81 results on '"Shin-Ae Kang"'
Search Results
2. Supplementary Figure from Elevated WBP2 Expression in HER2-positive Breast Cancers Correlates with Sensitivity to Trastuzumab-based Neoadjuvant Therapy: A Retrospective and Multicentric Study
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Yoon Pin Lim, Soo Chin Lee, Swee Ho Lim, Joohyuk Sohn, Thomas Choudary Putti, Mihir Gudi, Puay Hoon Tan, Chow Yin Wong, Joaquín Arribas, Cristina Bernadó, Aye Aye Thike, Tinghine Chu, Hock Jin Tan, Jye Swei Guan, and Shin-Ae Kang
- Abstract
Supplementary Figure 1 and 2
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- 2023
3. Supplementary Methods from Elevated WBP2 Expression in HER2-positive Breast Cancers Correlates with Sensitivity to Trastuzumab-based Neoadjuvant Therapy: A Retrospective and Multicentric Study
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Yoon Pin Lim, Soo Chin Lee, Swee Ho Lim, Joohyuk Sohn, Thomas Choudary Putti, Mihir Gudi, Puay Hoon Tan, Chow Yin Wong, Joaquín Arribas, Cristina Bernadó, Aye Aye Thike, Tinghine Chu, Hock Jin Tan, Jye Swei Guan, and Shin-Ae Kang
- Abstract
Supplementary Methods
- Published
- 2023
4. Data from Elevated WBP2 Expression in HER2-positive Breast Cancers Correlates with Sensitivity to Trastuzumab-based Neoadjuvant Therapy: A Retrospective and Multicentric Study
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Yoon Pin Lim, Soo Chin Lee, Swee Ho Lim, Joohyuk Sohn, Thomas Choudary Putti, Mihir Gudi, Puay Hoon Tan, Chow Yin Wong, Joaquín Arribas, Cristina Bernadó, Aye Aye Thike, Tinghine Chu, Hock Jin Tan, Jye Swei Guan, and Shin-Ae Kang
- Abstract
Purpose:Trastuzumab-based chemotherapy has shown remarkable clinical benefits for patients with HER2-positive breast cancer. However, treatment regimens involving trastuzumab had little or no effect for a subset of patients. Preliminary studies revealed WW-binding protein 2 (WBP2), an oncogenic transcription coactivator, to be coamplified with HER2 in 36% of HER2-positive breast cancers. We hypothesize that WBP2 regulates and correlates with the response of HER2-positive breast cancer to trastuzumab.Experimental Design:The coexpression of WBP2 and HER2 in breast tumors was validated using IHC. The role and mechanism of WBP2 in regulating breast cancer response to trastuzumab was elucidated using in vitro, patient-derived xenograft and murine xenograft models. A multicenter retrospective study involving 143 patients given neoadjuvant trastuzumab-based chemotherapy was conducted to determine whether WBP2 expression correlates with pathologic complete response (pCR).Results:Elevated expression of WBP2 significantly enhanced breast cancer's response to trastuzumab by augmenting trastuzumab-induced HER2 downregulation and cell-cycle arrest via inhibition of cyclin D expression. High level of WBP2 correlated with better pCR (67.19%) compared with low WBP2 level (26.58%). The highest response was observed in subgroups of patients with high WBP2–expressing tumors also aged below 50 years (77.78%) or were premenopausal in status (73.33%). Retrospectively, WBP2 demonstrated sensitivity of 80% to 81% and specificity of 76.5% to 80% in discriminating between patients showing pCR and non-pCR.Conclusions:WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy.
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- 2023
5. Free-Living Amoeba Vermamoeba vermiformis Induces Allergic Airway Inflammation
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Da-In Lee, Sung Hee Park, Shin-Ae Kang, Do Hyun Kim, Sun Hyun Kim, So Yeon Song, Sang Eun Lee, and Hak Sun Yu
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Eosinophils ,Inflammation ,Mice ,Infectious Diseases ,Animals ,Water ,Parasitology ,Acanthamoeba ,Amoeba ,Bronchoalveolar Lavage Fluid - Abstract
The high percentage of Vermamoeba was found in tap water in Korea. This study investigated whether Vermamoeba induced allergic airway inflammation in mice. We selected 2 free-living amoebas (FLAs) isolated from tap water, which included Korean FLA 5 (KFA5; Vermamoeba vermiformis) and 21 (an homolog of Acanthamoeba lugdunensis KA/ E2). We axenically cultured KFA5 and KFA21. We applied approximately 1 × 106 to mice’s nasal passages 6 times and investigated their pathogenicity. The airway resistance value was significantly increased after KFA5 and KFA21 treatments. The eosinophil recruitment and goblet cell hyperplasia were concomitantly observed in bronchial alveolar lavage (BAL) fluid and lung tissue in mice infected with KFA5 and KFA21. These infections also activated the Th2-related interleukin 25, thymic stromal lymphopoietin, and thymus and activation-regulated chemokines gene expression in mouse lung epithelial cells. The CD4+ interleukin 4+ cell population was increased in the lung, and the secretion of Th2-, Th17-, and Th1-associated cytokines were upregulated during KFA5 and KFA21 infection in the spleen, lung-draining lymph nodes, and BAL fluid. The pathogenicity (allergenicity) of KFA5 and KFA21 might not have drastically changed during the long-term in vitro culture. Our results suggested that Vermamoeba could elicit allergic airway inflammation and may be an airway allergen.
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- 2022
6. Trichinella spiralis nurse cell formation is regulated via CCR7 + dendritic cells
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Mi‐Kyung Park, Shin Ae Kang, Min‐Kyoung Cho, and Hak Sun Yu
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Immunology ,Parasitology - Published
- 2022
7. Bioorthogonal Catalysis for Treatment of Solid Tumors Using Thermostable, Self-Assembling, Single Enzyme Nanoparticles and Natural Product Conversion with Indole-3-acetic Acid
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Samira Sadeghi, Nihar D. Masurkar, Girish Vallerinteavide Mavelli, Siddharth Deshpande, Warren Kok Yong Tan, Sherman Yee, Shin-Ae Kang, Yoon-Pin Lim, Edward Kai-Hua Chow, and Chester L. Drum
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Biological Products ,Neoplasms ,Iron ,General Engineering ,General Physics and Astronomy ,Animals ,Humans ,Nanoparticles ,General Materials Science ,Ferric Compounds ,Horseradish Peroxidase ,Catalysis - Abstract
Bioorthogonal catalysis (BC) generates chemical reactions not present in normal physiology for the purpose of disease treatment. Because BC catalytically produces the desired therapy only at the site of disease, it holds the promise of site-specific treatment with little or no systemic exposure or side effects. Transition metals are typically used as catalytic centers in BC; however, solubility and substrate specificity typically necessitate a coordinating enzyme and/or stabilizing superstructure for
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- 2022
8. Trichinella spiralis nurse cell formation is regulated via CCR7
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Mi-Kyung, Park, Shin Ae, Kang, Min-Kyoung, Cho, and Hak Sun, Yu
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Mice ,Receptors, CCR7 ,Animals ,Cytokines ,Trichinellosis ,Dendritic Cells ,Trichinella spiralis - Abstract
The chemokine receptor CCR7 is a well-established homing receptor for dendritic cells (DCs) and T-cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7-induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis-infected mice. The CCR7-expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7-expressing cells in PLNs increased by more than 30% at 28 days post-infection; however, this increase was significantly inhibited in CCR7-blocked mice treated with CCR7-specific antibodies. T helper 2 (Th2)-and regulatory T (T
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- 2022
9. The Production of Narrative Figure Paintings of the Virtuous Gathering of Chen and Xun Family in the Late Chosŏn and Its Meaning
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Shin-Ae Kang
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Literature ,Painting ,Chen ,biology ,business.industry ,media_common.quotation_subject ,Production (economics) ,Narrative ,Meaning (existential) ,Art ,business ,biology.organism_classification ,media_common - Published
- 2021
10. Trichinella spiralis infection ameliorated diet-induced obesity model in mice
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Hak Sun Yu, Mi-Jin Jeong, Kyung-Wan Baek, Da In Lee, Shin Ae Kang, and Jun Ho Choi
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0301 basic medicine ,medicine.medical_specialty ,Normal diet ,030231 tropical medicine ,Trichinella spiralis ,Adipose tissue ,Diet, High-Fat ,Weight Gain ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Internal medicine ,medicine ,Animals ,Obesity ,biology ,Lachnospiraceae ,food and beverages ,biology.organism_classification ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,Endocrinology ,Female ,Parasitology ,medicine.symptom ,Weight gain - Abstract
Obesity is an increasingly prevalent disease worldwide, and genetic and environmental factors are known to regulate the development of obesity and associated metabolic diseases. Emerging studies indicate that innate and adaptive immune cell responses in adipose tissue play critical roles in the regulation of metabolic homeostasis. Parasitic helminths are the strongest natural inducers of type 2 inflammatory responses, and several studies have revealed that helminth infections inversely correlate with metabolic syndrome. Hence, this study investigated whether helminth infections could have preventative effects on high fat diet-induced obesity. Female C57BL/6 mice were maintained on either a low fat diet (LFD, 10% fat) or a high fat diet (HFD, 60% fat) for 6 weeks after Trichinella spiralis infection. The mice were randomly divided into four groups and were fed a normal diet, LFD, LFD after T. spiralis infection (Inf + LFD), a high fat diet (HFD), or HFD after T. spiralis infection (HFD + inf). All groups were assayed for body weight, food efficiency ratio (FER), total body weight gain (g)/total food intake amount (g) fat weight, and blood biochemical parameters. Our data indicate that the HFD + inf group significantly reduced body weight gain, fat mass, total cholesterol, and FER. Analysis of immune cell composition by flow cytometry revealed that T. spiralis promoted strong decreases in proinflammatory adipose macrophages (F4/80+CD11c+) and T cells. The alterations in microbiota from fecal samples of mice were analyzed, which showed that T. spiralis infection decreased the ratio of Firmicutes to Bacteriodetes, thereby restoring the previously increased ratio of Firmicutes to Bacteriodetes in HFD-fed mice. Moreover, elimination of T. spiralis retained the protective effects in the HFD-fed obese mice whereas flubendazole (FLBZ) treatment increased levels of the families Lachnospiraceae and Ruminococcaceae. In summary, we provided novel data suggesting that helminth infection protects against obesity and the protection was closely related to M2 macrophage proliferation, an inhibiting proinflammatory response. In addition, it alters the microbiota in the gut.
