• Asian Pacific Journal of Cancer Prevention
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• 제16권10호
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• pp.4251-4256
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• 2015

Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

• Tuberculosis and Respiratory Diseases
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• 제38권4호
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• pp.372-378
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• 1991

Some kinds of newer fluoroquinolone antibiotics are known to interact with theophylline, which is widely used as a potent bronchodilator in asthma or chronic obstructive lung disease. To evaluate the effect of enoxacin and ciprofloxacin on the metabolism of theophylline, aminophylline was administered intravenously in bolus (6 mg/kg) over 30 minutes to 6 healthy volunteers (age: $23.3{\pm}4.2$ year, body weight: $63.2{\pm}9.0\;kg$, height: $169.0{\pm}6.5\;cm$, female 3, male 3) before and after per oral 5-day medication of enoxacin and ciprofloxacin, respectively and we measured the level of theophylline in serum. The results were as follows: 1) Enoxacin and ciprofloxacin did not influence the volume of distribution significantly. 2) Enoxacin decreased the clearance of theophylline significantly (from $42.9{\pm}14.6\;ml/min$ to $30.1{\pm}6.3\;ml/min$: p<0.05), but ciprofloxacin did not cause significant decrease (to $32.8{\pm}6.2\;ml/min$: p>0.005). 3) Enoxacin increased the elimination half life of theophylline significantly (from $496{\pm}83\;min$ to $693{\pm}32\;min$: p<0.001), but ciprofloxacin did not cause significant increase (to $687{\pm}222\;min$: p>0.05). These results suggested that enoxacin influenced clearance and elimination half life significantly and thorough monitoring of the level of theophylline in patients with coadminstration of enoxacin and theophylline was necessary. In case of ciprofloxacin, the influence on the metabolism of theophylline was not statistically significant, but one exceptionally large decrease of the clearance and increase of the elimination halflife of theophylline suggested the necessity of monitoring of theophylline level during coadministration of ciprofloxacin and theophylline.

• Journal of Microbiology and Biotechnology
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• 제27권1호
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• pp.49-56
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• 2017

In the human airway, mucus exists to protect the respiratory system as a primary barrier of the innate immune system. However, hyperexpressed mucus limits airflow, resulting in a decrease of lung function. Among more than 20 mucin family members, MUC5AC and MUC5B are major glycoproteins in human airway mucus. The epidermal growth factor receptor (EGFR) signaling pathway is one of the mechanisms of these mucins expression and specificity protein-1 (Sp1) transcription factor is the downstream signal of this pathway, playing pivotal roles in mucin expression. Even though there are some drugs for treating mucus hypersecretion, no drug has proven effects on humans. We found that the flavonoid tilianin regulated MUC5AC expression and also inhibited Sp1 phosphorylation. In this study, we investigated how tilianin would modulate EGFR signaling and regulate mucin production. In conclusion, tilianin inhibited MUC5AC expression mediated via modulating the EGFR-MEK-ERK-Sp1 signaling pathway in NCI-H292 human airway epithelial cells. This study may provide the basis for the novel treatment of mucus hypersecretion.

• Journal of Preventive Medicine and Public Health
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• 제41권3호
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• pp.195-199
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• 2008

Objectives : Malondialdehyde (MDA), a lipid peroxidation by-product, has been widely used as an indicator of oxidative stress. Urinary 2-naphthol, a urinary PAH metabolite, is used as a marker of ambient particulate exposure and is associated with lung cancer and chronic obstructive pulmonary disease. However, the stability and intra-individual variation associated with urinary MDA and 2-naphthol have not been thoroughly addressed. The objective of this study was to assess the stability and intra-individual variation associated with urinary MDA and 2-naphthol. Methods : Urine samples were collected from 10 healthy volunteers (mean age 34, range $27{\sim}42$ years old). Each sample was divided into three aliquots and stored under three different conditions. The levels of urinary MDA and 2-naphthol were analyzed 1) just after sampling, 2) after storage at room temperature ($21^{\circ}C$) for 16 hours, and 3) after storage in a $-20^{\circ}C$ freezer for 16 hours. In addition, an epidemiological study was conducted in 44 Chinese subjects over a period of 3 weeks. The urinary MDA and 2-naphthol were measured by HPLC three times. Results : There was no difference in the levels of urinary MDA and 2-naphthol between the triplicate measurements (n=10, p=0.84 and p=0.83, respectively). The intra-class correlation coefficients (ICC) for urinary MDA and 2-naphthol were 0.74 and 0.42, respectively. However, the levels of PM2.5 in the air were well correlated with the levels of both MDA and 2-naphthol in the epidemiological study. Conclusions : These results suggest that urinary MDA and 2-naphthol remain stable under variable storage conditions, even at room temperature for 16 hours, and indicate that these markers can be used in epidemiological studies involving various sample storage conditions. The intra-CC of urinary 2-naphthol and MDA were acceptable for application to epidemiological studies.

