• Title/Summary/Keyword: Lung development

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Cynomolgus Macaque Model for COVID-19 Delta Variant

  • Seung Ho Baek;Hanseul Oh;Bon-Sang Koo;Green Kim;Eun-Ha Hwang;Hoyin Jung;You Jung An;Jae-Hak Park;Jung Joo Hong
    • IMMUNE NETWORK
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    • v.22 no.6
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    • pp.48.1-48.13
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    • 2022
  • With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.

Generation of Induced Pluripotent Stem Cells from Lymphoblastoid Cell Lines by Electroporation of Episomal Vectors

  • Myunghyun Kim;Junmyeong Park;Sujin Kim;Dong Wook Han;Borami Shin;Hans Robert Scholer;Johnny Kim;Kee-Pyo Kim
    • International Journal of Stem Cells
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    • v.16 no.1
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    • pp.36-43
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    • 2023
  • Background and Objectives: Lymphoblastoid cell lines (LCLs) deposited from disease-affected individuals could be a valuable donor cell source for generating disease-specific induced pluripotent stem cells (iPSCs). However, generation of iPSCs from the LCLs is still challenging, as yet no effective gene delivery strategy has been developed. Methods and Results: Here, we reveal an effective gene delivery method specifically for LCLs. We found that LCLs appear to be refractory toward retroviral and lentiviral transduction. Consequently, lentiviral and retroviral transduction of OCT4, SOX2, KFL4 and c-MYC into LCLs does not elicit iPSC colony formation. Interestingly, however we found that transfection of oriP/EBNA-1-based episomal vectors by electroporation is an efficient gene delivery system into LCLs, enabling iPSC generation from LCLs. These iPSCs expressed pluripotency makers (OCT4, NANOG, SSEA4, SALL4) and could form embryoid bodies. Conclusions: Our data show that electroporation is an effective gene delivery method with which LCLs can be efficiently reprogrammed into iPSCs.

Review of Chakra Systems Based on Tibetan Medical Literature: Focus on Indian and Tibetan Chakra (티베트 의학 문헌에 기반한 차크라 시스템 비교 연구 : 인도와 티베트 차크라를 중심으로)

  • Youn-Kyung Jun
    • Journal of The Korean Society of Integrative Medicine
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    • v.12 no.3
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    • pp.201-212
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    • 2024
  • Purpose : In this study, we aimed to explore the concept of chakra in Tibetan medicine, elucidate its unique characteristics, and assess the differences between the Tibetan and Indian chakra systems to enhance the understanding of the Tibetan chakra system. Methods : Here, relevant on Tibetan medicine and chakra system were collected from Google Scholar and Korean Academic Information Databases and meticulously analyzed. Moreover, number of main chakras, characteristics of the five elements, and principles of each chakra system were evaluated. Results : Development and precise location of chakras are extensively detailed in Tibetan medicine, indicating an in-depth and comprehensive understanding of the chakra system. The Indian chakra system consists of seven chakras, whereas the Tibetan chakra system is composed of five chakras. Tibetan medicine focuses on three distinct energy elements, Lung, Tripa, and Beken, corresponding to the lower, middle, and upper sections of the body, respectively, with each exhibiting different arrangements and functions for each chakra in the Tibetan chakra system compared to those in the Indian chakra system. Furthermore, Tibetan medicine adheres to Buddhist principles, which attribute diseases to mental causes, thus exhibiting therapeutic potential for psychosomatic illnesses. Conclusion : Owing to the distinct and significant differences between the two chakra systems, the five chakras of the Tibetan system are challenging to conceptualize using the Indian framework of seven chakras. Hence, comprehensive understanding of the Tibetan culture and medicine is necessary to elucidate the Tibetan chakra system. Overall, this study provides compelling evidence for the existence of chakra and highlights the attributes of two key chakra systems, thereby providing valuable insights for energy medicine based on the intricate energy pathways of the body.

HPLC, NMR Based Characterization, Antioxidant and Anticancer Activities of Chemical Constituents from Therapeutically Active Fungal Endophytes