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- 2021
11. The Relationship between Managerial Ability and Foreign Exchange Exposure and the Role of Foreign Investors
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Shin-Ae Kang
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Business ,Foreign exchange ,Monetary economics - Published
- 2020
12. The Effects of Financial Constraints on Investments in Korean Stock Market
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Shin Ae Kang
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Stock market ,Business ,Monetary economics - Published
- 2019
13. A Research on the Relationship between Accrual-based Earnings Management and Real Earnings Management in the Retail Industry
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Kim Taejoong and Shin-Ae Kang
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Marketing ,Economics and Econometrics ,ComputingMilieux_THECOMPUTINGPROFESSION ,Accrual ,business.industry ,Enterprise value ,ComputingMilieux_PERSONALCOMPUTING ,ComputerApplications_COMPUTERSINOTHERSYSTEMS ,Accounting ,GeneralLiterature_MISCELLANEOUS ,Retail industry ,Earnings management ,Corporate value ,ComputingMilieux_COMPUTERSANDEDUCATION ,Business ,Business and International Management - Abstract
Purpose - In this paper, we examine the effect of accrual earnings management and real earnings management on the corporate value of retail...
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- 2019
14. Author response for 'Trichinella spiralis nurse cell formation is regulated via CCR7 + dendritic cells'
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null Mi‐Kyung Park, null Shin Ae Kang, null Min‐Kyoung Cho, and null Hak Sun Yu
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- 2021
15. Extracellular vesicles of Echinococcus granulosus have therapeutic effects in allergic airway inflammation
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Hak Sun Yu, Mi Jin Jeong, Jun Ho Choi, Da In Lee, and Shin Ae Kang
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Ovalbumin ,medicine.medical_treatment ,Immunology ,Biology ,T-Lymphocytes, Regulatory ,Extracellular Vesicles ,Mice ,Airway resistance ,Immune system ,medicine ,Animals ,IL-2 receptor ,Echinococcus granulosus ,Inflammation ,Mice, Inbred BALB C ,medicine.diagnostic_test ,FOXP3 ,respiratory system ,biology.organism_classification ,Bronchoalveolar lavage ,Cytokine ,biology.protein ,Cytokines ,Parasitology ,Bronchoalveolar Lavage Fluid - Abstract
Background Previous studies have shown that Echinococcus granulosus cystic fluid can alleviate Th2 allergic airway inflammatory responses by increasing the number of CD4+ CD25+ Foxp3+ T (regulatory T; Treg) cells. Parasite-derived extracellular vesicles (EV) are known to not only promote parasite infection by communicating between parasites but also regulate the inflammatory response by acting as an immunomodulatory agent in the host. Methods To evaluate the effect of EV extracted from the cystic fluid of E. granulosus on allergic airway inflammation, gene expression was investigated after administering EV to mouse lung epithelial cells (MLE-12) following 2 h of pretreatment with Aspergillus proteins. An allergic airway inflammation animal model was used to investigate the regulation of the inflammatory response by EV and induced with ovalbumin. Results EV treatment significantly reduced airway resistance and the number of eosinophils and other immune cells in the bronchoalveolar lavage fluid and Th2- and Th17-related cytokine levels. EV pretreatment decreased the number of IL-4+ CD4+ T cells and increased the number of Treg cells in the lung-draining lymph nodes and spleen. Conclusions Echinococcus granulosus cystic fluid derived EV ameliorated Th2 allergic airway inflammatory through Treg cells, similar to whole cystic fluid treatment. Thus, EV may be important immunomodulatory molecules in cystic fluid.
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- 2021
16. Author response for 'Extracellular vesicles of Echinococcus granulosus have therapeutic effects in allergic airway inflammation'
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Jun Ho Choi, Shin Ae Kang, Da In Lee, Mi Jin Jeong, and Hak Sun Yu
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biology ,Allergic airway inflammation ,business.industry ,Therapeutic effect ,Immunology ,Medicine ,business ,Echinococcus granulosus ,biology.organism_classification ,Extracellular vesicles - Published
- 2021
17. An advanced protocol for the purification of whipworm eggs from feces for use as therapeutic agents
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Eunmin Kim, Sung Hee Park, Mi Kyung Park, Shin Ae Kang, So Myong Song, Sang Kyun Park, Hak Sun Yu, Hye-Jin Kim, Jun Ho Choi, and Da-In Lee
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Gastric Juice ,Chromatography ,biology ,Gastric fluid ,Swine ,Embryonated ,Trichuris suis ,Ethyl acetate ,Acetates ,Hydrogen-Ion Concentration ,biology.organism_classification ,Autoimmune Diseases ,Feces ,chemistry.chemical_compound ,Trichuris ,Infectious Diseases ,chemistry ,Reagent ,Animals ,Female ,Parasitology ,Acids ,Parasite Egg Count ,Ovum - Abstract
Recent studies have attempted to treat autoimmune diseases using Trichuris suis. whipworm) eggs. Large quantities of eggs can be obtained efficiently by collecting from the feces of the porcine hosts rather than by extracting from the female worm uterus. However, it is difficult to process large amounts of feces using the current methods. In the present study, we propose a method to collect the eggs from bulk feces more efficiently. Collecting the eggs using washing meshes (25 μm sieve) yields 65.7% (56.0–70.7) of eggs (median, min-max) from 100 g feces. Our method, which uses ethyl acetate and simulated gastric fluid, yielded 91.4% (91.4–94.0) of the eggs from 100 g feces into the separated aqueous solution. Egg collection using simulated gastric fluid (SGF) method was also 60 min faster than that using the sieve method. As the SGF used in the experiment is a strongly acidic reagent with a pH of 1–2, embryonation of the eggs was induced by the rapid pH change. As a result, 37.1% (8.0–77.8) of the eggs had embryonated two months after SGF stimulation. Using the developed method, we could process the feces quickly and efficiently. Furthermore, after purification, egg embryonation could be induced without any harmful reagent treatment. This method is expected to be helpful for further research using Trichuris suis eggs.
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- 2019
18. Therapeutic effects of Echinococcus granulosus cystic fluid on allergic airway inflammation
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Hak Sun Yu, Tai Soon Yong, Kyu-Jae Lee, Uktamjon Suvonkulov, Shin Ae Kang, Myeong Heon Shin, Hye-Jin Kim, and Gab Man Park
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CD4-Positive T-Lymphocytes ,0301 basic medicine ,030231 tropical medicine ,Immunology ,Spleen ,Biology ,T-Lymphocytes, Regulatory ,Host-Parasite Interactions ,Mice ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,Airway resistance ,Immune system ,Hypersensitivity ,medicine ,Animals ,IL-2 receptor ,Echinococcus granulosus ,Inflammation ,Sheep ,medicine.diagnostic_test ,Airway Resistance ,Cyst Fluid ,FOXP3 ,General Medicine ,respiratory system ,030108 mycology & parasitology ,biology.organism_classification ,Specific Pathogen-Free Organisms ,Eosinophils ,Mice, Inbred C57BL ,Disease Models, Animal ,Infectious Diseases ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Cytokines ,Female ,Parasitology ,Interleukin-4 ,Lymph Nodes ,Airway ,Bronchoalveolar Lavage Fluid - Abstract
Previous studies showed that Echinococcus granulosus infection reduces allergic airway inflammation in experimentally infected hosts and the cystic fluid of E. granulosus is known to activate regulatory T (CD4+CD25+Foxp3+T, Treg) cells. To evaluate the effects of cystic fluid of E. granulosus on allergic airway inflammation, we investigated the regulation of the inflammatory reaction by cystic fluid using an allergic airway inflammation animal model. Cystic fluid was administered to C57BL/6 mice seven times every other day, after which allergic airway inflammation was induced using ovalbumin and aluminum. The airway resistance, number of eosinophils and other immune cells in the bronchoalveolar lavage fluid, and levels of Th2 and Th17-related cytokines were significantly reduced by cystic fluid pre-treatment in allergic airway inflammation-induced mice. The number IL-4+CD4+ T cells decreased, the number of Treg cells increased in the lung-draining lymph nodes and spleen of cystic fluid pre-treated mice. In conclusion, E. granulosus-derived cystic fluid may alleviate the Th2 allergic airway inflammatory response via Treg cells. Further studies of the immune regulation of cystic fluid may lead to the development of therapeutic agents for immune disorders.
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- 2019
19. Author response for 'Acceleration of Trichinella spiralis worm expulsion by leukotriene B4 receptor binding inhibition'
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Hak Sun Yu and Shin Ae Kang
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Trichinella spiralis worm ,Chemistry ,Leukotriene B4 receptor ,Binding inhibition ,Molecular biology - Published
- 2021
20. Intranasally Administered Extracellular Vesicles from Adipose Stem Cells Have Immunomodulatory Effects in a Mouse Model of Asthma
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Hwan-Jung Roh, Kyu-Sup Cho, Shin Ae Kang, Sue Jean Mun, Hye-Kyung Park, and Hak Sun Yu
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0301 basic medicine ,Article Subject ,animal diseases ,education ,Adipose tissue ,Pharmacology ,behavioral disciplines and activities ,Extracellular vesicles ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Internal medicine ,Molecular Biology ,Asthma ,business.industry ,hemic and immune systems ,Cell Biology ,respiratory system ,medicine.disease ,RC31-1245 ,respiratory tract diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Nasal administration ,Stem cell ,business ,psychological phenomena and processes ,Research Article - Abstract
Asthma is a chronic eosinophilic airway disease characterized by type 2 helper T cell-driven inflammation. Adipose stem cells (ASCs) and the ASC culture supernatant are known to improve allergic airway inflammation; however, the immunomodulatory effects of ASC-derived extracellular vesicles (EVs) on allergic airway diseases remain unclear. Thus, we assessed the effects of ASC-derived EVs on allergic airway inflammation in a mouse model of asthma. EVs were isolated from the culture supernatant of murine ASCs and characterized. Six-week-old female C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. Before the OVA challenge, 10 μg/50 μl of ASC-derived EVs was administered intranasally to the experimental group. ASC-derived EVs significantly attenuated airway hyperresponsiveness (AHR) in asthmatic mice ( p = 0.023 ). ASC-derived EVs resulted in a remarkable reduction of the total number of inflammatory cells ( p = 0.005 ) and eosinophils ( p = 0.023 ) in the bronchoalveolar lavage fluid (BALF), the degree of eosinophilic lung inflammation ( p < 0.001 ), and the serum total and OVA-specific immunoglobulin (Ig)E ( p = 0.048 and p = 0.001 ) and total IgG1 ( p < 0.001 ). Interleukin- (IL-) 4 was significantly inhibited with ASC-derived EV pretreatment in the BALF and lung draining lymph nodes (LLNs) ( p = 0.040 and p = 0.011 ). Furthermore, ASC-derived EV administration resulted in a significant increase of the regulatory T cell (Treg) populations in LLNs. ASC-derived EVs alleviated AHR and allergic airway inflammation caused by the induction of Treg expansion in a mouse model of asthma. There seems to be a role for ASC-derived EVs as a modifier in allergic airway disease.
