Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out?

Liu, Jing-Nan,Suh, Dong-Hyeon,Yang, Eun-Mi,Lee, Seung-Ihm,Park, Hae-Sim,Shin, Yoo Seob Nature Publishing Group 2014 Experimental and molecular medicine Vol.46 No.9

<P>Although some studies have explained the immunomodulatory effects of statins, the exact mechanisms and the therapeutic significance of these molecules remain to be elucidated. This study not only evaluated the therapeutic potential and inhibitory mechanism of simvastatin in an ovalbumin (OVA)-specific asthma model in mice but also sought to clarify the future directions indicated by previous studies through a thorough review of the literature. BALB/c mice were sensitized to OVA and then administered three OVA challenges. On each challenge day, 40 mg kg<SUP>−1</SUP> simvastatin was injected before the challenge. The airway responsiveness, inflammatory cell composition, and cytokine levels in bronchoalveolar lavage (BAL) fluid were assessed after the final challenge, and the T cell composition and adhesion molecule expression in lung homogenates were determined. The administration of simvastatin decreased the airway responsiveness, the number of airway inflammatory cells, and the interleukin (IL)-4, IL-5 and IL-13 concentrations in BAL fluid compared with vehicle-treated mice (<I>P</I><0.05). Histologically, the number of inflammatory cells and mucus-containing goblet cells in lung tissues also decreased in the simvastatin-treated mice. Flow cytometry showed that simvastatin treatment significantly reduced the percentage of pulmonary CD4<SUP>+</SUP> cells and the CD4<SUP>+</SUP>/CD8<SUP>+</SUP> T-cell ratio (<I>P</I><0.05). Simvastatin treatment also decreased the expression of the vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 proteins, as measured in homogenized lung tissues (<I>P</I><0.05) and human epithelial cells. The reduction in the T cell influx as a result of the decreased expression of cell adhesion molecules is one of the mechanisms by which simvastatin attenuates airway responsiveness and allergic inflammation. Rigorous review of the literature together with our findings suggested that simvastatin should be further developed as a potential therapeutic strategy for allergic asthma.</P>

The Prevalence of Serum Specific IgE to Superantigens in Asthma and Allergic Rhinitis Patients

Jing Nan Liu,신우섭,유혜수,남영희,진현정,예영민,남동호,박해심 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.3

Staphylococcus aureus is the most common bacterium present in upper respiratory tract, and the toxins it produced are involved in allergic inflammationpathogenesis. In this study, we investigated the clinical significance of IgE in association with staphylococcal superantigens in allergic asthmawith rhinitis (BAwAR) and allergic rhinitis alone (AR). We recruited 100 patients with BAwAR (group I), 100 patients with AR (group II), and 88healthy controls (group III). Patients were clinically diagnosed by physicians, and were sensitized to house dust mites. Specific IgE antibodies to staphylococcalsuperantigen A (SEA), B (SEB), and toxic shock syndrome toxin-1 (TSST-1) were measured using the ImmunoCAP system. Other clinical parameterswere retrospectively analyzed. All specific IgE antibodies to SEA, SEB, and TSST-1 were detected most frequently in group I (22%, 21%,and 27%), followed by group II (11%, 14%, and 21%) and group III (4.5%, 3.4%, and 2.3%). Absolute values of serum specific IgE to SEA, SEB, andTSST-1 were also significantly higher in group I (0.300±1.533 kU/L, 0.663±2.933 kU/L, and 0.581±1.931 kU/L) and group II (0.502±2.011 kU/L,0.695±3.337 kU/L, and 1.067±4.688 kU/L) compared to those in group III (0.03±0.133 kU/L, 0.03±0.14 kU/L, and 0.028±0.112 kU/L). The prevalenceof serum specific IgE to SEA was significantly higher in group I compared to group II (P=0.025). Blood eosinophil counts were significantly higherin patients with specific IgE to SEA or SEB, and higher serum levels of specific IgE to house dust mites were noted in patients with specific IgE toTSST-1. In conclusion, the present study suggested that IgE responses to staphylococcal superantigens are prevalent in the sera of both BAwAR andAR patients. This may contribute to an augmented IgE response to indoor allergens and eosinophilic inflammation.