  • Waqas Hussain Shah;Wajiha Khan;Sobia Nisa;Michael H.J. Barfuss;Johann Schinnerl;Markus Bacher;Karin Valant-Vetschera;Ashraf Ali;Hiba-Allah Nafidi;Yousef A. Bin Jardan;John P. Giesy
    • Journal of Microbiology and Biotechnology
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    • v.34 no.7
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    • pp.1452-1463
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    • 2024
  • Fungi generate different metabolites some of which are intrinsically bioactive and could therefore serve as templates for drug development. In the current study, six endophytic fungi namely Aspergillus flavus, Aspergillus tubigenesis, Aspergillus oryzae, Penicillium oxalicum, Aspergillus niger, and Aspergillus brasiliensis were isolated and identified from the medicinal plant, Silybum marianum. These endophytic fungi were identified through intra transcribed sequence (ITS) gene sequencing. The bioactive potentials of fungal extracts were investigated using several bioassays such as antibacterial activity by well-diffusion, MIC, MBC, anti-biofilm, antioxidant, and haemolysis. The Pseudomonas aeruginosa PAO1 was used to determine the antibiofilm activity. The ethyl acetate extract of Aspergillus flavus showed strong to moderate efficacy against Staphylococcus aureus, Escherichia coli, P. aeruginosa, and Bacillus spizizenii. Aspergillus flavus and Aspergillus brasiliensis exhibited significant antibiofilm activity with IC50 at 4.02 and 3.63 mg/ml, while A. flavus exhibited maximum antioxidant activity of 50.8%. Based on HPLC, LC-MS, and NMR experiments kojic acid (1) and carbamic acid (methylene-4, 1-phenylene) bis-dimethyl ester (2) were identified from A. flavus. Kojic acid exhibited DPPH free radical scavenging activity with an IC50 value of 99.3 ㎍/ml and moderate activity against ovarian teratocarcinoma (CH1), colon carcinoma (SW480), and non-small cell lung cancer (A549) cell lines. These findings suggest that endophytic fungi are able to produce promising bioactive compounds which deserve further investigation.

CLINICAL CHARACTERISTICS OF SECOND PRIMARY CANCER IN ORAL CANCER PATIENTS (구강암 환자에서 발생하는 이차암의 임상적 특징 분석)

  • Jo, Sae-Hyung;Shin, Jeong-Hyun;Lee, Ui-Ryoung;Park, Joo-Young;Choi, Sung-Weon
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.1
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    • pp.57-61
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    • 2010
  • Objective: Second primary malignancy (SPM) that occur in various period and region are important factors that deteriorate long-term survival rate in patients who recovered from oral cancer. Researches such as chemoprevention are being tried to reduce occurrence of SPMs. Only if analysis of clinical features of patients who develop SPM such as period, region and factors precedes, adequate prevention and treatment of SPM is possible. But, there are few researches about clinical features of SPMs that have primary lesion in oral cavity. In this study, we analysis that occurrence rates, regions that happen, risk factors and effect to survival rates of 2nd primary malignancies in oral cancer patients. From this survey, we willing to collect basic data for prevention and early diagnosis of SPMs. Methods: The medical records of 139 patients of oral oncology clinic of National Cancer Center who had up to 2-years follow up records after surgical or radiological treatment due to squamus cell carcinoma of oral cavity were reviewed. In these patients, survey of occurrence rate of SPMs, duration, survival rate and risk factors about occurrence of SPMs such as history of smoking, body mass index, age, sex, stage of primary lesion and history of radiologic treatment were achieved. Results: There are 15 patients who developed SPM in 139 cases. The actual occurrence rate of SPM was 10.79% and SPM were more likely to occur in male patients with 11 male Vs 4 female patients. Median age of these patient is 61.47 within 32 to 74 range. The regions that develop SPM are oral cavities (2 cases), stomach (4 cases), esophagus (2 cases), lung (2 cases) and others (1 case each breast, larynx, cervix, liver and kidney). In addition, metachronous cancers were 11 cases which happened more common than 4cases of synchronous cancers. Surveys of risk factors that relate to development of SPMs, such as sex, age, history of radiologic treatment, body mass index, history of smoking and stage of primary disease were done. Among them, factor of sex is only appear statistically significant (P=0.001), but rest are not significant in statistically. Conclusion: Occurrence rates of SPMs were reported from 10% to 20% by precede study. In this study, occurrence rate of SPMs is 10.79% that is similar to results of precede research. In comparison of 5-yr survival rates of groups that develop SPMs or not, there is statistically significance between two groups. Present treatment modalities of SPMs are surgical operation, radiotherapy, chemotherapy and combination of these modalities. In choosing the treatment modality, we must consider the first treatment modality, region of primary disease, region of SPMs and general conditions of patient. Because development of SPMs have big effect on prognosis, prevention of SPMs must regard to important objective of treatments in patients of SCCa in oral cavity.