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- 2020
21. Screening and Functional Pathway Analysis of Pulmonary Genes Associated with Suppression of Allergic Airway Inflammation by Adipose Stem Cell-Derived Extracellular Vesicles
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Sung-Dong Kim, Hwan-Jung Roh, Kyu-Sup Cho, Hak Sun Yu, Shin Ae Kang, and Yong-Wan Kim
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Article Subject ,biology ,Mesenchymal stem cell ,Adipose tissue ,Cell Biology ,RC31-1245 ,Formyl peptide receptor 1 ,Ovalbumin ,Immunology ,Gene expression ,biology.protein ,Stem cell ,KEGG ,Biological regulation ,Molecular Biology ,Internal medicine ,Research Article - Abstract
Background. Although mesenchymal stem cell- (MSC-) derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have explored the molecular mechanisms of MSC-derived EVs in allergic airway diseases. The objective of this study was to evaluate differentially expressed genes (DEGs) in the lung associated with the suppression of allergic airway inflammation using adipose stem cell- (ASC-) derived EVs. Methods. C57BL/6 mice were sensitized to ovalbumin (OVA) by intraperitoneal injection and challenged intranasally with OVA. To evaluate the effect of ASC-derived EVs on allergic airway inflammation, 10 μg/50 μL of EVs were administered intranasally prior to OVA challenge. Lung tissues were removed and DEGs were compared pairwise among the three groups. DEG profiles and hierarchical clustering of the identified genes were analyzed to evaluate changes in gene expression. Real-time PCR was performed to determine the expression levels of genes upregulated after treatment with ASC-derived EVs. Enrichment analysis based on the Gene Ontology (GO) database and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to further identify the function of DEGs. Results. Expression of paraoxonase 1 (PON1), brain-expressed X-linked 2 (Bex2), insulin-like growth factor binding protein 6 (Igfbp6), formyl peptide receptor 1 (Fpr1), and secretoglobin family 1C member 1 (Scgb1c1) was significantly increased in asthmatic mice following treatment with ASC-derived EVs. GO enrichment and KEGG pathway analysis showed that these genes were strongly associated with immune system processes and their regulation, cellular processes, single-organism processes, and biological regulation. Conclusion. These results suggest that the DEGs identified in this study (PON1, Bex2, Igfbp6, Fpr1, and Scgb1c1) may be involved in the amelioration of allergic airway inflammation by ASC-derived EVs.
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- 2020
22. Sea Cucumber Lipid-Soluble Extra Fraction Prevents Ovalbumin-Induced Allergic Airway Inflammation
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U-Cheol Jeong, Hak Sun Yu, Feng Jin, Jeong-Yeol Lee, Anisuzzaman, Shin Ae Kang, Da-In Lee, and Seok-Joong Kang
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0301 basic medicine ,Ovalbumin ,Sea Cucumbers ,Anti-Inflammatory Agents ,Medicine (miscellaneous) ,Biology ,Pharmacology ,Mice ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,medicine ,Splenocyte ,Animals ,Humans ,Lung ,chemistry.chemical_classification ,Nutrition and Dietetics ,medicine.diagnostic_test ,Fatty Acids ,Fatty acid ,respiratory system ,Eosinophil ,biology.organism_classification ,Eicosapentaenoic acid ,Asthma ,Mice, Inbred C57BL ,030104 developmental biology ,Bronchoalveolar lavage ,medicine.anatomical_structure ,chemistry ,Immunology ,Apostichopus japonicus ,biology.protein ,Cytokines ,Th17 Cells ,Female ,030211 gastroenterology & hepatology ,Cell activation ,Bronchoalveolar Lavage Fluid - Abstract
In a previous study, our research group demonstrated that sea cucumber (Apostichopus japonicus) extracts ameliorated allergic airway inflammation through CD4+CD25+Foxp3+ T (regulatory T; Treg) cell activation and recruitment to the lung. In this study, we aimed to determine which components of sea cucumber contribute to the amelioration of airway inflammation. We used n-hexane fractionation to separate sea cucumber into three phases (n-hexane, alcohol, and solid) and evaluated the ability of each phase to elevate Il10 expression in splenocytes and ameliorate symptoms in mice with ovalbumin (OVA)/alum-induced asthma. Splenocytes treated with the n-hexane phase showed a significant increase in Il10 expression. In the n-hexane phase, 47 fatty acids were identified. Individual fatty acids that comprised at least 5% of the total fatty acids were 16:0, 16:1n-7, 18:0, 18:1n-7, 20:4n-6, and 20:5n-3 (eicosapentaenoic acid). After administering the n-hexane phase to mice with OVA/alum-induced asthma, their asthma symptoms were ameliorated. Several immunomodulatory effects were observed in the n-hexane phase-pretreated group, compared with a vehicle control group. First, eosinophil infiltration and goblet cell hyperplasia were significantly reduced around the airways. Second, the concentrations of Th2-related cytokines (IL-4, IL-5, and IL-13) and Th17-related cytokines (IL-17) were significantly decreased in the spleen and bronchoalveolar lavage fluid (BALF). Finally, the concentrations of TGF-β and IL-10, which are associated with Treg cells, were significantly increased in the BALF and splenocyte culture medium. In conclusion, a fatty acid-rich fraction (n-hexane phase) of sea cucumber extract ameliorated allergic airway inflammation in a mouse model.
- Published
- 2018
23. Insulin protocol to control post-pancreatectomy diabetes
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Shin Ae Kang
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geography ,Type 1 diabetes ,medicine.medical_specialty ,geography.geographical_feature_category ,business.industry ,medicine.medical_treatment ,Pancreatic islets ,Insulin ,Urology ,Islet ,medicine.disease ,Partial Pancreatectomy ,medicine.anatomical_structure ,Diabetes mellitus ,Pancreatectomy ,medicine ,General Materials Science ,Pancreas ,business - Abstract
Lecture Diabetes is a disease by which blood glucose level is elevated by defects in insulin secretion or by resistance to insulin. As pancreatectomy inevitably results in the reduction of the total islet mass, the majority of clinicians tended to believe that pancreatectomy itself would immediately cause blood glucose elevation and subsequent diabetes development. In partial pancreatectomy surgery (distal pancreatectomy or PPPD), however, not all patients develop diabetes for at least a number of years after. This is because the remnant pancreatic islets can produce relatively enough amount of insulin to maintain blood glucose level. After this compensatory time period passes after partial pancreatectomy, the pancreas eventually undergoes atrophy after surgery and the insulin secretory function decreases in the remnant islet. This will lead to delayed development of diabetes after pancreatectomy. Under these situations, insulin injection together with oral anti-diabetic medication would be critical for controlling the blood glucose level. In contrast, patients who undergo total pancreatectomy will develop diabetes immediately after the surgery because of the absolute deficiency of insulin. In this situation, the patients will need a tightly-controlled, delicate insulin injection protocol with multiple subcutaneous insulin injections. Recently, with only a small patch applied to the body, continuous glucose monitoring system (CGMS) enables the reporting of the blood glucose level into the patient's smartphone every 1-5 minutes. The CGMS has gained popularity, is clinically helpful, and is even supported by the health insurance system for type 1 diabetes patients (the patients who undergoes total pancreatectomy can be categorized as type 1 diabetes by the Health Insurance Review System). In this lecture, I will be addressing the different glucose management protocols and/or methods in a variety of pancreatectomy cases and will also introduce the usefulness of CGMS for total pancreatectomy patients.
- Published
- 2021
24. The Effects of Business Cycle, Investor Sentiment and Foreign Investors on Real Earnings Management
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Shin Ae Kang
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Investor profile ,Earnings management ,Business cycle ,Financial system ,Business - Published
- 2017
25. The Effects of Corporate Social Responsibility on Corporate Activity: Comparing Domestic and Multinational Corporations in Korea
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Shin Ae Kang and Young-Su Jung
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Marketing ,Economics and Econometrics ,business.industry ,Corporate governance ,05 social sciences ,Stakeholder ,Accounting ,06 humanities and the arts ,0603 philosophy, ethics and religion ,Multinational corporation ,0502 economics and business ,Corporate social responsibility ,060301 applied ethics ,Business ,Business and International Management ,050203 business & management - Published
- 2016
26. Dendritic cells and M2 macrophage play an important role in suppression of Th2-mediated inflammation by adipose stem cells-derived extracellular vesicles
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Sung-Dong Kim, Shin Ae Kang, Hak Sun Yu, Hwan-Jung Roh, Kyu-Sup Cho, and Sue-Jean Mun
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0301 basic medicine ,Eotaxin ,Macrophage polarization ,Inflammation ,03 medical and health sciences ,Extracellular Vesicles ,Mice ,0302 clinical medicine ,Th2 Cells ,medicine ,Macrophage ,Animals ,lcsh:QH301-705.5 ,Cells, Cultured ,CD40 ,biology ,Interleukins ,Macrophages ,Stem Cells ,Mesenchymal stem cell ,Cell Differentiation ,Epithelial Cells ,Cell Biology ,General Medicine ,Dendritic Cells ,M2 Macrophage ,Cell biology ,Interleukin-10 ,Mice, Inbred C57BL ,030104 developmental biology ,Adipose Tissue ,lcsh:Biology (General) ,biology.protein ,Stem cell ,medicine.symptom ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Although stem cell-derived extracellular vesicles (EVs) have been shown to facilitate regeneration of injured tissue, there is no report that evaluates the immune-modulating effect of stem cell-derived EVs on Th2-mediated inflammation. In this study, we evaluated the immunomodulatory effects of adipose stem cells (ASCs)-derived EVs on Th2-mediated inflammation induced by Aspergillus protease antigen in lung epithelial cells. The EVs were isolated from supernatant of ASCs and the diameters of EVs were measured by using dynamic light scattering. The mice primary lung epithelial cells and mouse lung epithelial cell line (MLE12) were pre-treated with 200 ng/ml of Aspergillus protease and then treated with 1 μg/ml of ASC-derived EVs. Real time PCR was performed to determine the expression levels of eotaxin, IL-25, TGF-β, and IL-10 mRNAs after EV treatment. To evaluate the role of EVs in macrophage polarization and dendritic cells (DCs) differentiation, in vitro bone marrow-derived macrophage and DCs stimulation assay was performed. EV treatment significantly decreased the expression of eotaxin and IL-25 and increased TGF-β and IL-10 in both lung epithelial cells. EV treatment significantly increased the expression of co-stimulatory molecules such as CD40, CD80, and CD 86 in immature DCs. Furthermore, EV treatment significantly enhanced the gene expression of M2 macrophage marker such as Arg1, CCL22, IL-10, and TGF-β. In conclusion, EVs of ASCs ameliorated Th2-mediated inflammation induced by Aspergillus protease antigen through the activation of dendritic cells and M2 macrophage, accompanied by down-regulation of eotaxin and IL-25, and up-regulation of TGF-β and IL-10 in mouse lung epithelial cells. Keywords: Mesenchymal stromal cells, Extracellular vesicles, Immunosuppression, Macrophages, Dendritic cells, Transforming growth factor beta, Interleukin-10
- Published
- 2019
27. Differences in macrophage polarization in the adipose tissue of obese mice under various levels of exercise intensity
- Author
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Da-In Lee, Hak Sun Yu, Shin Ae Kang, and Kyung-Wan Baek
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Normal diet ,Physiology ,Macrophage polarization ,Adipose tissue ,030209 endocrinology & metabolism ,Inflammation ,Diet, High-Fat ,Biochemistry ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Physical Conditioning, Animal ,Medicine ,Animals ,Obesity ,business.industry ,Macrophages ,digestive, oral, and skin physiology ,nutritional and metabolic diseases ,food and beverages ,Cell Polarity ,General Medicine ,Macrophage Activation ,medicine.disease ,Mice, Inbred C57BL ,030104 developmental biology ,Endocrinology ,Adipose Tissue ,Exercise intensity ,lipids (amino acids, peptides, and proteins) ,Animal studies ,medicine.symptom ,Insulin Resistance ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Animal studies have demonstrated that the ratio of M1 (M1Φ) to M2 (M2Φ) macrophage-specific gene expression in adipose tissue (AT) may be altered by chronic exercise; however, whether macrophage polarization is induced under these conditions has not yet been reported. Therefore, this study aimed to investigate the effect of chronic exercise on M1Φ/M2Φ polarization in the AT of high-fat diet (HFD)-induced obese mice. Exercise-induced differences in M1Φ/M2Φ polarization were verified via an exercise intensity study (EIS) in which different levels of exercise intensity were evaluated. Obesity was induced in male C57BL/6 J mice by feeding them with an HFD for 6 weeks. The study consisted of four groups: control group (CON), HFD-fed group (HFD), HFD-fed with exercise group (HFD + EXE), dietary conversion from HFD to normal diet (ND) group (DC), and dietary conversion from HFD to ND group (DC + EXE). For EIS, the HFD + EXE group was divided into three subgroups: low- (LI), mid- (MI), and high- (HI) intensity exercise. The total intervention period was 8 weeks. M1Φ/M2Φ polarization was confirmed by flow cytometry. M2Φ polarization in the AT of obese mice was significantly higher in HFD + EXE mice than in HFD mice, despite the HFD intake. In the EIS, M2Φ polarization was most pronounced in HFD + EXE-HI mice than in HFD mice. It can be proposed that the enhanced insulin resistance and inflammation by obesity can be improved by the increase of M2Φ polarization which is achieved by relatively high-intensity exercise.
