• IMMUNE NETWORK
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• 제23권2호
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• pp.15.1-15.17
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• 2023

Innate lymphoid cells (ILCs) are critical immune-response mediators. Although they largely reside in mucosal tissues, the kidney also bears substantial numbers. Nevertheless, kidney ILC biology is poorly understood. BALB/c and C57BL/6 mice are known to display type-2 and type-1 skewed immune responses, respectively, but it is unclear whether this extends to ILCs. We show here that indeed, BALB/c mice have higher total ILCs in the kidney than C57BL/6 mice. This difference was particularly pronounced for ILC2s. We then showed that three factors contributed to the higher ILC2s in the BALB/c kidney. First, BALB/c mice demonstrated higher numbers of ILC precursors in the bone marrow. Second, transcriptome analysis showed that compared to C57BL/6 kidneys, the BALB/c kidneys associated with significantly higher IL-2 responses. Quantitative RT-PCR also showed that compared to C57BL/6 kidneys, the BALB/c kidneys expressed higher levels of IL-2 and other cytokines known to promote ILC2 proliferation and/or survival (IL-7, IL-33, and thymic stromal lymphopoietin). Third, the BALB/c kidney ILC2s may be more sensitive to the environmental signals than C57BL/6 kidney ILC2s since they expressed their transcription factor GATA3 and the IL-2, IL-7, and IL-25 receptors at higher levels. Indeed, they also demonstrated greater responsiveness to IL-2 than C57BL/6 kidney ILC2s, as shown by their greater STAT5 phosphorylation levels after culture with IL-2. Thus, this study demonstrates previously unknown properties of kidney ILC2s. It also shows the impact of mouse strain background on ILC2 behavior, which should be considered when conducting research on immune diseases with experimental mouse models.

• 생명과학회지
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• 제22권3호
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• pp.298-305
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• 2012

Lutein은 식물에서 발견되는 carotenoid 계열에 속하는 물질로 항산화 기능을 가지고 있는 것으로 널리 알려져 있지만, 호흡기 질환과 관련하여 아직까지 lutein의 효능과 작용 기작이 잘 알려져 있지 않다. Ovalbumin (OVA)으로 유도한 천식(asthma) 생쥐모델에서 lutein은 기도 과민성을 억제하였고, 기관지 폐포 세척액에서 OVA의 감작에 의하여 증가한 각종 염증성 지표들을 감소시켰다. 또한, OVA의 감작에 의하여 증가한 제2형 협조 T 세포(Th2 cell)의 증가된 반응을 약화시키는 결과를 볼 수 있었다. 본 실험에서 lutein이 ovalbumin (OVA)으로 유도한 천식 생쥐 모델에서 제 2형 협조 T세포의 싸이토카인과 유전자 발현을 조절할 수 있는 면역약리학적 기능을 할 수 있는 물질로서의 가능성이 있음을 확인할 수 있었다.

• Molecules and Cells
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• 제45권11호
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• pp.833-845
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• 2022

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

• Childhood Kidney Diseases
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• 제26권1호
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• pp.40-45
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• 2022

Purpose: Chronic kidney disease (CKD) has various underlying causes in children. Identification of the underlying causes of CKD is important. Genetic causes comprise a significant proportion of pediatric CKD cases. Methods: In this study, we performed whole-exome sequencing (WES) to identify genetic causes of pediatric CKD. From January to June 2021, WES was performed using samples from pediatric patients with CKD of unclear etiology. Results: Genetic causes were investigated using WES in 37 patients (17 males) with pediatric CKD stages 1 (n=5), 2 (n=7), 3 (n=2), 4 (n=2), and 5 (n=21). The underlying diseases were focal segmental glomerulosclerosis (n=9), congenital anomalies of the kidney and urinary tract including reflux nephropathy (n=8), other glomerulopathies (n=7), unknown etiology (n=6), and others (n=7). WES identified genetic causes of CKD in 12 of the 37 patients (32.4%). Genetic defects were discovered in the COL4A4 (n=2), WT1 (n=2), ACTN4, CEP290, COL4A3, CUBN, GATA3, LAMA5, NUP107, and PAX2 genes. WT1 defects were found in patients whose pathologic diagnosis was membranoproliferative glomerulonephritis, and identification of CUBN defects led to discontinuation of immunosuppressive agents. Genetic diagnosis confirmed the clinical diagnosis of hypoparathyroidism, sensorineural deafness, and renal disease; Alport syndrome; and Joubert syndrome in three of the patients with CKD of unknown etiology (COL4A4 [n=2], CUBN [n=1]). Extrarenal symptoms were considered phenotypic presentations of WT1, PAX2, and CEP290 defects. Conclusions: WES provided a genetic diagnosis that confirmed the clinical diagnosis in a significant proportion (32.4%) of patients with pediatric CKD.

