• Journal of Embryo Transfer
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• v.30 no.3
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• pp.249-255
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• 2015

Diabetes mellitus, the most common metabolic disorder, is divided into two types: type 1 and type 2. The essential treatment of type 1 diabetes, caused by immune-mediated destruction of ${\beta}-cells$, is transplantation of the pancreas; however, this treatment is limited by issues such as the lack of donors for islet transplantation and immune rejection. As an alternative approach, stem cell therapy has been used as a new tool. The present study revealed that bone marrowderived mesenchymal stromal cells (BM-MSCs) could be transdifferentiated into pancreatic cells by the insertion of a key gene for embryonic development of the pancreas, the pancreatic and duodenal homeobox factor 1 (PDX1). To avoid immune rejection associated with xenotransplantation and to develop a new cell-based treatment, BM-MSCs from ${\alpha}$-1,3-galactosyltransferase knockout (GalT KO) pigs were used as the source of the cells. Transfection of the EGFP-hPDX1 gene into GalT KO pig-derived BM-MSCs was performed by electroporation. Cells were evaluated for hPDX1 expression by immunofluorescence and RT-PCR. Transdifferentiation into pancreatic cells was confirmed by morphological transformation, immunofluorescence, and endogenous pPDX1 gene expression. At 3~4 weeks after transduction, cell morphology changed from spindle-like shape to round shape, similar to that observed in cuboidal epithelium expressing EGFP. Results of RT-PCR confirmed the expression of both exogenous hPDX1 and endogenous pPDX1. Therefore, GalT KO pig-derived BM-MSCs transdifferentiated into pancreatic cells by transfection of hPDX1. The present results are indicative of the therapeutic potential of PDX1-expressing GalT KO pig-derived BM-MSCs in ${\beta}-cell$ replacement. This potential needs to be explored further by using in vivo studies to confirm these findings.

• Genomics & Informatics
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• v.18 no.1
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• pp.3.1-3.8
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• 2020

Patient-derived xenograft (PDX) mouse models are frequently used to test the drug efficacy in diverse types of cancer. They are known to recapitulate the patient characteristics faithfully, but a systematic survey with a large number of cases is yet missing in lung cancer. Here we report the comparison of genomic characters between mouse and patient tumor tissues in lung cancer based on exome sequencing data. We established PDX mouse models for 132 lung cancer patients and performed whole exome sequencing for trio samples of tumor-normal-xenograft tissues. Then we computed the somatic mutations and copy number variations, which were used to compare the PDX and patient tumor tissues. Genomic and histological conclusions for validity of PDX models agreed in most cases, but we observed eight (~7%) discordant cases. We further examined the changes in mutations and copy number alterations in PDX model production and passage processes, which highlighted the clonal evolution in PDX mouse models. Our study shows that the genomic characterization plays complementary roles to the histological examination in cancer studies utilizing PDX mouse models.

• Genomics & Informatics
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• v.18 no.1
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• pp.6.1-6.9
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• 2020

Acute leukemia represents the most common pediatric malignancy comprising diverse subtypes with varying prognosis and treatment outcomes. New and targeted treatment options are warranted for this disease. Patient-derived xenograft (PDX) models are increasingly being used for preclinical testing of novel treatment modalities. A novel approach involving targeted error-corrected RNA sequencing using ArcherDX HemeV2 kit was employed to compare 25 primary pediatric acute leukemia samples and their corresponding PDX samples. A comparison of the primary samples and PDX samples revealed a high concordance between single nucleotide variants and gene fusions whereas other complex structural variants were not as consistent. The presence of gene fusions representing the major driver mutations at similar allelic frequencies in PDX samples compared to primary samples and over multiple passages confirms the utility of PDX models for preclinical drug testing. Characterization and tracking of these novel cryptic fusions and exonal variants in PDX models is critical in assessing response to potential new therapies.