Analysis of Mammographic Breast Density in a Group of Screening Chinese Women and Breast Cancer Patients

Liu, Jing,Liu, Pei-Fang,Li, Jun-Nan,Qing, Chun,Ji, Yu,Hao, Xi-Shan,Zhang, Xue-Ning Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.15

Background: A dense breast not only reduces the sensitivity of mammography but also is a moderate independent risk factor for breast cancer. The percentage of Western women with fat breast tissue is higher aged 40 years or older. To a certain extent, mammography as a first choice of screening imaging method for Western women of this group is reasonable. Hitherto, the frequency and age distribution of mammographic breast density patterns among Chinese women had not been characterized. The purpose of this study was to investigate the frequency and age distribution of mammographic breast density patterns among a group of Chinese screening women and breast cancer patients in order to provide useful information for age-specific guidelines for breast cancer screening in Chinese women. Methods: A retrospective review of a total of 3,394 screening women between August and December 2009 and 2,527 breast cancer patients between July 2011 and June 2012 was conducted. Descriptive analyses were used to examine the association between age and breast density. The significance of differences of breast density between the screening women and the breast cancer patients was examined using nonparametric tests. Results: There was a significant inverse relationship between age and breast density overall (r=-0.37, p< 0.01). Breast density of the breast cancer patients in the subgroups of 40-49 years old was greater compared with that of the screening women, the same in those aged 50-54 years and in those 55 years old or older, less than in the screening group. Conclusions: With regard to the Chinese women younger than 55 years old, the diagnostic efficiency of breast cancer screening imaging examinations may be potentially improved by combining screening mammography with ultrasound.

Attenuation of airway inflammation by simvastatin and the implications for asthma treatment: is the jury still out?

Jing-Nan Liu,서동현,양은미,이승임,박해심,신유섭 생화학분자생물학회 2014 Experimental and molecular medicine Vol.46 No.-

Although some studies have explained the immunomodulatory effects of statins, the exact mechanisms and the therapeutic significance of these molecules remain to be elucidated. This study not only evaluated the therapeutic potential and inhibitory mechanism of simvastatin in an ovalbumin (OVA)-specific asthma model in mice but also sought to clarify the future directions indicated by previous studies through a thorough review of the literature. BALB/c mice were sensitized to OVA and then administered three OVA challenges. On each challenge day, 40mgkg1 simvastatin was injected before the challenge. The airwayresponsiveness, inflammatory cell composition, and cytokine levels in bronchoalveolar lavage (BAL) fluid were assessed after the final challenge, and the T cell composition and adhesion molecule expression in lung homogenates were determined. The administration of simvastatin decreased the airway responsiveness, the number of airway inflammatory cells, and the interleukin (IL)-4, IL-5 and IL-13 concentrations in BAL fluid compared with vehicle-treated mice (Po0.05). Histologically, the numberof inflammatory cells and mucus-containing goblet cells in lung tissues also decreased in the simvastatin-treated mice. Flow cytometry showed that simvastatin treatment significantly reduced the percentage of pulmonary CD4+ cells and the CD4+/CD8+ T-cell ratio (Po0.05). Simvastatin treatment also decreased the expression of the vascular cell adhesion molecule 1 and intercellular adhesion molecule 1 proteins, as measured in homogenized lung tissues (Po0.05) and human epithelial cells. The reduction in the T cell influx as a result of the decreased expression of cell adhesion molecules is one of the mechanisms by which simvastatin attenuates airway responsiveness and allergic inflammation. Rigorous review of the literature together with our findings suggested that simvastatin should be further developed as a potential therapeutic strategy for allergic asthma.

