed in the Euglena-treated group, suggesting that Euglena's beneficial components, such as carotenoids, could regulate these genes by influencing immune lymphocytes and inflammatory cytokines in CCP-induced mice. This study validated the immunomodulatory effects of Euglena and highlighted its underlying mechanisms, suggesting a positive contribution to the determination of phenotypes associated with immune-related diseases and the research and development of immunotherapies.

• Journal of Life Science
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• v.22 no.2
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• pp.133-141
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• 2012

In this study, we established a radiodermatitis animal model and investigated the change in immune cell proportions in the secondary lymphoid organs. The cells responsible for the increased transforming growth factor-${\beta}1$ (TGF-${\beta}1$) and interleukin-10 (IL-10) production in the lesions following irradiation were also investigated. The radiodermatitis model was constructed by locally exposing the posterior dorsal region of hairless-1 (HR-1) mice to 10 Gy electron (E)-ray/day for six consecutive days. The change in immune cell proportions was analyzed by FACS. Immunohistochemistry was carried out to detect the expression of cytokines and cell-specific markers in the skin. The proportions of antigen-presenting cells, T cells, and B cells in the lymph nodes and spleen were affected by E-irradiation. After irradiation, TGF-${\beta}1$ and IL-17 were co-localized in the papillary region of the dermis with keratin-14 (K-14)-positive cells rather than with regulatory T cells (Treg). IL-10 was not co-stained with Treg, T helper 17 (Th17) cells, dendritic cells, or macrophages. Our data indicate that TGF-${\beta}1$ is over-expressed mainly by proliferated keratinocytes in the lesions of a radiodermatitis animal model.

• The Journal of Internal Korean Medicine
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• v.27 no.3
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• pp.639-652
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• 2006

Objective : The etiology of chronic prostatitis is likely multifactorial, resulting from either a cascade of events after an initiating factor or from a variety of etiologic mechanisms. There is substantiating evidence to support the role of the inflammatory responses in its pathogenesis, and the clinical value in the evaluation of therapeutic efficacy. Forsythiae Frucus has been traditionally used in treatment of inflammatory diseases, including of prostatitis and urinary tract inflammation. In this study, we investigated the effects of Forsythiae Frucus on inflammatory cytokines and cyto-pathological alternation in the rat model of chronic non-bacterial prostatitis induced by castration and $17{\beta}$-estradiol treatment. Methods : Two-month-old rats were treated with $17{\beta}$-estradiol after castration for induction of experimental non-bacterial prostatitis. which is similar to human chronic prostatitis in histopathological profiles. Forsythiae Frucus as an experimental specimen, and testosterone as a positive control, were administered orally. The prostates were evaluated by histopathologlcal parameters including the epithelial score and epithelio-stromal ratio for glandular damage. and the expression of inflammatory cytokine genes including interleukin (IL)-$1{\beta}$, IL-5, IL-12, tumor necrosis factor (TNF)-$\alpha$. eotaxin, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2(cox-2). Results : While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation. the rats treated with Forsythiae Frucus showed a diminished range of tissue damage. Epithelial score was improved in the Forsythiae Frucus group over that of the control (P<0.05). The epithelia-stromal ratio was lower in the Forsythiae Frucus group when compared to that of the control (P<0.05). In the reverse transcription-polymerase chain reaction (RT-PCR) of inflammatory cytosine genes. Forsythiae Frucus inhibited the expression of IL-$1{\beta}$, TNF-$\alpha$, iNOS, cox-2 genes, while it modulated the expression of IL-5, which is an anti-inflammatory cytokine. Conclusions : These findings suggest that Forsythiae Frucus may protect the glandular epithelial cells and also inhibit stromal proliferation in association with the immune modulation including the suppression of inflammatory cytokines and increase of anti-inflammatory cytokines. From theses results. we suggest that Forsythiae Frucus could be a useful remedy agents for treating chronic non-bacterial prostatitis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.3
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• pp.711-718
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• 2003

Wanpae-tang is suggested to have antitumor activity on lung cancer. This study was performed to investigate antitumor, immune response, and apoptotic effects by Wanpae-tang in the cancer cell lines and C57BL/6 mice. Experimental studies were progressed through the anticancer activities such as, survival time, cell cytotoxicity, natural killer cell activity, productivity of interleukins and apoptotio effects. The results were summarized as follows: 1. Median survival time of Wanpae-tang treated group was prolonged to 4.1%, as compared with control group, but was not significant. 2. On the MTT assay, half-maximal inhibitory concentration(IC50) of Wanpae-tang was 15.00 ㎎/㎖ in HeLa cell, and 4.158 ㎎/㎖ in HRT-18 cell. 3. Natural killer cell activity in Wanpae-tang treated group was decreased in case of 100:1 and 10:1 effect cell/target cell ratio. 4. Production of interleukin-2, 4, 12 in Wanpae-tang treated group were significantly increased. 5. On the studies of Wanpae-tang induced apoptosis, a DNA fragmentation patterns were not appeared.

