Publications by authors named "Ji Young Kang"

123 Publications

Improved cardiac-specific delivery of RAGE siRNA within small extracellular vesicles engineered to express intense cardiac targeting peptide attenuates myocarditis.

Mol Ther Nucleic Acids 2021 Jun 1;24:1024-1032. Epub 2021 May 1.

Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

Small extracellular vesicles (sEVs) are nanometer-sized membranous vesicles secreted by cells, with important roles in physiological and pathological processes. Recent research has established the application of sEVs as therapeutic vehicles in various conditions, including heart disease. However, the high risk of off-target effects is a major barrier for their introduction into the clinic. This study evaluated the use of modified sEVs expressing high levels of cardiac-targeting peptide (CTP) for therapeutic small interfering RNA (siRNA) delivery in myocarditis, an inflammatory disease of heart. sEVs were extracted from the cell culture medium of HEK293 cells stably expressing CTP-LAMP2b (referred to as C-sEVs). The cardiac targeting ability of C-sEVs with the highest CTP-LAMP2b expression was >2-fold greater than that of normal sEVs (N-sEVs). An siRNA targeting the receptor for advanced glycation end products (RAGE) (siRAGE) was selected as a therapeutic siRNA and loaded into C-sEVs. The efficiency of cardiac-specific siRNA delivery via C-sEVs was >2-fold higher than that via N-sEVs. Furthermore, siRAGE-loaded C-sEVs attenuated inflammation in both cell culture and an model of myocarditis. Taken together, C-sEVs may be a useful drug delivery vehicle for the treatment of heart disease.
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http://dx.doi.org/10.1016/j.omtn.2021.04.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167198PMC
June 2021

Platycodin D attenuates airway inflammation via suppression Th2 transcription factor in a murine model of acute asthma.

J Asthma 2021 Jun 23:1-11. Epub 2021 Jun 23.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Bronchial asthma is a common chronic inflammatory condition of the airway tissue. Platycodin D (PLD) has antiinflammatory effects in a mouse model of allergic asthma. In this work, the anti-asthma potential of PLD was studied by investigation of its effect to suppress airway inflammation and mucin production, a murine model of asthma and the possible mechanisms. Mice were randomly assigned to five experimental groups: control, ovalbumin (OVA), OVA+ICS (intranasal fluticasone), OVA+PLD and OVA+PLD/ICS. Airway histological studies were evaluated by the H&E staining; IL-4, IL-5, and IL-13 in bronchoalveolar lavage fluid were evaluated by ELISA; GATA3 and IRF4 mRNA of airway were measured by RT-PCR and their protein level were measured by Western blotting. Our study showed that PLD suppressed eosinophilic inflammation and mucin production in bronchial mucosa. Moreover, PLD inhibited production of Th2 cytokines such as IL-4, IL-5, and IL-13. Protein production of GATA3 and IRF4, were also decreased in PLD treated OVA asthma model. Taken together, our results provided evidence that PLD inhibits the airway inflammation via suppression of Th2 transcription factor production. These findings suggest that PLD may effectively ameliorate the progression of asthma. These results suggest that PLD could be used as a therapy for allergic asthma.
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http://dx.doi.org/10.1080/02770903.2021.1941084DOI Listing
June 2021

Clinical significance of microbial colonization identified by initial bronchoscopy in patients with lung cancer requiring chemotherapy.

J Thorac Dis 2021 Mar;13(3):1306-1314

Division of Infectious Disease, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: There are limited data on the association between bronchial colonization and respiratory infections in people with lung cancer requiring cytotoxic chemotherapy. We investigated whether bronchial colonization in initial bronchoscopy specimens can predict the development of pneumonia after chemotherapy in patients with lung cancer.

Methods: Four hundred thirteen patients with lung cancer included in the Catholic Medical Center lung cancer registry were enrolled from March 2015 to August 2018. Demographic data, microbiology results, development of pneumonia after chemotherapy, and clinical information about lung cancer were analyzed retrospectively.

Results: A total of 206 lung cancer patients treated with chemotherapy were included in the analysis. Forty patients (19.4%) had positive results for the bronchial washing culture during the initial evaluation of lung cancer. The most common organisms were (n=14) and (n=6) in the surveillance culture, and (n=12) and (n=8) at the time of pneumonia development. Eighty-nine patients (43.2%) had pneumonia after chemotherapy, but the occurrence of pneumonia did not differ according to the colonization. There were no patients for whom the initial isolated organism was a causative microbe for the development of pneumonia after or during chemotherapy. The pneumonia group had poorer prognosis than the non-pneumonia group (378 705 days, P=0.0004).

Conclusions: Microbial colonization in bronchoscopy specimens was not associated with pneumonia development or mortality after chemotherapy for lung cancer. This finding suggests that testing surveillance culture may not be helpful for predicting pneumonia or improving survival in lung cancer patients with chemotherapy.
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http://dx.doi.org/10.21037/jtd-20-2722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024789PMC
March 2021

Marivivens aquimaris sp. nov., isolated from seawater.

Arch Microbiol 2021 Aug 9;203(6):3229-3234. Epub 2021 Apr 9.

Microbial Biotechnology Research Center, Jeonbuk Branch Institute, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 181 Ipsin-gil, Jeongeup, Jeonbuk, 56212, Republic of Korea.

A Gram-stain-negative, strictly aerobic, non-flagellated, rod-shaped bacterium, designated GSB7, was isolated from seawater collected at the Yellow Sea coast of South Korea. Catalase and oxidase activities were positive. Growth occurred at pH 6.0-9.0 (optimum pH 7.0), 10-40 °C (optimum 30 °C) and with 0-8% NaCl (optimum 1-2%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain GSB7 belonged to the genus Marivivens, showing the sequence similarities of 96.3, 96.1, and 96.0% with Marivivens niveibacter HSLHS2, Limimaricola hongkongensis DSM17492, and Marivivens donghaensis AM-4, respectively. The respiratory quinone was ubiquinone-10 and the major fatty acids were summed feature 8 (C ω7c and/or C ω6c), C ω7c 11-methyl, C and C 3-OH. The polar lipids comprised phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid, and five unidentified lipids. The DNA G + C content calculated from the whole-genome sequence was 60.6 mol%. On the basis of phenotypic, chemotaxonomic and genotypic characteristics presented in this study, strain GSB7 is suggested to represent a novel species of the genus Marivivens, for which the name Marivivens aquimaris sp. nov. is proposed. The type strain is GSB7 (= KCTC 82026 = JCM 34042).
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http://dx.doi.org/10.1007/s00203-021-02305-7DOI Listing
August 2021

Tuberculosis Surveillance and Monitoring under the National Public-Private Mix Tuberculosis Control Project in South Korea 2016-2017.

