Glioblastoma multiforme (GBM) is one of the most common brain malignancies and has a very poor prognosis. Recent evidence suggests that the presence of cancer stem cells (CSC) in GBM and the rare CSC subpopulation that is resistant to chemotherapy may be responsible for the treatment failure and unfavorable prognosis of GBM. A garlic-derived compound, Z-ajoene, has shown a range of biological activities, including anti-proliferative effects on several cancers. Here, we demonstrated for the first time that Z-ajoene specifically inhibits the growth of the GBM CSC population. CSC sphere-forming inhibition was achieved at a concentration that did not exhibit a cytotoxic effect in regular cell culture conditions. The specificity of this inhibitory effect on the CSC population was confirmed by detecting CSC cell surface marker CD133 expression and biochemical marker ALDH activity. In addition, stem cell-related mRNA profiling and real-time PCR revealed the differential expression of CSC-specific genes, including Notch, Wnt, and Hedgehog, upon treatment with Z-ajoene. A proteomic approach, i.e., reverse-phase protein array (RPPA) and Western blot analysis, showed decreased SMAD4, p-AKT, 14.3.3 and FOXO3A expression. The protein interaction map (http://string-db.org/) of the identified molecules suggested that the AKT, ERK/p38 and $TGF{\beta}$ signaling pathways are key mediators of Z-ajoene's action, which affects the transcriptional network that includes FOXO3A. These biological and bioinformatic analyses collectively demonstrate that Z-ajoene is a potential candidate for the treatment of GBM by specifically targeting GBM CSCs. We also show how this systemic approach strengthens the identification of new therapeutic agents that target CSCs.
The purpose of this study was to determine the acute pulmonary toxicity of metallic silver nanoparticles (MSNPs, 20.30 nm in diameter). Acute pulmonary toxicity and body distribution of inhaled MSNPs in mice were evaluated using a nose-only exposure chamber (NOEC) system. Bronchoalveolar lavage (BAL) fluid analysis, Western blotting, histopathological changes, and silver burdens in various organs were determined in mice. Mice were exposed to MSNPs for 6 hrs. The mean concentration, total surface area, volume and mass concentrations in the NOEC were maintained at $1.93{\times}10^7$ particles/$cm^3$, $1.09{\times}10^{10}\;nm^2/cm^3$, $2.72{\times}10^{11}\;nm^3/cm^3$, and 2854.62 ${\mu}g/m^3$, respectively. Inhalation of MSPNs caused mild pulmonary toxicity with distribution of silver in various organs but the silver burdens decreased rapidly at 24-hrs post-exposure in the lung. Furthermore, inhaled MSNPs induced activation of mitogen-activated protein kinase (MAPK) signaling in the lung. In summary, single inhaled MSNPs caused mild pulmonary toxicity, which was associated with activated MAPK signaling. Taken together, our results suggest that the inhalation toxicity of MSNPs should be carefully considered at the molecular level.
Plant regeneration system from floral stem of Mymphoides indica via somatic embryogenesis was established. After four weeks of culture onto 1/2MS medium containing 2,4-D, pale-yellow globular structures and calluses were formed on the cut surface of floral stem explants. Upon transfer to 1/2MS basal medium, pale-yellow globular structures were developed into somatic embryos and normal plantlets. These results indicated that pale-yellow globular structures and calluses from floral stem were globular embryos and embryogenic calluses, respectively. The frequency of embryogenic callus formation from floral stem was reached to nearly 100% when floral stem was cultured onto 1/2Ms medium supplemented with low concentration of 2,4-D (0.1 to 0.3 mg/L). However, the higher concentration of 2,4-D resulted in decrease of the frequency of embryogenic callus formation. In this study, low concentration of 2,4-D had a stimulative role in embryogenic callus formation, whereas BA showed inhibitory role in callus formation. In comparison to floral stem, leaf explants showed low frequency of embryogenic callus formation. The highest frequency of embryogenic callus formation from leaf explants was 9.5% when leaf explants were cultured onto 1/2MS medium supplemented with 0.3 mg/L of 2,4-D. The plant regeneration system of Nymphoides indica established in this study, might be applied to mass proliferation, conservation of genetic resources and genetic transformation for molecular breeding.