• Journal of Society of Preventive Korean Medicine
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• v.15 no.3
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• pp.163-178
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• 2011

Objective : This study is conducted to evaluate the efficiency of ethanol extracts of 4 mixed herbs(CP001 or CP002) on mouse model of atopic dermatitis induced by ovalbumin. Methods : Female BALB/c mice were internally sensitized with ovalbumin($20{\mu}g$) plus aluminum hydroxide hydrate(4mg) once per week. After 3 weeks, they were dermally challenged with patches containing ovalbumin ($100{\mu}g$) plus aluminum hydroxide hydrate(20mg) every other day for 3 weeks. After induction of atopic dermatitis, mice back skin were gently rubbed with CP001 or CP002(200mg/$m{\ell}$, $100{\mu}{\ell}$) for two weeks(every 2 days). Results : In CP001 or CP002 treated group, there was a remarkable reduction in infiltration of eosinophils on the skin areas and diminution of mast cells and total T cells in blood samples as compared with control group. Cutaneous expressions of interleukin-13, 17 were also decreased by CP001 or CP002. Moreover, blood immunoglobulin E level was decreased by drug administration while there was no decrease in OVA sensitization group. Conclusion : In summary, our result shows that herbal extracts(CP001 and CP002) could be potential candidates for the treatment of chronic atopic dermatitis.

• The Journal of Korean Obstetrics and Gynecology
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• v.15 no.4
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• pp.17-31
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• 2002

Objective : This study was carried out to investigate the effects of the hormones and cytokines associated with bone metabolism in ovariectomized rats. Method : Twenty-four Female-Sprague-Dawley rats were divided into sham operated(normal) group, ovariectomized(control)group, ovariectomized and treated with extract Caraganae Sinicae Radix(treated) group. Each group was investigated the changes of body weight at 3,5,7weeks after treatment, and femur weight, femur/body weight, thickness of compact bone of body of femur, area of cancellous bone of distal epiphysis of femur, serum estrogen, serum calcitonin, serum parathormone, serum Tumor Necrosis $Factor-{\alpha}$, serum $lnterleukin-1{\beta}$ at 7weeks after treatment. The results were summerized as follows; 1. The treated group showed significant change in body weight compared with the control group at 5,7weeks after treatment. 2. The treated group revealed significant increases in femur/body weight compared with the control group. 3. The treated group showed a little thicker compact bone of body of femur than the control group. 4. The area of cancellous bone of distal epiphysis of femur in treated group was increased significantly compared with control group. 5. The level of serum estrogen showed no change compared with control group. 6. The level of serum calcitonin showed no change compared with control group. 7. The level of serum parathormone was decreased in treated group significantly compared with control group. 8. The level of serum $TNF-{\alpha}$ was decreased in treated group significantly compared with control group. 9. The level of serum $interleukin-1{\beta}$ showed no change compared with control group. The results indicate that Caraganae Sinicae Radix inhibits bones resorption in ovariectomized rats by it's lowering effects on serum parathormone and $TNF-{\alpha}$.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1254-1260
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• 2008

The aim of the present study was to prepare nanosample of fucoidan using lecithin as encapsulated material and to investigate the anticancer and immunomodulatory activity of nanoparticle in vitro. The nanoparticles have been characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Confocal microscopy confirmed the internalization of the fucoidan conjugates into the immune cells. The uptake of nanoparticles was confirmed with confocal microscopy demonstrating their localization in the cells. The anticancer activity was increased over 5-10% in different cancer cells of fucoidan nanoparticle as compare with fucoidan. The human B and T cells growth and the secretion of interleukin-6 and tumor necrosis factor-a from B cell were also improved by fucoidan nanoparticle because of the rapid absorption of nanoparticle into the cells as compare to fucoidan. At 0.6 mg/mL concentrations, the fucoidan nanoparticle showed better activity than 1.0 mg/mL concentration in T cell growth because the cells reached their saturation capacity. When the fucoidan was encapsulated in lecithin, its anticancer as well as its immunomodulatory activity proved to be superior from that of itself in pure form.