Tuberc Respir Dis (Seoul) 2020 Jul 18;83(3):218-227. Epub 2020 Jun 18.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals.

Methods: TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017.

Results: The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001).

Conclusion: This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.
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http://dx.doi.org/10.4046/trd.2020.0016DOI Listing
July 2020

MicroRNA-21 inhibition attenuates airway inflammation and remodelling by modulating the transforming growth factor β-Smad7 pathway.

Korean J Intern Med 2021 05 18;36(3):706-720. Epub 2021 Feb 18.

Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: Current asthma therapies remain unsatisfactory for controlling airway remodelling in asthma. MicroRNA-21 is a key player in asthma pathogenesis, but the molecular mechanisms underlying its effects on airway remodelling are not completely understood. We investigated the effects of inhibition of microRNA-21 on allergic airway inflammation and remodelling.

Methods: Female BALB/c mice were divided into four groups: control, ovalbumin-sensitized and -challenged for 3 months, microRNA-negative control-treated ovalbumin-treated, and microRNA-21 inhibitor-treated ovalbumin-treated groups. Parameters related to airway remodelling, cytokine production, airway inflammation, and airway hyperresponsiveness were compared between groups. Human bronchial smooth muscle cells were used in a mechanism study.

Results: In this asthma model, ovalbumin-sensitized and -challenged mice exhibited allergic airway inf lammation and airway remodelling. MicroRNA-21 inhibitor-treated mice had fewer inflammatory cells, lower TH2 cytokine production, and suppressed parameters related to remodelling such as goblet cell hyperplasia, collagen deposition, hydroxyproline content, and expression of smooth muscle actin. Inhibition of microRNA-21 decreased transforming growth factor β1 expression and induced Smad7 expression in lung tissue. In human bronchial smooth muscle cells stimulated with transforming growth factor β1, microRNA-21 inhibition upregulated Smad7 expression and decreased markers of airway remodelling.

Conclusion: Inhibition of microRNA-21 had both anti-inflammatory and anti-remodelling effects in this model of ovalbumin-induced chronic asthma. Our data suggest that the microRNA-21-transforming growth factor β1-Smad7 axis modulates the pathogenesis of ovalbumin-induced chronic asthma and in human bronchial smooth muscle cells. MicroRNA-21 inhibitors may be a novel therapeutic target in patients with allergic asthma, especially those with airway remodelling.
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http://dx.doi.org/10.3904/kjim.2020.132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137415PMC
May 2021

Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.

Pulm Pharmacol Ther 2021 Apr 12;67:102003. Epub 2021 Feb 12.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Background: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known.

Methods: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Ovalbumin (OVA) sensitization and challenges were performed for 7 weeks. The mice were injected intraperitoneally with GLP-1R agonist 5 times a week for 4 weeks after OVA sensitization. After AHR measurement, expression of Th2, Th17 cytokines, and interleukin (IL)-33 were measured in BALF and lung tissues. Moreover, IL-1β and activity level of nucleotide oligomerization domain-like receptor protein 3 (NLRP3) were analyzed to investigate the mechanism of GLP-1R agonist on asthmatic airway inflammation.

Results: HFD induced significant weight gain, OVA sensitization and challenge in obese mice made eosinophilic airway inflammation, and increased AHR. Treatment with GLP-1R agonist-induced weight loss suppressed eosinophilic airway inflammation and decreased AHR. Expression of IL-4, 5, and 33 was increased in BALF of obese asthma mice followed by a decrease in response to GLP-1R agonist treatment. Moreover, lung tissue H&E stain revealed that peribronchial inflammation induced by obesity and OVA was effectively suppressed by GLP-1R agonist. Expressions of NLRP3, activated caspase-1, and IL-1β were increased in lung tissues of obese asthma mice and demonstrated a decrease in response to GLP-1R agonist treatment.

Conclusions: GLP-1R agonist effectively induced weight loss, suppressed eosinophilic bronchial airway inflammation, and AHR in obese asthma mice. These effects were mediated by suppression of NLRP3 inflammasome activity and IL-1β. GLP-1R agonist is proposed as a novel anti-asthmatic agent targeting the obese asthmatics.
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http://dx.doi.org/10.1016/j.pupt.2021.102003DOI Listing
April 2021

MicroRNA-21 Inhibition Suppresses Alveolar M2 Macrophages in an Ovalbumin-Induced Allergic Asthma Mice Model.

Allergy Asthma Immunol Res 2021 Mar;13(2):312-329

Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Purpose: MicroRNA-21 (miR-21) influences the Th2 immune pathway by suppressing the expressions of interleukin (IL)-12 and interferon (IFN)-γ. The effects of miR-21 suppression on alveolar macrophage polarization and airway inflammation are not known.

Methods: BALB/c and miR-21 knockout (KO) mice were sensitized and challenged with ovalbumin (OVA). The anti-miR-21 antagomir was administered to BALB/c mice by intranasal inhalation from the day of OVA sensitization. Changes in cell counts, cytokine levels in bronchoalveolar lavage fluid (BALF), and airway hyperresponsiveness (AHR) were examined. Total, M1, and M2 macrophages were examined in the lung tissues by immunohistochemistry (IHC). M2 macrophages from the OVA mice lung were inhaled into the anti-miR-21 antagomir-treated asthmatic mice. Moreover, the polarization of M0 to M2 macrophages upon IL-4 stimulation was analyzed after anti-miR-21 antagomir transfection.

