• IMMUNE NETWORK
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• 제11권6호
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• pp.309-323
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• 2011

MicroRNAs (miRNAs) are a class of naturally occurring small non-coding RNAs of about 22 nucleotides that have recently emerged as important regulators of gene expression at the posttranscriptional level. Recent studies provided clear evidence that microRNAs are abundant in the lung, liver and kidney and modulate a diverse spectrum of their functions. Moreover, a large number of studies have reported links between alterations of miRNA homeostasis and pathological conditions such as infectious diseases, sickle cell disease and endometrium diseases as well as lung, liver and kidney diseases. As a consequence of extensive participation of miRNAs in normal functions, alteration and/or abnormalities in miRNAs should have importance in human diseases. Beside their important roles in patterning and development, miRNAs also orchestrated responses to pathogen infections. Particularly, emerging evidence indicates that viruses use their own miRNAs to manipulate both cellular and viral gene expression. Furthermore, viral infection can exert a profound impact on the host cellular miRNA expression profile, and several RNA viruses have been reported to interact directly with cellular miRNAs and/or to use these miRNAs to augment their replication potential. Here I briefly summarize the newly discovered roles of miRNAs in various human diseases including infectious diseases, sickle cell disease and enodmetrium diseases as well as lung, liver and kidney diseases.

• Biomolecules & Therapeutics
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• 제19권4호
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• pp.411-418
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• 2011

Ginsenoside Rp1 (G-Rp1) is a novel ginseng saponin derivative with anti-tumor activity. However, the biochemical and molecular mechanisms of G-Rp1 on anti-tumor activity are not fully understood. In the present study, we report that G-Rp1 inhibits lung cancer cell proliferation, migration and adhesion in p53 wild-type A549 and p53-defi cient H1299 cells. Anti-proliferative activity of G-Rp1 in lung cancer cells is mediated by enhanced nuclear localization of cyclin-dependent kinase inhibitors including $p27^{Kip1}$ and $p21^{WAF1/Cip1}$, and subsequent inhibition of pRb phosphorylation. We also show that these anti-tumor activities of G-Rp1 in both A549 and H1299 cells appear to be mediated by suppression of mitogenic signaling pathways such as ERK, Akt and $p70^{S6K}$. Taken together, these findings suggest further development and evaluation of G-Rp1 for the treatment of lung cancers with mutated p53 as well as wild-type p53.

• Journal of Life Science
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• 제10권2호
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• pp.55-60
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• 2000

We examined the effects of Kamgil-Tang on the process of lipopolysaccharide (LPS)-induced unclear factor (NF)-${\kappa}$ Bp65 and inhibitory (I)-${\kappa}$ B${\alpha}$ alteration in RAW 264.7 cell and acute lung injury in rats. Immunoblot analysis showed that LPS-induced degradation of I-${\kappa}$ B${\alpha}$ in RAW 264.7 was inhibited by pretreatment of Kamgil-Tang. The total cells of bronchoalveolar lavage fluid by LPS challenge markedly decreased in the Kamgil-Tang pretreatment rats. Kamgil-Tang pretreatment caused also a decline in neutrophils infiltration into interstitium of the lung. In the alveolar macrophages and neutrophils, decreased NF-${\kappa}$ Bp65 and inducible nitric oxide synthase and increased I-${\kappa}$ B${\alpha}$ immunoreaction were detected in Kamgil-Tang pretreated rats compared with LPS alone treated ones. It may be concluded that Kamgil-Tang attenuates the development of LPS-induced inflammation by reduction of NF-${\kappa}$ Bp65 activation and neutrophil-mediated acute lung injury. Kamgil-Tang would be useful as a therapeutic agent for endotoxin-induced lung disease.

• 한국환경농학회지
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• 제33권2호
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• pp.138-143
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• 2014

님추출물과 고삼추출물은 식물추출물 유기농업자재로 우리나라에 등록되어 친환경농산물 재배에 널리 사용되고 있다. 본 연구에서는 님추출물 2종과 고삼추출물 2종에 대한 안전성을 확인하고자 Chinese hamster lung cells을 이용한 in vitro 소핵시험(vitMN)을 통해 유전독성을 평가하였다. 시험은 cytochalasin B 적용군과 비적용군으로 구분하여 시험하였으며, 양성대조물질로 mitomycin C와 colchicine을 사용하였다. 시험 결과, 님추출물 시료 2종과 고삼추출물 시료 2종은 처리 농도에 따라 소핵발생 비율이 증가하였으나 모든 시료 처리군에서 전체 발생률이 2.2% 미만으로, 음성대조군 대비 2배 미만의 소핵이 관찰되었다. 따라서 님추출물 및 고삼추출물 시료는 본 시험의 vitMN 결과 최종적으로 음성으로 확인되었다. 또한 본 연구와 동일한 시료를 이용한 선행연구에서 복귀돌연변이 시험에서 음성을 보인 결과를 근거로 battery system에 의거해 종합적으로 평가하였을 때 님추출물과 고삼추출물 시료는 유전독성을 일으키지 않는 것으로 최종 판정하였다.