• Food Science of Animal Resources
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• v.38 no.6
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• pp.1226-1236
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• 2018

Ovotransferrin (OTF) is a well-known protein of the transferrin family with strong iron chelating activity, resulting in its antimicrobial activity. Furthermore, OTF is known to have antioxidant, anticancer, and antihypertensive activities. However, there have been few studies about the immune-enhancing activity of OTF. In current study, we investigated the immune-enhancing activity of OTF using the murine macrophage cells in vitro. The effect of OTF on production of pro-inflammatory mediators and cytokines were determined using Griess assay and quantitative real-time PCR. Using Neutral Red uptake assay, we confirmed the effect of OTF on phagocytic activity of macrophages. Ovotransferrin significantly increased the production of nitric oxide (NO) and secretion of inducible nitric oxide synthase (iNOS) mRNA with no cytotoxic activity. Ovotransferrin (2 mg/mL) stimulated NO production up to $31.9{\pm}3.5{\mu}M$. Ovotransferrin significantly increased the mRNA expression levels of pro-inflammatory cytokines which are tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), Interleukin-$1{\beta}$ (IL-$1{\beta}$), and IL-6: OTF (2 mg/mL) treatment increased the secretion of mRNA for TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 by 22.20-, 37.91-, and 6.17-fold of the negative control, respectively. The phagocytic activity of macrophages was also increased by OTF treatment significantly compared with negative control. Also, OTF treatment increased phosphorylation level of MAPK signaling pathways. These results indicated that OTF has immune-enhancing activity by activating RAW 264.7 macrophages via MAPK pathways.

• The Korea Journal of Herbology
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• v.34 no.3
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• pp.9-17
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• 2019

Objectives : This study was performed to compare the effect of two Cudrania tricuspidata cultivars; Sancheong native (CT) and varieties in china(SCT) on immediate hypersensitivity of the anaphylactic type and Ova-induced allergic asthma mouse model by calculating serum cytokines and IgE. Methods : We investigated the free radical scavanging effect and quantify total phenol contents and total flavonoids of two Cudrania tricuspidata cultivars; Sancheong native(CT) and varieties in china(SCT). The sample was extracted by 80% EtOH. To induce the allergic asthma, in the control group and the CT group, mice of each group were sensitized intraperitoneally with ovalbumin (OVA) solution at the 1st, the 7th and the 14th day. After then, sensitization was performed by aerosol allergen challenges with 1% OVA solution intratracheally at the 21th, the 23th, 25th and the 27th day. At the 29th day, the mice were killed and the changes of interferon-${\gamma}$, interleukin-4, 5 and 10, total IgE and OVA-specific IgE in serum were checked. Results : CT inhibited compound 48/80-induced systemic anaphylaxis 90% with a dose of 100 mg/kg body weight at 1 hr before injection of compound 48/80. In the allergic asthma mouse model, IFN-${\gamma}$ was did not increased in the CT and SCT group than that in the control group. IL-4, IL-5, the total IgE and OVA-specific IgE were decreased in the CT group as compared with the control group and these results were statistically significant. Conclusions : Considering the above experimental results, this study showed that Sancheong native cultivar could reduce the allergic reaction.

• Animal Bioscience
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• v.36 no.8
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• pp.1167-1179
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• 2023

Objective: Matrix metalloproteinases (MMPs) are a family of endoproteases produced by various tissues and cells and play important roles in angiogenesis, tissue repair, immune response, and endometrial remodeling. However, the expression and function of MMPs in the pig endometrium during the estrous cycle and pregnancy have not been fully elucidated. Thus, we determined the expression, localization, and regulation of MMP2, MMP8, MMP9, MMP12, and MMP13 in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in pigs. Methods: Endometrial tissues during the estrous cycle and pregnancy and conceptus and chorioallantoic tissues during pregnancy were obtained and the expression of MMPs was analyzed. The effects of steroid hormones and cytokines on the expression of MMPs were determined in endometrial explant cultures. Results: Expression levels of MMP12 and MMP13 changed during the estrous cycle, while expression of MMP2, MMP9, MMP12, and MMP13 changed during pregnancy. Expression of MMP2, MMP8, and MMP13 mRNAs was cell type-specific at the maternal-conceptus interface. Gelatin zymography showed that enzymatically active MMP2 was present in endometrial tissues. In endometrial explant cultures, estradiol-17β induced the expression of MMP8 and MMP12, progesterone decreased the expression of MMP12, interleukin-1β increased the expression of MMP2, MMP8, MMP9, and MMP13, and interferon-γ increased the expression of MMP2. Conclusion: These results suggest that MMPs expressed in response to steroids and cytokines play an important role in the establishment and maintenance of pregnancy by regulating endometrial remodeling and processing bioactive molecules in pigs.