The application of high pressure on cellular morphology, proliferation and protein expression of Jurkat cells (human T lymphocyte cell line) has been extensively investigated. In the present study, we manufactured a novel pressure chamber that modulates 5% $CO_{2}$, temperature and pressure (up to 3 ATA). Jurkat cells was incubated 2 ATA pressure and analyzed cellular morphology and growth using an electron microscopy and MTT assay. The cells showed the morphological changes in the cell surface, which appeared to cause a severe damage in cell membrane. The growth rate of the cells under 2 ATA pressure decreased as cultured time got increased. Furthermore, a long term exposure of high pressure on Jurkat cells may act as one of the important cellular stresses that leads to inducing cell death. Cellular proteomes were separated by 2-dimensional electrophoresis with pH 3-10 ranges of IPG Dry strips. And many proteins showed significant up-and-down expressions with hyperbaric pressure. Out of all, 10 spots were identified significantly using matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometry. We and found that 9 protein expressions were decreased and one protein, heat shock protein HSP 60, was increased in Jurkat cells under 2 ATA. Identified proteins were related to lipid metabolism and signal transduction.
Oncoplastic surgery (OPS) combines oncologically safe tumor resection with aesthetically satisfying reconstruction of defects using established plastic surgery techniques. OPS is characterized by initial excision as extensive as is beneficial for oncological safety, and, once sufficient resection is complete, displacement or replacement techniques are selected based on remnant volume. The size of the lesion and the individual patient are important factors when considering the appropriate approach, and when pre-operative imaging, including MRI, is used to determine the technique, the complete removal of cancer cells by permanent pathology is essential. A frozen section is used during the operation to reduce the reoperation rate, but it is difficult to cover the entire margin surface theoretically and even harder in practice. A recent report about adequate margins has empowered OPS in its oncological safety. Considering the patients to whom each modality could be applied, basic breast volume is an important factor, and this is influenced by ethnic differences. In Europe or the US, for example, the average breast size is 36D (600 ㎤) and reduction mammoplasty is predominantly used. However, the average size of patients in our institution is 33A (300 ㎤), and so quite different approaches are selected in most cases. New techniques involving radiofrequency and fluorescence have been proposed as safe and easily accessible ways of reducing complications.
Kim, Su-Jeong;Seo, Jeong-Min;Cho, Yun-Woo;Park, Hea-Woon;Lee, Joon-Ha;Hwang, Se-Jin;Ahn, Sang-Ho
The Journal of Korean Physical Therapy
/
v.22
no.3
/
pp.71-77
/
2010
Purpose: To determine whether upregulation of inducible nitric oxide synthase (iNOS) transcription and translation is related to radicular pain in a model of lumbar disc herniation. Also, to investigate the temporal changes of mRNA expression of iNOS and the identity of iNOS and transient receptor potential vanilloid (TRPV) 1 channel expression cells in dorsal root ganglion (DRG) of a model of lumbar disc herniation. Methods: A lumbar disc herniated rat model was developed by implantation of the autologous nucleus pulposus, harvested from the coccygeal vertebra of each tail, on the left L5 nerve root just proximal to the DRG. Rats were tested for mechanical allodynia of the plantar surface of both hind paws 2 days before surgery and 1, 5, 10, 20 and 30 days postoperatively. Reverse transcription polymerase chain reaction (RT-PCR) was used to follow iNOS mRNA expression. To stain iNOS and TRPV1 in DRG, an immunohistochemical study was done 10 days after surgery. Results: A significant drop in mechanical withdrawal threshold on the ipsilateral and contralateral hind paws was observed 1 day after surgery and was prolonged to 30 days in rats with lumbar disc herniation. The expression of mRNA for iNOS peaked at postoperative day 10 on both sides of the DRG. iNOS-positive sensory neurons in the DRG varied in size from large to small diameter cells. A majority of small and intermediate sensory neurons were TRPV1-positive cells. Double immunofluorescence staining for TRPV1 and iNOS revealed that most intermediate TRPV1-positive sensory neurons co-localized with iNOS-positive neurons. Conclusion: Nucleus pulposus-induced mechanical allodynia can be generated without mechanical compression. This pain is related to temporal changes in expression of iNOS mRNA in the DRG. Co-localization of TRPV1 and iNOS in intermediate neurons of the DRG is correlated with pain modality and intensity.