Results: The miR-21 KO mice showed decreases in AHR, total cell and eosinophil counts in BALF, and in the levels of IL-4, IL-5, IL-10, and IL-13. Expression of IL-12 and IFN-γ were increased in the miR-21 KO mice. Peribronchial inflammation and goblet cell dysplasia were significantly decreased in the lung tissues of miR-21 KO OVA mice compared to the wild type OVA mice. IHC for M1, M2, and total macrophage in the lung tissues showed that miR-21 inhalation suppressed alveolar M2 macrophages in KO mice. M2 macrophage inhalation restored AHR and eosinophilic airway inflammation in the miR-21 antagomir-treated mice. Moreover, anti-miR-21 antagomir transfection decreased the expression of M2 markers and increased the expression of M1 markers in M0 macrophages after IL-4 stimulation.

Conclusions: The results suggest that miR-21 antagonism could suppress alveolar M2 macrophage polarization, decreasing not only the Th2 eosinophilic airway inflammation but also AHR and airway remodeling process.
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http://dx.doi.org/10.4168/aair.2021.13.2.312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840870PMC
March 2021

Co-delivery of curcumin and miRNA-144-3p using heart-targeted extracellular vesicles enhances the therapeutic efficacy for myocardial infarction.

J Control Release 2021 03 16;331:62-73. Epub 2021 Jan 16.

Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea. Electronic address:

Curcumin exerts therapeutic effects in heart disease, but has limited bioavailability. Extracellular vesicles (EVs) have gained attention as nanovehicles; however, the poor targeting ability of systemically administered EVs still remains a crucial issue. Herein, we generated heart-targeted EVs (CTP-EVs) by functionalizing EVs surface with cardiac targeting peptide (CTP) using genetic modification of EVs-secreting cells, and further loaded curcumin into CTP-EVs (CTP-EVs-Cur). Consequently, CTP-EVs were able to specifically deliver curcumin to the heart. In addition, curcumin-loaded CTP-EVs possess improved bioavailability, and are fully functional with a high cardioprotective efficiency. Moreover, we loaded miR-144-3p in CTP-EVs-Cur following validation of miR-144-3p as a major contributor in curcumin-mediated therapeutic effects. The simultaneous packing of curcumin and miR-144-3p in CTP-EVs not only retains the active heart-targeting ability but also achieves enhanced cardioprotective effects both in vitro and in vivo, indicating the possibility of combining and sustaining their therapeutic potential by simultaneously loading in CTP-EVs. Therefore, CTP-EVs could be a potential and effective strategy for the delivery of therapeutic molecules, thereby providing a promising nanomedicine for MI therapy.
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http://dx.doi.org/10.1016/j.jconrel.2021.01.018DOI Listing
March 2021

Impact of COVID-19 Pandemic on the National PPM Tuberculosis Control Project in Korea: the Korean PPM Monitoring Database between July 2019 and June 2020.

J Korean Med Sci 2020 Nov 9;35(43):e388. Epub 2020 Nov 9.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems and endangered the control and prevention of tuberculosis (TB). We investigated the nationwide effects of COVID-19 on the national Public-Private Mix (PPM) TB control project in Korea, using monitoring indicators from the Korean PPM monitoring database.

Methods: The Korean PPM monitoring database includes data from patients registered at PPM hospitals throughout the country. Data of six monitoring indicators for active TB cases updated between July 2019 and June 2020 were collected. The data of each cohort throughout the country and in Daegu-Gyeongbuk, Seoul Metropolitan Area, and Jeonnam-Jeonbuk were collated to provide nationwide data. The data were compared using the χ² test for trend to evaluate quarterly trends of each monitoring indicator at the national level and in the prespecified regions.

Results: Test coverages of sputum smear ( = 0.622) and culture ( = 0.815), drug susceptibility test ( = 0.750), and adherence rate to initial standard treatment ( = 0.901) at the national level were not significantly different during the study period. The rate of loss to follow-up among TB cases at the national level was not significantly different ( = 0.088); however, the treatment success rate among the smear-positive drug-susceptible pulmonary TB cohort at the national level significantly decreased, from 90.6% to 84.1% ( < 0.001). Treatment success rate in the Seoul metropolitan area also significantly decreased during the study period, from 89.4% to 84.5% ( = 0.006).

Conclusion: Our study showed that initial TB management during the COVID-19 pandemic was properly administered under the PPM project in Korea. However, our study cannot confirm or conclude a decreased treatment success rate after the COVID-19 pandemic due to limited data.
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http://dx.doi.org/10.3346/jkms.2020.35.e388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653169PMC
November 2020

Urban particulate matter regulates tight junction proteins by inducing oxidative stress via the Akt signal pathway in human nasal epithelial cells.

Toxicol Lett 2020 Oct 17;333:33-41. Epub 2020 Jul 17.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Recent studies have revealed that increased reactive oxidative stress (ROS) induced by particulate matter (PM) affects tight junction (TJ) functions; however, the molecular mechanisms underlying this effect have not been evaluated fully. Cultured human epithelial cells obtained from inferior turbinate tissues were exposed to an urban PM (UPM) standard reference material (SRM 1648a). Intracellular ROS level and expression of proinflammatory cytokines and TJ proteins were examined. Expression level of phosphorylated (p)-Akt, p38, p65 were compared between exposed and unexposed cells. Cells were pretreated with the ROS scavenger N-acetylcysteine (NAC) or Akt inhibitor MK-2206 before exposure to determine whether the changes in cellular ROS and TJ protein expression could be reversed. Exposure to UPM significantly increased ROS levels and inflammatory cytokine expression levels, and decreased expression of TJ proteins zonula occludins (ZO)-1, occludin, claudin-1, and E-cadherin. UPM exposure increased p-Akt, p-p38, and p65 expression levels, and NAC pretreatment reversed these effects. Akt inhibition decreased UPM-induced ROS formation and p38 and p65 protein phosphorylation, and restored the decreased ZO-1 and E-cadherin expression. Akt inhibition and ROS scavenging may provide targets for maintaining epithelial integrity by restoring decreased TJ protein expression during exposure to UPM.
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http://dx.doi.org/10.1016/j.toxlet.2020.07.017DOI Listing
October 2020

Tuberculosis Surveillance and Monitoring under the National Public-Private Mix Tuberculosis Control Project in South Korea 2016-2017.