- Published
- 2019
28. Adoptive transfer of Trichinella spiralis-activated macrophages can ameliorate both Th1- and Th2-activated inflammation in murine models
- Author
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So Myong Song, Hak Sun Yu, Mi-Kyung Park, Shin Ae Kang, Sang Kyun Park, Jun Ho Choi, and Da In Lee
- Subjects
0301 basic medicine ,Adoptive cell transfer ,medicine.medical_treatment ,Trichinella spiralis ,lcsh:Medicine ,Inflammation ,Article ,Proinflammatory cytokine ,Mice ,03 medical and health sciences ,Th2 Cells ,0302 clinical medicine ,Immune system ,Transforming Growth Factor beta ,medicine ,Animals ,Colitis ,lcsh:Science ,Immunological disorders ,Multidisciplinary ,biology ,business.industry ,Macrophages ,lcsh:R ,Forkhead Transcription Factors ,Dendritic Cells ,Th1 Cells ,Eosinophil ,biology.organism_classification ,medicine.disease ,Interleukin-10 ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,Cytokine ,Immunology ,Female ,Parasitology ,lcsh:Q ,medicine.symptom ,business ,030217 neurology & neurosurgery - Abstract
Trichinella spiralis is a zoonotic nematode and food borne parasite and infection with T. spiralis leads to suppression of the host immune response and other immunopathologies. Alternative activated macrophages (M2) as well as Treg cells, a target for immunomodulation by the helminth parasite, play a critical role in initiating and modulating the host immune response to parasite. The precise mechanism by which helminths modulate host immune response is not fully understood. To determine the functions of parasite-induced M2 macrophages, we compared the effects of M1 and M2 macrophages obtained from Trichinella spiralis-infected mice with those of T. spiralis excretory/secretory (ES) protein-treated macrophages on experimental intestinal inflammation and allergic airway inflammation. T. spiralis infection induced M2 macrophage polarization by increasing the expression of CD206, ARG1, and Fizz2. In a single application, we introduced macrophages obtained from T. spiralis-infected mice and T. spiralis ES protein-treated macrophages into mice tail veins before the induction of dextran sulfate sodium (DSS)-induced colitis, ovalbumin (OVA)-alum sensitization, and OVA challenge. Colitis severity was assessed by determining the severity of colitis symptoms, colon length, histopathologic parameters, and Th1-related inflammatory cytokine levels. Compared with the DSS-colitis group, T. spiralis-infected mice and T. spiralis ES protein-treated macrophages showed significantly lower disease activity index (DAI) at sacrifice and smaller reductions of body weight and proinflammatory cytokine level. The severity of allergic airway inflammation was assessed by determining the severity of symptoms of inflammation, airway hyperresponsiveness (AHR), differential cell counts, histopathologic parameters, and levels of Th2-related inflammatory cytokines. Severe allergic airway inflammation was induced after OVA-alum sensitization and OVA challenge, which significantly increased Th2-related cytokine levels, eosinophil infiltration, and goblet cell hyperplasia in the lung. However, these severe allergic symptoms were significantly decreased in T. spiralis-infected mice and T. spiralis ES protein-treated macrophages. Helminth infection and helminth ES proteins induce M2 macrophages. Adoptive transfer of macrophages obtained from helminth-infected mice and helminth ES protein-activated macrophages is an effective treatment for preventing and treating airway allergy in mice and is promising as a therapeutic for treating inflammatory diseases.
- Published
- 2019
29. Acanthamoeba profilin elicits allergic airway inflammation in mice
- Author
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So Myung Song, Hak Sun Yu, Shin Ae Kang, Dong-Hee Kim, Hye-Kyung Park, Se Bok Jang, and So Young Park
- Subjects
0301 basic medicine ,Chemokine ,RC955-962 ,Acanthamoeba ,Plant Science ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Biochemistry ,Mice ,Profilins ,0302 clinical medicine ,Allergen ,Arctic medicine. Tropical medicine ,Allergies ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,Immune Response ,Lung ,Protozoans ,Interleukin-13 ,biology ,Plant Anatomy ,Chemotaxis ,Interleukin ,Eukaryota ,Proteases ,Amebiasis ,respiratory system ,Enzymes ,Cell Motility ,Infectious Diseases ,Aspergillus ,Profilin ,Fungal Molds ,Pollen ,Female ,medicine.symptom ,Antibody ,Public aspects of medicine ,RA1-1270 ,Chemokines ,Research Article ,Immunology ,Inflammation ,Research and Analysis Methods ,03 medical and health sciences ,Signs and Symptoms ,Diagnostic Medicine ,medicine ,Respiratory Hypersensitivity ,Animals ,Humans ,Rats, Wistar ,Immunoassays ,business.industry ,Mucin ,Public Health, Environmental and Occupational Health ,Organisms ,Fungi ,Biology and Life Sciences ,Proteins ,Cell Biology ,Allergens ,biology.organism_classification ,Parasitic Protozoans ,respiratory tract diseases ,Rats ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Enzymology ,Immunologic Techniques ,Clinical Immunology ,Interleukin-4 ,Clinical Medicine ,business ,030217 neurology & neurosurgery - Abstract
Background In previous studies, we suggested that Acanthamoeba is a new aero-allergen and that patients who showed positive results for the skin-prick test response to Acanthamoeba cross-reacted with several pollen allergens. Additionally, patients with common antibodies reacted to the 13–15 kDa Acanthamoeba unknown allergen. Objective We examined whether profilin of Acanthamoeba is a human airway allergic agent because of its molecular weight. Methods We expressed recombinant Ac-PF (rAc-PF) protein using an Escherichia coli expression system and evaluated whether Ac-PF is an airway allergic agent using an allergic airway inflammation animal model. Results Airway hyperresponsiveness was increased in rAc-PF-inoculated mice. The number of eosinophils and levels of Th2 cytokines, interleukin (IL)-4, IL-5, and IL-13 were increased in the bronchial alveolar lavage fluid of rAc-PF-treated mice. The lungs of the rAc-PF-treated mice group showed enhanced mucin production and metaplasia of lung epithelial cells and goblet cells. Conclusion In this study, we demonstrated that rAc-PF may be an allergen in Acanthamoeba, but further studies needed to identify the mechanisms of allergenic reactions induced by Ac-PF., Author summary Recently, the number of asthma patients have increased sharply. Among patients with asthma have a high serum IgE titer, but despite this, some of these patients do not react to known allergens in skin prick tests, that suggests the presence of unknown environmental allergens. The protozoa Acanthamoeba live in very diverse environment including water, soil, air and even human nasal cavities, throat, pharynx and lung. In previous study, Acanthamoeba could be a new aero-allergen. Patients who showed positive results for the skin-prick test response to Acanthamoeba, their serum could be cross-reacted with several pollen allergens as well as Acanthamoeba total proteins. Additionally, the patients have common antibodies reacted to the 13–15 kDa Acanthamoeba unknown allergen. Profilin, which is found in all eukaryotic organisms in most cells, is an actin-binding protein that interferes with nucleation and restructuring of new filaments. Recent studies showed that profilin functions as a pan-allergen recognized by IgE in approximately 20% of birch pollen and plant food allergic patients. In Acanthamoeba, two isoforms of profilin (Ac-PF) have been identified: profilin-I and profilin-II. We examined profilin from Acanthamoeba as a potential human airway allergic agent because of its molecular weight (13–14 kDa) and cross-reactivity with several pollen allergens in the skin prick test showing positive results for Acanthamoeba in chronic cough patients. In this study, we expressed recombinant Ac-PF (rAc-PF) protein using an Escherichia coli expression system and evaluated whether Ac-PF is an airway allergic agent using an asthma animal model. Our study showed that rAc-PF may be an allergen in Acanthamoeba, but further studies needed to identify the mechanisms of allergenic reactions induced by Ac-PF.
