• 한국식품영양과학회지
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• 제43권3호
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• pp.349-354
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• 2014

세포내 $Ca^{{+}{+}}$의 증가는 비만세포에서 수용체 활성을 거치지 않고 탈과립을 유도한다. 괴화는 천연 염색 재료로 사용되고 있으며, 또한 항염증 작용과 $Fc{\varepsilon}RI$와 IgE 가교에 의한 항알레르기 효능도 보고되었다. 이번 연구에서 비만세포에서 $Ca^{{+}{+}}$ 유입에 의해 생산되는 알레르기 매개물에 대한 괴화 추출물의 조절 기능을 보고한다. 괴화 추출물은 A23187에 의해 유도되는 IL-4와 TNF-${\alpha}$의 생산과 탈과립을 저해하였다. 또한 괴화 추출물은 DNFB로 유도한 알레르기 피부염의 동물 모델에서 알레르기 반응을 억제하였다. 괴화추출물 50 mg/kg을 경구투여 또는 도말을 한 경우, DNFB를 단독으로 처리한 군보다 IL-4, TNF 그리고 IFN-${\gamma}$와 같은 염증성 사이토카인의 생산량이 감소하였다. 또한 괴화 추출물을 처리한 경우 혈청 내 IgE의 함량이 DNFB를 단독으로 처리한 군보다 감소하였다. 괴화 추출물을 처리한 군에서의 비장과 림프절의 무게도 DNFB를 단독으로 처리한 군보다 감소하였다. 이러한 결과를 토대로 괴화는 비만세포에서 $Fc{\varepsilon}RI$ 자극뿐만 아니라 $Ca^{{+}{+}}$의 유입에 의한 항알레르기 효능이 있다는 것을 보고한다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4215-4218
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• 2015

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancer deaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have been associated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth, proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatory elements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigate the influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for the first time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controls were recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statistically analyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regression analysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition, no significant association between genotypes and clinicopathological features was observed (p value>0.05). The frequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%, 2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. The frequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively. Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerful genetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.871-876
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• 2014

Objective: Desmogleins (DSGs) are major members among the desmosomal cadherins critically involved in cell-cell adhesion and the maintenance of normal tissue architecture in epithelia. Reports exploring links of DSG family member expression with cancers are few and vary. The aim of this study was to investigate the ratio of DSG2 and DSG3 mRNA expression in esophageal squamous cell carcinoma (ESCC) tissue to normal tissue (T/N ratio) and evaluate correlations with clinical parameters. Methods: The mRNA expression of DSGs, as well as ${\gamma}$-catenin and desmoplakin, was detected by real-time quantitative RT-PCR in 85 cases of ESCC tissue specimens. Results: The expression level of DSG3 mRNA was significantly higher than that of DSG2 in ESCC specimens (p=0.000). DSG3 mRNA expression highly correlated with histological grade (p=0.009), whereas that of DSG2 did not significantly relate to any clinicopathologic parameter. Kaplan-Meier survival analysis showed that only DSG3 expression had an impact on the survival curve, with negative DSG3 expression indicating worse survival (p=0.038). Multivariate Cox regression analysis demonstrated DSG3 to be an independent prognostic factor for survival. Furthermore, correlation analysis demonstrated the mRNA level of DSG3 to highly correlate with those of ${\gamma}$-catenin and desmoplakin in ESCC samples (p=0.000), implying that the expression of desmosomal components might be regulated by the same upstream regulatory molecules. Conclusions: Our findings suggest that DSG3 may be involved in the progression of ESCC and serve as a prognostic marker, while expression of DSG2 cannot be used as a predictor of ESCC patient outcome.

• 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.

• International Journal of Oral Biology
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• 제33권4호
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• pp.163-177
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• 2008

