• Anatomy & Biological Anthropology
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• v.26 no.1
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• pp.41-49
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• 2013

Dental epithelial and mesenchymal cells that form the teeth undergo dynamic changes in cell cycle during tooth development and morphogenesis. Although proliferation has been known as a key event during odontogenesis, the cell cycle phases and their relations with the complicated molecular mechanisms of tooth development are not fully understood yet. This study comparatively examined the expression patterns of Ki-67, cyclin A, and cyclin D1 during tooth development in the mouse incisor and molar in order to identify the cell-cycle characteristics during odontogenesis. We found that Ki-67 and cyclin A were expressed in the proliferating cells in the dental epithelial and mesenchymal tissues at the bud, cap and bell stages. Cycln D1 showed distinct expression in the incisor odontoblast region and the enamel knot, in which Ki-67 nor cyclin A was expressed. Our results provide specific information on the cell cycle phases during tooth development that may provide clues to relate them with the complex odontogenic mechanisms. Furthermore, we suggest that our findings enlightened the previous studies on the incisor odontoblasts and the enamel knot during tooth development.

• Polymer(Korea)
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• v.38 no.1
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• pp.43-48
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• 2014

In this paper, we made a new polycationic polymeric liposome composed of low molecular weight polyethylenimine (PEI) and 10,12-pentacosadiynoic acid (PCDA). PCDA liposome was prepared by ultraviolet irradiation. PEI was further conjugated on the surface of the polymerized PCDA liposome using coupling reagents to make PCDA-PEI. The blue-to-red transition of PCDA liposome was observed during the coupling reaction. The size distribution of liposome and complexes with plasmid DNA was measured by dynamic light scattering (DLS). The complex formation was also identified by agarose gel electrophoresis and PicoGreen reagent assay. We confirmed the complex formation of the polymeric liposome with DNA and then performed transfection and cytotoxicity assay in HEK 293 and HeLa cells. As a result, PCDA-PEI showed significant gene transfection efficiency and low cytotoxicity. This study shows that PEI-conjugated PCDA liposome could be an efficient gene or drug delivery carrier.

• Journal of Life Science
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• v.33 no.1
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• pp.102-113
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• 2023

This review discusses the cellular and molecular mechanisms by which the endometrial estrogen and progesterone receptors regulate local estrogen production, expression of the specific estrogen receptors, progesterone resistance, inflammatory responses and the differentiation and survival of endometriotic cells in endometrial inflammation. The epigenetic aberrations of endometrial stromal cells play an important role in the pathogenesis and progression of endometriosis. In particular, differential methylation of the estrogen receptor genes changes in the stromal cells the dominancy of estrogen receptor from ERα into ERβ, and results in the abnormal estrogen responses including inflammation, progesterone resistance and the disturbance of retinoid synthesis. These stromal cells also stimulate local estrogen production in response to PGE2 and the SF-1 mediated induction of steroidogenic enzyme expression, and the increased estradiol then feeds back into the ERβ to repeat the vicious inflammatory cycle through the activation of COX-2. In addition, high levels of ERβ expression may also change the chromatin structure of endometrial mesenchymal stem cells, and together with the repeated menstrual cycles can induce formation of the endometriotic tissue. The cascade of these serial events then leads to cell adhesion, angiogenesis and survival of the differentiation-disregulated stromal cells through the action of inflammatory factors such as ERβ-mediated estrogen, TNF-α and TGF-β1. Therefore, understanding of the dynamic hormonal changes during the menstrual cycle and the corresponding signal transduction mechanisms of the related nuclear receptors in endometrium would provide new insights for treating inflammatory diseases such as the endometriosis.