Pneumococcal Surface Protein A of Streptococcus pneumoniae Isolates from Koreans (한국인에서 Streptococcus pneumoniae 분리주의 폐구균 표면 단백 A)

  • Kim, Kyung Hyo
    • Clinical and Experimental Pediatrics
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    • v.48 no.11
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    • pp.1206-1211
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    • 2005
  • Purpose : Pneumococcal protein vaccine based on pneumococcal surface protein A (PspA) is in development with the potential to offer a broad range of protection against different strains. PspA elicits protection in mice against fatal sepsis as well as carriage and lung infection. This study was performed to investigate the frequency of PspA families among Streptococcus pneumoniae recovered from Korean children and adults. Methods : A total of 89 pneumococcal isolates was included in the study. They were capsule serotyped by the slide agglutination assay with commercial antisera. PspA families were determined with polymerase chain reaction using the pair of primers for family 1 and family 2. Results : Seventeen pneumococcal serotypes were found in a total of 89 isolates. PspA typing was able to ascertain 79 of the 89 isolates (88.8 percent). Among these, 20 (22.5 percent) isolates were family 1 PspA, 59 (66.3 percent) were family 2. Moreover, because 9 (10.1 percent) isolates were of positive reactions for both, families 1 and 2 primers, the potential coverage of PspA vaccine was 98.9 percent. PspA families were not associated with age group, source of isolates, or penicillin susceptibility. However, the relative distribution of family 1 isolates to family 2 isolates was significantly different over capsular serotypes. Conclusion : The finding that 98.9 percent of Korean isolates belonging to PspA families 1 and 2 support the hypothesis that a human PspA vaccine covering a few PspA families could be broadly effective. The monitoring of the PspA families derived from large population-based isolates will be necessary in the context of vaccine development.

Genotoxicity Studies on Corn Silk Extract Containing High Maysin (고메이신 함유 옥수수수염 추출물의 유전독성학적 안전성 연구)

  • Ha, Ae Wha;Kang, Hyeon Jung;Kim, Sun Lim;Kim, Myung Hwan;Kim, Woo Kyoung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.9
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    • pp.1045-1052
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    • 2017
  • In this study, a battery of genetic-toxicity studies on corn silk extract with high maysin content were performed according to internationally accepted protocols. In a mutation test using Salmonella Typhimurium TA1535, TA1537, TA98, and TA100, the number of mutant colonies did not significantly increase up to a maximum concentration of $5,000{\mu}g/plate$ in the presence or absence of the S9 metabolic activation system. In the chromosome aberration test using Chinese hamster lung fibroblasts, negative results were observed in the concentration up to $1,250{\mu}g/mL$ of corn silk extract. In the micronucleus test using ICR mice, incidence of polymorphonuclear erythrocytes with a maximum concentration of 2,000 mg/kg corn silk extract did not show any significant difference compared to the negative control group. Based on these results, the test substance, con silk extract, did not influence genotoxicity.

Influencing Factors of Peripheral Blood Lymphocyte subsets in Workers with Chronic Obstructive Pulmonary Disease Exposed to Inorganic Dust (만성폐쇄성폐질환을 동반한 무기분진 노출 이직근로자의 혈중 림프구 아형분포에 미치는 영향요인)

  • Baek, Jin Ee;Shin, Jae Hoon;Hwang, Joo Hwan;Lee, Youlim;Lee, Jong Seong;Choi, Byung-Soon
    • Journal of Korean Society of Occupational and Environmental Hygiene
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    • v.31 no.3
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    • pp.286-293
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    • 2021
  • Objectives: Inorganic dust is known to be a risk factor for chronic obstructive pulmonary disease (COPD) regardless of smoking and pneumoconiosis. Adaptive and innate immunity, including lymphocyte infiltrate, are involved in the pathogenesis of COPD. The purpose of this study was to analyze the lymphocyte subsets in the blood of workers exposed to inorganic dust and confirm the influencing factors. Methods: The general characteristics of the subjects (n=107) were analyzed through a personal questionnaire. Diagnosis of COPD was established according to pulmonary function tests with FEV1/FVC post bronchodilator lower than 70%, according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. For lymphocyte analysis, blood was stained with a fluorescent CD marker and analyzed by flow cytometry. Results: The increase in CD4+ T lymphocytes was associated with a decrease in age (𝛽=-0.273, p=0.008) and an increase in the cumulative smoking amount (𝛽=0.205, p=0.034). The increase in NK cells was associated with an increase in age (𝛽=0.325, p=0.001) and a decrease in cumulative smoking (𝛽=-0.220, p=0.019). The period of exposure to dust, %FVC predicted and %FEV1/FVC, and the relative population of peripheral blood lymphocytes did not show a statistically significant relationship. Conclusions: CD4+ T lymphocytes and CD56+CD16+ NK cells in peripheral blood were more related to age and cumulative smoking than the duration of dust exposure. Age and smoking are major risk factors for the development of COPD, so it can be predicted that peripheral blood CD4+ T lymphocytes and CD56+CD16+ NK cells are related to the development of COPD in workers exposed to inorganic dust.