• Journal of dental hygiene science
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• v.23 no.4
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• pp.343-350
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• 2023

Background: Digital panoramic dental X-ray equipment (PDX) is frequently used by patients and dental workers for diagnosis and examination in dental institutions; however, infection control has not been properly implemented. Therefore, in this study, we aimed to systematically review the potential risk of cross-infection in the dental environment by investigating the contamination level of general aerobic bacteria and Staphylococcus aureus, which are important in hospital infections, in PDX areas that people mainly contact. Methods: This survey was conducted from March to May 2023 and covered one general hospital, three dental hospitals, and nine dental clinics equipped with PDX. Bacteria samples were collected from the left-handle, right-handle, forehead support, and head side support as the patient's contact areas, as well as the X-ray exposure switch and left-click mouse button as the dental hygienist's contact areas of the PDX. The collected bacteria were spread on Petrifilm, and colonies formed after 48 hours of culture were counted. Results: General aerobic bacteria and S. aureus were detected in all areas investigated. Significant differences in bacterial counts between different regions of the PDX were observed in both groups (p<0.001). The detection rates of general aerobic bacteria (p<0.001) and S. aureus (p<0.001) were significantly higher in the contact areas of patients than those of dental hygienists. A positive correlation was observed between the forehead and the temple region in terms of general aerobic bacteria and S. aureus detection (r=1) (p<0.01). Conclusion: Taken together, the presence of many bacteria, including S. aureus, detected in PDX indicates that PDX has a potential cross-infection risk. Our results therefore highlight the need for the development of appropriate disinfection protocols for reusable medical devices such as PDX and periodic infection prevention training for hospital-related workers, including dental hygienists.

• Applied Chemistry for Engineering
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• v.16 no.4
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• pp.581-587
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• 2005

In order to obtain a highly purified p-dioxanone (PDX) as monomer of biodegradable polymer, suitable solvent must be selected. The selection was based on the solubility of impurities, and partial layer melt crystallization were carried out under the presence of solvent. The solubility of PDX in various solvents such as ethyl acetate, tetrahydrofuran, acetone, alcohols (methanol, ethanol, 1-propanol, 1-butanol and 1-pentanol) were measured over the temperature range of $-10{\sim}15^{\circ}C$. As solubility parameters, the mixing and dissolution enthalpy between the PDX and the solvents was studied based on empirical equations and the regular solution theory. The solubility and the temperature dependency of the solubility with the solvents of acetone, ethylacetate, and tetrahydrofuran of PDX were shown to have relatively high values compared to the alcohol type solvents. Also, in same alcohols, the smaller molecules and higher polarity gave higher solvency. In partial layer melt crystallization, small amount of ethylacetate selectively dissolved impurities and gave highly purified p-dioxanone, over 99.9% purity.

• Journal of Gastric Cancer
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• v.20 no.1
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• pp.60-71
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• 2020

Purpose: The utility of 18-fluordesoxyglucose positron emission tomography ([¹⁸F]-FDG-PET) combined with computer tomography or magnetic resonance imaging (MRI) in gastric cancer remains controversial and a rationale for patient selection is desired. This study aims to establish a preclinical patient-derived xenograft (PDX) based [¹⁸F]-FDG-PET/MRI protocol for gastric cancer and compare different PDX models regarding tumor growth and FDG uptake. Materials and Methods: Female BALB/c nu/nu mice were implanted orthotopically and subcutaneously with gastric cancer PDX. [¹⁸F]-FDG-PET/MRI scanning protocol evaluation included different tumor sizes, FDG doses, scanning intervals, and organ-specific uptake. FDG avidity of similar PDX cases were compared between ortho- and heterotopic tumor implantation methods. Microscopic and immunohistochemical investigations were performed to confirm tumor growth and correlate the glycolysis markers glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) with FDG uptake. Results: Organ-specific uptake analysis showed specific FDG avidity of the tumor tissue. Standard scanning protocol was determined to include 150 μCi FDG injection dose and scanning after one hour. Comparison of heterotopic and orthotopic implanted mice revealed a long growth interval for orthotopic models with a high uptake in similar PDX tissues. The H-score of GLUT1 and HK2 expression in tumor cells correlated with the measured maximal standardized uptake value values (GLUT1: Pearson r=0.743, P=0.009; HK2: Pearson r=0.605, P=0.049). Conclusions: This preclinical gastric cancer PDX based [¹⁸F]-FDG-PET/MRI protocol reveals tumor specific FDG uptake and shows correlation to glucose metabolic proteins. Our findings provide a PET/MRI PDX model that can be applicable for translational gastric cancer research.