• 동의생리병리학회지
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• 제18권5호
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• pp.1347-1355
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• 2004

In this study, the immunological effect of a traditional Korea herbal acupuncture, that has been widely used for the treatment of various immunological disorders including inflammation in Korea, was examined in vitro and in vivo. In our previous study demonstrated that BV increased the expression of IFN-γ mRNA, that plays pivotal role in T cell response. This study was designated to evaluate the effect of BV on helper T cell development by monitoring Th1/Th2 specific cytokine secretion patterns in artificially induced Th1/Th2 polarized condition and in vivo. The results demonstrated that BV didn't have mitogenic effects on the unstimulated CD4+ T cell, but increased the CD4+ T cell proliferation upon activation with anti-CD3/CD28 antibody. The Th1 cells were over-populated dramatically in Th1 driven condition with BV treatment, while the Th2 cells were increased slightly in Th2 skewed condition. Furthermore, under Th1-skewed conditions, the level of IFN-γ was considerably increased with BV treatment. Besides, the expression of T-bet, a transcription factor that plays pivotal role in Th1 lineage programming, was increased with BV treatment. The expressions of IFN-γ and T-bet were also significantly increased in vivo. The results that Th1 specific cytokine secretion were considerably increased and Th2 specific cytokine secretion were not significantly changed in vitro and in vivo indicated that BV enhances Th1 lineage development, Therefore, these results suggest that BV might be desirable agent for correction of Th1 dominant pathological disorders.

• 대한본초학회지
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• 제29권6호
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• pp.27-33
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• 2014

Objectives : The aims of this study were to exploring the therapeutic effect of Imperatae Rhizoma Extract(IRE) on Asthma. Methods : To investigate biological modulation activities of IRE, we conducted the cell-based assay whether IRE could regulate T helper 2 cells activity with EL4 T cells and mouse splenocytes, and followed animal study to conform the efficacy of their therapeutic potential on OVA-induced asthmatic mouse. Results : In cell study, IRE suppress the nuclear translocation of GATA binding protein-3 protein in phorbol 12-myristate 13-acetate/Ionomycin-stimulated EL4 T cells and Interleukine(IL)-4, IL-5 and IL-13 production in splenocytes at concentration dependent manner. In animal study, IRE-treated groups both 100mg/ml and 200mg/ml improve airway hypersensitibility reaction(AHR) response to methacholine about 30% and 40% with positive control group. Peritoneal blood analysis reveal that eosinophil number and ovalbumin-specific IgE is reduced by IRE treatment. Cell number of eosinophil is also reduced in bronchoalveolar lavage of IRE group like to peritoneal cell and real time-polymerase chain reaction data show that expression levels of IL-4, IL-5 and IL-13 were down regulated in lung tissue. Finally, histological analysis indicate that IRE protect the bronchial tissue damages through the accumulation of inflammatory cells and collagen, and these effect may be cause by interfering Th2 cells activity. Conclusions : Our data represent that IRE potentiates therapeutic activities to the allergic diseases such as asthma by regulating Th2 cells differentiation.