• Journal of Trauma and Injury
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• 제26권4호
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• pp.291-296
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• 2013

Purpose: Prolonged ventilation leads to a higher incidence of ventilator-associated pneumonia (VAP), resulting in weaning failure and increased medical costs. The aim of this study was to analyze clinical results and prognostic factors of VAP in patients with blunt chest trauma. Methods: From 2007 to 2011, one hundred patients undergoing mechanical ventilation for more than 48 hours were divided into two groups: a VAP-negative group, (32 patients, mean age; 53 years, M:F=25:7) and a VAP- positive group, (68 patients, mean age; 60 years, M:F=56:12). VAP was diagnosed using clinical symptoms, radiologic findings and microorganisms. The injury severity score (ISS), shock, combined injuries, computerized tomographic pulmonary findings, transfusion, chronic obstructive lung disease (COPD), ventilation time, stay in intensive care unit (ICU) and hospital stays, complications such as sepsis or disseminated intravascular coagulation (DIC) and microorganisms were analyzed. Chi square, t-test, Mann-Whitney U test and logistic regression analysies were used with SPSS 18 software. Results: Age, sex, ISS, shock and combined injuries showed no differences between the VAP - negative group and - positive group (p>0.05), but ventilation time, ICU and hospital stays, blood transfusion and complications such as sepsis or DIC showed significant differencies (p<0.05). Four patients(13%) showed no clinical symptoms eventhough blood cultures were positive. Regardless of VAP, mortality-related factors were shock (p=0.036), transfusion (p=0.042), COPD (p=0.029), mechanical ventilation time (p=0.011), ICU stay (p=0.032), and sepsis (p=0.000). Microorgnisms were MRSA(43%), pseudomonas(24%), acinetobacter(16%), streptococcus(9%), klebsiela(4%), staphillococus aureus(4%). However there was no difference in mortality between the two groups. Conclusion: VAP itself was not related with mortality. Consideration of mortality-related factors for VAP and its aggressive treatment play important roles in improving patient outcomes.

• Tuberculosis and Respiratory Diseases
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• 제81권2호
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• pp.138-147
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• 2018

Background: Recent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear. Methods: In this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death. Results: Our results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE. Conclusion: These findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.

• Experimental and Molecular Medicine
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• 제50권11호
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• pp.9.1-9.10
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• 2018

Although the positive effects of recombinant fibroblast growth factor-2 (rFGF-2) in chronic obstructive pulmonary disease (COPD) have been implicated in previous studies, knowledge of its role in COPD remains limited. The mechanism of FGF2 in a COPD mouse model and the therapeutic potential of rFGF-2 were investigated in COPD. The mechanism and protective effects of rFGF-2 were evaluated in cigarette smoke-exposed or elastase-induced COPD animal models. Inflammation was assessed in alveolar cells and lung tissues from mice. FGF-2 was decreased in the lungs of cigarette smoke-exposed mice. Intranasal use of rFGF-2 significantly reduced macrophage-dominant inflammation and alveolar destruction in the lungs. In the elastase-induced emphysema model, rFGF-2 improved regeneration of the lungs. In humans, plasma FGF-2 was decreased significantly in COPD compared with normal subjects (10 subjects, P = 0.037). The safety and efficacy of inhaled rFGF-2 use was examined in COPD patients, along with changes in respiratory symptoms and pulmonary function. A 2-week treatment with inhaled rFGF-2 in COPD (n = 6) resulted in significantly improved respiratory symptoms compared with baseline levels (P < 0.05); however, the results were not significant compared with the placebo. The pulmonary function test results of COPD improved numerically compared with those in the placebo, but the difference was not statistically significant. No serious adverse events occurred during treatment with inhaled rFGF-2. The loss of FGF-2 production is an important mechanism in the development of COPD. Inhaling rFGF-2 may be a new therapeutic option for patients with COPD because rFGF-2 decreases inflammation in lungs exposed to cigarette smoke.

