Insulin resistance mediates high-fat diet-induced pulmonary fibrosis and airway hyperresponsiveness through the TGF-β1 pathway

Park, Yoon Hee,Oh, Eun Yi,Han, Heejae,Yang, Misuk,Park, Hye Jung,Park, Kyung Hee,Lee, Jae-Hyun,Park, Jung-Won Nature Publishing Group UK 2019 Experimental and molecular medicine Vol.51 No.5

<▼1><P>Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)−4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity.</P></▼1><▼2><P><B>Obesity: A trigger for asthma onset</B></P><P>Insulin resistance may be an important causative factor underlying the increased risk of asthma and other respiratory issues in obese individuals. Obesity doubles the likelihood of developing asthma, with symptoms that are more difficult to control than in non-obese patients. The connection between these conditions is poorly understood, but researchers led by Jung-Won Park, Yonsei University College of Medicine, Seoul, South Korea, have identified a potential mechanism. They demonstrated that a signaling molecule called TGF-β1 contributes to airway sensitivity and tissue scarring in a mouse model of diet-induced obesity. Subsequent experiments showed that treatment with insulin also gives rise to increased TGF-β1 production in the mouse lung. Since insulin resistance is a common feature of obesity, resulting in abnormally high levels of circulating insulin, this could also account for the increased risk of respiratory problems.</P></▼2>

내장형 시스템을 위한 자바 클래스 파일에서 상수풀 항목에 대한 통계

양희재,권중장 경성대학교 공학기술연구소 2002 공학기술연구지 Vol.9 No.-

Constant pool is known to occupy the biggest part in size in a typical Java class file. It is very important for any embedded system to restrict the usage of memory since memory is one of the most vital resource of the system. Because constant pool holds the majority of Java class file in size, we are interested in knowing how to reduce its effect. In this paper we have analyzed all entries in constant pool and gathered the statistics in detail. Specifically, we have investigated a hundred of Java class files for embedded system, one from the J2ME/CLDC classes of Sun Microsystems, and others from the simpleRTJ classes of RTJ Computing. The statistics said that there are forty four constants on the average in the pool and only six percents of them are actually used to execute the bytecode instructions. Another seventy eight percents of the constant are used merely for type-checking and linking classes. It suggests the possibility of reducing memory usage by restricting runtime type-checking and dynamic class loading, which is not an extraordinary condition for embedded system. The result would be applied to build a more memory-efficient embedded Java system.

Development of Particular Matter-Induced Airway Inflammatory Mouse Model and Exploration of Therapeutic Agents

( Heejae Han ),( Eun-yi Oh ),( Jae-hyun Lee ),( Jung-won Park ),( Hye Jung Park ) 대한결핵 및 호흡기학회 2020 대한결핵 및 호흡기학회 추계학술대회 초록집 Vol.128 No.-

Effects of Particulate Matter 10 Inhalation on Lung Tissue RNA expression in a Murine Model

( Heejae Han ),( Eun-yi Oh ),( Jae-hyun Lee ),( Jung-won Park ),( Hye Jung Park ) 대한결핵 및 호흡기학회 2021 Tuberculosis and Respiratory Diseases Vol.84 No.1

Background: Particulate matter 10 (PM₁₀; airborne particles <10 μm) inhalation has been demonstrated to induce airway and lung diseases. In this study, we investigate the effects of PM₁₀ inhalation on RNA expression in lung tissues using a murine model. Methods: Female BALB/c mice were affected with PM₁₀, ovalbumin (OVA), or both OVA and PM₁₀. PM₁₀ was administered intranasally while OVA was both intraperitoneally injected and intranasally administered. Treatments occurred 4 times over a 2-week period. Two days after the final challenges, mice were sacrificed. Full RNA sequencing using lung homogenates was conducted. Results: While PM₁₀ did not induce cell proliferation in bronchoalveolar fluid or lead to airway hyper-responsiveness, it did cause airway inflammation and lung fibrosis. Levels of interleukin 1β, tumor necrosis factor-α, and transforming growth factor-β in lung homogenates were significantly elevated in the PM₁₀-treated group, compared to the control group. The PM₁₀ group also showed increased RNA expression of Rn45a , Snord22 , Atp6v0c-ps2 , Snora28 , Snord15b , Snora70 , and Mmp12 . Generally, genes associated with RNA splicing, DNA repair, the inflammatory response, the immune response, cell death, and apoptotic processes were highly expressed in the PM₁₀-treated group. The OVA/PM₁₀ treatment did not produce greater effects than OVA alone. However, the OVA/PM₁₀-treated group did show increased RNA expression of Clca1, Snord22, Retnla, Prg2, Tff2, Atp6v0c-ps2, and Fcgbp when compared to the control groups. These genes are associated with RNA splicing, DNA repair, the inflammatory response, and the immune response. Conclusion: Inhalation of PM₁₀ extensively altered RNA expression while also inducing cellular inflammation, fibrosis, and increased inflammatory cytokines in this murine mouse model.

