• The Journal of Korean Medicine
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• v.32 no.4
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• pp.83-99
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• 2011

Objective: This study aimed to evaluate the protective effects of Socheongryong-tang (SCRT) on elastase-induced lung injury. Materials and Methods: The extract of SCRT was treated to A549 cells and elastase-induced COPD mice model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results: SCRT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. SCRT treatment also revealed the protective effect on elastase-induced COPD mice model. This effect was evidenced via histopathological findings including immunofluoresence stains against elastin, collagen, and caspase 3, and protein level of Cdc2, cyclin B1, and phospho-Erk1/2 in lung tissue. Conclusion: These data suggest that SCRT has pharmaceutical properties on COPD. This study provides scientific evidence for the efficacy of SCRT for clinical application to patients with COPD.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.158-165
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• 2019

Background: A recent study reported that mesenchymal stem cells possess potential cellular therapeutic properties for treating patients with chronic obstructive pulmonary disease, which is characterized by emphysema. We examined the potential therapeutic effect of Wharton's Jelly-derived mesenchymal stem cells (WJMSCs), following pretreatment with pioglitazone, in lung regeneration mouse emphysema models. Methods: We used two mouse emphysema models, an elastase-induced model and a cigarette smoke-induced model. We intravenously injected WJMSCs ($1{\times}10^4/mouse$) to mice, pretreated or not, with pioglitazone for 7 days. We measured the emphysema severity by mean linear intercepts (MLI) analysis using lung histology. Results: Pioglitazone pretreated WJMSCs (pioWJMSCs) were associated with greater lung regeneration than non-augmented WJMSCs in the two mouse emphysema models. In the elastase-induced emphysema model, the MLIs were $59.02{\pm}2.42{\mu}m$ (n=6), $72.80{\pm}2.87{\mu}m$ (n=6), for pioWJMSCs injected mice, and non-augmented WJMSCs injected mice, respectively (p<0.01). Both pioWJMSCs and non-augmented WJMSCs showed regenerative effects in the cigarette smoke emphysema model (MLIs were $41.25{\pm}0.98$ [n=6] for WJMSCs and $38.97{\pm}0.61{\mu}m$ [n=6] for pioWJMSCs) compared to smoking control mice ($51.65{\pm}1.36{\mu}m$, n=6). The mean improvement of MLI appeared numerically better in pioWJMSCs than in non-augmented WJMSCs injected mice, but the difference did not reach the level of statistical significance (p=0.071). Conclusion: PioWJMSCs may produce greater lung regeneration, compared to non-augmented WJMSCs, in a mouse emphysema model.

• Tuberculosis and Respiratory Diseases
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• v.82 no.2
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• pp.166-172
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• 2019

Background: The purpose of this study was to determine whether components of the ProVent model can predict the high medical costs in Korean patients requiring at least 21 days of mechanical ventilation (prolonged mechanical ventilation [PMV]). Methods: Retrospective data from 302 patients (61.6% male; median age, 63.0 years) who had received PMV in the past 5 years were analyzed. To determine the relationship between medical cost per patient and components of the ProVent model, we collected the following data on day 21 of mechanical ventilation (MV): age, blood platelet count, requirement for hemodialysis, and requirement for vasopressors. Results: The mortality rate in the intensive care unit (ICU) was 31.5%. The average medical costs per patient during ICU and total hospital (ICU and general ward) stay were 35,105 and 41,110 US dollars (USD), respectively. The following components of the ProVent model were associated with higher medical costs during ICU stay: age <50 years (average 42,731 USD vs. 33,710 USD, p=0.001), thrombocytopenia on day 21 of MV (36,237 USD vs. 34,783 USD, p=0.009), and requirement for hemodialysis on day 21 of MV (57,864 USD vs. 33,509 USD, p<0.001). As the number of these three components increased, a positive correlation was found betweeen medical costs and ICU stay based on the Pearson's correlation coefficient (${\gamma}$) (${\gamma}=0.367$, p<0.001). Conclusion: The ProVent model can be used to predict high medical costs in PMV patients during ICU stay. The highest medical costs were for patients who required hemodialysis on day 21 of MV.