- Published
- 2018
30. Identification of a host collagen inducing factor from the excretory secretory proteins of Trichinella spiralis
- Author
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So Young Park, Shin Ae Kang, Hae-Jin Kim, Min Kyoung Cho, Hak Sun Yu, Mi Kyung Park, and Se Bok Jang
- Subjects
0301 basic medicine ,Life Cycles ,Cell signaling ,Gene Expression ,Muscle Proteins ,Helminth genetics ,SMAD ,Signal transduction ,Biochemistry ,0302 clinical medicine ,Larvae ,Gene expression ,biology ,Chemistry ,Muscles ,lcsh:Public aspects of medicine ,Signaling cascades ,Trichinellosis ,Helminth Proteins ,Proteases ,Recombinant Proteins ,Enzymes ,Infectious Diseases ,030220 oncology & carcinogenesis ,Female ,Collagen ,Research Article ,Antigenicity ,Cell biology ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Trichinella spiralis ,Host-Parasite Interactions ,03 medical and health sciences ,Protein Domains ,Immunoscreening ,Genetics ,Animals ,Humans ,Amino Acid Sequence ,Base Sequence ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Proteins ,lcsh:RA1-1270 ,biology.organism_classification ,Molecular biology ,Mice, Inbred C57BL ,030104 developmental biology ,Secretory protein ,TGF-beta signaling cascade ,Antigens, Helminth ,Enzymology ,Serine Proteases ,Collagens ,Developmental Biology - Abstract
Background In a previous study, we found that Trichinella spiralis muscle larva excretory and secretory proteins (ES-P) most likely activate collagen synthesis via TGF-β/Smad signaling, and this event could influence collagen capsule formation. Methodology/Principal findings In order to identify the specific collagen inducing factor, ES-P was fractionated by a Superdex 200 10/300 GL column. We obtained three large fractions, F1, F2, and F3, but only F3 had collagen gene inducing ability. After immunoscreening, 10 collagen inducing factor candidates were identified. Among them, TS 15–1 and TS 15–2 were identical to the putative trypsin of T. spiralis. The deduced TS 15–1 (M.W. = 72 kDa) had two conserved catalytic motifs, an N-terminal Tryp_SPc domain (TS 15-1n) and a C-terminal Tryp_SPc domain (TS 15-1c). To determine their collagen inducing ability, recombinant proteins (rTS 15-1n and rTS 15-1c) were produced using the pET-28a expression system. TS 15–1 is highly expressed during the muscle larval stage and has strong antigenicity. We determined that rTS 15-1c could elevate collagen I via activation of the TGF-β1 signaling pathway in vitro and in vivo. Conclusion/Significance In conclusion, we identified a host collagen inducing factor from T. spiralis ES-P using immunoscreening and demonstrated its molecular characteristics and functions., Author summary Trichinella spiralis can make collagen capsules in host muscle cells during its life cycle, which encapsulates muscle stage larvae. Many investigators have tried to reveal the complex mechanism behind this collagen capsule architecture, and it has been suggested that several serine proteases in excretory-secretory proteins of the parasite are potential collagen capsule inducing factors. In addition, collagen synthesis is activated through the TGF-β/Smad signaling pathway and these events are closely related with protease activated receptor 2 which was activated by various serine proteases. In this study, we isolated and characterized a collagen gene expression inducer from T. spiralis ES-P using immunoscreening and investigated the candidate protein for its usefulness as a wound healing therapeutic agent.
- Published
- 2018
31. Effects of lifelong spontaneous exercise on the M1/M2 macrophage polarization ratio and gene expression in adipose tissue of super-aged mice
- Author
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Ji-Seok Kim, Yongho Choe, Jun-Il Yoo, Shin Ae Kang, Da-In Lee, Kyung-Wan Baek, Hak Sun Yu, and Mi-Jin Jeong
- Subjects
0301 basic medicine ,Aging ,medicine.medical_specialty ,Macrophage polarization ,Gene Expression ,Adipose tissue ,Motor Activity ,Biochemistry ,Energy homeostasis ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Gene expression ,Genetics ,Animals ,Medicine ,Macrophage ,ARG1 ,Molecular Biology ,business.industry ,Macrophages ,Cell Biology ,Flow Cytometry ,M2 Macrophage ,030104 developmental biology ,Adipose Tissue ,Tumor necrosis factor alpha ,business ,030217 neurology & neurosurgery - Abstract
In the adipose tissue (AT), an increase in the M1 macrophage (M1Ø)/M2 macrophage (M2Ø) polarization ratio can be a risk factor enhancing the inflammatory response during aging, as well as increasing the risk of chronic disease, thereby reducing lifespan, or at least reducing "healthy" lifespan. The purpose of this study was to analyze and compare the AT M1Ø/M2Ø polarization ratio at the final lifespan stage in aged and control animals performing lifelong spontaneous wheel running. Based on flow cytometric analysis, the AT ratio of macrophages revealed M2Ø polarization following lifelong spontaneous exercise (LSE) regardless of age. However, for Icam1 and Tnf, the qPCR analysis showed no difference in gene expressions in young mice; Arg1 expression was higher in Young-EXE (exercising) than in Young-CON (control) mice (p .0001). In Old-EXE, Icam1 (p .0001) and Tnf (p .0001) expression were lower than in Old-CON; for Arg1, gene expression in Old-EXE was higher than in Old-CON (p .0001). LSE prevents deterioration of physical fitness owing to aging, maintaining high M2Ø polarization levels in the AT. Additionally, LSE does not downregulate Icam1 and Tnf in the AT but appears to suppress the increased M1Ø polarization ratio attributed to aging by upregulating Arg1.
- Published
- 2020
32. Wnt Signaling Promotes Breast Cancer by Blocking ITCH-Mediated Degradation of YAP/TAZ Transcriptional Coactivator WBP2
- Author
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Yoon Pin Lim, Puay Hoon Tan, Shen Kiat Lim, Siew Wee Chan, Shin Ae Kang, Aye Aye Thike, Marius Sudol, Hock Jin Tan, Zilin Li, Jye Swei Guan, Wanjin Hong, Thomas Choudary Putti, Zhen Ning Adrian Wee, J. Sivaraman, Vishnu Priyanka Reddy Chichili, Ssu Yi Lu, and David M. Virshup
- Subjects
0301 basic medicine ,Proteasome Endopeptidase Complex ,Cancer Research ,medicine.medical_specialty ,Ubiquitin-Protein Ligases ,Breast Neoplasms ,Cell Cycle Proteins ,medicine.disease_cause ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Cell Line, Tumor ,Wnt3A Protein ,Internal medicine ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,Wnt Signaling Pathway ,Transcription factor ,Adaptor Proteins, Signal Transducing ,Hippo signaling pathway ,biology ,Tumor Suppressor Proteins ,Wnt signaling pathway ,Nuclear Proteins ,Ubiquitin ligase ,ErbB Receptors ,Repressor Proteins ,030104 developmental biology ,Endocrinology ,Oncology ,Hippo signaling ,030220 oncology & carcinogenesis ,Transcription Coactivator ,Trans-Activators ,biology.protein ,Cancer research ,Female ,Carcinogenesis ,Acyltransferases ,Transcription Factors - Abstract
Cross-talk between the Hippo and Wnt pathways has been implicated recently in breast cancer development, but key intersections have yet to be fully defined. Here we report that WBP2, a transcription coactivator that binds the Hippo pathway transcription factor YAP/TAZ, contributes to Wnt signaling and breast cancer pathogenesis. Clinically, overexpression of WBP2 in breast cancer specimens correlated with malignant progression and poor patient survival. In breast cancer cells, nuclear entry and interaction of WBP2 with β-catenin was stimulated by Wnt3A, thereby activating TCF-mediated transcription and driving malignant invasive character. Mechanistic investigations showed WBP2 levels were controlled by the E3 ligase ITCH, which bound and target WBP2 for ubiquitin-dependent proteasomal degradation. Accordingly, ITCH silencing could elevate WBP2 levels. Wnt signaling upregulated WBP2 by disrupting ITCH–WBP2 interactions via EGFR-mediated tyrosine phosphorylation of WBP2 and TAZ/YAP competitive binding. Conversely, ITCH-mediated downregulation of WBP2 inhibited TCF/β-catenin transcription, in vitro transformation, and in vivo tumorigenesis. We identified somatic mutations in ITCH, which impaired its ability to degrade WBP2 and to block its function in cancer, even while retaining binding capacity to WBP2. Thus, the Wnt pathway appeared to engage WBP2 primarily by affecting its protein stability. Our findings show how WBP2/ITCH signaling functions to link the intricate Wnt and Hippo signaling networks in breast cancer. Cancer Res; 76(21); 6278–89. ©2016 AACR.
- Published
- 2016
33. The Effects of an English Lecture for a Korean Business Student: Enhancing Understanding and Learning Outcomes
- Author
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Shin Ae Kang and Myoung-Sook Kim
- Subjects
Marketing ,Economics and Econometrics ,Medical education ,English proficiency ,Business and International Management ,Psychology - Published
- 2016
34. Activation and Recruitment of Regulatory T Cells via Chemokine Receptor Activation in Trichinella spiralis-Infected Mice
- Author
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Shin Ae Kang, Hak Sun Yu, Jeong Bin Ahn, and Dong-Hee Kim
- Subjects
0301 basic medicine ,Chemokine ,biology ,Trichinella spiralis ,CCR9 ,hemic and immune systems ,chemical and pharmacologic phenomena ,CXCR3 ,biology.organism_classification ,GZMB ,03 medical and health sciences ,Chemokine receptor ,030104 developmental biology ,0302 clinical medicine ,Infectious Diseases ,Immunology ,biology.protein ,Parasitology ,CCR10 ,IL-2 receptor ,030215 immunology - Abstract
As most infections by the helminth parasite elicit the recruitment of CD4(+)CD25(+)Foxp3(+) T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated Treg cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of Treg cells in the muscle tissue.