Tuberc Respir Dis (Seoul) 2020 Jul 18;83(3):218-227. Epub 2020 Jun 18.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: The national Public-Private Mix (PPM) tuberculosis (TB) control project provides for the comprehensive management of TB patients at private hospitals in South Korea. Surveillance and monitoring of TB under the PPM project are essential toward achieving TB elimination goals.

Methods: TB is a nationally notifiable disease in South Korea and is monitored using the surveillance system. The Korea Centers for Disease Control and Prevention quarterly generates monitoring indicators for TB management, used to evaluate activities of the PPM hospitals by the central steering committee of the national PPM TB control project. Based on the notification date, TB patients at PPM hospitals were enrolled in each quarter, forming a cohort, and followed up for at least 12 months to identify treatment outcomes. This report analyzed the dataset of cohorts the first quarter of 2016 through the fourth quarter of 2017.

Results: The coverage of sputum, smear, and culture tests among the pulmonary TB cases were 92.8% and 91.5%, respectively. The percentage of positive sputum smear and culture test results were 30.7% and 61.5%, respectively. The coverage of drug susceptibility tests among the culture-confirmed cases was 92.8%. The treatment success rate among the smear-positive drug-susceptible cases was 83.2%. The coverage of latent TB infection treatment among the childhood TB contacts was significantly higher than that among the adult contacts (85.6% vs. 56.0%, p=0.001).

Conclusion: This is the first official report to analyze monitoring indicators, describing the current status of the national PPM TB control project. To sustain its effect, strengthening the monitoring and evaluation systems is essential.
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http://dx.doi.org/10.4046/trd.2020.0016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7362746PMC
July 2020

Age-stratified anti-tuberculosis drug resistance profiles in South Korea: a multicenter retrospective study.

BMC Infect Dis 2020 Jun 23;20(1):446. Epub 2020 Jun 23.

Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Incheon St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 56, Dongsu-ro, Bupyeong-gu, Incheon, 21431, Republic of Korea.

Background: The emergence of drug-resistant tuberculosis (DR-TB) is a major healthcare concern worldwide. Here, we analyzed age-related trends in DR-TB rates in South Korea.

Methods: Drug susceptibility test results were collected from patients with culture-confirmed TB between 2015 and 2018 from eight university-affiliated hospitals. Patients were divided into three subgroups: younger (15-34 years), middle (35-59 years), and older (≥60 years) to compare drug-resistance patterns. To evaluate trends in age-stratified drug-resistance, chi-square test for linear trends was performed.

Results: Among enrolled native patients aged ≥15 years, 4.1% (179/4417), 1.2% (53/4417) and 7.2% (316/4417) were multidrug-resistant TB (MDR-TB), rifampicin-mono-resistant TB (RR-TB), and isoniazid-mono-resistant TB (Hr-TB), respectively. Proportions of Hr-TB cases were 5.4% (40/734), 7.2% (114/1593), and 7.8% (162/2090) in the younger, middle and older age groups, respectively. MDR/RR-TB case rates decreased significantly with age from 8.6% (63/734) in younger age group to 3.3% (68/2090) in older age group. Fluoroquinolone resistance was highest among second-line drugs, and there were no differences in resistance to fluoroquinolones and second-line injectable drugs among the three age groups.

Conclusions: The number of MDR/RR-TB cases was highest in young patients. Effective public health interventions should include increased focus on rifampicin resistance in young patients.
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http://dx.doi.org/10.1186/s12879-020-05157-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310538PMC
June 2020

Evaluation of Human MSCs Treatment Frequency on Airway Inflammation in a Mouse Model of Acute Asthma.

J Korean Med Sci 2020 Jun 15;35(23):e188. Epub 2020 Jun 15.

Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background: Studies in experimental models of allergic asthma have shown that mesenchymal stem cells (MSCs) have therapeutic potential for T-helper 2 (T2) cell-mediated inflammation. However, the mechanisms underlying these therapeutic effects are not fully understood and their safety has not been confirmed.

Methods: Using a mouse model of experimental allergic asthma, we investigated the efficacy of human adipose-derived mesenchymal stem cells (hADSCs) or human bone marrow-derived mesenchymal stem cells (hBMSCs) according to treatment frequency and timing.

Results: Ovalbumin (OVA)-sensitized and -challenged mice exhibited airway hyperresponsiveness (AHR), airway inflammation, and significant increases in T2 cytokine levels. Both double and single human mesenchymal stem cell (hMSC) treatments significantly decreased AHR and bronchoalveolar lavage fluid counts. In addition, single treatment with hMSCs showed significant attenuation of allergic airway inflammation. However, double treatment with hMSCs during OVA -sensitization and -challenge further increased inflammatory cell infiltration, and T2 cytokine levels.

Conclusion: The results of treatment with hADSCs or hBMSCs suppresses AHR and airway inflammation. However, double hMSC treatment significantly induces eosinophilic airway inflammation and lung histological changes. Therefore, double hMSC treatment is ineffective against asthma and single injection frequency appears to be more important for the treatment of asthma. These results suggest that hMSC therapy can be used for treatment of asthma patients but that it should be used carefully.
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http://dx.doi.org/10.3346/jkms.2020.35.e188DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295606PMC
June 2020

Types of multidimensional vulnerability and well-being among the retired in the U.S.

Aging Ment Health 2021 Jul 4;25(7):1361-1372. Epub 2020 Jun 4.

Department of Social Welfare, Daegu University, Gyeongsan-si, Republic of Korea.

Background: An extensive study investigated the risk factors for low well-being in post-retirement. Most previous studies have taken a unidimensional perspective, focusing on single factors such as financial status, physical health, and mental health.

Objective: Drawing on the vulnerability framework, we first identify and describe the empirical subgroups of vulnerability among retirees in the United States across four major domains of later life: material, physical, social, and mental vulnerability. Then, we investigate the association between vulnerability profiles and well-being.

Method: The sample included 3,158 retirees aged 65+ who participated in the Health and Retirement Study (HRS). Latent class analysis was utilized to identify the heterogeneous subgroups of vulnerability, and then a series of OLS regression analyses was conducted to examine the relationship between patterns of vulnerability and well-being.

