• International Journal of Stem Cells
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• v.17 no.1
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• pp.30-37
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• 2024

The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.

• 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.

• Progress in Medical Physics
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• v.31 no.2
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• pp.9-19
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• 2020

Purpose: This study aims to develop a multi-purpose electron beam irradiation device for preclinical research and material testing using the research electron linear accelerator installed at the Dongnam Institute of Radiological and Medical Sciences. Methods: The fabricated irradiation device comprises a dual scattering foil and collimator. The correct scattering foil thickness, in terms of the energy loss and beam profile uniformity, was determined using Monte Carlo calculations. The ion-chamber and radiochromic films were used to determine the reference dose-rate (Gy/s) and beam profiles as functions of the source to surface distance (SSD) and pulse frequency. Results: The dose-rates for the electron beams were evaluated for the range from 59.16 Gy/s to 5.22 cGy/s at SSDs of 40-120 cm, by controlling the pulse frequency. Furthermore, uniform dose distributions in the electron fields were achieved up to approximately 10 cm in diameter. An empirical formula for the systematic dose-rate calculation for the irradiation system was established using the measured data. Conclusions: A wide dose-rate range electron beam irradiation device was successfully developed in this study. The pre-clinical studies relating to FLASH radiotherapy to the conventional level were made available. Additionally, material studies were made available using a quantified irradiation system. Future studies are required to improve the energy, dose-rate, and field uniformity of the irradiation system.

• Journal of Chest Surgery
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• v.47 no.4
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• pp.333-343
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• 2014

Background: A preclinical study was conducted for evaluating a valved conduit manufactured with a glutaraldehyde (GA)-fixed bovine pericardium treated using an anticalcification protocol. Methods: Bovine pericardia were decellularized, fixed with GA in an organic solvent, and detoxified. We prepared a valved conduit using these bovine pericardia and a specially designed mold. The valved conduit was placed under in vitro circulation by using a mock circulation model, and the durability under mechanical stress was evaluated for 2 months. The valved conduit was implanted into the right ventricular outflow tract of a goat, and the hemodynamic, radiologic, histopathologic, and biochemical results were obtained for 6 months after the implantation. Results: The in vitro mock circulation demonstrated that valve motion was good and that the valved conduit had good gross and microscopic findings. The evaluation of echocardiography and cardiac catheterization demonstrated the good hemodynamic status and function of the pulmonary xenograft valve 6 months after the implantation. According to specimen radiography and a histopathologic examination, the durability of the xenografts was well preserved without calcification at 6 months after the implantation. The calcium and inorganic phosphorus concentrations of the explanted xenografts were low at 6 months after the implantation. Conclusion: This study demonstrated that our synergistic employment of multiple anticalcification therapies has promising safety and efficacy in the future clinical study.

• Proceedings of the Korean Society of Crop Science Conference
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• 2017.06a
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• pp.259-259
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• 2017

Wheat is one of important food crop in the world. However, wheat has some negative things that are allergen. Wheat includes four different allergen kwon as alpha-, beta- and gamma gliadin and amylase inhibitor. Recently, people are interesting to gluten free food or low gliadin food. To study about wheat allergies and research trend is important for future research like as wheat breeding and allergy reduction technology. In this study, we analyzed that the reported on the research field of wheat allergy have been reported until now, and was to provide direction for future research. The analysis of 235 episodes of major papers published from 2007 to 2016. The last 5 years from 2012, wheat allergy appears increasing number of related papers. The ratio of national papers 13% and 60% were published by the United States and other European countries, respectively. The fields of wheat allergen-related preclinical technology and wheat allergen related to genome research for discovery technology were represented high rate by 58% and 26%, respectively. In the case of Korea, significantly account genetic and breeding areas. Recently, however, the research of glutenin protein which is closely linked to wheat allergy is in progress. So, we expected to increase wheat allergy of the research is in the future in Korea.

