• 대한본초학회지
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• 제21권2호
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• pp.189-195
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• 2006

Objectives : The purpose of this study was to investigate the anti-inflammatory effects of extract Asarum sieboldii(AS) on the peritoneal macrophage. Methods : To evaluate of anti-inflammatory of AS, we examined cytokines production in lipopolysacchride (LPS)-induced macrophages. Furthermore, we checked molecular mechanism using western blot. Results : 1. Extract from AS reduced LPS-induced Nitric oxide (NO), tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-12 production in peritoneal macrophages 2. Extract from AS itself does not have any cytotoxic effect. AS inhibited the activation of mitogen-activated protein kinases (MAPKs) such as p38, extracelluar signal-regulated kinase B a (IkBa) in the LPS-stimulated peritoneal macrophages Conclusion : AS down-regulated LPS-induced NO and cytokines production, which could provide a clinical basis for anti-inflammatory properties of AS

• 대한의생명과학회지
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• 제12권3호
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• pp.289-301
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• 2006

Cardiopulmonary bypass (CPB) for cardiac surgery triggers the production and release of numerous chemotactic substances and cytokines, ensuing systemic inflammatory response that leads to postoperative major organ dysfunction. Traditionally, corticosteroids (steroid) have been administered to patients undergoing cardiac surgery to ward off these detrimental physiologic alterations. However, the majority of the studies have been performed on adult patients with high-dose steroid. We carried out a randomized, prospective, double-blind study to compare the efficacy of low-dose steroid with that of high-dose steroid and to determine the adequate dose of pretreated-steroid for prophylactic effects in pediatric cardiac surgery. Thirty pediatric patients scheduled for elective cardiac surgery were randomly assigned to two groups; fifteen patients received low-dose methylprednisolone (10mg/kg intravenously, n=15, low-dose group) and the others received high-dose methylprednisolone (30mg/kg intravenously, n=15, high-dose group) 1 hour prior to CPB. Arterial blood samples were taken before CPB (Pre-CPB), 10 minutes after start of CPB (CPB-10), and immediately after CPB-end (CPB-OFF) for measuring total leukocyte counts (T-WBC) and diff-counts, platelet counts, interleukin-6 (IL-6), myeloperoxidase (MPO), total antioxidant (TAO), neuron-specific enolase (NSE), troponin I (TNI), aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine, and blood urea nitrogen (BUN) levels. Other parameters such as volumes of urine output, pulmonary index $(PI,\;PaO_2/FiO_2)$, mechanical ventilating period, intensive care unit (ICU)-staying period, postoperative complications (fever, wound problem), postoperative 24 hrs and total volumes in blood loss, and hospitalized days were also assessed. All parameters were compared between two groups. There were no significant differences in T-WBC counts, monocyte fraction, platelet counts, TA levels, NSE levels, creatinine levels, BUN levels, the volumes of total urine output, PI, the incidences of fever and wound problem, postoperative 24hrs- and total-blood loss volumes and ICU-staying period between two groups (P>0.05). At CPB-OFF, neutrophil fraction, MPO level, TNI level, and AST level were higher in the high-dose group than in the low-dose group (P<0.05). IL-6 level at CPB-10 was higher in the high dose-group than in the low-dose group (P<0.05). Furthermore, mechanical ventilating periods and hospitalized days of the high-dose group were significantly longer than those of low-dose group (P<0.05). The high-dose group had significantly low lymphocyte fi-action at CPB-OFF compared with the low-dose group (P<0.001). These findings suggest that pretreatment of high-dose steroid is not superior to that of low-dose steroid regrading its potential benefits in pediatric cardiac surgery. Therefore, the conventional strategy of steroid treatment, high-dose pretreatment, should be modified in the cardiac surgery with CPB. However, further studies must be performed on the larger number of patients in as much as small number of patients in this study.