- Published
- 2016
35. Evaluation of allergic sensitivity to Acanthamoeba allergen in patients with chronic cough
- Author
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Hye-Kyung Park, Hak Sun Yu, Mi-Kyung Park, Soon Cheol Ahn, Shin Ae Kang, Ki Uk Kim, Sang Kyun Park, and Dong-Hee Kim
- Subjects
Adult ,Male ,Pulmonary and Respiratory Medicine ,Allergy ,030231 tropical medicine ,Acanthamoeba ,Antigens, Protozoan ,medicine.disease_cause ,Immunoglobulin E ,Immunoglobulin G ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Allergen ,Antigen ,Antibody Specificity ,parasitic diseases ,Hypersensitivity ,otorhinolaryngologic diseases ,medicine ,Humans ,Immunology and Allergy ,Aged ,Skin Tests ,biology ,business.industry ,General Medicine ,Allergens ,Middle Aged ,medicine.disease ,biology.organism_classification ,respiratory tract diseases ,Chronic cough ,Cough ,Case-Control Studies ,Chronic Disease ,Immunology ,030221 ophthalmology & optometry ,biology.protein ,Female ,Antibody ,medicine.symptom ,business - Abstract
Background Acanthamoeba and their proteins can elicit severe allergic airway inflammation in experimental mice. Objective Although Acanthamoeba can induce severe allergic airway inflammation in mice, there is no allergenicity data for humans. Methods We performed a skin-prick test on 65 patients with chronic cough by using 54 previously known allergens and Acanthamoeba excretory-secretory proteins and enzyme-linked immunosorbent assay on 34 patients to evaluate Acanthamoeba-specific serum immunoglobulin (Ig) levels. To detect a novel Acanthamoeba allergen, Western blot analysis was performed on serum from patients who reacted positively to Acanthamoeba or some pollen allergens. Results After skin-prick testing, 29 patients (44.6%) showed positive reactions to one or more common aeroallergens. Acanthamoeba allergenicity was evaluated in 4 of 65 subjects (6.1%). An Acanthamoeba-positive reaction was closely related to several pollen allergens, especially willow tree, poplar, elm, oak, velvet grass, and cockroach. Average levels of Acanthamoeba-specific IgG subtypes in patient serum did not differ compared with healthy subjects; however, Acanthamoeba-specific IgE titers of patients were significantly higher than in healthy subjects. IgE antibodies of patients who tested positive in the skin-prick test reacted strongly to the 15 kDa excretory-secretory protein. Moreover, these antigens also reacted with those who tested positive in the skin-prick test to pollens. Conclusion Taken together, our results indicated that some patients with allergy showed a positive response to the skin-prick test and that they also have high IgE serum levels. However, further experimental investigation is warranted because our preliminary findings indicated that Acanthamoeba might be a new allergen in humans.
- Published
- 2016
36. Prevalence of scabies in long-term care hospitals in South Korea
- Author
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Hak Sun Yu, Young Choon Park, Sook Young Yun, Dong-Hee Kim, and Shin Ae Kang
- Subjects
Male ,0301 basic medicine ,Economics ,Epidemiology ,Cross-sectional study ,Ectoparasitic Infections ,Health Care Providers ,RC955-962 ,Nurses ,Social Sciences ,Scabies ,Medical Conditions ,0302 clinical medicine ,Arctic medicine. Tropical medicine ,Health care ,Medicine and Health Sciences ,Prevalence ,Medicine ,Infection control ,Public and Occupational Health ,Medical Personnel ,Aged, 80 and over ,Incidence ,Incidence (epidemiology) ,Middle Aged ,Hospitals ,Professions ,Infectious Diseases ,Female ,Public aspects of medicine ,RA1-1270 ,Research Article ,Neglected Tropical Diseases ,Employment ,Adult ,medicine.medical_specialty ,Patients ,Health Personnel ,030231 tropical medicine ,Sexually Transmitted Diseases ,Young Adult ,03 medical and health sciences ,Republic of Korea ,Parasitic Diseases ,Humans ,Aged ,Retrospective Studies ,Infection Control ,business.industry ,Public health ,Public Health, Environmental and Occupational Health ,Tropical Diseases ,medicine.disease ,Long-Term Care ,Patient Care Management ,Health Care ,Long-term care ,Cross-Sectional Studies ,030104 developmental biology ,Health Care Facilities ,Labor Economics ,Family medicine ,People and Places ,Population Groupings ,business - Abstract
Background Scabies is a common contagious skin disease. With the economic growth in South Korea, the incidence of scabies has decreased. However, with the recent advancements in medical facilities, mainly the establishment of long-term care hospitals (LTCHs), scabies is now considered an emerging public health problem. Methodology/Principal findings To examine the prevalence and management of scabies in LTCHs in South Korea, we contacted all 1,336 LTCHs registered at the Health Insurance Review and Assessment Service in South Korea in 2018. A total of 110 LTCHs completed a questionnaire, and we analyzed their responses. In the last 5 years, 71.8% (79/110) of LTCHs had a high incidence of scabies (suspected/confirmed cases). Usually, patients aged older than 80 years (45.5%) were diagnosed with the disease, with more women being affected than men. Only 30.0% of the patients were transferred to scabies-restricted rooms, and very few LTCHs (7.0%) had special departments for scabies. Fifty-five (61.1%) of 90 LTCHs reported contact between scabies patients and nurses, nurse aides, caregivers, and other employees (hereinafter, referred to as primary exposure), with 29 (32.2%) LTCHs reporting infections due to primary exposure. The most common challenges in managing scabies were patient isolation (47.8%), diagnosis (31.1%), management of individuals exposed to an individual with scabies (17.8%), lack of staff for managing the patients (16.7%), and treatment (11.1%). Conclusions The incidence rate of scabies in LTCHs in South Korea has increased. Regular and enhanced staff training is needed, considering that most hospitals rarely focused on the handling of equipment and furniture used by scabies patients and on educating their healthcare staff. These findings can be used to develop various strategies to reduce the prevalence of scabies., Author summary This study aimed to present a plan for scabies control by investigating the current status of scabies and management in long-term care hospitals (LTCHs) and by identifying the general characteristics of nursing staff managing scabies patients at nursing homes. To determine the incidence of scabies in LTCHs, we contacted all the 1,336 LTCHs registered at the Health Insurance Review and Assessment Service in South Korea in 2018. Among them, 256 LTCHs agreed to participate in the present study, but only 110 LTCHs completed the survey questionnaire. Studies have shown that scabies is common in LTCHs, and secondary bacterial infection is also common in patients with scabies. Moreover, the incidence rate of scabies has increased in the last 5 years even in LTCHs with highly educated healthcare staff, manuals on the prevention and management of scabies, and infection reporting systems. Regular and enhanced staff training is needed, considering that most hospitals have rarely focused on the handling of equipment and furniture used by scabies patients and on educating their healthcare staff. These findings can be used to develop various strategies to reduce the prevalence of scabies.
- Published
- 2020
37. Elevated WBP2 Expression in HER2-positive Breast Cancers Correlates with Sensitivity to Trastuzumab-based Neoadjuvant Therapy: A Retrospective and Multicentric Study
- Author
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Swee Ho Lim, Soo-Chin Lee, Mihir Gudi, Yoon Pin Lim, Thomas C. Putti, Tinghine Chu, Chow Yin Wong, Joohyuk Sohn, Puay Hoon Tan, Hock Jin Tan, Shin Ae Kang, Aye Aye Thike, Cristina Bernadó, Joaquín Arribas, and Jye Swei Guan
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,Cyclin D ,0302 clinical medicine ,Trastuzumab ,Antineoplastic Combined Chemotherapy Protocols ,Gene Regulatory Networks ,Phosphorylation ,skin and connective tissue diseases ,Neoadjuvant therapy ,biology ,Cell Cycle ,Middle Aged ,Neoadjuvant Therapy ,Gene Expression Regulation, Neoplastic ,Treatment Outcome ,030220 oncology & carcinogenesis ,Immunohistochemistry ,Female ,medicine.drug ,Signal Transduction ,Adult ,medicine.medical_specialty ,Breast Neoplasms ,03 medical and health sciences ,Breast cancer ,Downregulation and upregulation ,Internal medicine ,Cell Line, Tumor ,medicine ,Animals ,Humans ,neoplasms ,Aged ,Neoplasm Staging ,Retrospective Studies ,Chemotherapy ,business.industry ,Gene Amplification ,Retrospective cohort study ,medicine.disease ,Xenograft Model Antitumor Assays ,Disease Models, Animal ,030104 developmental biology ,biology.protein ,Trans-Activators ,Neoplasm Grading ,business - Abstract
Purpose: Trastuzumab-based chemotherapy has shown remarkable clinical benefits for patients with HER2-positive breast cancer. However, treatment regimens involving trastuzumab had little or no effect for a subset of patients. Preliminary studies revealed WW-binding protein 2 (WBP2), an oncogenic transcription coactivator, to be coamplified with HER2 in 36% of HER2-positive breast cancers. We hypothesize that WBP2 regulates and correlates with the response of HER2-positive breast cancer to trastuzumab. Experimental Design: The coexpression of WBP2 and HER2 in breast tumors was validated using IHC. The role and mechanism of WBP2 in regulating breast cancer response to trastuzumab was elucidated using in vitro, patient-derived xenograft and murine xenograft models. A multicenter retrospective study involving 143 patients given neoadjuvant trastuzumab-based chemotherapy was conducted to determine whether WBP2 expression correlates with pathologic complete response (pCR). Results: Elevated expression of WBP2 significantly enhanced breast cancer's response to trastuzumab by augmenting trastuzumab-induced HER2 downregulation and cell-cycle arrest via inhibition of cyclin D expression. High level of WBP2 correlated with better pCR (67.19%) compared with low WBP2 level (26.58%). The highest response was observed in subgroups of patients with high WBP2–expressing tumors also aged below 50 years (77.78%) or were premenopausal in status (73.33%). Retrospectively, WBP2 demonstrated sensitivity of 80% to 81% and specificity of 76.5% to 80% in discriminating between patients showing pCR and non-pCR. Conclusions: WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy.
- Published
- 2018
38. Identification of a host collagen inducing factor from the excretory secretory proteins ofTrichinella spiralisusing immunoscreening
- Author
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Hye-Jin Kim, Hak Sun Yu, Min Kyung Cho, Se Bok Jang, So Young Park, Mi Kyung Park, and Shin Ae Kang
- Subjects
Antigenicity ,biology ,Chemistry ,Trichinella spiralis ,SMAD ,biology.organism_classification ,Trypsin ,Molecular biology ,In vitro ,law.invention ,Secretory protein ,law ,Immunoscreening ,medicine ,Recombinant DNA ,medicine.drug - Abstract
BackgroundIn a previous study, we found thatTrichinella spiralisexcretory and secretory proteins (ES-P) most likely activate collagen synthesis via TGF-β/Smad signaling, and this event could influence collagen capsule formation.Methodology/Principal FindingsIn order to identify the specific collagen inducing factor, ES-P was fractionated by a Superdex 200 10/300 GL column. We obtained three large fractions, F1, F2, and F3, but only F3 had collagen gene inducing ability. After immunoscreening, 10 collagen inducing factor candidates were identified. Among them, TS 15-1 and TS 15-2 were identical to the putative trypsin ofT. spiralis. The deduced TS 15-1 (M.W. = 72 kDa) had two conserved catalytic motifs, an N-terminal Tryp_SPc domain (TS 15- 1n) and a C-terminal Tryp_SPc domain (TS 15-1c). To determine their collagen inducing ability, recombinant proteins (rTS 15-1n and rTS 15-1c) were produced using the pET-28a expression system. TS 15-1 is highly expressed during the muscle larval stage and has strong antigenicity. We determined that rTS 15-1c could elevate collagen I via activation of the TGF-β1 signaling pathwayin vitroandin vivo.Conclusion/SignificanceIn conclusion, we identified a host collagen inducing factor fromT. spiralisES-P using immunoscreening and demonstrated its molecular characteristics and functions.Author SummaryTrichinella spiraliscan make collagen capsules in host muscle cells during its life cycle, which encapsulates muscle stage larvae. Many investigators have tried to reveal the complex mechanism behind this collagen capsule architecture, and it has been suggested that several serine proteases in excretory-secretory proteins of the parasite are potential collagen capsule inducing factors. In addition, collagen synthesis is activated through the TGF-β/Smad signaling pathway and these events are closely related with protease activated receptor 2 which was activated by various serine proteases. In this study, we isolated and characterized a collagen gene expression inducer fromT. spiralisES-P using immunoscreening and investigated the candidate protein for its usefulness as a wound healing therapeutic agent.