Results: Five vulnerability patterns were identified: material vulnerable (12%), health & social vulnerable (14%), material, health & social vulnerable (6%), least vulnerable (34%), and social vulnerable (35%). The had the strongest negative influence on well-being among all subgroups. As the largest subgroup, the negative influence on well-being stood out, with a stronger effect than that of material privation experienced by those in the

Conclusion: By empirically identifying subgroups of differential vulnerability patterns among retirees, this study showed that post-retirement vulnerability reflects complex interactions among multiple disadvantages. Findings of this study enhance understanding of the disparities in well-being within the retired population, pointing to the possibility of targeted policy and program development.
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http://dx.doi.org/10.1080/13607863.2020.1768212DOI Listing
July 2021

Neuropilin1 Expression Acts as a Prognostic Marker in Stomach Adenocarcinoma by Predicting the Infiltration of Treg Cells and M2 Macrophages.

J Clin Med 2020 May 12;9(5). Epub 2020 May 12.

Department of Health Industry, Sookmyung Women's University, Seoul 04310, Korea.

Neuropilin1 (NRP1) plays a critical role in tumor progression and immune responses. Although the roles of NRP1 in various tumors have been investigated, the clinical relevance of NRP1 expression in stomach adenocarcinoma (STAD) has not been studied. To investigate the use of NRP1 as a prognostic biomarker of STAD, we analyzed NRP1 mRNA expression and its correlation with patient survival and immune cell infiltration using various databases. NRP1 mRNA expression was significantly higher in STAD than normal tissues, and Kaplan-Meier survival analysis showed that NRP1 expression was significantly associated with poor prognosis in patients with STAD. To elucidate the related mechanism, we analyzed the correlation between NRP1 expression and immune cell infiltration level. In particular, the infiltration of immune-suppressive cells, such as regulatory T (Treg) cells and M2 macrophage, was significantly increased by NRP1 expression. In addition, the expression of interleukin (IL)-35, IL-10, and TGF-β1 was also positively correlated with NRP1 expression, resulting in the immune suppression. Collectively in this study, our integrated analysis using various clinical databases shows that the significant correlation between NRP1 expression and the infiltration of Treg cells and M2 macrophage explains poor prognosis mechanism in STAD, suggesting the clinical relevance of NRP1 expression as a prognostic biomarker for STAD patients.
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http://dx.doi.org/10.3390/jcm9051430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7290937PMC
May 2020

Therapeutic potential of miR-21 regulation by human peripheral blood derived-small extracellular vesicles in myocardial infarction.

Clin Sci (Lond) 2020 04;134(8):985-999

Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

Small extracellular vesicles (sEVs) as natural membranous vesicles are on the frontiers of nanomedical research, due to their ability to deliver therapeutic molecules such as microRNAs (miRNAs). The miRNA-21 (miR-21) is thought to be involved in the initiation and development of myocardial infarction (MI). Here, we examined whether miR-21 regulation using human peripheral blood-derived sEVs (PB-sEVs) could serve as a potential therapeutic strategy for MI. First, we examined miR-21 levels in hypoxic conditions and validated the ability of PB-sEVs to serve as a potential delivery system for miRNAs. Further, bioinformatics analysis and luciferase assay were performed to identify target genes of miR-21 mechanistically. Among numerous target pathways, we focused on nitrogen metabolism, which remains relatively unexplored compared with other possible miR-21-mediated pathways; hence, we aimed to determine novel target genes of miR-21 related to nitrogen metabolism. In hypoxic conditions, the expression of miR-21 was significantly up-regulated and correlated with nitric oxide synthase 3 (NOS3) levels, which in turn influences cardiac function. The down-regulation of miR-21 expression by PB-sEVs loaded with anti-miR-21 significantly improved survival rates, consistent with the augmentation of cardiac function. However, the up-regulation of miR-21 expression by PB-sEVs loaded with miR-21 reversed these effects. Mechanistically, miR-21 targeted and down-regulated the mRNA and protein expression of striatin (STRN), which could regulate NOS3 expression. In conclusion, we identified a novel therapeutic strategy to improve cardiac function by regulating the expression of miR-21 with PB-sEVs as an miR-21 or anti-miR-21 delivery vehicle and confirmed the miR-21-associated nitrogen metabolic disorders in MI.
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http://dx.doi.org/10.1042/CS20191077DOI Listing
April 2020

Blockade of thymic stromal lymphopoietin and CRTH2 attenuates airway inflammation in a murine model of allergic asthma.

Korean J Intern Med 2020 05 19;35(3):619-629. Epub 2020 Mar 19.

Division of Allergy and Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Background/aims: Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a key role in Th2-mediated inflammation, both directly by promoting the proliferation of naïve CD4 Th2 cells, and indirectly by activating dendritic cells (DCs). TSLP-activated DCs induce the expansion of chemoattractant receptor homologous molecule expressed on Th2 (CRTH2)+ CD4+ Th2 memory cells, which undergo a Th2 response and express prostaglandin D2 (PGD2) synthase. CRTH2, a PGD2 receptor, is a selective Th2-cell surface marker. We investigated the effects of an anti-TSLP antibody (Ab) and a CRTH2 antagonist, as well as their mechanisms of action, in a mouse model of acute asthma.

Methods: BALB/c mice were sensitized and challenged with ovalbumin. We then evaluated the effects of the administration of an anti-TSLP Ab either alone or together with a CRTH2 antagonist on cell counts, Th2 cytokine levels in bronchoalveolar fluid, and the levels of epithelium-derived cytokines such as TSLP, interleukin (IL) 33, and IL-25 in lung homogenates, as well as airway hyper-responsiveness (AHR).

Results: Anti-TSLP Ab and the CRTH2 antagonist significantly attenuated eosinophilic airway inflammation, AHR, and the expression of Th2 cytokines. The expression of GATA-3 and the levels of IL-33 and IL-25 in lung tissues were affected by the combined anti-TSLP and CRTH2 antagonist treatment.

Conclusion: These results suggest that the dual blockade of TSLP and CRTH2 may serve as an effective treatment target for eosinophilic asthma.
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http://dx.doi.org/10.3904/kjim.2018.248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214371PMC
May 2020

It's Time for Latent Tuberculosis Infection Screening in HIV-infected Individuals.