• Asian Pacific Journal of Cancer Prevention
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• 제13권10호
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• pp.5233-5236
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• 2012

CK2 is a serine threonine kinase that participates in a variety of cellular processes with more than 300 defined substrates. This critical enzyme is known to be upregulated in cancers, but the role of this upregulation in carcinogenesis is not yet fully understood but c-myc, one of the defined CK2 substrates, is a well-known proto-oncogene that is normally essential in developmental process but is also involved in tumor development. We evaluated the optimal enzyme and substrate concentrations for CK2 activity in both neoplastic and non-neoplastic human lung tissues using the c-$myc^{424-434}$ peptide (EQKLISEEDL) as a substrate. The activities measured for the neoplastic tissue were 600-750 U/mg protein while those for the control tissue was in the range of 650-800 U/mg. $K_m$ value for c-myc peptide was determined as $0.33{\mu}M$ in non-neoplastic tissue and $0.18{\mu}M$ in neoplastic tissue. In this study, we did not observe an increased activity in the neoplastic tissue when compared with the non-neoplastic lung tissue, but we recorded two times higher affinity for c-$myc^{424-434}$ in cancer tissue. Considering the metabolic position of c-$myc^{424-434}$, our results suggest that phosphorylation by CK2 may be important in dimerization and thus it might affect the regulation of c-myc in cancer tissues.

• 대한예방한의학회지
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• 제27권2호
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• pp.23-33
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• 2023

Objectives : Sojadodamgangki-tang and its main components are traditional korean medicinal methods for treatment of cough, sputum and dyspnea. Using a respiratory inflammatory model, we intend to reveal the anti-inflammatory effect and its immune mechanism of Sojadodamgangki-tang. Methods : We used a papain-induced respiratory inflammatory mouse model. 8-week-old female BALB/C mice were divided into 3 groups as follows: the following groups: saline control group, papain treated group (vehicle), papain and Sojadodamgangki-tang(200 mg/kg) treated group (n=4). To evaluate the anti-inflammatory effect of Sojadodamgangki-tang extracts, inflammatory cell infiltration was measured in bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF). In addition, the effects of Sojadodamgangki-tang extracts on Th2 cell population in lung were determined by using flow cytometry. Results : Sojadodamgangki-tang extracts administration reduced inflammatory cell infiltration in BALF and NALF, especially of eosinophils. Furthermore, total immunogloblin (Ig)-E levels was reduced in BALF and serum by drug administration. Interestingly, Sojadodamgangki-tang extracts treatment also decreased the Th2 cell (CD4⁺GATA3⁺) population in lung. Conclusions : Our findings indicate Sojadodamgangki-tang extracts have anti-inflammatory effects by mediating Th2 cell and B cell activation.

• 운동영양학회지
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• 제23권4호
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• pp.26-31
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• 2019

[Purpose] Numerous epidemiological studies have shown that it is possible to prescribe exercise for neurodegenerative disease, such as Alzheimer's disease and Parkinson's disease. However, despite the availability of diverse scientific knowledge, the effects of exercise in this regard are still unclear. Therefore, this study attempted to investigate a substance, such as black chokeberry (Aronia melanocapa L.) that could improve the ability of the treatment and enhance the benefits of exercising in neurodegenerative diseases. [Methods] The cell viability was tested with 2,3-bis[2-methyloxy-4-nitro-5-sulfophenyl]-2H-tetrazolim-5-carboxanilide and the cells were stained with ethidium homodimer-1 solution. The mRNA expression levels were evaluated by microarray. The active compounds of black chokeberry ethanolic extract (BCE) were analyzed by gas chromatography. The chemical shift analysis in the brain was performed using magnetic resonance spectroscopy. [Results] BCE treatment decreased hydrogen peroxide-induced L6 cell death and beta amyloid induced primary neuronal cell death. Furthermore, BCE treatment significantly reduced the mRNA levels of the inflammatory factors, such as IL-1α, Cxcl13, IL36rn, Itgb2, Epha2, Slamf8, Itgb6, Kdm6b, Acvr1, Cd6, Adora3, Cd27, Gata3, Tnfrsf25, Cd40lg, Clec10a, and Slc11a1, in the primary neuronal cells. Next, we identified 16 active compounds from BCE, including D-mannitol. In vivo, BCE (administered orally at a dosage of 50 mg/kg) significantly regulated chemical shift in the brain. [Conclusion] Our findings suggest that BCE can serve as a candidate for neurodegenerative disease therapy owing to its cyto-protective and anti-inflammatory effects. Therefore, BCE treatment is expected to prevent damage to the muscles and neurons of the athletes who continue high intensity exercise. In future studies, it would be necessary to elucidate the effects of combined BCE intake and exercise.