The role of autophagy in allergic inflammation: a new target for severe asthma

Jing-Nan Liu,서동현,Hoang Kim Tu Trinh,채용준,박해심,신유섭 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

Autophagy has been investigated for its involvement in inflammatory diseases, but its role in asthma has been little studied. This study aimed to explore the possible role of autophagy and its therapeutic potential in severe allergic asthma. BALB/c mice were sensitized with ovalbumin (OVA) on days 0 and 14, followed by primary OVA challenge on days 28–30. The mice received a secondary 1 or 2% OVA challenge on days 44–46. After the final OVA challenge, the mice were assessed for airway responsiveness (AHR), cell composition and cytokine levels in bronchoalveolar lavage fluid (BALF). LC3 expression in lung tissue was measured by western blot and immunofluorescence staining. Autophagosomes were detected by electron microscopy. 3-Methyladenine (3-MA) treatment and Atg5 knockdown were applied to investigate the potential role of autophagy in allergic asthma mice. AHR, inflammation in BALF and LC3 expression in lung tissue were significantly increased in the 2% OVA-challenged mice compared with the 1% OVA-challenged mice (Po0.05). In addition, eosinophils showed prominent formation of autophagosomes and increased LC3 expression compared with other inflammatory cells in BALF and lung tissue. After autophagy was inhibited by 3-MA and Atg5 shRNA treatment, AHR, eosinophilia, interleukin (IL)-5 levels in BALF and histological inflammatory findings were much improved. Finally, treatment with an anti-IL-5 antibody considerably reduced LC3 II expression in lung homogenates. Our findings suggest that autophagy is closely correlated with the severity of asthma through eosinophilic inflammation, and its modulation may provide novel therapeutic approaches for severe allergic asthma.

Part two: Library Research : Effect of combined pesticides during pregnancy on hippocampal expression of NMDAR-1 protein in the offspring rats

( Jing Lin Wang ),( Ping Liu ),( Xi Nan Wu ) 한국환경보건학회(구-한국환경위생학회) 2004 Current Challenges and Advances in Environmental H Vol.- No.-

Surface Modification of Titanium Based Biomaterial by Ion Beam

Liu Xianghuai,Huang Nan,Chen Yuanru,Yang Ping,Xiao Jing 한국진공학회 1995 한국진공학회 학술발표회초록집 Vol.- No.-

Clinical Features and the Diagnostic Value of Component Allergen-Specific IgE in Hymenoptera Venom Allergy

신유섭,Jing Nan Liu,허규영,Eui-Kyung Hwang,Young Hee Nam,Hyun Jung Jin,이상민,예영민,남동호,박해심 대한천식알레르기학회 2012 Allergy, Asthma & Immunology Research Vol.4 No.5

Purpose: Although patient history is vital for the diagnosis of hymenoptera venom allergy, specific IgE detection is also important to identify the culprit insect and monitor the effect of immunotherapy. We evaluated the diagnostic value of serum-specific IgE detection of hymenoptera venom component allergens and documented changes in allergen-specific IgE after immunotherapy. Methods: Fifty-six hymenoptera venom allergy patients receiving venom immunotherapy were recruited from Ajou University Hospital, Korea. The clinical manifestations of the patients were noted,and serum-specific IgE detection was performed, using conventional venom extracts as well as component allergens. Data were analyzed retrospectively. Results: A total of 35 (62.5%) patients were male, and 33 (73.3%) patients were atopic. The mean patient age was 44.9±13.8 years. Localized reactions occurred in 23.2% of patients, and systemic reactions occurred in 76.8%. The most common clinical manifestations included skin involvement, such as urticaria and angioedema, and respiratory involvement. Yellow jackets were the most frequent culprit insect, followed by yellow hornets, white-faced hornets, honeybees, and paper wasps, as determined at the time of diagnosis. Double sensitization to both Apidae and Vespidae species was detected in 70.9% of patients. The positive predictive values (PPV) of rVes v 5-specific and rPol d 5-specific IgE detection were 85.7%and 87.5%, respectively, which correlated well with conventional venom extract-specific IgE detection (r=0.762 and r=0.757, respectively). In contrast,the PPV of rApi m 1-specific IgE detection at the time of diagnosis was 34.8%. Three years of venom immunotherapy resulted in decreased venom-specific IgE, particularly IgE specific for Vespidae venom components. Conclusions: Stings by yellow jackets and male sex may be risk factors for hymenoptera venom allergy in Korea. Vespidae component-specific IgE, but not Apidae component-specific IgE, had diagnostic and monitoring value in hymenoptera venom allergy comparable to that of conventional hymenoptera venom extract-specific IgE.