J Korean Med Sci 2019 10 21;34(40):e276. Epub 2019 Oct 21.

Division of Pulmonology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

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http://dx.doi.org/10.3346/jkms.2019.34.e276DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6801226PMC
October 2019

Pravastatin alleviates allergic airway inflammation in obesity-related asthma mouse model.

Exp Lung Res 2019 Nov - Dec;45(9-10):275-287. Epub 2019 Oct 12.

Division of Allergy, Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Obesity is one of the factors associated with severe, uncontrolled asthma. The effect of pravastatin on asthmatic airway inflammation in obesity has not been evaluated. C57BL/6 mice were fed a high-fat diet (HFD) to induce obesity with or without ovalbumin (OVA) sensitization and challenge. Pravastatin was administered intraperitoneally during the OVA treatment. Airway inflammation and airway hyper-responsiveness (AHR) were analyzed and lung tissues were examined. The changes in mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/Akt signaling pathways were measured in the lung tissues. HFD with OVA sensitization and challenge exacerbated eosinophilic and neutrophilic airway inflammation and increased AHR compared to lean asthma mice. The levels of cytokines examined in bronchoalveolar lavage fluid (BALF) revealed that the expressions of IL-4, 5, and 17 were elevated in the obese asthmatic group and decreased after pravastatin treatment, indicating that both the Th2 and Th17 pathways were stimulated by HFD-induced obesity and OVA challenge and suppressed by pravastatin treatment. Moreover, the serum leptin and adiponectin ratio was elevated only in obese asthmatic mice and decreased with pravastatin administration. Pravastatin successfully alleviated the airway inflammation of lung tissues and AHR in both obese and lean asthmatic mice, however, treatment with pravastatin had no effects on BALF cell counts and cytokines in lean asthma mice. In lung tissues, the phosphorylation of p38 MAPK was significantly decreased in lean as well as obese asthmatic mice. Pravastatin treatment in obese asthmatic mice suppressed allergic airway infiltration and AHR by inhibition of Th2 and Th17-associated signaling pathways, decreasing the leptin expression and downstream p38 MAPK signaling pathways. The effect on lean asthmatic mice was different, independent of airway cell counts and cytokines.
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http://dx.doi.org/10.1080/01902148.2019.1675807DOI Listing
May 2020

A case of early diagnosis of pulmonary capillary hemangiomatosis in a worker with exposure to silica.

BMC Pulm Med 2019 Jul 23;19(1):133. Epub 2019 Jul 23.

Division of Allergy and Pulmonology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Background: Pulmonary capillary hemangiomatosis (PCH) is a progressive and refractory vascular disease in the lung. Pulmonary hypertension is frequently combined with PCH when capillary proliferation invades to nearby pulmonary vascular systems. It is difficult to differentiate PCH from other diseases such as pulmonary venoocclusive disease and pulmonary arterial hypertension that cause pulmonary hypertension as they frequently overlap.

Case Presentation: A 29-year-old female who had worked at a bathtub factory presented with progressive exertional dyspnea for the past 2 years. Computed tomography revealed centrilobular, diffusely spreading ground-glass opacities sparing subpleural parenchyma with some cystic lesions and air-trapping in both lungs, suggesting a peculiar pattern of interstitial lung disease with airway involvement. There was not any evidence of right heart failure or pulmonary hypertension on echocardiogram, as well as radiography. Microscopic examination of the lung by thoracoscopic resection showed atypical proliferation of capillary channels within alveolar walls and interlobar septa, without invasion of large vessels.

Conclusion: We experienced a pathologically diagnosed PCH in a young female complaining progressive dyspnea with prior exposure to occupational silica or organic solvent without elevated right ventricular systolic pressure (RVSP) who showed atypical pattern of radiologic findings.
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http://dx.doi.org/10.1186/s12890-019-0896-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6651969PMC
July 2019

Calcium chloride enhances the delivery of exosomes.

PLoS One 2019 22;14(7):e0220036. Epub 2019 Jul 22.

Division of Cardiology, Yonsei University College of Medicine, Seoul, Republic of Korea.

Exosomes might have an unimproved potential to serve as effective delivery vehicles. However, when exosomes are developed for therapeutic applications, a method to enhance their delivery is important. This study aimed to evaluate wheather calcium chloride (CaCl2) or other chloride compounds could enhance exosome delivery to various cells without causing toxicity. Exosomes were purified from human serum by using the ExoQuick exosome precipitation kit. Isolated exosomes were mixed with CaCl2 at concentrations ranging from 100 μM to 1 mM, and then washed using Amicon filter for treating the cells. The delivery efficiency of exosomes and the viability of the cells [HEK 293 (human kidney cells) and H9C2 (rat cardiomyocytes)] were evaluated. Cellular uptake of exosomes was observed using a confocal microscope based on PKH26 labeling of exosomes. CaCl2 increased the delivery of exosomes in a dose- and treatment time-dependent manner. In HEK 293 cells, a CaCl2 concentration of 400 μM and exposure time of 12 h increased the delivery of exosomes by >20 times compared with controls. In H9C2 cells, a CaCl2 concentration of 400 μM and exposure time of >24 h increased the delivery of exosomes by >400 times compared with controls. The viability of both cell lines was maintained up to a CaCl2 concentration of 1 mM. However, cobalt chloride, cupric chloride, and magnesium chloride did not change the delivery of exosomes in both cell lines. These results suggest that the use of CaCl2 treatment might be a useful method for enhancing the delivery of exosomes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0220036PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6645520PMC
February 2020

Korean Guidelines for Diagnosis and Management of Interstitial Lung Diseases: Part 3. Idiopathic Nonspecific Interstitial Pneumonia.

Tuberc Respir Dis (Seoul) 2019 Oct 31;82(4):277-284. Epub 2019 May 31.

Department of Pulmonary and Critical Care Medicine, Chungnam National University Hospital, Daejeon, Korea.