• Natural Product Sciences
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• 제18권1호
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• pp.60-66
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• 2012

Human skin is the first line of defense for the protection of the internal organs of the body from different stimuli. Ultraviolet B (UVB) irradiation induces skin damage and inflammation through the secretion of various cytokines, which are immune regulators produced by cells. To prevent the initiation of skin inflammation, keratinocytes that have been irreversibly damaged by radiation must be removed through the apoptotic mechanism. Ixeris dentata (family: Asteraceae) is a perennial medicinal herb indigenous to Korea. It has been used in Korea, China, and Japan to treat in digestion, pneumonia, diabetes, hepatitis, and tumors. To gain insight into the anti-inflammatory effects of I. dentata, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells), by observing cells that were stimulated with UVB in the presence or absence of I. dentata. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription polymerase chain reaction, and western blot analysis to measure the activation of mitogen-activated protein kinase (MAPKs). I. dentata inhibited UVBinduced production of the pro-inflammatory cytokine interleukin (IL)-6 in a dose-dependent manner. Further, I. dentata inhibited the UVB-induced expression of cyclooxygenase (COX)-2. Furthermore, I. dentata inhibited the phosphorylation of c-Jun NH2-terminal kinase and p38 MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8, and COX-2 expression, by blocking MAPK phosphorylation. These results suggest that I. dentate can potentially protect against UVB-induced skin inflammation.

• Asian-Australasian Journal of Animal Sciences
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• 제25권11호
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• pp.1617-1626
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• 2012

The objective of this study was to evaluate the effects of adding essential oils to the diet of weaned pigs on performance, nutrient utilization, immune response and intestinal health. A total of 96 weaning pigs ($8.37{\pm}1.58$ kg) were allotted to one of three dietary treatments. The treatments consisted of an unsupplemented basal diet (negative control, NC) or similar diets supplemented with 0.01% of an essential oil product which contained 18% thymol and cinnamaldehyde (EOD) as well as a diet supplemented with 0.19% of an antibiotic mixture which provided 150 ppm chlortetracycline, 80 ppm colistin sulfate and 50 ppm kitasamycin (positive control, PC). Each treatment was provided to eight pens of pigs with four pigs per pen. Over the entire 35 d experiment, ADG and fecal score were improved (p<0.05) for pigs fed the PC and EOD compared with the NC. Dry matter and crude protein digestibility as well as lymphocyte proliferation for pigs fed the PC and EOD diets were increased significantly compared with NC (p<0.05). IGF-I levels in plasma were significantly increased (p<0.05) in pigs fed the PC diet compared with pigs fed the NC diet. Interleukin-6 concentration was lower (p<0.05) and the tumor necrosis factor-${\alpha}$ level was higher (p<0.05) in the plasma of pigs fed the EOD diet than the NC diet. Plasma total antioxidant capacity level increased (p<0.05) in pigs fed the EOD diet compared with pigs fed the NC. Villus height to crypt depth ratio in the jejunum was greater (p<0.05) in pigs fed the PC and EOD diets than the NC. The numbers of E. coli in the cecum, colon and rectum were reduced (p<0.05) in pigs fed the PC and EOD diets compared with the control. In the colon, the ratio of Lactobacilli to E. coli was increased (p<0.05) in pigs fed the EOD diet compared with NC diet. Total aerobe numbers in the rectum were decreased (p<0.05) in pigs fed the PC and EOD diets compared with the control. Collectively, these results indicate that blends of essential oils could be a candidate for use as an alternative to traditional antibiotics in weaning pig diets.

• Asian Pacific Journal of Cancer Prevention
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• 제16권14호
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• pp.6073-6080
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• 2015

Background: Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24), a unique tumor suppressor gene, has killing activity in a broad spectrum of cancer cells. Herein, plasmids producing mda-7 proteins fused to different RGD peptides (full RGD4C and shortened RGD, tRGD) were evaluated for apoptosis induction with a hepatocellular carcinoma cell line, Hep-G2. The study aim was to improve the apoptosis potency of mda-7 by tethering to RGD peptides. Materials and Methods: Three plasmids including mda-7, mda-7-RGD and mda-7-tRGD genes beside a control vector were transfected into Hep-G2 cells. After 72 hours incubation, cell viability was evaluated by MTT assay. In addition, the rate of apoptosis was analyzed by flow cytometry using PI/annexin staining. To detect early events in apoptosis, 18 hours after transfection, expression of the BAX gene was quantified by real time PCR. Modeling of proteins was also performed to extrapolate possible consequences of RGD modification on their structures and subsequent attachment to receptors. Results and Conclusions: In MTT assays, while all mda-7 forms showed measurable inhibition of proliferation, unmodified mda-7 protein exhibited most significant effect compared to control plasmid (P<0.001). Again, flow cytometry analysis showed a significant apoptosis induction by simple mda-7 gene but not for those RGD-fused mda-7 proteins. These findings were also supported by expression analysis of BAX gene (P<0.001). Protein modelling analysis revealed that tethering RGD at the end of IL-24/Mda7 disrupt attachment to cognate receptor, IL-20R1/IL-20R2. In conclusion, fusion of RGD4C and shortened RGD peptides to carboxyl terminal of mda7, not only reduce apoptosis property in vitro but also disrupt receptor attachment as demonstrated by protein modelling.

