• The Journal of Internal Korean Medicine
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• v.27 no.1
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• pp.208-220
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• 2006

Objective: Eosinophils are typically characterized by a bilobar nucleus with highly condensed chromatin and cytoplasm containing two major types of granules, specific and primary granules, and lipid bodies. The role of inflammation in asthma and other allergic diseases of the airways is widely appreciated, and airway inflammation is now included as a defining feature of asthma. The importance of the presence of eosinophils in the airways of patients with fetal asthma has long been recognized, but the mechanism by which these cells are recruited and retained in the lungs are only now being elucidated. Eotaxin is a potent and specific eosinophil chemoattractant that is mobilized in the respiratory epithelium after allergic stimulation. Methods : Water extracts of Armeniacae Amarum Semen(AAS) and pulmonary epithelial cell lines A549(alveolar typeII epithelial cells) and human eosinophils were used. Cytotoxic effects of AAS and MIS assay were estimated, as well as the effects of AAS on chemokines from prestimulated A549 cells by sandwich ELISA and RI-PCR. Chemotaxis assay was conducted on prestimulated eosinophils treated with AAS. Results : In this study it is demonstrated that $TGF-{\alpha}$, IL-4 and $IL-1{\beta}$ induced the accumulation of chemokine mRNAs in the alveolar epithelial cell lines A549 in dose-dependent manner. Eotaxin and IL-8 were inhibited by AAS in dose-dependent manner(p<0.05). Eosinophil migration was inhibited at high concentrations of AAS(p<0.05). Conculusions : These findings are indicative of suppression of eotaxin and IL-8, and suggest that this is accomplished through AAS treatment. This raises the possibility that AAS is of therapeutic value in diseases such as asthma.

• Biomolecules & Therapeutics
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• v.26 no.6
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• pp.576-583
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• 2018

Human rhinoviruses (HRV) are one of the major causes of common cold in humans and are also associated with acute asthma and bronchial illness. Heat-shock protein 90 (Hsp90), a molecular chaperone, is an important host factor for the replication of single-strand RNA viruses. In the current study, we examined the effect of the Hsp90 inhibitor pochonin D, in vitro and in vivo, using a murine model of human rhinovirus type 1B (HRV1B) infection. Our data suggested that Hsp90 inhibition significantly reduced the inflammatory cytokine production and lung damage caused by HRV1B infection. The viral titer was significantly lowered in HRV1B-infected lungs and in Hela cells upon treatment with pochonin D. Infiltration of innate immune cells including granulocytes and monocytes was also reduced in the bronchoalveolar lavage (BAL) by pochonin D treatment after HRV1B infection. Histological analysis of the lung and respiratory tract showed that pochonin D protected the mice from HRV1B infection. Collectively, our results suggest that the Hsp90 inhibitor, pochonin D, could be an attractive antiviral therapeutic for treating HRV infection.

• Toxicological Research
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• v.24 no.4
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• pp.253-261
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• 2008

Allergic asthma is a worldwide public health problem and a major socioeconomic burden disease. It is a chronic inflammatory disease marked by airway eosinophilia and goblet cell hyperplasia with mucus hypersecretion. Mouse models have proven as a valuable tool for studying human asthma. In the present report we describe a comparison of mouse asthma models. The experiments were designed as follows: Group I was injected with ovalbumin (OVA, i.p.) on day 1 and challenged with 1% OVA (aerosol exposure) on days $14{\sim}21$. Group II was injected on day 1, 14 and aerosol-immunized on days $14{\sim}21$. Group III was injected on day 1, 14 and immunized by 1% OVA aerosol on days $18{\sim}21$. We assessed asthma induction by determining the total number of white blood cells (WBC) and eosinophils as well as by measuring cytokine levels in bronchoalveolar lavage fluid (BALF). In addition, we evaluated the histopathological changes of the lungs and determined the concentration of immunoglobulin E (IgE) in serum. Total WBC, eosinophils, Th2 cytokines (IL-4, IL-13) and IgE were significantly increased in group I relative to the other groups. Moreover, histopathological studies show that group I mice show an increase in the infiltration of inflammatory cell-in peribronchial and perivascular areas as well as an overall increase in the number of mucus-containing goblet cells relative to other groups. These data suggest that group I can be a useful model for the study of human asthma pathobiology and the evaluation of existing and novel therapeutic agents.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.893-901
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• 2018

Influenza viruses that cause recurrent seasonal epidemics to humans can be controlled with vaccine and antiviral therapy. However, the medical treatments often exhibit limited efficacy in the elderly or immunosuppressed individuals. In these cases, daily uptake of probiotics may be an option to bring in health benefits against influenza. Here, we demonstrate the effects of probiotics Lactobacillus plantarum (Lp) and Leuconostoc mesenteroides (Lm) against seasonal and avian influenza viruses. As assessed by the plaque size reduction of human H1N1 and avian influenza H7N9 viruses, including green fluorescent protein-tagged H1N1 strain in cells, the selected Lp and Lm strains restrained viral replication in mouse lungs with statistical significance. Against lethal viral challenge, the Lp and Lm strains exhibited their beneficial effects by increasing the mean days and rates of survival of the infected mice. These results suggest that, despite rather narrow ranges of protective efficacy, the dietary supplement of Lactobacillus and Leuconostoc probiotics may promote health benefits against influenza.

