• 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.

• Journal of Life Science
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• v.27 no.4
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• pp.383-389
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• 2017

This study intends to analyze the contents of rutin, procyanidin B3, quercetin, kaempferol, known to have antioxidant, anti-inflammatory and anti-carcinogenic effects, among the polyphenol type contained in the grape pruning stem extracts (GPSE), utilizing grape stems being discarded after harvest, measure the effects on the skin moisture, inhibition of skin cell proliferation, anti-inflammatory on the damaged skin of a HR-1 mice induced with UVB, and verify the applicability as a material for functional food and functional cosmetics. The results of verifying the photoprotection effects through the skin proliferation control through of GPSE showed similar result to suncream was achieved at the GPSE concentration of 2,000 mg/kg on the epidermis (p<0.05). The results showed anti-inflammatory effects on all groups applied with GPSE as compared to the control group irradiated with UVB, but at the GPSE concentration of 1,000 mg/kg, a lower COX-2 protein expression at 8%, lower than the 22% of suncream, was observed to achieve an excellent anti-inflammatory effect (p<0.05). The results of this study confirmed the existence of active polyphenol type, such as rutin, kaempferol, querocetin and procyanidin B3, within the GPSE, and GPSE has improvement effects on moisturizing effects, skin proliferation control effect, inflammatory control effect and improvement effects on the skin barrier function through UV ray damage. GPSE is a functional ingredient with a potential for skin protection effects, and has high utilization as an ingredient for functional food and functional cosmetics.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.2
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• pp.95-110
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• 2006

The treatment for oral and maxillofacial carcinoma with chemotherapeutic agents is evaluated by many effective methods to reduce the tumor mass and cancer cell proliferation. However these chemotherapy have many serious side effects, such as bone marrow suppression, renal toxicity, G-I troubles. Therefore a possible approach to develop a clinically applicable chemotherapeutic agent is to screen anticancer activity of Taxol which is known to have very little side effect and have been used to breast cancer and ovarian carcinoma. Taxol is a new anti-microtubular anti-cancer agent extracted from the bark of the Pacific yew, Taxus brevifolia. Paclitaxel(Taxol) acts by promoting tubulin polymerization and over stabilizing microtubules agianst depolymerization. Despite the constant improvements of methods of the cancer treatment especially chemotherapy, the rate of cancer metastasis and recurrent are not decreased. Thus the investigation of new drug which have very little side effect and a possible clinically application continues to be a high priority. Considering that the Taxol have shown very effective chemotherapeutic agent with relatively low toxicity in many solid tumors, it deserves to evaluate its efficacy in oral squamous cell carcinoma. In this study, to investigate the in-vivo and in-vitro anti-cancer efficacy of Taxol in oral squamous cell carcinoma and lastly, the potency of Paclitaxel in the clinical application for oral cancer was evaluated. In vivo study, after HN22 cell line were xenografted in nude mice, the growth of tumor mass was observed, 3 mg/Kg taxol was injected intraperitoneally into nude mice containing tumor mass. The methods of these study were measurement of total volume of tumor mass, histopathologic study, immunohistochemical study, drug resistance assay, growth curve, MTT assay, flow cytometry, cDNA microarray in vivo and in vitro. The results were obtained as following. 1. The visual inspection of the experimental group showed that the volume of the tumor mass was slightly decreased but no significant difference with control group. 2. Ki-67 index was decreased at weeks 4 in experimental group. 3. Microscopic view of the xenografted tumor mass showed well differentiated squamous cell carcinoma and after Taxol injection, some necrotic tissue was seen weeks 4. 4. The growth curve of the tumor cells were decreased after 1day Taxol treatment. 5. According to the MTT assay, HN22 cell line showed relative drug resistancy above $5\;{\mu}g/ml$ concentrations of Taxol. 6. In drug resistance assay, the decrease of cell counts was seen relatively according to concentration. 7. In Flow cytometry, G2M phase cell arrests were seen in low concentration of the Taxol, while S phase cell arrests were seen in high concentration of the Taxol. 8. Using cDNA microarray technique, variable gene expression of ANGPTL4, TXNRD1, FAS, RRAGA, CTGF, CYCLINEA, P19, DUSP5, CEBPG, BTG1 were detacted in the oral squamous cell carcinoma cell after taxol treatment. In this study paclitaxel is effective against oral squamous cell carcinoma cell lines in vitro, but week effect was observed in vivo. So we need continuous study about anticancer effect of taxol in vivo in oral squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• v.51 no.5
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• pp.437-447
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• 2001