• Asian Pacific Journal of Cancer Prevention
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• 제14권10호
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• pp.5825-5831
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• 2013

Background/Objectives: Maintenance of cellular function in culture is vital for transfer and development following adoptive immunotherapy. Dual properties of IL-21 in activating T cells and reducing activation induced cell death led us to explore the mechanism of action of IL-21 enhanced proliferation and cytotoxic potential of CIK cells. Method: CIK cells cultured from PBMCs of healthy subjects were stimulated with IL-21 and cellular viability and cytotoxicity to K562 cells were measured. To elucidate the mechanism of action of IL-21, mRNA expression of cytotoxic factors was assessed by RT-PCR and protein expression of significantly important cytotoxic factors and cytokine secretion were determined through flow cytometry and ELISA. Western blotting was performed to check the involvement of the JAK/STAT pathway following stimulation. Results: We found that IL-21 did not enhance in vitro proliferation of CIK cells, but did increase the number of cells expressing the CD3+/CD56+ phenotype. Cytotoxic potential was increased with corresponding increase in perforin ($0.9831{\pm}0.1265$ to $0.7592{\pm}0.1457$), granzyme B ($0.4084{\pm}0.1589$ to $0.7319{\pm}0.1639$) and FasL ($0.4015{\pm}0.2842$ to $0.7381{\pm}0.2568$). Interferon gamma and TNF-alpha were noted to increase ($25.8{\pm}6.1ng/L$ to $56.0{\pm}2.3ng/L$; and $5.64{\pm}0.61{\mu}g/L$ to $15.14{\pm}0.93{\mu}g/L$, respectively) while no significant differences were observed in the expression of granzyme A, TNF-alpha and NKG2D, and NKG2D. We further affirmed that IL-21 signals through the STAT-3 and STAT-5b signaling pathway in the CIK cell pool. Conclusion: IL-21 enhances cytotoxic potential of CIK cells through increasing expression of perforin, granzyme B, IFN-gamma and TNF-alpha. The effect is brought about by the activation of STAT-3 and STAT-5b proteins.

• Clinical and Experimental Pediatrics
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• 제56권11호
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• pp.482-489
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• 2013

Purpose: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. Methods: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df ) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS. Airway responsiveness and cell infiltration, differential cell counts in BALF, and cytokine and chemokine concentrations in BALF were measured 24 hours after intranasal RV1B infection. Results: RV infection increased the enhanced pause (Penh) in both the Df sensitized and challenged mice (Df mice) and PBS-treated mice (PBS mice) (P<0.05). Airway eosinophil infiltration increased in Df mice after RV infection (P<0.05). The levels of interleukin (IL) 13, tumor necrosis factor alpha, and regulated on activation, normal T cells expressed and secreted (RANTES) increased in response to RV infection in Df mice, but not in PBS mice (P<0.05). The level of IL-10 significantly decreased following RV infection in Df mice (P<0.05). Conclusion: Our findings suggest that the augmented induction of proinflammatory cytokines, Th2 cytokines, and chemokines that mediate an eosinophil response and the decreased induction of regulatory cytokines after RV infection may be important manifestations leading to airway inflammation with eosinophil infiltration and changes in airway responsiveness in the asthma model.