• Biomolecules & Therapeutics
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• v.30 no.2
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• pp.126-136
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• 2022

Liver fibrosis is part of the wound healing process to help the liver recover from the injuries caused by various liver-damaging insults. However, liver fibrosis often progresses to life-threatening cirrhosis and hepatocellular carcinoma. To overcome the limitations of current in vivo liver fibrosis models for studying the pathophysiology of liver fibrosis and establishing effective treatment strategies, we developed a new mouse model of liver fibrosis using polyhexamethylene guanidine phosphate (PHMG-p), a humidifier sterilizer known to induce lung fibrosis in humans. Male C57/BL6 mice were intraperitoneally injected with PHMG-p (0.03% and 0.1%) twice a week for 5 weeks. Subsequently, liver tissues were examined histologically and RNA-sequencing was performed to evaluate the expression of key genes and pathways affected by PHMG-p. PHMG-p injection resulted in body weight loss of ~15% and worsening of physical condition. Necropsy revealed diffuse fibrotic lesions in the liver with no effect on the lungs. Histology, collagen staining, immunohistochemistry for smooth muscle actin and collagen, and polymerase chain reaction analysis of fibrotic genes revealed that PHMG-p induced liver fibrosis in the peri-central, peri-portal, and capsule regions. RNA-sequencing revealed that PHMG-p affected several pathways associated with human liver fibrosis, especially with upregulation of lumican and IRAK3, and downregulation of GSTp1 and GSTp2, which are closely involved in liver fibrosis pathogenesis. Collectively we demonstrated that the PHMG-p-induced liver fibrosis model can be employed to study human liver fibrosis.

• IMMUNE NETWORK
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• v.23 no.4
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• pp.31.1-31.18
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• 2023

Evidence suggests that the human respiratory tract, as with the gastrointestinal tract, has evolved to its current state in association with commensal microbes. However, little is known about how the airway microbiome affects the development of airway immune system. Here, we uncover a previously unidentified mode of interaction between host airway immunity and a unique strain (AIT01) of Staphylococcus epidermidis, a predominant species of the nasal microbiome. Intranasal administration of AIT01 increased the population of neutrophils and monocytes in mouse lungs. The recruitment of these immune cells resulted in the protection of the murine host against infection by Pseudomonas aeruginosa, a pathogenic bacterium. Interestingly, an AIT01-secreted protein identified as GAPDH, a well-known bacterial moonlighting protein, mediated this protective effect. Intranasal delivery of the purified GAPDH conferred significant resistance against other Gram-negative pathogens (Klebsiella pneumoniae and Acinetobacter baumannii) and influenza A virus. Our findings demonstrate the potential of a native nasal microbe and its secretory protein to enhance innate immune defense against airway infections. These results offer a promising preventive measure, particularly relevant in the context of global pandemics.

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.397-404
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• 2011

Background: To evaluate chest CT findings of pandemic influenza A/H1N1 pneumonia without co-infection. Methods: Among 56 patients diagnosed with pandemic influenza A/H1N1 pneumonia, chest CT was obtained in 22 between October 2009 and Februrary 2010. Since two patients were co-infected with bacteria, the other twenty were evaluated. Predominant parenchymal patterns were categorized into consolidation, ground glass opacity (GGO), and mixed patterns. Distribution of parenchymal abnormalities was assessed. Results: Median age was 46.5 years. The CURB-65 score, which is the scoring system for severity of community acquired pneumonia, had a median of 1. Median duration of symptoms was 3 days. All had abnormal chest x-ray findings. The median number of days after the hospital visit that Chest CT was performed was 1. The reasons for chest CT performance were radiographic findings unusual for pneumonia (n=13) and unexplained dyspnea (n=7). GGO was the most predominant pattern on CT (n=13, 65.0%). Parenchymal abnormalities were observed in both lungs in 13 cases and were more extensive in the lower lung zone than the upper. Central and peripheral distributions were identified in ten and nine cases, respectively. One showed diffuse distribution. Peribronchial wall thickening was found in 16 cases. Centrilobular branching nodules (n=7), interlobular septal thickening (n=4), atelectasis (n=1), pleural effusion (n=5), enlarged hilar and mediastinal lymph nodes (n=6 and n=7) were also noted. Conclusion: Patchy and bilateral GGO along bronchi with predominant involvement of lower lungs are the most common chest CT findings of pandemic influenza A/H1N1 pneumonia.