Association of Single Nucleotide Polymorphisms in Interleukin-12 Receptor (IL-12Rβ1 and IL-12Rβ2) with Asthma in a Korean Population

  • Jung, Jaemee;Park, Sangjung;Kim, Sung-Soo;Hong, Mijin;Choi, Eunhye;Jin, Hyun-Seok;Hwang, Dahyun
    • Biomedical Science Letters
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    • v.26 no.4
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    • pp.344-350
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    • 2020
  • Asthma is a chronic disease and occurs in airway in the lung. The cause of the disease has not been identified, it is assumed that both genetic and environmental risk factors play an important role in the development of asthma. Interleukin (IL)-12 is a cytokine regulating T-cell and NK cell. In this study, we analyzed the genetic polymorphisms of IL-12 receptor genes (IL-12Rβ1 and IL-12Rβ2) in asthma patients and normal individuals in a Korean population. We analyzed single nucleotide polymorphisms (SNPs) in IL-12Rβ1 and IL-12Rβ2 using the genotype data of 193 asthma cases and 3,228 healthy controls from the Korea Association REsource for their correlation with asthma case. IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant polymorphism association with asthma case. As a results, 16 SNPs from IL-12Rβ1 and IL-12Rβ2 genes showed statistically significant association with asthma. Among them, rs375947 SNP in IL-12Rβ1 showed the greatest statistical correlation with asthma (P-value = 0.028, Odds Ratio = 1.27, 95% Confidence Interval = 1.03~1.57). The groups with minor allele of IL-12Rβ1 and IL-12Rβ2 showed increased risk of asthma. The genotype-based mRNA expression analysis showed that the group of minor allele of IL-12Rβ1 showed decreased mRNA expression. Decreased IL-12Rβ1 expression causes decreased IL-12 signaling, and this affects developing asthma. In conclusion, the SNPs in IL-12Rβ1 and IL-12Rβ2 may contribute to development of asthma in a Korean population.

Clinical Features and Treatment Response in 18 Cases with Idiopathic Nonspecific Interstitial Pneumonia (특발성 비특이성 간질성 폐렴 18례의 임상상 및 치료반응)

  • Kang, Eun-Hae;Chung, Man-Pyo;Kang, Soo-Jung;An, Chang-Hyeok;Ahn, Jong-Woon;Han, Joung-Ho;Lee, Kyung-Soo;Lim, Si-Young;Suh, Gee-Young;Kim, Ho-Joong;Kwon, O-Jung;Rhee, Chong-H.
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.4
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    • pp.530-542
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    • 2000
  • Background : Nonspecific interstitial pneumonia (NSIP) has been reported recently to have shown much better response to medical treatment and better prognosis compared with idiopathic UIP. However, clinical characteristics of idiopathic NSIP discriminating it from UIP have not been clearly defined. Method : Among 120 patients with biopsy-proven diffuse interstitial lung diseases admitted to the Samsung Medical Center between July 1996 and March 2000, 18 patients with idiopathic NSIP were included in this study. Retrospective chart review and radiographic analysis were performed. Results : 1) At diagnosis, 17 patients were female and the average age was $55.2{\pm}8.4$ years (44~73 years). The average duration from development of respiratory symptom to surgical lung biopsy was $9.9{\pm}17.1$ months. Increase in bronchoalveolar lavage fluid lymphocytes ($23.0{\pm}13.1%$) was noted. On HRCT, ground glass and irregular linear opacity were observed, but honeycombing was absent in all patients. 2) Corticosteroids were initially given to 13 patients, but the medication was stopped in 3 patients due to severe side effects. Further medical therapy was not possible in 1 patient who experienced streroid-induced psychosis. Herpes zoster (n=3), tuberculosis (n=1), avascular necrosis of the hip (n=1), cataract (n=2) and diabetes mellitus (n=1) developed during prolonged corticosteroid administration. Of the 7 patients receiving oral cyclophosphamide therapy, hemorrhagic cystitis hindered one patient from continuing with the medication. 3) After medical treatment, 14 of 17 patients improved, and 3 patients remained stable (mean follow-up ; $24.1{\pm}11.2$ months). FVC increased by $20.2{\pm}11.2%$ of predicted value and the extent of ground glass opacity on HRCT decreased significantly ($15.7{\pm}14.7%$). 4) Of the 14 patients who had stopped medication, 5 showed recurrence of NSIP and 2 became aggravated during steroid tapering. All patients with recurrence showed deterioration within one year after completion of initial treatment. Conclusion : Since idiopathic NSIP has unique clinical profiles and shows good prognosis, diagnosis different from UIP, and aggressive medical treatment are needed.

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