Background: TNF-alpha is related to the generation of lung fibrosis in patients with UIP. The precise mechanism leading to lung fibrosis by TNF-alpha is unknown. However, the activation of a transcription factor like AP-1(down stream of c-jun N-terminal kinase, JNK) by TNF-alpha may be related to the induction of fibrogenic cytokines like PDGF or IGF-I. Furthermore, JNK was reported to be activated in the radiation-induced lung fibrosis model. This study examined JNK activity in patients with UIP. Methods : The expression of phosphorous JNK(p-JNK), macrophage/monocyte specific markers, CD68, and cytokeratin was evaluated by immunohistochemical(IHC) staining of lung tissues from patients with UIP and lung cancer. An in vitro kinase assay was performed with alveolar macrophages obtained by a bronchol-avleolar lavage from patients with UIP and healthy persons as the control. Results : The IHC stain showed that p-JNK is expressed in the almost all of the alveolar macrophages and smooth muscle cells in patients with UIP. In case of the normal areas of the lung from patients with lung cancer, the alveolar macrophages showed little p-JNK expression. Interestingly, increased JNK activity was not found in the in vitro kinase assay of the alveolar macrophages obtained from both patients with UIP and healthy persons as the control. Furthermore, 10 ng/mL of TNF-alpha failed to increase the JNK activity of the alveolar macrophages in both patients with UIP and healthy people. Conclusion : The JNK was activated constitutionally in patients with UIP. However, the role of JNK in the pathogenesis of lung fibrosis needs to be clarified.

• Journal of Food Hygiene and Safety
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• v.16 no.3
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• pp.212-220
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• 2001

To investigate the modifying effect of Kwao Kreu, Pueraria mirifica (PM), we performed two kind of studies which are the non-surgical medium-term carcinogenicity study and the modulation of gap junctional intercellular communication study. The first study, a non-surgical medium-term carcinogenicity bioassay was done to investigate the modifying effect of Kwao Keru, Pueyaria mirifca (PH), a rejuvenating folk medicine from Thailand, on the male F344 rat liver. Specific pathogen free, male 6-week-old F3444 rats were divided into ten groups. To induce hepatocarcinogenesis, those in all groups were given a single i.p. injection of DEN (200 mg/kg) and were received two i.p. injection of DGA (300 mg/kg) at the ends of weeks 2 and 5. Rats of group 3-6 were given sodium phenobarbital (PB 0.05% in drink). A diet containing 10 mg/kg PM was given to group 2 during the post-initiation phase and to groups 4 and 5 during promotion and initiation phase, respectively. Group 6 was given the experimental diet alone throughout the experiment (8 weeks). Rats of group 7, 8, 9 and 10 were fed 1000 mg/kg PH in the same manner as group 2, 4, 5 and 6. All animals were sacrificed at 8 weeks after DEN administration. Result of the immunohistochemical staining of the glutathione S-transferase placental form (GST-p) indicated that the numbers and areas of the preneoplastic leisions were not significantly changed in all PM treatment group comparing to control group. Also the numbers and areas of GST-p positive foci among group 7, 8, 9 and 10 were not significantly changed in comparing to control group. To study the effect of PM on the modulation of gap junctional intercellular communication, the present study was performed scrape-loading dye transfer (SL/DT) assay in human keratinocytes. The results showed that PM could not modulate GJIC. These results indicate that Pueraria mirifica may have no carcinogenic effects on experimental hepatocarcinogenesis in rats and gap junctional intercellular communication in human keratinocyte.

• Tuberculosis and Respiratory Diseases
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• v.39 no.6
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• pp.502-510
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• 1992

Background: Neuron specific enolase (NSE) is a neuronal form of the glycolytic enzyme enolase which was first found in extracts of brain tissue, and later in a variety of APUD cells and neurons of the diffuse endocrine system. SCLC shares many APUD properties with normal neuroendocrine cells. NSE immunostaining and serum NSE measurement may be a useful marker of neuroendocrine differentiation in lung tumors and diagnosis of small cell carcinoma. Methods: NSE immunohistochemical staining was done and at the same time serum NSE levels were measured in 22 small cell lung cancer and 21 non small cell lung cancer which were confirmed histologically. Results: 1) NSE immunoreactivity was detected in 9 of the 18 (50%) small cell lung cancer, in 5 of the 16 non small cell lung cancer. 2) Whereas the mean value in non-small cell lung cancer group was $11.79{\pm}4.47\;ng/ml$, the mean level of serum NSE in small cell lung cancer increased up to $59.3{\pm}77.8\;ng/ml$. In small cell lung cancer patients, mean value of limited disease group was $20.19{\pm}12.91\;ng/ml$, while mean value of extended disease group was $91.9{\pm}94.2\;ng/ml$ showing statistically significant difference. If serum levels above 20 ng/ml were tentatively defined as positive, 16 of 22 (73%) patients with SCLC had positive serum NSE level, but only one patient with NSCLC did. There was no correlation between serum NSE level and immunoreactivity of NSE. Conclusion: These studies indicate that serum NSE measurement may be a useful marker for the diagnosis and disease extent and NSE immunostaining can be used to demonstrate the neuroendocrine components of lung tumor.