Periodontal disease, a form of chronic inflammatory bacterial infectious disease, is known to be a risk factor for cardiovascular disease (CVD). Porphyromonas gingivalis has been implicated in periodontal disease and widely studied for its role in the pathogenesis of CVD. A previous study demonstrating that periodontopathic P. gingivalis is involved in CVD showed that invasion of endothelial cells by the bacterium is accompanied by an increase in cytokine production, which may result in vascular atherosclerotic changes. The present study was performed in order to further elucidate the role of P. gingivalis in the process of atherosclerosis and CVD. For this purpose, invasion of human aortic smooth muscle cells (HASMC) by P. gingivalis 381 and its isogenic mutants of KDP150 ($fimA^-$), CW120 ($ppk^-$) and KS7 ($relA^-$) was assessed using a metronidazole protection assay. Wild type P. gingivalis invaded HASMCs with an efficiency of 0.12%. In contrast, KDP150 failed to demonstrate any invasive ability. CW120 and KS7 showed relatively higher invasion efficiencies, but results for these variants were still negligible when compared to the wild type invasiveness. These results suggest that fimbriae are required for invasion and that energy metabolism in association with regulatory genes involved in stress and stringent response may also be important for this process. ELISA assays revealed that the invasive P. gingivalis 381 increased production of the proinflammatory cytokine interleukin (IL)-$1{\beta}$ and the chemotactic cytokines (chemokine) IL (interleukin)-8 and monocyte chemotactic (MCP) protein-1 during the 30-90 min incubation periods (P<0.05). Expression of RANTES (regulation upon activation, normal T cell expressed and secreted) and Toll-like receptor (TLR)-4, a pattern recognition receptor (PRR), was increased in HASMCs infected with P. gingivalis 381 by RT-PCR analysis. P. gingivalis infection did not alter interferon-$\gamma$-inducible protein-10 expression in HASMCs. HASMC nonspecific necrosis and apoptotic cell death were measured by lactate dehydrogenase (LDH) and caspase activity assays, respectively. LDH release from HASMCs and HAMC caspase activity were significantly higher after a 90 min incubation with P. gingivalis 381. Taken together, P. gingivalis invasion of HASMCs induces inflammatory cytokine production, apoptotic cell death, and expression of TLR-4, a PRR which may react with the bacterial molecules and induce the expression of the chemokines IL-8, MCP-1 and RANTES. Overall, these results suggest that invasive P. gingivalis may participate in the pathogenesis of atherosclerosis, leading to CVD.

• 동의생리병리학회지
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• 제17권2호
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• pp.542-548
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• 2003

The present study was aimed to investigate whether glycyrrhizin, which is the major component of Glycyrrhiza uralensis, has an antioxidant effect and regulatory effect on Na,K-ATPase in gentamicin-induced acute renal failure (ARF) rats . It is well known that reactive oxygen species (ROS), such as superoxide anion and hydroxyl radical, are main pathophysiological factor in gentamicin-induced ARF. Glycyrrhizin showed potent in vitro antioxidant activity, especially superoxide scavenging activity, in a dose-dependent manner. Plasma lipid peroxide level was restored to normal level by oral administration of glycyrrhizin (200 mg/kg) in the gentamicin-induced ARF rats. The expression of Na,K-ATPase α1 subunit was restored in the gentamicin-induced ARF rats by administration of glycyrrhizin, whereas β1 subunit was not restored. The renal functional parameters including urine volume, cleatinine clearance, urine osmolality, solute-free water reabroption were also partially restored in gentamicin-ARF rats by administration of glycyrrhizin. Taken together, the amelioration of renal functions and the expression of sodium pump by administration of glycyrrhizin in the gentamicin-induced ARF was appear to be mediated by the scavenging of ROS.

• Nuclear Medicine and Molecular Imaging
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• 제41권5호
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• pp.343-349
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• 2007

방사성옥소는 갑상선암의 핵의학적 영상과 방사성치료에 널리 그리고 성공적으로 사용되어 왔다. 최근 세포의 옥소섭취를 담당하는 운반체로서 Na/I symporter (NIS)의 분자세포학적 특성이 규명되고 그 유전자가 클로닝되면서 앞으로는 갑상선암 이외의 각종 암에도 NIS 유전자를 외부에서 전달함으로써 방사성옥소 치료를 적용하는 새로운 암치료 기술이 가능할 것으로 기대되고 있다. 방사성옥소를 이용한 암치료의 성공을 위해서는 NIS를 통한 표적세포의 옥소 섭취를 극대화 시키는 것이 핵심이다. TSH는 갑상선 세포의 NIS 발현을 항진시키고 retinoic acid는 갑상선암과 유방암 세포의 NIS발현을 증가시키는 효과가 있다. 또 일반 암세포에는 NIS 유전자를 전달하여 발현 시킬 수 있다. 그러나 NIS 발현 만으로는 원하는 수준의 방사성옥소 섭취를 충분히 얻지 못할 수 있다. 이는 세포의 옥소 섭취가 NIS 단백질의 총량이 아니라 세포막에 위치한 NIS의 양에 의해 결정되기 때문이다. 즉, 옥소를 섭취하려는 전사된 NIS단백질이 세포막으로 이동하여 정상적으로 기능하게 하는 조절 기전이 중요하다. NIS의 세포막 이동 기전은 아직 밝혀져 있지 않으나 다른 운반체와 유사하게 단백질의 전사후 glycosylation이나 phosphorylation이 관여할 것으로 생각된다. 본 연구진은 NIS 유전자를 전달한 암세포에서epidermal growth factor를 통한 extracellular signal regulated kinase 신호경로의 활성화가 방사성옥소 섭취를 항진시킴을 관찰하여 NIS의 전사외 기능조절 기전을 조사하고 있다. 앞으로 NIS기능에 대한 조절기전이 보다 자세하게 밝혀지면 방사성옥소 치료기술과 NIS유전자 영상기술의 개선과 발전에 도움이 될 것으로 기대된다.