A Constraint Satisfaction Problem Approach to Solving Nonogram Puzzle

Heejae Jung(정희재),Seong-Bae Park(박성배) 한국정보과학회 2020 한국정보과학회 학술발표논문집 Vol.2020 No.7

한국어 속성기반 감성 분석을 위한 음식 리뷰 도메인 데이터셋 제작 및 평가

정희재(Heejae Jung),이원희(Won Hee Lee) 한국정보과학회 2021 한국정보과학회 학술발표논문집 Vol.2021 No.12

Toxic and adjuvant effects of silica nanoparticles on ovalbumin-induced allergic airway inflammation in mice

Han, Heejae,Park, Yoon Hee,Park, Hye Jung,Lee, Kangtaek,Um, Kiju,Park, Jung-Won,Lee, Jae-Hyun BioMed Central 2016 Respiratory research Vol.17 No.-

<P><B>Background</B></P><P>Silica nanoparticles (SNPs) can easily enter in respiratory system via inhalation because of their low molecular weight and ease of dispersion. Toxicity and adverse effects of SNPs vary according to the physical characteristics of the particle.</P><P><B>Methods</B></P><P>To evaluate the toxic and adjuvant effects of 3 types of SNPs in the airway system, six-week-old female BALB/c mice were intranasally administered 3 types of SNPs (spherical [S-SNP], mesoporous [M-SNP], and polyethylene glycol-conjugated [P-SNP]) alone or SNPs/ovalbumin (OVA), three times weekly for 2 weeks. Airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs were analyzed.</P><P><B>Results</B></P><P>The S-SNPs/OVA group and M-SNPs/OVA group showed significant AHR, compared to the control group. Among all SNP-treated groups, the group administered SNPs/OVA showed greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1β, and IFN-γ) than those administered SNPs alone or saline/OVA.</P><P><B>Conclusion</B></P><P>Exposure to SNPs alone and SNPs/OVA induced toxicity in the respiratory system. SNPs alone showed significant toxic effects on the airway system. Meanwhile, SNPs/OVA exerted adjuvant effects to OVA of inducing allergic airway inflammation. In particular, M-SNPs showed the most severe airway inflammation in both direct toxicity and adjuvant effect assays. P-SNPs induced less inflammation than the other types of SNPs in both models.</P>

Roflumilast Ameliorates Airway Hyperresponsiveness Caused by Diet-Induced Obesity in a Murine Model

Park, Hye Jung,Lee, Jae-Hyun,Park, Yoon Hee,Han, Heejae,Sim, Da Woon,Park, Kyung Hee,Park, Jung-Won American Thoracic Society 2016 AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR Vol.55 No.1

Acute exposure to silica nanoparticles aggravate airway inflammation: different effects according to surface characteristics

Park, Hye Jung,Sohn, Jung-Ho,Kim, Yoon-Ju,Park, Yoon Hee,Han, Heejae,Park, Kyung Hee,Lee, Kangtaek,Choi, Hoon,Um, Kiju,Choi, In-Hong,Park, Jung-Won,Lee, Jae-Hyun Nature Publishing Group 2015 Experimental and molecular medicine Vol.47 No.7

<P>Silica nanoparticles (SNPs) are widely used in many scientific and industrial fields despite the lack of proper evaluation of their potential toxicity. This study examined the effects of acute exposure to SNPs, either alone or in conjunction with ovalbumin (OVA), by studying the respiratory systems in exposed mouse models. Three types of SNPs were used: spherical SNPs (S-SNPs), mesoporous SNPs (M-SNPs), and PEGylated SNPs (P-SNPs). In the acute SNP exposure model performed, 6-week-old BALB/c female mice were intranasally inoculated with SNPs for 3 consecutive days. In the OVA/SNPs asthma model, the mice were sensitized two times via the peritoneal route with OVA. Additionally, the mice endured OVA with or without SNP challenges intranasally. Acute SNP exposure induced significant airway inflammation and airway hyper-responsiveness, particularly in the S-SNP group. In OVA/SNPs asthma models, OVA with SNP-treated group showed significant airway inflammation, more than those treated with only OVA and without SNPs. In these models, the P-SNP group induced lower levels of inflammation on airways than both the S-SNP or M-SNP groups. Interleukin (IL)-5, IL-13, IL-1β and interferon-γ levels correlated with airway inflammation in the tested models, without statistical significance. In the mouse models studied, increased airway inflammation was associated with acute SNPs exposure, whether exposed solely to SNPs or SNPs in conjunction with OVA. P-SNPs appear to be relatively safer for clinical use than S-SNPs and M-SNPs, as determined by lower observed toxicity and airway system inflammation.</P>

Methodology and Capability of APro’s Dose Assessment Module

Heejae Ju,Minjeong Kim,Soobin Kim,Jung-Woo Kim 한국방사성폐기물학회 2023 한국방사성폐기물학회 학술논문요약집 Vol.21 No.2

The Korea Atomic Energy Research Institute (KAERI) is currently developing a process-based performance assessment model known as APro. Distinguished from the previous system-level safety assessment model developed by KAERI, APro exhibits the capacity to encompass a threedimensional biosphere domain, evolving over the long term. In this study, we elucidate the methodology employed in developing the dose assessment module of APro and present the module’s functionalities. The procedural steps underlying radiation dose calculations within the APro framework can be succinctly outlined as follows: 1) Definition of a landscape model, utilizing information derived from a specified snapshot period provided by the APro biosphere transport module; 2) Generation of unit biotope objects spanning the landscape; 3) Evaluation of radionuclide transfer within the soil medium; 4) Calculation of activity concentration for flora and fauna groups; 5) Assessment of the distribution of effective dose among representative human groups; 6) Progressing through successive time steps. The APro dose calculation module exhibits notable capabilities that encompass: 1) Accounting for radionuclide decay and ingrowth; 2) Facilitating transfer through unsaturated porous media; 3) Considering sorption effects; 4) Addressing the inheritance of radioactivity between various landscape models; 5) Offering customizable ecosystem parameters; 6) Providing flexibility for user-defined exposure pathways. Leveraging these functionalities of the dose assessment module, APro is proficient in evaluating the distribution of radiological doses and associated risks for representative population groups, all while accounting for the dynamic, long-term evolution of the biosphere, including alterations in land cover.