• Molecules and Cells
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• v.46 no.10
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• pp.592-610
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• 2023

The Hippo kinase cascade functions as a central hub that relays input from the "outside world" of the cell and translates it into specific cellular responses by regulating the activity of Yes-associated protein 1 (YAP1). How Hippo translates input from the extracellular signals into specific intracellular responses remains unclear. Here, we show that transforming growth factor β (TGFβ)-activated TAK1 activates LATS1/2, which then phosphorylates YAP1. Phosphorylated YAP1 (p-YAP1) associates with RUNX3, but not with TEAD4, to form a TGFβ-stimulated restriction (R)-point-associated complex which activates target chromatin loci in the nucleus. Soon after, p-YAP1 is exported to the cytoplasm. Attenuation of TGFβ signaling results in re-localization of unphosphorylated YAP1 to the nucleus, where it forms a YAP1/TEAD4/SMAD3/AP1/p300 complex. The TGFβ-stimulated spatiotemporal dynamics of YAP1 are abrogated in many cancer cells. These results identify a new pathway that integrates TGFβ signals and the Hippo pathway (TGFβ→TAK1→LATS1/2→YAP1 cascade) with a novel dynamic nuclear role for p-YAP1.

• Analytical Science and Technology
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• v.7 no.2
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• pp.213-224
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• 1994

Several isotopomers of cyclooctanone were prepared by selective deuterium substitution. Intrinsic isotope effects on $^{13}C$ NMR chemical shifts of these isotopomers were investigated systematically at low temperature. These istope effects were discussed in relation to the preferred boat-chair conformation of cyclooctanone. Deuterium isotope effects on NMR chemical shifts have been known for a long time. Especially in a conformationally mobile molecule, isotope perturbation could affect NMR signals through a combination of isotope effects on equilibria and intrinsic effects. The distinction between intrinsic and nonintrinsic effects is quite difficult at ambient temperature due to involvement of both equilibrium and intrinsic isotope effects. However if equilibria between possible conformers of cyclooctanone are slowed down enough on the NMR time scale by lowering temperature, it should be possible to measure intrinsic isotope shifts from the separated signals at low temperature. $^{13}C$ NMR has been successfully utilized in the study on molecular conformation in solution when one deals with stable conformers or molecules were rapid interconversion occurs at ambient temperature. The study of dynamic processes in general requires analysis of spectra at several temperature. Anet et al. did $^1H$ NMR study of cyclooctanone at low temperature to freeze out a stable conformation, but were not able initially to deduce which conformation was stable because of the complexity of alkyl region in the $^1H$ NMR spectrum. They also reported the $^1H$ and $^{13}C$ NMR spectra of the $C_9-C_{16}$ cycloalkanones with changing temperature from $-80^{\circ}C$ to $-170^{\circ}C$, but they did not report a variable temperature $^{13}C$ NMR study of cyclooctanone. For the analysis of the intrinsic isotope effect with relation to cylooctanone conformation, $^{13}C$ NMR spectra are obtained in the present work at low temperatures (up to $-150^{\circ}C$) in order to find the chemical shifts at the temperature at which the dynamic process can be "frozen-out" on the NMR time scale and cyclooctanone can be observed as a stable conformation. Both the ring inversion and pseudorotational processes must be "frozen-out" in order to see separate resonances for all eight carbons in cyclooctanone. In contrast to $^1H$ spectra, slowing down just the ring inversion process has no apparent effects on the $^{13}C$ spectra because exchange of environments within the pairs of methylene carbons can still occur by the pseudorotational process. Several isotopomers of cyclooctanone were prepared by selective deuterium substitution (fig. 1) : complete deuterium labeling at C-2 and C-8 positions gave cyclooctanone-2, 2, 8, $8-D_4$ : complete labeling at C-2 and C-7 positions afforded the 2, 2, 7, $7-D_4$ isotopomer : di-deuteration at C-3 gave the 3, $3-D_2$ isotopomer : mono-deuteration provided cyclooctanone-2-D, 4-D and 5-D isotopomers : and partial deuteration on the C-2 and C-8 position, with a chiral and difunctional case catalyst, gave the trans-2, $8-D_2$ isotopomer. These isotopomer were investigated systematically in relation with cyclooctanone conformation and intrinsic isotope effects on $^{13}C$ NMR chemical shifts at low temperature. The determination of the intrinsic effects could help in the analysis of the more complex effects at higher temperature. For quantitative analysis of intrinsic isotope effects, the $^{13}C$ NMR spectrum has been obtained for a mixture of the labeled and unlabeled compounds because the signal separations are very small.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.4
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• pp.317-325
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• 2007