• 한국재료학회:학술대회논문집
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• 한국재료학회 2010년도 춘계학술발표대회
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• pp.6.1-6.1
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• 2010

원자층 증착 기술 (Atomic Layer Deposition)은 기판 표면에서 한 원자층의 화학적 흡착 및 탈착을 이용한 nano-scale 박막 증착 기술이기 때문에, 표면 반응제어가 우수하며 박막의 물리적 성질의 재현성이 우수하고, 대면적에서도 균일한 두께의 박막 형성이 가능하며 우수한 계단 도포성을 확보 할 수 있다. 최근 ALD에 의한 박막증착 방법 중 플라즈마를 이용한 ALD 증착 방법에 대한 다양한 연구가 진행되고 있다. 플라즈마는 반응성이 좋은 이온과 라디컬을 생성하여 소스간 반응성을 좋게 하여, 소스 선택의 폭을 넓어지게 하고, 박막의 성질을 좋게 하며, 생산성을 높일 수 있는 장점이 있다. 그러나 플라즈마를 사용함으로써 플라즈마 내에 이온들이 가속되서 박막 증착 중에 기판 및 박막에 손상을 입혀 박막 특성을 열화 시킬 가능성이 있다. 따라서 플라즈마 발생 영역을 기판으로부터 멀리 떨어뜨린 원거리 플라즈마 원자층 공정이 개발 되었다. 이 기술은 플라즈마에서 생성된 ion이 기판이나 박막에 닫기 전에 전자와 재결합 되거나 공정 chamber에서 소멸하여 그 영향을 최소하고 반응성이 좋은 라디칼과의 반응만을 유도하여 향상된 막질을 얻을 수 있도록 하였다. 따라서 이 원거리 플라즈마 원자층 증착기술은 나노 테크놀러지 소자 개발하기 위한 나노 박막 기술에 있어서 그 활용이 점점 확대될 것이다. 그 적용으로써 리모트 플라즈마 원자층 증착 방법을 이용한 고유전 물질 개발이 있다. 반도체 소자의 고집적화 및 고속화가 요구됨에 따라 집적회로의 크기를 혁신적으로 축소하여 스위칭 속도(switching speed)를 증가시키고, 전력손실 (power dissipation)을 줄이려는 시도가 이루어지고 있다. 그 중 하나로 고유전율 절연막은 트렌지스터 소자의 스케일링 과정에 수반하여 커지는 게이트 누설 전류를 억제하기 위한 목적으로 도입되었다. 유전율이 크면 동일한 capacitance를 내는데 필요한 물리적인 두께를 늘릴 수 있어 전자의 tunneling을 억제할 수 있고 전력손실을 줄일 수 있기 때문이다. 이와 같은 고유전율 물질이 게이트 산화막으로 사용되기 위해서 높은 유전상수 열역학적 안정성, 낮은 계면 전하밀도, 낮은 EOT, 전극 물질과의 양립성 등의 특성이 요구되는데, 이에 따라 많은 유전물질에 대한 연구가 진행되었다. 기존 gata oxide를 대체하기 위한 가장 유력한 후보 재료로 주목 받고 있는 high-k 물질들로는 Al2O3, HfO2, ZrO2, La2O3 등이 있다. 본 발표에서는 ALD의 종류에 따른 기술을 소개하고 그 응용으로 고유전율 물질 개발 연구 (고유전율 산화물 박막의 증착, 고유전율 산화물의 열적 안정성 평가, Flatband 매카니즘 규명, 전기적 물리적 특성 분석)에 대해서 발표 하고자 한다.