• The Journal of Dong Guk Oriental Medicine
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• v.6 no.1
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• pp.117-128
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• 1997

Abdominal skin tissues of ICR mouse painted with Dinitrochlorobenzene (DNCB) were observed to investigate the delayed type hypersensitivity of skin by chemical allergen as hapten. The abdominal skin tissues were obtained at hour 48 after secondary DNCB sensitization that were stained by Luna's method for mast cell, and immunohistochemical stain method for IL-2 receptor. The superficial perivascular lymphocytic aggregation were shown in basement membrane after DNCB secondary painting and the large size capillaries in dermis were appeared. The infiltration of lymphocyte to epithelium, the vacuolation of epithelial cell and intercellular space were increased. The number of mast cell in dermis was increased and these shape is degranulation type. The number of IL-2 receptor positive cell was increased in dermis. As results indicated that the hypersensitivy of immune system were induced by DNCB, subsequently to damage evoke inflammation in skin.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.1
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• pp.65-75
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• 2003

Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.

• Journal of Life Science
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• v.14 no.3
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• pp.375-384
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• 2004

Fibroblast growth factors (FGFs) are known to induce multiple functions in early development, including mesoderm formation, gastrulation movement and antero-posterior patterning. The induction of mesoderm from Xenopus presumptive ectoderm and the combination effect on inducing organs of bFGF(basic FGF) and HGF (Hepatocyte Growth Factor) were studied. Explants were cultured in the combined solution for 3 days to normal embryo arrive at St. 43. These effects on combined dose were examined by histological experiment and by immunohistochemical method. The concentrations of growth factors were tested in 0, 0.5, 1, 10 and also tested in 50 ng/ml of bFGF, and 0, 1, 10, 50 and 100ng/ml of HGF respectively. The synergistic effects were seen in the combined-dose of bFGF and HGF rather than in single dose. Various organs were differentiated and highest inducing effects were seen at the combined concentration of 1 ng/ml of bFGF and 10ng/ml of HGF, and at the concentration 10ng/ml of bFGF and 1 ng/ml of HGF. The bFGF induces various organs from cultured animal cap explants and the effects are time and dose-dependent. HGF is also a potent mitogen for renal tubular cells and for mature hepatocytes in primary culture. Eyes were developed in high percentage at the combined concentration of 1 and 10ng/ml of bFGF, and 1 and 10 ng/ml of HGF. From the induced eye and normal embryonic eye, RPE65 was commonly detected by monoclonal antibodies 40All and 25F5 and the localization of RPE65 was seen by AP reaction.

• Korean Journal of Medicinal Crop Science
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• v.26 no.1
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• pp.8-18
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• 2018

Background: This present study was conducted to evaluate the anti-inflammatory and immune regulatory effects of Aucklandia lappa Decne (AL). Methods and Results: We measured cytotoxicity, nitric oxide (NO) content, mRNA expression (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$), protein expression (iNOS, COX-2, and $I{\kappa}B$) and phagocytic activity in RAW264.7 cells. Male BALB/c mice were fed 100 mg/kg AL (Aucklandia lappa Decneon 70% ethanol extract) and 250 mg/kg AL for 4 weeks; thereafter, we observed B/T or $CD4^+/CD8^+$ lymphocyte subpopulation change, and expression patterns of $CD4^+$ and $CD8^+$ lymphocytes by immunohistochemical staining in mouse splenocytes and/or thymocytes. To determine the experimental concentration of AL, cell viability was measured by MTT assay and tested at $12.5{\mu}g/m{\ell}$ or less. AL inhibited the levels of NO, lymphokine production (IL-$1{\beta}$, and TNF-${\alpha}$), and mRNA (iNOS, IL-1${\alpha}$, IL-$1{\beta}$, and TNF-${\alpha}$) and protein (iNOS, and COX-2) expression. Additionally, the levels of $I{\kappa}B$, phagocytic activity, and splenic and thymic T lymphocytes, especially $T_H$ and $T_C$ cells were significantly increased in AL administered mice. The immuno-reactive density of $CD4^+$ and $CD8^+$ lymphocytes was stronger in AL groups than in the normal group. AL stimulated NO, iNOS, and COX-2, and regulated IL-1${\alpha}$, IL-$1{\beta}$, TNF-${\alpha}$, and $I{\kappa}B$ in macrophages treated with LPS (lipopolysaccharide). In addition, AL increased the phagocytic activity of macrophages and the immunity of mouse T ($T_H$, and $T_C$) cells. Conclusions: These results suggested that AL might show anti-inflammatory activity via the suppression of various inflammatory markers and immuno-regulatory activity.