Purpose: Biological parameters can be quantified using dynamic PET data with compartment modeling and Nonlinear Least Square (NLS) estimation. However, the generation of parametric images using the NLS is not appropriate because of the initial value problem and excessive computation time. In irreversible model, Patlak graphical analysis (PGA) has been commonly used as an alternative to the NLS method. In PGA, however, the start time ($t^*$, time where linear phase starts) has to be determined. In this study, we suggest a new Multiple Linear Analysis for irreversible radiotracer (MLAIR) to estimate fluoride bone influx rate (Ki). Methods: $[^{18}F]Fluoride$ dynamic PET scans was acquired for 60 min in three normal mini-pigs. The plasma input curve was derived using blood sampling from the femoral artery. Tissue time-activity curves were measured by drawing region of interests (ROls) on the femur head, vertebra, and muscle. Parametric images of Ki were generated using MLAIR and PGA methods. Result: In ROI analysis, estimated Ki values using MLAIR and PGA method was slightly higher than those of NLS, but the results of MLAIR and PGA were equivalent. Patlak slopes (Ki) were changed with different $t^*$ in low uptake region. Compared with PGA, the quality of parametric image was considerably improved using new method. Conclusion: The results showed that the MLAIR was efficient and robust method for the generation of Ki parametric image from $[^{18}F]Fluoride$ PET. It will be also a good alternative to PGA for the radiotracers with irreversible three compartment model.

• Ultrasonography
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• v.32 no.1
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• pp.59-65
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• 2013

Purpose: The purpose of this study is to establish the methodology regarding synthesis of ultrasound contrast agent imaging, and to evaluate the characteristics of the synthesized ultrasound contrast agents, including size or degradation interval and image quality. Materials and Methods: The ultrasound contrast agent, composed of liposome and SF6, was synthesized from the mixture solution of $21{\mu}mol$ DPPC (1, 2-Dihexadecanoyl-sn-glycero-3-phosphocholine, $C_{40}H_{80}NO_8P$), $9{\mu}mol$ cholesterol, $1.9{\mu}mol$ of DCP (Dihexadecylphosphate, $[CH_3(CH_2)_{15}O]_2P(O)OH$), and chloroform. After evaporation in a warm water bath and drying during a period of 12-24 hours, the contrast agent was synthesized by the sonication process by addition of buffer and SF6 gas. The size of the contrast agent was controlled by use of either extruder or sonication methods. After synthesis of contrast agents, analysis of the size distribution of the bubbles was performed using dynamic light scattering measurement methods. The degradation curve was also evaluated by changes in the number of contrast agents via light microscopy immediate, 12 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, and 84 hours after synthesis. For evaluation of the role as an US contrast agent, the echogenicity of the synthesized microbubble was compared with commercially available microbubbles (SonoVue, Bracco, Milan, Italy) using a clinical ultrasound machine and phantom. Results: The contrast agents were synthesized successfully using an evaporation-drying-sonication method. The majority of bubbles showed a mean size of 154.2 nanometers, and they showed marked degradation 24 hours after synthesis. ANOVA test revealed a significant difference among SonoVue, synthesized contrast agent, and saline (p < 0.001). Although no significant difference was observed between SonoVue and the synthesized contrast agent, difference in echogenicity was observed between synthesized contrast agent and saline (p < 0.01). Conclusion: We could synthesize ultrasound contrast agents using an evaporation-drying-sonication method. On the basis of these results, many prospective types of research, such as anticancer drug delivery, gene delivery, including siRNA or microRNA, targeted molecular imaging, and targeted therapy can be performed.

• Investigative Magnetic Resonance Imaging
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• v.18 no.3
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• pp.208-218
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• 2014