• Journal of the Korean Society of Radiology
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• v.16 no.5
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• pp.559-565
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• 2022

In this study, we intend to develop a granulation tissue formation model. As a pilot experiment, a contrast agent was injected into the pylorus in 3 rats, the normal pylorus lumen size was confirmed, and a stent was placed. Stent migration was confirmed in to the duodenum within 1 week. In this experiment, stent was sutured and fixed to induce granulation tissue formation after gastrostomy under a fluoroscopic guidance. Twenty rats were divided into Healthy Group / Gastrostomy Group. After anesthesia of the Gastrostomy Group, an abdominal incision was performed, and gastrostomy was performed under a fluoroscopic guidance, and a stent was placed into the pylorus. In order to prevent stent migration due to peristalsis, suture between the pylorus and the proximal end of the stent was performed. Postoperative behavior and weight changes were monitored daily. Four weeks after surgery, gastrointestinal fluoroscopy imaging was performed and rats were sacrifices. To evaluate the degree of granulation formation, the stent was sectioned transversely. Gastrostomy group was statistically significantly higher than Healthy Group in granulation area ratio (all p<.001). In conclusion, it is considered that the level of tissue overgrowth formation for preclinical evaluation of the pylorus stricture model through gastrostomy is appropriate as a research evaluation tool.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.6 no.1
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• pp.20-26
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• 2020

Accelerator mass spectrometry (AMS) is a powerful detection technique with the exquisite sensitivity and high precision compared with other traditional analytical techniques. Accelerator mass spectrometry can be widely applied in the technique of radiocarbon dating in the fields of archeology, geology and oceanography. The ability of accelerator mass spectrometry to measure rare ¹⁴C concentrations in microgram and even sub-microgram amounts suggests that extension of ¹⁴C-accelerator mass spectrometry to biomedical field is a natural and attractive application of the technology. Drug development processes are costly, risky, and time consuming. However, the use of ¹⁴C-accelerator mass spectrometry allows absorption, distribution, metabolism and excretion (ADME) studies easier to understand pharmacokinetics of drug candidates. Over the last few decades, accelerator mass spectrometry and its applications to preclinical/clinical trials have significantly increased. For accelerator mass spectrometry analysis of biological samples, graphitization processes of samples are important. In this paper, we present a detailed sample preparation procedure to apply to graphitization of biological samples for accelerator mass spectrometry.

• Archives of Pharmacal Research
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• v.19 no.6
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• pp.554-558
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• 1996

High-performance liquid chromatographic method was developed for the determination or LB 20304 (compound 1) in the plasma of rats and dogs. The analyte was deproteinized with 1 volume of methanol and 1/2 volume of 10% zinc sulfate, and the supernatant was injected onto a reversed-phase HPLC column. The mobile phase was a mixture of 24 parts of acetonitrile and 76 parts of 0.1% trifluoroacetic acid. The flow rate was 1 ml/min, and the effluent was monitored by fluorescence detector at an excitation wavelength of 337 nm and an emission wavelength of 460 nm. The retention time of compound 1 was 6.3 min. The assay of compound 1 was linear over the concentration range of 0.2-100.mu.g/ml in the plasma of rats and dogs. The lower limit of quantification was 0.2.mu.g/ml using 100.mu.l of plasma with a 97-99% accuracy and a 12-14% precision. In the 0.5, 5, and 50.mu.g/ml quality control samples, the intra- and inter-day accuracy were 88-95% and 88-97%, whereas intra- and interday precision were 0.5-6.6% and 0.2-9.3%, respectively, in the plasma of rats and dogs. The recoveries were 68-71% independent of concentration and species in the plasma. No interferences from endogenous substances were observed. Taken together, the above HPLC assay method by deproteinization and fluorescence detection was suitable for the determination of compound 1 in the preclinical pharmacokinetics.

• BMB Reports
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• v.56 no.3
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• Journal of Korean Dental Science
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• v.16 no.2
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• pp.172-181
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• 2023

Purpose: To investigate the effect of epidermal growth factor (EGF) with collagen matrix (CM) for increasing gingival thickness. Materials and Methods: In five mongrel dogs, bilateral gingival defects were surgically made on the maxillary canines. After two months, either a subepithelial connective tissue graft (group SCTG) or CM with EGF (0.1 ug/ml, group EGF) was grafted, and the flap was coronally positioned to cover the graft materials. The animals were sacrificed after three months. Intraoral scanning was performed for soft tissue analysis. Histologic and histomorphometric analyses were performed. Result: Two animals exhibited wound dehiscence during the healing phase, leaving three for analysis. No statistically significant difference was found in soft tissue changes (P>0.05). The level of gingival margin (GM) increased in both groups (1.02±0.74 mm in group SCTG vs. 1.24±0.83 mm in group EGF). Linear increases at the GM pre-augmentation in the soft tissue profile were 1.08±0.58 mm in group SCTG and 0.96±0.73 mm in group EGF. Histomorphometric parameters (keratinized tissue height, tissue thickness, and rete peg density) were not significantly different between the groups (P>0.05). Conclusion: EGF loaded onto CM led to comparable gingival phenotype enhancement to SCTG.