• Tuberculosis and Respiratory Diseases
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• v.52 no.1
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• pp.54-61
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• 2002

Background: Tracheal stenosis is an urgent but uncommon disease. Therefore, primary care clinicians have limited clinical experience. Animal models of a tracheal stenosis can be used conveniently for the learning, teaching, and developing new diagnostic and therapeutic modalities for tracheal stenosis. Recently, a canine model of a tracheal stenosis was developed using a Nd-YAG laser. To describe the methods and results of developed animal model, we performed this study. Methods : Six Mongrel dogs were generally anesthetized and the anterior 180 degree of tracheal cartilage of the animal was photo-coagulated using a Nd-YAG laser. The animals were bronchoscopically evaluated every week for 4 weeks and a pathologic evaluation was also made. Results : Two weeks after the laser coagulation, the trachea began to stenose and the stenosis progressed through 4 weeks. All animals suffered from shortness of breath, wheezing, and weight loss in the 3 weeks after the laser treatment, and two died of respiratory failure just before the fourth week. The gross pathologic findings showed the loss of cartilage and a dense fibrosis, which resulted in a fibrous stricture of the trachea. Microscopy also showed that the fibrous granulation tissue replaced destroyed cartilage. Conclusion : The canine model can assist in the understanding and development of new diagnostic and therapeutic modalities for tracheal stenosis.

• The Journal of Internal Korean Medicine
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• v.31 no.1
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• pp.84-101
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• 2010

Objectives : This study aimed to evaluate the protective effects of Seonpyejeongcheon-tang (SJT) on elastase-induced lung injury. Materials and Methods : The extract of SJT was treated to A549 cells and an elastase-induced lung injury mouse model. Then, various parameters such as cell-based cytoprotective activity and histopathological findings were analyzed. Results : SJT showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of cyclin B 1, Cdk1, and Erk1/2, and gene expression of TNF-$\alpha$ and IL-$1{\beta}$ in A549 cells. SJT treatment also revealed a protective effect on elastase-induced lung injury in mouse model. This effect was evidenced via histopathological findings, including immunofluoresence stains against elastin, collagen, and caspase 3, and protein levels of cyclin B1, Cdc2, and Erk1/2 in lung tissue. Conclusion : These data suggest that SJT has pharmaceutical properties on lung injury. This study thus provides scientific evidence for the efficacy of SJT for clinical application to patients with chronic obstructive pulmonary disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.6
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• pp.1042-1052
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• 2010

This study aimed to evaluate the protective effects of Mundongcheongpye-eum (MCE) on elastase-induced lung injury. The extract of MCE was treated to A549 cells and elastase-induced lung injury mice model. Then, various parameters such as cell-based cyto-protective activity and histopathological finding were analyzed. MCE showed a protective effect on elastase-induced cytotoxicity in A549 cells. This effect was correlated with analysis for caspase 3 levels, collagen and elastin contents, protein level of cyclin B1, Cdc2, and Erk1/2, and gene expression of TNF-${\alpha}$ and IL-$1{\beta}$ in A549 cells. MCE treatment also revealed the protective effect on elastase-induced lung injury in mice model. This effect was evidenced via histopathological finding including immunofluence stains against elastin, collagen, caspase 3, and protein level of cyclin B1, Cdc2, and Erk1/2 in lung tissue. These data suggest that MCE has a pharmaceutical properties on lung injury. This study would provide an scientific evidence for the efficacy of MCE for clinical application to patients with chronic obstructive pulmonary disease.

• Journal of Microbiology and Biotechnology
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• v.30 no.3
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• pp.427-438
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• 2020