Idiopathic nonspecific interstitial pneumonia (NSIP) is one of the varieties of idiopathic interstitial pneumonias. Diagnosis of idiopathic NSIP can be done via multidisciplinary approach in which the clinical, radiologic, and pathologic findings were discussed together and exclude other causes. Clinical manifestations include subacute or chronic dyspnea and cough that last an average of 6 months, most of which occur in non-smoking, middle-aged women. The common findings in thoracic high-resolution computed tomography in NSIP are bilateral reticular opacities, traction bronchiectasis, reduced volume of the lobes, and ground-glass opacity in the lower lungs. These lesions can involve diffuse bilateral lungs or subpleural area. Unlike usual interstitial pneumonia, honeycombing is sparse or absent. Pathology shows diffuse interstitial inflammation and fibrosis which are temporally homogeneous, namely NSIP pattern. Idiopathic NSIP is usually treated with steroid only or combination with immunosuppressive agents such as azathioprine, cyclophosphamide, cyclosporine, and mycophenolate mofetil. Prognosis of idiopathic NSIP is better than idiopathic pulmonary fibrosis. Many studies have reported a 5-year survival rate of more than 70%.
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http://dx.doi.org/10.4046/trd.2018.0092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6778744PMC
October 2019

[Corrigendum] Human peripheral blood‑derived exosomes for microRNA delivery.

Int J Mol Med 2019 07 20;44(1):358. Epub 2019 May 20.

Division of Cardiology, Yonsei University College of Medicine, Yonsei University, Seoul 03722, Republic of Korea.

Exosomes serve important functions in cell‑to‑cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood‑derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR‑21 using a human peripheral blood derived‑exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL‑1 cells, miR‑21 expression was successfully regulated by treatment with human peripheral blood derived‑exosomes loaded with an miR‑21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor‑loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR‑21 mimic‑ or inhibitor‑loaded exosomes. Furthermore, miR‑21 mimic‑loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA‑loaded human peripheral blood derived‑exosomes may be used as a therapeutic tool for cardiac diseases. [the original article was published in International Journal of Molecular Medicine 43: 2319‑2328, 2019; DOI:10.3892/ijmm.2019.4150].
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http://dx.doi.org/10.3892/ijmm.2019.4202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559309PMC
July 2019

Clinical implications of discrepant results between genotypic MTBDR and phenotypic Löwenstein-Jensen method for isoniazid or rifampicin drug susceptibility tests in tuberculosis patients.

J Thorac Dis 2019 Feb;11(2):400-409

Department of Internal Medicine, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

Background: The widespread use of molecular, genotypic drug susceptibility tests (DSTs) for antituberculosis (anti-TB) drugs has led to the dilemma of interpreting discordant results between genotypic and conventional, phenotypic DSTs. We investigated the clinical characteristics, including treatment patterns and outcomes, of TB patients with a genotype-phenotype discrepancy in susceptibility to isoniazid (INH) or rifampicin (RIF).

Methods: We retrospectively reviewed the medical records of TB patients who had results for 2 DSTs (genotypic method, MTBDR test for INH and RIF, and phenotypic method) treated between August 2010 and October 2016 in a tertiary university hospital.

Results: Among 1,069 TB patients, 63 (5.9%) had discrepant results for the 2 DSTs. Of the 57 multidrug-resistant (MDR) TB cases diagnosed by either DST, 18 (31.6%) showed discordant results for INH or RIF. The most frequent pattern of discordance was genotypic susceptibility with phenotypic resistance to INH. RIF-discordant subjects with genotypic resistance were more likely to have been exposed previously to anti-TB drugs and to have an MDR TB diagnosis and concurrent INH resistance. Forty-five of the 54 patients managed in our hospital (83.3%) had a favorable outcome with a mean treatment duration of 14.0 months. Ten of the 16 INH-discrepant patients with a genotypic mutation continued taking INH, but more than half patients in the RIF-discrepant group (8/14) with a genotypic mutation discontinued taking RIF.

Conclusions: Despite the low frequency, discordant results were obtained between the genotypic and phenotypic DSTs for INH or RIF, especially for patients with MDR TB or INH resistance. Furthermore, it seemed that RIF discrepancy with a genotypic mutation might have a greater impact on the clinical outcome than INH discrepancy.
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http://dx.doi.org/10.21037/jtd.2019.01.58DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6409268PMC
February 2019

Human peripheral blood‑derived exosomes for microRNA delivery.

Int J Mol Med 2019 06 28;43(6):2319-2328. Epub 2019 Mar 28.

Division of Cardiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

Exosomes serve important functions in cell‑to‑cell communication and biological functions by serving as a delivery cargo shuttle for various molecules. The application of an improved delivery method for microRNAs (miRNAs/miRs) may enhance their potential as a therapeutic tool in cardiac diseases. Thus, the present study investigated whether human peripheral blood‑derived exosomes may be used as a delivery cargo system for miRNAs, and whether the delivery of miR‑21 using a human peripheral blood derived‑exosome may influence the degree of remodeling following myocardial infarction (MI). In H9C2 and HL‑1 cells, miR‑21 expression was successfully regulated by treatment with human peripheral blood derived‑exosomes loaded with an miR‑21 mimic or inhibitor compared with untreated cells. In addition, the mRNA and protein expression levels of SMAD family member 7 (Smad7), phosphatase and tensin homolog (PTEN) and matrix metalloproteinase 2 (MMP2), which are involved in cardiac fibrosis, were associated with the uptake of miR‑21 mimic‑ or inhibitor‑loaded exosomes. Similarly, the in vivo mRNA and protein expression of Smad7, PTEN and MMP2 were altered following treatment with miR‑21 mimic‑ or inhibitor‑loaded exosomes. Furthermore, miR‑21 mimic‑loaded exosomes enhanced fibrosis, whereas miR‑21 inhibitor‑loaded exosomes reduced fibrosis in a mouse MI model. These results suggested that miRNA‑loaded human peripheral blood derived‑exosomes may be used as a therapeutic tool for cardiac diseases.
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http://dx.doi.org/10.3892/ijmm.2019.4150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488179PMC
June 2019

Perception of Child Abuse and Child Disciplinary Practice among Adults Abused as Children: Comparison to General Population.

Soa Chongsonyon Chongsin Uihak 2019 Mar;30(2):57-65

Division of Child Welfare & Studies, College of Human Ecology, Sookmyung Women's University, Seoul, Korea.