• BMB Reports
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• 제53권7호
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• pp.367-372
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• 2020

Cell cycle-related kinase (CCRK) has a conserved role in ciliogenesis, and Ccrk defects in mice lead to developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, retinal degeneration, and polycystic kidney. Here, we found that Ccrk is highly expressed in mouse trachea and bronchioles. Ccrk mutants exhibited pulmonary hypoplasia and abnormal branching morphogenesis in respiratory organ development. Furthermore, we demonstrated that Ccrk mutant lungs exhibit not only impaired branching morphogenesis but also a significant sacculation deficiency in alveoli associated with reduced epithelial progenitor cell proliferation. In pseudoglandular stages, Ccrk mutant lungs showed a downregulation of Hedgehog (Hh) signaling and defects in cilia morphology and frequency during progenitor-cell proliferation. Interestingly, we observed that activation of the Hh signaling pathway by small-molecule smoothened agonist (SAG) partially rescued bud morphology during branch bifurcation in explants from Ccrk mutant lungs. Therefore, CCRK properly regulates respiratory airway architecture in part through Hh-signal transduction and ciliogenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제14권3호
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• pp.2037-2042
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• 2013

Background: Different methods of diagnosis have been found to be inefficient in terms of screening and early diagnosis of lung cancer. Cancer cells produce proteins whose serum levels may be elevated during the early stages of cancer development. Therefore, those proteins may be recognized as potential cancer markers. The aim of this study was to differentiate healthy individuals and lung cancer cases by analyzing their serum protein profiles and evaluate the efficacy of this method in the early diagnosis of lung cancer. Materials and Methods: 170 patients with lung cancer, 53 under high risk of lung cancer, and 47 healthy people were included in our study. Proteomic analysis of the samples was performed with the SELDI-TOF-MS approach. Results: The most discriminatory peak of the high risk group was 8141. When tree classification analysis was performed between lung cancer and the healthy control group, 11547 was determined as the most discriminatory peak, with a sensitivity of 85.5%, a specificity of 89.4%, a positive predictive value (PPV) of 96.7% and a negative predictive value (NPV) of 62.7%. Conclusions: We determined three different protein peaks 11480, 11547 and 11679 were only present in the lung cancer group. The 8141 peak was found in the high-risk group, but not in the lung cancer and control groups. These peaks may prove to be markers of lung cancer which suggests that they may be used in the early diagnosis of lung cancer.

• Tuberculosis and Respiratory Diseases
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• 제82권4호
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• pp.348-356
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• 2019

Background: Recently, the number of lung transplants in South Korea has increased. However, the long-term outcome data is limited. In this study, we aimed to investigate the long-term outcomes of adult lung transplantation recipients. Methods: Among the patients that underwent lung transplantation at a tertiary referral center in South Korea between 2008 and 2017, adults patient who underwent deceased-donor lung transplantation with available follow-up data were enrolled. Their medical records were retrospectively reviewed. Results: Through eligibility screening, we identified 60 adult patients that underwent lung (n=51) or heart-lung transplantation (n=9) during the observation period. Idiopathic pulmonary fibrosis (46.7%, 28/60) was the most frequent cause of lung transplantation. For all the 60 patients, the median follow-up duration for post-transplantation was 2.6 years (range, 0.01-7.6). During the post-transplantation follow-up period, 19 patients (31.7%) died at a median duration of 194 days. The survival rates were 75.5%, 67.6%, and 61.8% at 1 year, 3 years, and 5 years, respectively. Out of the 60 patients, 8 (13.3%) were diagnosed with chronic lung allograft dysfunction (CLAD), after a mean duration of $3.3{\pm}2.8years$ post-transplantation. The CLAD development rate was 0%, 17.7%, and 25.8% at 1 year, 3 years, and 5 years, respectively. The most common newly developed post-transplantation comorbidity was the chronic kidney disease (CKD; 54.0%), followed by diabetes mellitus (25.9%). Conclusion: Among the adult lung transplantation recipients at a South Korea tertiary referral center, the long-term survival rates were favorable. The proportion of patients who developed CLAD was not substantial. CKD was the most common post-transplantation comorbidity.