• Molecules and Cells
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• v.41 no.12
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• pp.1033-1044
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• 2018

As sessile organisms, plants have evolved to adjust their growth and development to environmental changes. It has been well documented that the crosstalk between different plant hormones plays important roles in the coordination of growth and development of the plant. Here, we describe a novel recessive mutant, mildly insensitive to ethylene (mine), which displayed insensitivity to the ethylene precursor, ACC (1-aminocyclopropane-1-carboxylic acid), in the root under the dark-grown conditions. By contrast, mine roots exhibited a normal growth response to exogenous IAA (indole-3-acetic acid). Thus, it appears that the growth responses of mine to ACC and IAA resemble those of weak ethylene insensitive (wei) mutants. To understand the molecular events underlying the crosstalk between ethylene and auxin in the root, we identified the MINE locus and found that the MINE gene encodes the pyridoxine 5′-phosphate (PNP)/pyridoxamine 5′-phosphate (PMP) oxidase, PDX3. Our results revealed that MINE/PDX3 likely plays a role in the conversion of the auxin precursor tryptophan to indole-3-pyruvic acid in the auxin biosynthesis pathway, in which TAA1 (TRYPTOPHAN AMINOTRANSFERASE OF ARABIDOPSIS 1) and its related genes (TRYPTOPHAN AMINOTRANSFERASE RELATED 1 and 2; TAR1 and TAR2) are involved. Considering that TAA1 and TARs belong to a subgroup of PLP (pyridoxal-5′-phosphate)-dependent enzymes, we propose that PLP produced by MINE/PDX3 acts as a cofactor in TAA1/TAR-dependent auxin biosynthesis induced by ethylene, which in turn influences the crosstalk between ethylene and auxin in the Arabidopsis root.

• Korean Journal of Food Science and Technology
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• v.39 no.6
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• pp.701-707
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• 2007

Anti-diabetic effect of Platycodi radix (PR) extract fractions was determined if vitro by investigating insulin-like action, insulin sensitizing action, glucose-stimulated insulin secretion, gene expression related to ${\beta}-cell$ function and mass, and ${\alpha}$-glucoamylase suppressing action. Insulin-like activity was not promoted by the treatment of PR methanol factions in 373-L1 fibroblast. However, treatment with 0, 20 and 100% PR methanol fractions along with 1 ng/mL insulin increased insulin-stimulated glucose uptake in 373-L1 adipocytes. In addition, the treatment of 0% and 100% methanol fractions along with differentiation inducers significantly increased the differentiation of 373-L1 fibroblasts to adipocytes. These fractions may contain insulin sensitizer. The 20%, 80% and 100% methanol fractions enhanced glucose-stimulated insulin secretion in Min6 cells, insulin secreting cell line. This was related to the mechanism to promote glucose sensing and ${\beta}-cell$ proliferation, which was regulated by the induction of IRS-2, glucokinase and PDX-1 genes. As expected, 20, 80 and 100% methanol fractions increased mRNA levels of IRS-2, glucokinase and PDX-1 genes. However, PR fractions did not affect the ${\alpha}-glucoamylase$ activity in vitro. These data suggested that PR extract fractions have anti-diabetic actions through improving insulin sensitization, glucose-stimulated insulin secretion, and ${\beta}-cell$ proliferation. Therefore, PR extracts can be beneficial for anti-diabetic treatment in lean diabetic patients.

• Korean Chemical Engineering Research
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• v.43 no.5
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• pp.595-602
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• 2005

In order to purify diethylene glycol as main impurity included in p-dioxanone, SLE (solid-liquid equilibria) and mixture density on two components system of p-dioxanone and diethylene glycol were measured and a layered melt crystallization with seed has been applied. The SLE of p-dioxanone and diethylene glycol were a simple eutectic system and the temperature and PDX concentration at eutectic point were 0.08 and 246 K, respectively. Densities of their binary mixtures were well fitted by the best correlation equation, ${\rho}_l=0.405+1.361x+0.002T-0.004xT$. In the melt crystallization, the growth rate (G) was proportional to the 1.5th power of the subcooling degree. The effective distribution coefficient ($K_{eff}$) as the degree of impurity removal was observed to increase with increasing the growth rate and initial p-dioxanone concentration. And also, $K_{eff}$ was correlated with Z function using Wintermantel's model such as $K_{eef}=-0.0604+6.392{\times}Z$. Finally, PDX purity through the optimization of this process can be obtained over 99%.

• Journal of the Chungcheong Mathematical Society
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• v.31 no.2
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• pp.231-237
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• 2018

Hardy's inequality is refined non-trivially as the form $${\int_{0}^{{\infty}}}\{{\frac{1}{x}}{\int_{0}^{x}}f(t)dt\}^pdx{\leq}Q_f{\times}({\frac{p}{p-1}})^p{\int_{0}^{x}}f^p(x)dx$$ for some $Q_f:0{\leq}Q_f{\leq}1$. $P{\acute{o}}lya$-Knopp's inequality is also refined by the similar form.