Objectives: The aim of this study was to compare differences in perception and knowledge of child abuse and child disciplinary practices according to the history of child abuse victimization.

Methods: A questionnaire survey on child abuse was conducted with 491 adults raising children. We compared the perception and knowledge of child abuse and child disciplinary practices between two groups of adults with and without a history of childhood abuse victimization.

Results: The group with a history of childhood abuse had lower levels of knowledge of child abuse (F=6.990, p<0.01) and engaged in more negative disciplinary practices (F=5.974, p<0.05) than those without. However, no differences in the perception of child abuse were observed between the two groups.

Conclusion: The results suggest that adults with a history of childhood abuse have lower levels of knowledge of child abuse and use more negative disciplinary practices in raising their children. This highlights the need to administer not only educational but also more direct hands-on interventions to vulnerable parents in order to foster healthy parenting and disciplinary practices.
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http://dx.doi.org/10.5765/jkacap.180032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289501PMC
March 2019

Expression of miRNAs in circulating exosomes derived from patients with persistent atrial fibrillation.

FASEB J 2019 05 12;33(5):5979-5989. Epub 2019 Feb 12.

Division of Cardiology, Yonsei University College of Medicine, Seoul, South Korea.

Atrial fibrillation (AF), the most common type of cardiac arrhythmia, is thought to be regulated by changes in microRNA (miRNA) expression. However, the evidence for this is inconsistent. The high stability and expression of circulating exosomal miRNAs may allow their use as candidate biomarkers. For the discovery phase, exosomes were isolated from the serum of patients with supraventricular tachycardia (SVT) as the controls ( = 5) and with paroxysmal AF ( = 4) and persistent AF ( = 5) for microarray analysis of miRNAs. Forty-five miRNAs were expressed significantly higher (>1.5-fold) in patients with persistent AF, but not in patients with paroxysmal AF, relative to the levels in patients with SVT control. Notably, expression of 5 miRNAs (miRNA-103a, -107, -320d, -486, and let-7b) was elevated by more than 4.5-fold in patients with persistent AF. For the validation phase, miRNAs were analyzed using quantitative RT-PCR analysis in exosomes from the serum of patients with SVT control ( = 20) and patients with persistent AF ( = 40). These miRNAs and their target genes were involved in atrial function and structure, oxidative stress, and fibrosis pathways. These findings suggest that serum exosomal miRNAs might be used as novel biomarkers to reflect the progression of AF.-Mun, D., Kim, H., Kang, J.-Y., Park, H., Park, H., Lee, S.-H., Yun, N., Joung, B. Expression of miRNAs in circulating exosomes derived from patients with persistent atrial fibrillation.
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http://dx.doi.org/10.1096/fj.201801758RDOI Listing
May 2019

Metabolic health is more closely associated with decrease in lung function than obesity.

PLoS One 2019 23;14(1):e0209575. Epub 2019 Jan 23.

Division of Pulmonary Medicine, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Objective: Previous studies have evaluated the link between metabolic syndrome and obesity with impaired lung function, however findings have been controversial. We aimed to compare lung function among subjects with different metabolic health and obesity status.

Methods: Total 10,071 participants were evaluated at the Health Promotion Center in Seoul St. Mary's Hospital between January 2012 and December 2014. Being metabolically healthy was defined as having fewer than three of the following risk factors: high blood pressure, high fasting blood glucose, high triglyceride, low high-density lipoprotein cholesterol and abdominal obesity. Obesity status was defined as body mass index (BMI) higher than 25 kg/m2. Analyses of pulmonary function were performed in four groups divided according to metabolic health and obesity: metabolically healthy non-obese (MHNO), metabolically health obese (MHO), metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO).

Results: Metabolically unhealthy subjects were more prone to decreased lung function compared with their metabolically healthy counterparts, regardless of obesity status. When multinomial logistic regression analysis was performed according to quartiles of forced vital capacity (FVC) or forced expiratory volume in 1 second (FEV1) (% pred), after adjusting for age, sex, and smoking status, odds ratio (OR) for the lowest FVC and FEV1 (% pred) quartiles were significantly higher in MUHO subjects (1.788 [95% CI, 1.531-2.089] and 1.603 [95% CI, 1.367-1.881]) and lower in MHO subjects (0.768 [95% CI, 0.654-0.902] and 0.826 [95% CI, 0.700-0.976]) with MHNO group as the reference, when OR for highest FVC and FEV1 quartiles were considered as 1.0.

Conclusion: Metabolic health is more closely associated with impaired lung function than obesity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209575PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343891PMC
November 2019

Effect of nintedanib on airway inflammation in a mouse model of acute asthma.

J Asthma 2020 01 11;57(1):11-20. Epub 2019 Jan 11.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.

New treatments are needed for cases of asthma that are refractory to traditional therapies. In this study, we examined the effect of oral nintedanib, an intracellular inhibitor of tyrosine kinases, on airway hyper-responsiveness (AHR) and airway smooth muscle cells, using a mouse model of experimental asthma. Asthma was experimentally induced in mice via subcutaneous injection of ovalbumin (OVA). A group of saline-injected mice served as a control group. The OVA mice were then divided into four treatment groups according to the dose of nintedanib. AHR was examined via exposure to vaporized methacholine. Airway inflammation was assessed via bronchoalveolar lavage fluid (BALF) cell counts and Th2 cytokine concentrations. Baseline levels of AHR and airway inflammation were higher in OVA mice than in the control group. Treatment with nintedanib lowered AHR, BALF cell counts and BALF cytokine levels in a dose-dependent fashion. The effect of nintedanib was comparable to that of dexamethasone. In particular, treatment with nintedanib lowered the expression of transforming growth factor-β1 and inhibited the expression and phosphorylation of platelet-derived growth factor receptor-β, vascular endothelial growth factor receptor 1 (VEGFR1), VEGFR2, fibroblast growth factor receptor 2 (FGFR2), FGFR3, and extracellular signal-regulated kinase. Nintedanib lowered AHR and the expression of factors associated with airway inflammation and remodeling in a mouse model of experimental asthma. Our results suggest that nintedanib may be useful in the treatment of asthma.
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http://dx.doi.org/10.1080/02770903.2018.1544641DOI Listing
January 2020