Middle East respiratory syndrome coronavirus (MERS-CoV) infects the lower respiratory airway of humans, leading to severe acute respiratory failure. Unlike human dipeptidyl peptidase 4 (hDPP4), a receptor for MERS-CoV, mouse DPP4 (mDPP4) failed to support MERS-CoV infection. Consequently, diverse transgenic mouse models expressing hDPP4 have been developed using diverse methods, although some models show no mortality and/or only transient and mild-to-moderate clinical signs following MERS-CoV infection. Additionally, overexpressed hDPP4 is associated with neurological complications and breeding difficulties in some transgenic mice, resulting in impeding further studies. Here, we generated stable hDPP4-transgenic mice that were sufficiently susceptible to MERS-CoV infection. The transgenic mice showed weight loss, decreased pulmonary function, and increased mortality with minimal perturbation of overexpressed hDPP4 after MERS-CoV infection. In addition, we observed histopathological signs indicative of progressive pulmonary fibrosis, including thickened alveolar septa, infiltration of inflammatory monocytes, and macrophage polarization as well as elevated expression of profibrotic molecules and acute inflammatory response in the lung of MERS-CoV-infected hDPP4-transgenic mice. Collectively, we suggest that this hDPP4-transgenic mouse is useful in understanding the pathogenesis of MERS-CoV infection and for antiviral research and vaccine development against the virus.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4691-4698
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• 2015

Background: The tumor suppressor phosphatase and tensin homolog (PTEN) is an important negative regulator of cell-survival signaling. However, available results for the prognostic value of PTEN expression in patients with cancer remain controversial. Therefore, a meta-analysis of published studies investigating this issue was performed. Materials and Methods: A literature search via PubMed and EMBASE databases was conducted. Statistical analysis was performed by using the STATA 12.0 (STATA Corp., College, TX). Data from eligible studies were extracted and included into the meta-analysis using a random effects model. Results: A total of 3,810 patients from 27 studies were included in the meta-analysis, 22 investigating the relationship between PTEN expression and overall survival (OS) using univariate analysis, and nine with multivariate analysis. The pooled hazard ratio (HR) for OS was 1.64 (95% confidence interval (CI): 1.32-2.05) by univariate analysis and 1.56 (95% CI: 1.20-2.03) by multivariate analysis. In addition, eight papers including two disease-free-survival analyses (DFSs), four relapse-free-survival analyses (RFSs), three progression-free-survival analyses (PFSs) and one metastasis-free-survival analysis (MFS) reported the effect of PTEN on survival. The results showed that loss of PTEN expression was significant correlated with poor prognosis, with a combined HR of 1.74 (95% CI: 1.24-2.44). Furthermore, in the stratified analysis by the year of publication, ethnicity, cancer type, method, cut-off value, median follow-up time and neoadjuvant therapy in which the study was conducted, we found that the ethnicity, cancer type, method, median follow-up time and neoadjuvant therapy are associated with prognosis. Conclusions: Our study shows that negative or loss of expression of PTEN is associated with worse prognosis in patients with cancer. However, adequately designed prospective studies need to be performed for confirmation.

• Journal of Preventive Medicine and Public Health
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• v.52 no.5
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• pp.308-315
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• 2019

Objectives: Estimating influenza-associated mortality is important since seasonal influenza affects persons of all ages, causing severe illness or death. This study aimed to estimate influenza-associated mortality, considering both periodic changes and age-specific mortality by influenza subtypes. Methods: Using the Microdata Integrated Service from Statistics Korea, we collected weekly mortality data including cause of death. Laboratory surveillance data of respiratory viruses from 2009 to 2016 were obtained from the Korea Centers for Disease Control and Prevention. After adjusting for the annual age-specific population size, we used a negative binomial regression model by age group and influenza subtype. Results: Overall, 1 859 890 deaths were observed and the average rate of influenza virus positivity was 14.7% (standard deviation [SD], 5.8), with the following subtype distribution: A(H1N1), 5.0% (SD, 5.8); A(H3N2), 4.4% (SD, 3.4); and B, 5.3% (SD, 3.7). As a result, among individuals under 65 years old, 6774 (0.51%) all-cause deaths, 2521 (3.05%) respiratory or circulatory deaths, and 1048 (18.23%) influenza or pneumonia deaths were estimated. Among those 65 years of age or older, 30 414 (2.27%) all-cause deaths, 16 411 (3.42%) respiratory or circulatory deaths, and 4906 (6.87%) influenza or pneumonia deaths were estimated. Influenza A(H3N2) virus was the major contributor to influenza-associated all-cause and respiratory or circulatory deaths in both age groups. However, influenza A(H1N1) virus-associated influenza or pneumonia deaths were more common in those under 65 years old. Conclusions: Influenza-associated mortality was substantial during this period, especially in the elderly. By subtype, influenza A(H3N2) virus made the largest contribution to influenza-associated mortality.