• 한국식품과학회지
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• 제45권3호
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• pp.356-363
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• 2013

최근 연구에서 활성 산소 및 비만에 대한 유전자 발현이 비만과 노화를 촉진시키는 원인으로 주목 받고 있으며, 이를 통해 노화와 비만의 억제 체계를 규명하려는 다양한 방법들이 연구되고 있다. 본 연구에서는 우리나라 전국 각지의 산야지에 자생하며 농가에서 재배하기도 하는 국화과에 속하는 식물인 참취(Aster scaber Thunb.) 메탄올 추출물의 항산화력과 3T3-L1 전구지방세포의 지방세포형성과정에 미치는 영향을 확인하였다. 참취 메탄올 추출물에 존재하는 총 폴리페놀 및 플라보노이드 함량은 각각 $57.07{\pm}2.17$, $54.62{\pm}2.24{\mu}g/mg$으로 나타났다. 시료의 DPPH, ABTS radical 소거 활성을 측정한 결과 $RC_{50}$값이 각각 $22.24{\pm}0.40$, $53.19{\pm}1.61{\mu}g/mL$로 우수한 항산화 효과를 나타냈다. 참취의 메탄올 추출물이 3T3-L1 전구지방세포에서 분화유도 물질(IBMX, DEXA, Insulin)과 함께 처리했을 때 지방구의 형성을 농도 의존적으로 감소시켰다. 또한 이들은 지방세포의 증식 및 분화되는 과정에서 발현되는 adipogenic transcription factor 및 관련 유전자의 단백질 발현과 mRNA 발현을 유의적으로 감소시키는 것을 확인하였다. 이상의 결과로 참취 메탄올 추출물을 이용하여 항비만에 우수한 효능을 가지는 기능성 식품 소재로서의 개발이 가능할 것으로 생각된다.

• 생명과학회지
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• 제30권2호
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• pp.202-210
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• 2020

최근까지 근력 개선 또는 만성 근육 손실을 유발하는 질병을 치료하기 위해 많은 연구가 있어왔지만, 지금까지 근력 개선 유도를 위해 대표적으로 사용되는 약물은 단백질 동화 스테로이드(AAS)계열의 steroidal androgen들이 주로 이용되어 왔다. AAS는 다양한 근육 및 체중 손실성 치료를 목적으로 처방되고 있으나, 장기간 또는 과다한 복용은 피부질환, 생식 및 내분비 기능 저하, 심혈관 질환 등 다양한 부작용을 초래한다고 잘 알려져 있다. 따라서, 상대적으로 부작용이 적은 근육 신생을 촉진하는 천연물을 탐색하는 연구는 매우 중요하다. 현재까지 천연물의 처리로 인한 근육 신생의 촉진은 대표적으로 세가지 기전의 영향을 받으며, 그 기전으로는 근육조절인자(MRF)의 양성 조절, 단백질 합성 기전의 활성화 및 단백질 분해기전의 억제가 있다. 본 리뷰에서는, 근육 신생 촉진 효과가 보고된 Black ginseng, Plum 등과 같은 식물 추출물 및 Creatine, Catechin 및 여러 지방산 등 천연물 유래 단일물질에 대하여 소개하고, 더 나아가 현재까지 알려진 상기의 천연물질들의 처리에 의한 근육 신생 촉진 기전에 대하여 기전별로 요약하고자 한다.

• Biomolecules & Therapeutics
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• 제26권2호
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• pp.146-156
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• 2018

Spermidine is a naturally occurring polyamine compound that has recently emerged with anti-aging properties and suppresses inflammation and oxidation. However, its mechanisms of action on anti-inflammatory and antioxidant effects have not been fully elucidated. In this study, the potential of spermidine for reducing pro-inflammatory and oxidative effects in lipopolysaccharide (LPS)-stimulated macrophages and zebrafish was explored. Our data indicate that spermidine significantly inhibited the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$), and cytokines including tumor necrosis $factor-{\alpha}$ and $interleukin-1{\beta}$ in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects of spermidine accompanied by a marked suppression in their regulatory gene expression at the transcription levels. Spermidine also attenuated the nuclear translocation of $NF-{\kappa}B$ p65 subunit and reduced LPS-induced intracellular accumulation of reactive oxygen species (ROS) in RAW 264.7 macrophages. Moreover, spermidine prevented the LPS-induced NO production and ROS accumulation in zebrafish larvae and was found to be associated with a diminished recruitment of neutrophils and macrophages. Although more work is needed to fully understand the critical role of spermidine on the inhibition of inflammation-associated migration of immune cells, our findings clearly demonstrate that spermidine may be a potential therapeutic intervention for the treatment of inflammatory and oxidative disorders.