- Published
- 2018
39. TLR2-dependent amelioration of allergic airway inflammation by parasitic nematode type II MIF in mice
- Author
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Hye-Kyung Park, J. H. Lyu, Hak Sun Yu, Mi-Kyung Park, Shin Ae Kang, Sang Kyun Park, Dae-Seong Kim, and Mong Cho
- Subjects
Agonist ,Ovalbumin ,medicine.drug_class ,Immunology ,chemical and pharmacologic phenomena ,Inflammation ,Biology ,T-Lymphocytes, Regulatory ,Mice ,Gene expression ,Hypersensitivity ,otorhinolaryngologic diseases ,medicine ,Animals ,Secretion ,Lung ,Macrophage Migration-Inhibitory Factors ,Mice, Knockout ,Helminth Proteins ,T-Lymphocytes, Helper-Inducer ,respiratory system ,Anisakis ,Toll-Like Receptor 2 ,Interleukin-10 ,Mice, Inbred C57BL ,Disease Models, Animal ,TLR2 ,Knockout mouse ,biology.protein ,Alum Compounds ,Female ,Parasitology ,Macrophage migration inhibitory factor ,medicine.symptom - Abstract
In our previous studies, the recombinant type II macrophage migration inhibitory factor homologue (rAs-MIF) secreted from Anisakis simplex suppressed experimental inflammation mouse model through IL-10 production and CD4(+)CD25(+)Foxp3(+) T-cell recruitment. Also, TLR2 gene expression was significantly increased following rAs-MIF treatment. To know the relation between TLR2 and amelioration mechanisms of rAs-MIF, we induced allergic airway inflammation by ovalbumin and alum with or without rAs-MIF under TLR2 blocking systems [anti-TLR2-specific antibody (α-mTLR2 Ab) treatment and using TLR2 knockout mice]. As a result, the amelioration effects of rAs-MIF in allergic airway inflammation model (diminished inflammation and Th2 response in the lung, increased IL-10 secretion, CD4(+)CD25(+)Foxp3(+) T-cell recruitment) were diminished under two of the TLR2 blocking model. The expression of TLR2 on the surface of lung epithelial cell was significantly elevated by rAs-MIF treatment or Pam3CSK (TLR2-specific agonist) treatment, but they might have some competition effect on the elevation of TLR2 expression. In addition, the elevation of IL-10 gene expression by rAs-MIF treatment was significantly inhibited by α-mTLR2 Ab or Pam3CSK pretreatment. In conclusion, anti-inflammatory effects of the rAs-MIF on OVA-induced allergic airway inflammation might be closely related to TLR2.
- Published
- 2015
40. Allergenicity of two Anisakis simplex allergens evaluated in vivo using an experimental mouse model
- Author
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Hak Sun Yu, Yeonchul Hong, Hee-Jae Cha, Shin Ae Kang, Mi Kyung Park, Mee Sun Ock, Min Kyoung Cho, Rosa Rodriguez-Perez, María Luisa Caballero, and Teresa Pérez-Piñar
- Subjects
Allergy ,Thymic stromal lymphopoietin ,Respiratory System ,Immunology ,Immunoglobulin E ,Anisakis ,Mice ,In vivo ,Animals ,Medicine ,Lung ,Inflammation ,biology ,business.industry ,Anisakis simplex ,Helminth Proteins ,General Medicine ,Allergens ,respiratory system ,biology.organism_classification ,medicine.disease ,Recombinant Proteins ,Specific Pathogen-Free Organisms ,respiratory tract diseases ,Mice, Inbred C57BL ,CXCL1 ,Disease Models, Animal ,Infectious Diseases ,biology.protein ,Cytokines ,Female ,Parasitology ,Nasal administration ,Bronchial Hyperreactivity ,business ,Bronchoalveolar Lavage Fluid ,Spleen - Abstract
Anisakis (Anisakidae) is one of the most important causes of helminth-induced allergic reactions and elicits clinical responses that include urticaria, rhinitis, bronco-constriction, cough, and/or gastrointestinal symptoms. More than 13 reactive allergens have been identified in the serum of Anisakis allergy patients, but the allergenicity of only a few of these have been evaluated in vivo using a mouse model. To evaluate the allergenicity of two important allergens, Ani s 1 and Ani s 9, we induced experimental allergic airway inflammation in a mouse model by repeated intranasal administration of the allergens. Both recombinant proteins (rAni s 1 and rAni s 9) elicited increased airway hyperresponsivity, airway infiltration by inflammatory cells (especially eosinophils), bronchial epithelial cell hyperplasia, all of which are characteristic of allergic airway inflammation. These allergens significantly increased the levels of Th2-related cytokines (IL-4, IL-5, IL-13, and IL-25) and Th17 related cytokines (IL-6 and IL-17) in both splenocytes and airway (except IL-17 in airway by rAni s 9). OVA-specific IgE and total IgE were increased in rAni s 1 and rAni s 9 treated mice as compared with controls treated with OVA alone. In addition, these two allergens induced gene expression of thymic stromal lymphopoietin (TSLP) and IL-25 (initiators of the Th2 response), as well as CXCL1 (initiator of the Th17 response) in mouse lung epithelial cells. In conclusion, repeated intranasal treatments with rAni s 1 and rAni s 9 induced airway inflammation in mice by elevating of Th2 and Th17 responses in the lung.
- Published
- 2014
41. Discovery of ( E )-5-(benzylideneamino)-1 H -benzo[ d ]imidazol-2(3 H )-one derivatives as inhibitors for PTK6
- Author
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Seung Taek Lee, Hye Ran Yang, Hyun Jae Shim, Young Hoon Jung, Kyoung Tai No, Han Ie Kim, and Shin Ae Kang
- Subjects
Male ,Foreskin ,Clinical Biochemistry ,Pharmaceutical Science ,Biochemistry ,Chemical library ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Humans ,Structure–activity relationship ,Cytotoxicity ,Protein Kinase Inhibitors ,Molecular Biology ,Schiff Bases ,Dose-Response Relationship, Drug ,Molecular Structure ,Organic Chemistry ,HEK 293 cells ,Fibroblasts ,Protein-Tyrosine Kinases ,Molecular biology ,In vitro ,Neoplasm Proteins ,HEK293 Cells ,chemistry ,Molecular Medicine ,Phosphorylation ,Benzimidazoles ,PTK6 ,Lead compound - Abstract
A lead compound 1, which inhibits the catalytic activity of PTK6, was selected from a chemical library. Derivatives of compound 1 were synthesized and analyzed for inhibitory activity against PTK6 in vitro and at the cellular level. Selected compounds were analyzed for cytotoxicity in human foreskin fibroblasts using MTT assays and for selectivity towards PTK members in HEK 293 cells. Compounds 20 (in vitro IC50 = 0.12 μM) and 21 (in vitro IC50 = 0.52 μM) showed little cytotoxicity, excellent inhibition of PTK6 in vitro and at the cellular level, and selectivity for PTK6. Compounds 20 and 21 inhibited phosphorylation of specific PTK6 substrates in HEK293 cells. Thus, we have identified novel PTK6 inhibitors that may be used as treatments for PTK6-positive carcinomas, including breast cancer.
- Published
- 2014
42. Donation Expenses and Corporate Value: A Focus on the Corporate Governance Structure
- Author
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Shin Ae Kang
- Subjects
Marketing ,Finance ,Economics and Econometrics ,Focus (computing) ,business.industry ,Corporate governance ,Enterprise value ,Stakeholder ,Accounting ,Corporate reputation ,Corporate value ,Donation ,Business ,Business and International Management - Published
- 2014
43. Preventive Intra Oral Treatment of Sea Cucumber Ameliorate OVA-Induced Allergic Airway Inflammation
- Author
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Mi-Kyung Park, Shin Ae Kang, Da-In Lee, Hak Sun Yu, Jeong-Yeol Lee, Seok-Jung Kang, and Jun Ho Choi
- Subjects
0301 basic medicine ,Ovalbumin ,Sea Cucumbers ,Anti-Inflammatory Agents ,Administration, Oral ,T-Lymphocytes, Regulatory ,03 medical and health sciences ,Sea cucumber ,0302 clinical medicine ,Oral administration ,medicine ,Mesenteric lymph nodes ,Animals ,IL-2 receptor ,Lung ,Asthma ,biology ,business.industry ,Tissue Extracts ,FOXP3 ,General Medicine ,respiratory system ,medicine.disease ,biology.organism_classification ,respiratory tract diseases ,Eosinophils ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,medicine.anatomical_structure ,030228 respiratory system ,Complementary and alternative medicine ,Immunology ,biology.protein ,Female ,Lymph Nodes ,business - Abstract
Sea cucumber extracts have potent biological effects, including anti-viral, anti-cancer, antibacterial, anti-oxidant, and anti-inflammation effects. To understand their anti-asthma effects, we induced allergic airway inflammation in mice after 7 oral administrations of the extract. The hyper-responsiveness value in mice with ovalbumin (OVA)-alum-induced asthma after oral injection of sea cucumber extracts was significantly lower than that in the OVA-alum-induced asthma group. In addition, the number of eosinophils in the lungs of asthma-induced mice pre-treated with sea cucumber extract was significantly decreased compared to that of PBS pre-treated mice. Additionally, CD4[Formula: see text]CD25[Formula: see text]Foxp3[Formula: see text]T (regulatory T; Treg) cells significantly increased in mesenteric lymph nodes after 7 administrations of the extract. These results suggest that sea cucumber extract can ameliorate allergic airway inflammation via Treg cell activation and recruitment to the lung.