• Archives of Plastic Surgery
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• v.32 no.1
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• pp.5-11
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• 2005

Prostaglandin $E_1$($PGE_1$) is known to have various physiological action such as vasodilatation, decrease of blood pressure, angiogenesis, inhibition of platelet aggregation and so forth. $PGE_1$ has been developed in many different formulations in order to overcome its chemical instability and deactivation in the lungs when administered parenterally. Lipo-AS013 is a potent drug with higher chemical stability and greater vascular wall targeting than others. The study was done on $3{\times}10cm$ model flap of dorsal skin of Sprague-Dawley rats and the flap perfusion survival were observed and documented. The flap treated with Lipo-AS013 beforehand was given intravenously Sodium fluorescein 10 minutes later, and then Percent Dye Fluorescence Index(% DFI) was calculated. The results were compared to a control group and the group administered locally epinephrine.. In the control group, the % DFI and flap survival rate increased from $54.1{\pm}6.7$ to $65.0{\pm}2.6$(p<0.01) while in Lipo-AS013 group from $55.3{\pm}2.2$ to $67.4{\pm}1.9$(p<0.01), respectively. In the epinephrine group, the % DFI(p<0.05) and flap survival rate(p<0.001) decreased. In the both epinephrine and Lipo-AS013 group Percent DFI and flap survival rate are comparable with the control group.The result indicates that the potent Lipo-AS013 enhances the blood flow and flap survival. This highly potent Lipo-AS013 may have targeting ability and accumulate $PGE_1$ onto the vascular walls. A quantitative analysis of fluorescence on the skin surface is a reliable tool to measure the blood perfusion into an ischemic flap and its viability. Further comparative study with conventional $PGE_1$ and Lipo-$PGE_1$ is needed in order to clarify the action and efficiency of Lipo-AS013.

• Korean Journal of Plant Resources
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• v.31 no.2
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• pp.95-101
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• 2018

Doxorubicin is a anti-cancer drugs that interferes with the growth and spread of cancer cells in human body. Doxorubicin is used to treat different types of cancers that affect the ovary, thyoid and lungs, but induced side effect such as nephrotoxicity and cardiotoxicity. Thus, we investigated that the effect of iridin on doxorubicin-induced necrosis in HK-2 cells, a human proximal tubule cell. To confirm effect of iridin on doxorubicin-induced necrosis, HK-2 cells are treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ iridin. $80{\mu}M$ iridin reduced $10{\mu}M$ doxorubicin-induced necrosis, the mitochondrial over activation and caspase-3 activation. However, iridin reduces anti-cancer effect of doxorubicin such as PARP1 and caspase-3 activation, checkpoint proteins (CDK4 and CDK6) in NCI-H1129 cells (Human non-small cell lung cancer cell). In HCT-116 cells (Human colorectan cancer cell), iridin do not increased protein expression of CDK4 and CDK6 decreased by doxorubicin. Results indicate that treatment of iridin was diminished doxorubicin-induced necrosis in HK-2 cells. However, iridin was decreased anti-cancer effect of doxorubicin on NCI-H1229, but not HCT-116. Thus, further experiment are required to iridin treatment on various cancer cells and animal models because effect of iridin different cell type.

• Journal of Chest Surgery
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• v.36 no.12
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• pp.894-903
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• 2003

Protection against ischemia-reperfusion injury is crucial for successful transplantation of the lung. It has been known that nitric oxide has many favorable effects on the donor lungs but at the same time, has some potential side effects of cytotoxicity. In this regards, we investigated whether the administration of nitroglycerin could decrease ischemia-reperfusion injury in isolated rat lung reperfusion model for the confirmation of the effect of nitroglycerin, a donor of nitric oxide, on lung transplantation. Material and Method: 35 Sprague-Dawley species male white rats were used for this experiment. For nitroglycerin group (n=18), nitroglycerin was administered intravenously followed by mixed in flushing solution for preservation. As a control group (n=17), we used the same amount of normal saline. To evaluate the effect of nitroglycerin on the lung, heart-lung block was obtained, weighed and stored in University of Wisconsin Solution at 1$0^{\circ}C$ for 24 hours. In each group of the isolated lungs, reperfusion was carried out with Krebs-Hensleit-diluted human blood for 60 minutes. As parameters of the state of the isolated lung, peak inspiratory and pulmonary arterial pressures were continuously recorded. Oxygen and carbon dioxide tension of reperfusing blood were measured before and after 30, 60 minutes of reperfusion. After sixty minutes of reperfusion, protein content in bronchoalveolar lavage fluid was measured also for the evaluation of the degree of alveolar flooding. Lung myeloperoxidase activity was determined to verify the accumulation of neutrophils. Results: Although statistically significant differences were not noted in peak inspiratory and pulmonary arterial pressure between control and nitroglycerin group, latter group showed lowering tendency of pulmonary arterial pressure during the entire reperfusion period. Oxygen tension was higher (p<0.05) in nitroglycerin group compared with that of the control group, in contrast, there were no differences in carbon dioxide tension, protein content in bronchoalveolar lavage fluid and myeloperoxidase activity between the groups. In the examination of ultrastructural changes, nitroglycerin denoted the protective effect on the pulmonary architecture compared with that of control group. Conclusion: Collectively, on the bases of these experimental results, prior treatment of donor lung with nitroglycerin could result in better preservation of the lung. Consequently, these nitroglycerin preserved lungs are thought to be more suitable for successful transplantation of the lung.