• 한국식품영양과학회지
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• 제43권2호
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• pp.238-242
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• 2014

본 연구에서는 막걸리로부터 다당을 분리하여 자연면역계를 구성하고 있는 보체계 및 macrophage에 대한 면역자극활성을 측정하였다. 열수추출한 뒤 ethanol 침전을 통하여 조다당을 추출한 후 특성을 검토한 결과, 막걸리 조 다당체(RWW)의 neutral sugar 함량은 87.3%, uronic acid 함량은 2.5%, protein 함량은 10.2%이었다. RWW는 인체 초기 면역반응에 있어 중요한 역할을 담당하는 보체계에 대한 활성을 나타냈으며, 마우스 RAW 264.7 macrophage에서 세포증식 및 면역유도 cytokine 분비활성을 나타내었다. RWW를 1, 10, $100{\mu}g/mL$ 농도로 macrophage에 처리하여 면역자극을 유도한 결과 모든 처리 농도에서 IL-6, IL-12, TNF-${\alpha}$의 분비가 증가되었다. 이상의 결과를 종합해 볼 때, 막걸리 유래 다당체는 자연면역계를 구성하고 있는 보체계와 macrophage의 활성인자로 작용할 수 있음이 확인되었고, RWW를 통해 cytokine 분비를 유도, 조절함으로써 체내 면역기능을 증강시킬 가능성이 있을 것으로 사료되었다.

• 한국식품영양과학회지
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• 제45권6호
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• pp.911-917
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• 2016

본 연구에서는 야관문 에탄올 추출물의 인체 대장암세포 성장억제 효능 및 그 기전을 연구하였다. 야관문 에탄올 추출물을 0, 200, 400, $600{\mu}g/mL$ 농도로 48시간 처리하여 암세포 증식억제 효과를 측정한 결과 농도 의존적으로 감소하는 것으로 확인하였다. HT-29 세포에 대한 야관문 추출물의 $IC_{50}$ 값은 $554.26{\pm}8.81{\mu}g/mL$로 확인되었다. 또한 야관문 에탄올 추출물을 처리한 HT-29 세포에 대한 세포 성장 억제 기전을 확인한 결과 pro-caspase 3의 발현이 감소함에 따라 PARP의 분절 및 DNA 분절을 확인하고 anti-apoptotic단백질인 Bcl-2를 감소시켰으며 pro-apoptotic 단백질인 Bax의 수준을 증가시키는 것으로 확인하였다. 염증 관련 유전자 $TNF-{\alpha}$, IL-6 그리고 그의 전사인자인 $NF-{\kappa}B$는 야관문 에탄올 추출물 처리농도에 의존적으로 감소하는 것으로 확인하였고 유전자 SIRT1의 발현량도 증가하는 것으로 확인하였다. 그 결과 야관문 에탄올 추출물 처리에 따라서 HT-29의 세포 성장억제가 확인되어 apoptosis를 유도하는 것으로 확인되었고, 이러한 연구 결과는 야관문이 기능성 소재로서 기초적 데이터베이스로 활용될 수 있을 것으로 생각되며 앞으로 더욱더 야관문의 질병에 대한 효능 및 기전연구가 지속하여야 할 것으로 생각된다.

• Journal of Acupuncture Research
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• 제32권3호
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• pp.1-13
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• 2015

Purpose : This research was conducted to investigate the effect of sweet bee venom pharmacopuncture and low level laser acupuncture on paw edema, pain index, anti-inflammatory factor, AST, ALT and complete blood cell count of a rat model with Complete Freund's Adjuvant-induced arthritis. Methods : Five experimental groups were formed with each consisting of six rats: normal group, control group, sweet bee venom pharmacopuncture group, lower level laser acupuncture group, and sweet bee venom pharmacopuncture, lower level laser acupuncture group. The experimental model of arthritis was induced by two injections of Freund's adjuvant into the left knee joint of Sprague Dawley(SD) rats. The second injection of Freund's adjuvant was given ten days after the first one. Ten days later, sweet bee venom pharmacopuncture and low level laser acupuncture were administered separately or together by assigned groups at $GB_{34}$ and $GB_{39}$ of rats twice a week for a total of six times. Thereafter, edema rate, pain index, tumor necrosis factor-${\alpha}$, interleukin-6, aspartate aminortansferase, alanine aminotransferase and complete blood cell count were measured. Results : We noticed synergic effects of sweet bee venom pharmacopuncture and low level laser acupuncture according to the results of the paw edema and Von Frey pain index. The sweet bee venom pharmacopuncture(BVA) and sweet bee venom pharmacopuncture+ low level laser acupuncture(BVA+LLA) groups experienced a more significant effect when compared with the control group. Conclusions : These results suggest that Sweet Bee Venom Pharmacopuncture and low level laser acupuncture at GB34 and GB39 have a significant anti-inflammatory effect on Freund's adjuvant arthritis in rats.