• Journal of Ginseng Research
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• 제45권1호
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• pp.134-148
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• 2021

Background: Lung cancer has a high incidence worldwide, and most lung cancer-associated deaths are attributable to cancer metastasis. Although several medicinal properties of Panax ginseng Meyer have been reported, the effect of ginsenosides Rk1 and Rg5 on epithelial-mesenchymal transition (EMT) stimulated by transforming growth factor beta 1 (TGF-β1) and self-renewal in A549 cells is relatively unknown. Methods: We treated TGF-β1 or alternatively Rk1 and Rg5 in A549 cells. We used western blot analysis, real-time polymerase chain reaction (qPCR), wound healing assay, Matrigel invasion assay, and anoikis assays to determine the effect of Rk1 and Rg5 on TGF-mediated EMT in lung cancer cell. In addition, we performed tumorsphere formation assays and real-time PCR to evaluate the stem-like properties. Results: EMT is induced by TGF-β1 in A549 cells causing the development of cancer stem-like features. Expression of E-cadherin, an epithelial marker, decreased and an increase in vimentin expression was noted. Cell mobility, invasiveness, and anoikis resistance were enhanced with TGF-β1 treatment. In addition, the expression of stem cell markers, CD44, and CD133, was also increased. Treatment with Rk1 and Rg5 suppressed EMT by TGF-β1 and the development of stemness in a dose-dependent manner. Additionally, Rk1 and Rg5 markedly suppressed TGF-β1-induced metalloproteinase-2/9 (MMP2/9) activity, and activation of Smad2/3 and nuclear factor kappa B/extra-cellular signal regulated kinases (NF-kB/ERK) pathways in lung cancer cells. Conclusions: Rk1 and Rg5 regulate the EMT inducing TGF-β1 by suppressing the Smad and NF-κB/ERK pathways (non-Smad pathway).

• 대한본초학회지
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• 제34권5호
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• pp.21-28
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• 2019

Objectives : In present study, we investigated a therapeutic effect and optimum dose of Socheongryong-Tang (SCT) on LPS-induced lung inflammation rats model. Methods : Male Sprague-Dawley rats ($260{\pm}10g$) were divided into 12 groups : Group 1 included the normal rats, and Group 2-12 were administrated LPS by intranasal injection to induce experimental lung inflammation. After 1 day of LPS administration, Group 3-9 were treated with SCT ${\times}1/4$, ${\times}1/2$, ${\times}1$, ${\times}3$, ${\times}6$, ${\times}12$ or ${\times}18$, respectively. Group 10-12 (positive control) were treated with dexamethasone 1 mg/kg or acetylcystein 1.5 mg/kg or diclofenac sodium 0.4 mg/kg, respectively. After sacrifice, bronchoalveolar lavage fluid (BALF) was isolated. The levels of IL-$1{\beta}$, TNF-${\alpha}$, mucin glycoprotein 5AC (MUG5AC) were measured in BALF using enzyme-linked immunosorbent assay (ELISA). Results : LPS injected rats exhibited outstanding lung inflammation manifestations, including increased amount of total cells and neutrophil, and upregulated inflammatory cytokines level in BALF. However, the administration of SCT ${\times}1/4$, ${\times}1/2$ and ${\times}1$ decreased total cells and neutrophil, and suppressed the production of inflammatory cytokines, including $IL-1{\beta}$ and TNF-${\alpha}$, and MUG5AC in BALF. Notably, inhibitory effect of SCT ${\times}1/2$ and ${\times}1$ on the level of TNF-${\alpha}$ was markedly better than that of positive controls, dexamethasone and acetylcystein. Conclusions : Taken together, these results suggest that SCT ${\times}1/2$ and ${\times}1$ has therapeutic effects on LPS-induced lung inflammation rats model.

• 한국한의학연구원논문집
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• 제5권1호
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• pp.1-15
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• 1999

Chronic asthma is considered as an incurable disease in modern society. This study focused on development of an animal model for the chronic asthma to investigate new drugs from traditional herbal medicine. And we tested the animal model with a typical prescription, Chungsangboha-tang and tried to find biochemical markers such as catecholamines and cAMP in serum, and as densities of beta-receptor in lung tissues. SD rats were actively sensitized by exposure to ovalbumine (OA). Ten days after sensitization, rats were challenged with OA aerosol by nebulizer six times every three days. Mucin was increased in bronchoalveolar lavages (BALs) after antigen (OA) challenge. Serum concentration of epinephrine was decreased significantly although there were not changed much in serum concentration of cAMP and the densities of beta-receptor in lung tissues. Chungsangboha-tang (5 g/kg/day) was given orally to ovalbumin-sensitized rats (n=8) for 15 days. Mucin in bronchoalveolar lavages (BALs) was increased significantly after treatment of Chungsangboha-tang although concentrations of epinephrine and cAMP were not changed significantly. The densities of beta-receptor in lung tissues were not different from those of controls. These results suggest that the ovalbumin-sensitized rats can be a good animal model of chronic asthma and Chungsangboha-tang is a possible drug in the treatment of chronic asthma.