• Journal of Ginseng Research
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• 제48권2호
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• pp.181-189
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• 2024

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

• Tuberculosis and Respiratory Diseases
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• 제65권1호
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• pp.15-22
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• 2008

연구배경: 폐암은 우리나라 암 사망원인 질환의 가장 높은 비율을 차지하는 질환으로 특히 노령 인구에서 증가하는 추세이다. 그러나 노령의 폐암 환자는 동반된 질환, 노령에 따른 장기 기능의 저하 등의 이유로 적절한 치료를 받지못하는 경우가 많다. 이에 70세 이상의 노령 폐암 환자의 임상적 특징과 치료에 따른 생존기간 등을 알아보고자 한다. 방 법: 2005년 1월부터 2005년 12월까지 대구, 경북 지역에 소재하고 있는 대학병원 및 종합병원(경북대학병원, 구미 순천향병원, 대구가톨릭대학병원, 대구파티마병원, 동산의료원, 영남대학병원)에서 세포학적 혹은 조직학적으로 원발성 폐암을 진단받은 706명의 환자들을 70세 이상 환자군과 70세 미만 환자군으로 나누어 후향적으로 연구하였다. 결 과: 전체 환자 중 70세 이상의 환자는273명(38.7%)이었다. 70세 이상의 환자는 70세 미만보다 호흡곤란의 증상이 많았으며(p<0.001), 만성폐쇄성폐질환의 빈도가 높았고(p<0.001), 활동도가 좋은 경우가 적었다(p<0.001). 비소세포폐암 환자의 중앙생존기간은 70세 미만의 환자와 70세 이상의 환자에서 유의한 차이를 보였지만(962일 vs 298일, p=0.001), 한 가지라도 치료를 받았던 환자들을 대상으로 했을 때는 두 군간에 의미 있는 차이가 없었다(1,109일 vs 708일, p=0.14). 결 론: 70세 이상의 비소세포폐암 환자에서 환자의 활동도 등을 고려하여 적극적인 치료를 시행하는 것이 바람직할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
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• 제41권2호
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• pp.111-119
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• 1994

배경 및 목적: 폐암 환자의 다수가 흡연력이 있고 만성 폐쇄성 폐질환이 병발되어 있으므로 수술후 폐기능의 변화를 정확히 예측하는 것은 수술후 합병증을 예방하는데 중요하다. 폐 절제술 후 잔여 폐기능을 예측함에 있어 현재까지 99mTc-MAA를 이용한 폐관류 스캔이 많이 이용되어 왔지만 이론적으로 폐환기와 폐관류의 불일치가 있는 경우 오차가 있을 수 있어 $^{99m}Tc$-DTPA 연무흡입 환기 스캔을 이용해 잔류 폐기능을 예측하여 관류 스캔을 비교하여 보았다. 방법: 수술전 연무 흡입스캔과 관류 스캔을 시행하고 수술전에 폐기능을 실시하여 잔여 폐기능을 예측하고 수술후 2개월 뒤에 폐기능을 실시하여 상관관계를 비교하여 보았다. 전 폐절제술인 경우: 수술전 폐기능$\times$전체 폐에 대한 잔류폐의 비 폐엽 절제술인 경우: 수술전 폐기능$\times$(1-침범된 폐의 전체폐에 대한 비$\times$절제될 폐의 분절 수/침범된 폐의 총 분절 수) 결과: 1) $FEV_1$에서 연무 흡입스캔을 이용하여 예측한 값과 실측치 간의 상관 계수는 0.94(p<0.0001), 폐관류 스캔을 이용한 경우는 0.86(p<0.0001)이었으며 두 군간에 통계학적으로 유의한 차이는 없었다. 2) FVC에 흡입스캔을 이용한 경우 상관 계수가 0.91(p<0.0001)이었고 폐관류 스캔에서는 0.72(p=0.0005)로 연무 흡입스캔으로 예측한 군에서 상관 관계가 좋았다. 3) $FEF_{25-75%}$에서의 결과는 연무 흡입스캔을 이용한 경우 상관 계수가 0.87(p=0.0001), 폐관류 스캔에서는 상관 계수가 0.87(p<0.0001)로 두 군간에 유의한 차이는 없었다. 4) 두 스캔을 동시에 시행한 군에서 비교한 결과를 보면 연무 흡입 스캔에서 상관 계수는 $FEV_1$ 0.97(p<0.0001), FVC 0.95(p<0.0001), $FEF_{25-75%}$ 0.85(p<0.001)이었고 폐관류 스캔에서는 $FEV_1$ 0.97(p<0.0001), FVC 0.96(p<0.0001), $FEF_{25-75%}$ 0.83(p<0.002)로 두 군간에 유의한 차이는 없었다. 결론: 수술후 잔여 폐기능을 예측함에 있어 연무 흡입스캔 및 관류 스캔사이에 큰 차이가 없었으며 비교적 정확했고 폐기능중에서는 $FEV_1$이 가장 상관 관계가 좋았다.