Purpose : To evaluate the relationship between the speed of enhancement of hepatic hemangiomas on gadolinium-enhanced MRI and ADC values by using various parameters, including the D, f, $D^*$ and $ADC_{fit}$ on intravoxel incoherent motion (IVIM) MR Imaging. Materials and Methods: The institutional review board approved this retrospective study. A total of 47 hepatic hemangiomas from 39 patients were included (20 men and 19 women). The hemangiomas were classified into three types according to the enhancement speed of the hepatic hemangiomas on gadolinium-enhanced dynamic T1-weighted images: rapid (Type A), intermediate (Type B), and slow (Type C) enhancement. The D, f, $D^*$ and $ADC_{fit}$ values were calculated using IVIM MR imaging. The diffusion/perfusion parameters and ADC values were compared among the three types of hemangiomas. Results: Both the $ADC_{fit}$ and D values of type C were significantly lower than those of type A (P = 0.0022, P = 0.0085). However, for the f and $D^*$, there were no significant differences among the three types. On DWI with all b values (50, 200, 500 and $800sec/mm^2$), the ADC values of type C were significantly lower than those of the type A (P < 0.012). For b values with $800sec/mm^2$, the $ADC_{800}$ values of the type C hemangiomas were significantly lower than those of type B (P = 0.0021). We found a negative correlation between hepatic hemangioma enhancement type and $ADC_{50}$ (${\rho}=-0.357$, P = 0.014), $ADC_{200}$ (${\rho}=-0.537$, P = 0.0001), $ADC_{500}$ (${\rho}=-0.614$, P = 0.0001), and $ADC_{800}$ (${\rho}=-0.607$, P = 0.0001). Therefore, four ADC values of $ADC_{50}$, $ADC_{200}$, $ADC_{500}$, and $ADC_{800}$ were decreased with decreasing enhancement speed. Conclusion: Hepatic hemangiomas had variable ADCs according to the type of enhancement, and the reduced ADCs in slowly enhancing hemangiomas may be related to the reduced pure molecular diffusion (D).

• Korean Journal of Food Science and Technology
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• v.42 no.4
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• pp.424-430
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• 2010

Immuno-modulatory activities of peptides from Asterias amurensis were investigated using a nano-encapsulation process. The molecular weights of the peptides in the range of 5-7 kDa were separated using Sephadex G-75 gel filtration. Eighty-five percent of the nano-particles were in the 300 nm range using dynamic light scattering. The cytotoxicity of the A. amurensis nano-particles against CCD-986sk human dermal fibroblast cells was 11.64% after adding 1.0 mg/mL of the samples, which was lower than that from the control (13.28% collagen). The secretion of $NO^-$ from macrophages was estimated as $40\;{\mu}M$ after adding 1.0 mg/mL of gelatin nano-particles, which was higher than the others. Prostaglandin $E_2$ production from UV-induced human skin cells decreased greatly to 860 pg/mL after adding 1.0 mg/mL of the samples. Confocal microscopy revealed that nano-particles effectively penetrated the cells within 1 hour. From these results, we consider that nano-encapsulation of the peptides from A. amurensis can improve their biological functions.

• Journal of the Korean Society of Radiology
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• v.83 no.1
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• pp.149-161
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• 2022

Purpose To investigate the correlation between computer-aided diagnosis (CAD) parameters in 3-tesla (T) MRI and pathologic immunohistochemical (IHC) markers in invasive carcinoma of no special type (NST). Materials and Methods A total of 94 female who were diagnosed with NST carcinoma and underwent 3T MRI using CAD, from January 2018 to April 2019, were included. The relationship between angiovolume, curve peak, and early and late profiles of dynamic enhancement from CAD with pathologic IHC markers and molecular subtypes were retrospectively investigated using Dwass, Steel, Critchlow-Fligner multiple comparison analysis, and univariate binary logistic regression analysis. Results In NST carcinoma, a higher angiovolume was observed in tumors of higher nuclear and histologic grades and in lymph node (LN) (+), estrogen receptor (ER) (-), progesterone receptor (PR) (-), human epidermal growth factor 2 (HER2) (+), and Ki-67 (+) tumors. A high rate of delayed washout and a low rate of delayed persistence were observed in Ki-67 (+) tumors. In the binary logistic regression analysis of NST carcinoma, a high angiovolume was significantly associated with a high nuclear and histologic grade, LN (+), ER (-), PR (-), HER2 (+) status, and non-luminal subtypes. A high rate of washout and a low rate of persistence were also significantly correlated with the Ki-67 (+) status. Conclusion Angiovolume and delayed washout/persistent rate from CAD parameters in contrast enhanced breast MRI correlated with predictive IHC markers. These results suggest that CAD parameters could be used as clinical prognostic, predictive factors.