- Published
- 2016
44. Impact of CEO Leadership Styles on Firm Performance during Environmental Uncertainty: A Study of Privately Owned Korean Companies
- Author
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Jeong Sik Kim, Shin Ae Kang, and Hyun Jung Park
- Subjects
Organizational Behavior and Human Resource Management ,business.industry ,Management of Technology and Innovation ,Strategy and Management ,Leadership style ,Accounting ,Business and International Management ,business - Published
- 2013
45. Negligible Egg Positive Rate of Enterobius vermicularis and No Detection of Head Lice among Orphanage Children in Busan and Ulsan, Korea (2014)
- Author
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Jung Ha Park, Shin Ae Kang, Hak Sun Yu, Mi Kyung Park, Sang Hwa Lee, Sang Kyun Park, Hyun-Mi Son, Jun Ho Choi, and Dong-Hee Kim
- Subjects
Pediatrics ,medicine.medical_specialty ,media_common.quotation_subject ,Biology ,Head louse ,medicine.disease_cause ,medicine.disease ,Infectious Diseases ,Pinworm infection ,Personal hygiene ,Hygiene ,parasitic diseases ,medicine ,Parasitology ,Health education ,Enterobius ,Risk factor ,Head lice infestation ,Demography ,media_common - Abstract
To determine whether pinworm infections and head lice infestations spread among children in orphanages, 117 children from 4 orphanages in Busan-si and Ulsan-si, Korea, were examined for enterobiasis and head lice infestation between January and February 2014. The overall rate of Enterobius vermicularis egg positivity was 0.85%, whereas none of the children had head lice infestations. The rate of pinworm infection was much lower among the orphanage children compared to the rates observed in previous studies among kindergarten and primary school students. Moreover, the risk factors for enterobiasis were less frequent among these subjects than previously reported. The personal hygiene and health of the orphanage children were supervised by a regular, employed nurse through a health education program. In conclusion, pinworm infection was efficiently controlled among the children in orphanages, and this might be related to good personal hygiene practices in Korea.
- Published
- 2015
46. Comparison of Functional Gene Annotation of Toxascaris leonina and Toxocara canis using CLC Genomics Workbench
- Author
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Sang Kyun Park, Ho-jin Jung, Hak Sun Yu, Min Kyoung Cho, Ki Uk Kim, Kyung-Yun Kim, Shin Ae Kang, and Mi Kyung Park
- Subjects
Zoology ,Genomics ,Toxascaris ,Dogs ,parasitic diseases ,Animals ,Helminths ,Toxascaris leonina ,Dog Diseases ,Caenorhabditis elegans ,Toxascariasis ,Genetics ,Expressed sequence tag ,Toxocariasis ,CLC genomics workbench ,biology ,Toxocara canis ,Molecular Sequence Annotation ,biology.organism_classification ,Infectious Diseases ,Canis ,Parasitology ,Female ,Original Article ,Gene ontology - Abstract
The ascarids, Toxocara canis and Toxascaris leonina, are probably the most common gastrointestinal helminths encountered in dogs. In order to understand biological differences of 2 ascarids, we analyzed gene expression profiles of female adults of T. canis and T. leonina using CLC Genomics Workbench, and the results were compared with those of free-living nematode Caenorhabditis elegans. A total of 2,880 and 7,949 ESTs were collected from T. leonina and T. canis, respectively. The length of ESTs ranged from 106 to 4,637 bp with an average insert size of 820 bp. Overall, our results showed that most functional gene annotations of 2 ascarids were quite similar to each other in 3 major categories, i.e., cellular component, biological process, and molecular function. Although some different transcript expression categories were found, the distance was short and it was not enough to explain their different lifestyles. However, we found distinguished transcript differences between ascarid parasites and free-living nematodes. Understanding evolutionary genetic changes might be helpful for studies of the lifestyle and evolution of parasites.
- Published
- 2013
47. Alteration of Cytokine Production during Visceral Larva Migrans by Toxascaris leonina in Mice
- Author
-
Hak Sun Yu, Min Kyoung Cho, Mi-Kyung Park, and Shin Ae Kang
- Subjects
Thymic stromal lymphopoietin ,medicine.medical_treatment ,Spleen ,Brief Communication ,Th1 ,Toxascaris ,Andrology ,Th2 ,Mice ,Th2 Cells ,Thymic Stromal Lymphopoietin ,Visceral larva migrans ,cytokine ,medicine ,Animals ,Toxascaris leonina ,Lung ,biology ,Interleukins ,Muscles ,Brain ,Heart ,visceral larva migrans (VLM) ,Th1 Cells ,biology.organism_classification ,medicine.disease ,Intestines ,Mice, Inbred C57BL ,CXCL1 ,Infectious Diseases ,medicine.anatomical_structure ,Cytokine ,Gene Expression Regulation ,Liver ,Immunology ,Larva Migrans, Visceral ,Cytokines ,Th17 Cells ,Female ,Parasitology ,Cytokine secretion ,Th17 - Abstract
To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-α) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.
- Published
- 2013
48. Environmental Factors Related to Enterobiasis in a Southeast Region of Korea
- Author
-
Min Kyoung Cho, Hak Sun Yu, Shin Ae Kang, Mi Kyung Park, Sang Kyun Park, Dong-Hee Kim, and Bo-Young Kim
- Subjects
Male ,Veterinary medicine ,education ,Biology ,Brief Communication ,Risk Assessment ,Pinworm infection ,Environmental risk ,Surveys and Questionnaires ,Environmental health ,Enterobius vermicularis ,medicine ,Animals ,Humans ,kindergarten ,Enterobius ,Korea ,Enterobiasis ,Child Day Care Centers ,Environmental Exposure ,medicine.disease ,Infectious Diseases ,risk factor ,Child, Preschool ,behavior and behavior mechanisms ,Female ,Parasitology ,environment - Abstract
Pinworm infection can occur through contact with contaminated surfaces followed by ingestion or even through inhalation of infective eggs. We have limited information regarding environmental contamination by eggs of Enterobius vermicularis. In order to determine environmental risk factors associated with the rate of E. vermicularis infection, we investigated possible environmental risk factors using a questionnaire from 46 kindergartens in 3 different cities of the southeast area of Korea. In total, using the cellotape anal swab technique, 3,422 children were examined for E. vermicularis infection. We evaluated E. vermicularis egg of books, educational materials, toys, room door handles, dusts of window edges, desks, chairs, tables, and dusts of classrooms. The overall egg-positive rate for E. vermicularis was 6.0%, and the prevalence of enterobiasis in each kindergarten ranged between 0% and 16.9%. We found that 78.9% of egg positive kindergartens were managed by private foundations, which was significantly higher, compared with kindergartens managed by public foundations or the nation. Compared with public or national kindergartens, most private kindergartens were located in residential areas and the number of children in these areas was significantly higher. In conclusion, numbers of children in kindergartens was found to be an environmental risk factor associated with transmission of enterobiasis in Korea.
- Published
- 2013
49. Molecular characterization of 45kDa aspartic protease of Trichinella spiralis
- Author
-
Sang Kyun Park, Hak Sun Yu, Min Kyoung Cho, Mi-Kyung Park, Jong Nam Park, Shin Ae Kang, and Dong-Hee Kim
- Subjects
Proteases ,Aspartic Acid Proteases ,Molecular Sequence Data ,Trichinella spiralis ,Cathepsin D ,Biology ,Real-Time Polymerase Chain Reaction ,Gene Expression Regulation, Enzymologic ,Aspartic acid ,Animals ,Amino Acid Sequence ,Peptide sequence ,Phylogeny ,chemistry.chemical_classification ,General Veterinary ,Molecular mass ,Reverse Transcriptase Polymerase Chain Reaction ,cDNA library ,General Medicine ,biology.organism_classification ,Immunohistochemistry ,Molecular biology ,Amino acid ,chemistry ,Biochemistry ,Parasitology - Abstract
In a previous study, we identified an aspartic protease gene (Ts-Asp) from the Trichinella spiralis muscle stage larva cDNA library. The gene sequence of Ts-Asp was 1281 bp long and was found to encode a protein consisting of 405 amino acids, with a molecular mass of 45.248 kD and a pI of 5.95. The deduced Ts-Asp has a conserved catalytic motif with catalytic aspartic acid residues in the active site, a common characteristic of aspartic proteases. In addition, the deduced amino acid sequence of Ts-Asp was found to possess significant homology (above 50%) with aspartic proteases from nematode parasites. Results of phylogenetic analysis indicated a close relationship of Ts-Asp with cathepsin D aspartic proteases. For production of recombinant Ts-Asp (rTs-Asp), the pGEX4T expression system was used. Like other proteases, the purified rTs-Asp was able to digest collagen matrix in vitro. Abundant expression of Ts-Asp was observed in muscle stage larva. Ts-Asp was detected in ES proteins, and was able to elicit the production of specific antibodies. It is the first report of molecular characterization of aspartic protease isolated from T. spiralis.
- Published
- 2012
50. Trichinella spiralis Infection Suppressed Gut Inflammation with CD4+CD25+Foxp3+T Cell Recruitment
- Author
-
Mi Kyung Park, Hak Sun Yu, Soon Cheol Ahn, Shin Ae Kang, Seon Hee Choi, and Min Kyoung Cho
- Subjects
medicine.medical_treatment ,T cell ,Trichinella spiralis ,Spleen ,Biology ,Trichinosis ,Brief Communication ,dextran sulfate sodium (DSS) ,T-Lymphocytes, Regulatory ,CD4+CD25+Foxp3+ T (Treg) cells ,Mice ,intestinal inflammation ,medicine ,Animals ,IL-2 receptor ,Colitis ,Dextran Sulfate ,FOXP3 ,Forkhead Transcription Factors ,Trichinellosis ,biology.organism_classification ,medicine.disease ,Mice, Inbred C57BL ,Disease Models, Animal ,Infectious Diseases ,Cytokine ,medicine.anatomical_structure ,Gene Expression Regulation ,Larva ,Immunology ,Cytokines ,Female ,Parasitology - Abstract
In order to know the effect of pre-existing Trichinella spiralis infection on experimentally induced intestinal inflammation and immune responses, we induced colitis in T. spiralis-infected mice and observed the severity of colitis and the levels of Th1, Th2, and regulatory cytokines and recruitment of CD4(+)CD25(+)Foxp3(+) T (regulatory T; T(reg)) cells. Female C57BL/6 mice were infected with 250 muscle larvae; after 4 weeks, induction of experimental colitis was performed using 3% dextran sulfate sodium (DSS). During the induction period, we observed severity of colitis, including weight loss and status of stool, and evaluated the disease activity index (DAI). A significantly low DAI and degree of weight loss were observed in infected mice, compared with uninfected mice. In addition, colon length in infected mice was not contracted, compared with uninfected mice. We also observed a significant increase in production of pro-inflammatory cytokines, IL-6 and IFN-γ, in spleen lymphocytes treated with DSS; however, such an increase was not observed in infected mice treated with DSS. Of particular interest, production of regulatory cytokines, IL-10 and transforming growth factor (TGF)-β, in spleen lymphocytes showed a significant increase in mice infected with T. spiralis. A similar result was observed in mesenteric lymph nodes (MLN). Subsets of the population of T(reg) cells in MLN and spleen showed significant increases in mice infected with T. spiralis. In conclusion, T. spiralis infection can inhibit the DSS-induced colitis in mice by enhancing the regulatory cytokine and T(reg) cells recruitment.
- Published
- 2012
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