Non-thermal plasma enhances rice seed germination, seedling development, and root growth under low-temperature stress

Bian Jing-Yang,Guo Xiao-Yu,Lee Dong Hun,Sun Xing-Rong,Liu Lin-Shuai,Shao Kai,Liu Kai,Sun Hu-Nan,Kwon Taeho 한국응용생명화학회 2024 Applied Biological Chemistry (Appl Biol Chem) Vol.67 No.-

Recently, non-thermal plasma (NTP) technologies have found widespread application across diverse fields, including plant growth, medical science, and biological and environmental research. Rice (Oryza sativa L.) is exceptionally sensitive to temperature changes. Notably, low-temperature stress primarily affects the germination and reproductive stages of rice, often leading to reduced crop yield. This study aimed to identify optimal conditions for enhancing rice seed germination and seedling growth under low temperatures using NTP technology. Our research indicated that NTP treatment at 15.0 kV for 30 s optimally promotes rice seed germination and growth under low-temperature stress. Furthermore, NTP treatment increases the activity and expression of antioxidant enzymes, such as superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD), under low-temperature conditions. Moreover, it downregulates the expression of β-ketoacyl-[acyl carrier protein] synthase I (KASI) and cis-epoxy carotenoid dioxygenase 3 (NCED3) and upregulates the expression of alternative oxidase (AOX1B), BREVIS RADIX-like homologous gene (BRXL2), WRKY transcription factor 29 (WRKY29), and EREBP transcription factor 2 (EREBP2) in roots after tandem 7 days lowtemperature (16 ℃) and 7 days room-temperature (28 ℃) treatments. Transcriptomic analysis revealed the involvement of various key genes in phosphotransferase activity, phosphate-containing compound metabolic processes, and defense responses. These analyses provide comprehensive information on gene expression at the transcriptional level, offering new insights for a deeper understanding of candidate genes required for root growth in rice.

The Impact of Asthma Control on Salivary Cortisol Level in Adult Asthmatics

신유섭,Jing Nan Liu,김주희,남영희,최길순,박해심 대한천식알레르기학회 2014 Allergy, Asthma & Immunology Research Vol.6 No.5

Asthma is a chronic disease causing psychological stress which leads to the activation of hypothalamus-pituitary-adrenal axis. The purpose of thisstudy is to compare morning salivary cortisol levels in persistent asthma patients according to their disease severities and control status. Total 206adult asthma patients were recruited from four university hospitals. Spirometry, questionnaire of Asthma Quality of Life (AQOL) and Asthma ControlTest (ACT) were completed, and saliva samples were collected prospectively to measure morning cortisol level. The mean patient age was 56.5±15.3 years with mean asthma duration of 9.1±11.1 years. Sixty five patents (31.6%) were classified as mild persistent asthma, and 141 patients(68.4%) were classified as moderate persistent asthma according to the Expert Panel Report 3. The mean predicted FEV1 was 88.8%±18.4%, andthe methacholine PC20 was 9.6±8.5 mg/mL in all study population. The mean ACT score for all patients was 19.9±3.6, and there were 71 (34.5%)patients in poorly controlled and 135 (65.5%) in well controlled asthma. The poorly controlled asthma patients were characterized by significantlylower FEV1 (84.6%±17.6% vs 91.1%±18.5%, P=0.018), lower AQOL scores (46.0±13.9 vs 73.8±26.3, P<0.001), and lower salivary cortisol levels(0.14±0.08 vs 0.18±0.11 μg/dL, P=0.04) compared to well controlled asthma. The ACT score was significantly related to salivary cortisol levels(P=0.034) after adjusting for age. There was no significant difference in salivary cortisol levels (0.17±0.12 vs 0.16±0.08, P=0.725) when analyzedaccording to the dose of used corticosteroid and lung function. Asthma control status affects morning salivary cortisol level. Measuring themorning salivary cortisol level might be a simple and new way to assess asthma control status.