Journal of the Korean Society for Precision Engineering
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v.3
no.1
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pp.40-49
/
1986
Crack, craze and void are common defects which may be found in the bulk of polymeric materials such as either themoplastics or thermosets. The healing phenomena, autohesion, of these defects are known to be a intrinsic material property of various polymeric materials. However, only a few experimental and theoretical investigations on crack, void and craze healing phenomena for various polymeric materials have been reported up to date [1, 2, 3]. This may be partly due to the complications of healing processes and lacking of appropriate theoretical developments. Recently, some investigators have been urged to study the healing phenomena of various polymenic materials since the significance of the use of polymer based alloys or composites has been raised in terms of specific strength and energy saving. In the earlier published reports [1, 2, 3, 4], the crack and void healing velocity, healing toughness and some other healing mechanical and physical properties were measured experimentally and compared with predicted values by utilizing a simple model such as the reptation model under some resonable assumptions. It seems, however, that the general acceptance of the proposed modeling analyses is yet open question. The crack healing processes seem to be complicate and highly dependent on the state of virgin material in terms of mechanical and physical properties. Furthermore, it is also strongly dependent on the histories of crack, craze and void development including fracture suface morphology, the shape of void and the degree of disentanglement of fibril in the craze. The rate of crack healing may be a function of environmental factors such as healing temperature, time and pressure which gives different contact configurations between two separated surfaces. It seems to be reasonable to assume that the crack healing processes may be divided in several distinguished steps like stress relaxation with molecular chain arrangement, surface contact (wetting), inter- diffusion process and com;oete healing (to obtain the original strength). In this context, it is likely that we no longer have to accept the limitation of cumulative damage theories and fatigue life if it is probable to remove the defects such as crack, craze and void and to restore the original strength of polymers or polymer based compowites by suitable choice of healing histories and methods. In this paper, we wish to present a very simple and intuitive theoretical model for the prediction of healed fracture toughness of cracked or defective polymeric components. The central idea of this investigation, thus, may be the modeling of behavior of chain molecules under healing conditions including the effects of chain scission on the healing processes. The validity of this proposed model will be studied by making comparisons between theoretically predicted values and experimentally determined results in near future and will be reported elsewhere.
Kim, Myung-Chan;Heo, Cheol-Ho;Park, Jin-Hyo;Park, Seung-Jun;Han, Jeon-Geon
Proceedings of the Korean Vacuum Society Conference
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1999.07a
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pp.122-122
/
1999
Graphite with its advantages of high thermal conductivity, low thermal expansion coefficient, and low elasticity, has been widely used as a structural material for high temperature. However, graphite can easily react with oxygen at even low temperature as 40$0^{\circ}C$, resulting in CO2 formation. In order to apply the graphite to high temperature structural material, therefore, it is necessary to improve its oxidation resistive property. Silicon Carbide (SiC) is a semiconductor material for high-temperature, radiation-resistant, and high power/high frequency electronic devices due to its excellent properties. Conventional chemical vapor deposited SiC films has also been widely used as a coating materials for structural applications because of its outstanding properties such as high thermal conductivity, high microhardness, good chemical resistant for oxidation. Therefore, SiC with similar thermal expansion coefficient as graphite is recently considered to be a g행 candidate material for protective coating operating at high temperature, corrosive, and high-wear environments. Due to large lattice mismatch (~50%), however, it was very difficult to grow thick SiC layer on graphite surface. In theis study, we have deposited thick SiC thin films on graphite substrates at temperature range of 700-85$0^{\circ}C$ using single molecular precursors by both thermal MOCVD and PEMOCVD methods for oxidation protection wear and tribological coating . Two organosilicon compounds such as diethylmethylsilane (EDMS), (Et)2SiH(CH3), and hexamethyldisilane (HMDS),(CH3)Si-Si(CH3)3, were utilized as single source precursors, and hydrogen and Ar were used as a bubbler and carrier gas. Polycrystalline cubic SiC protective layers in [110] direction were successfully grown on graphite substrates at temperature as low as 80$0^{\circ}C$ from HMDS by PEMOCVD. In the case of thermal MOCVD, on the other hand, only amorphous SiC layers were obtained with either HMDS or DMS at 85$0^{\circ}C$. We compared the difference of crystal quality and physical properties of the PEMOCVD was highly effective process in improving the characteristics of the a SiC protective layers grown by thermal MOCVD and PEMOCVD method and confirmed that PEMOCVD was highly effective process in improving the characteristics of the SiC layer properties compared to those grown by thermal MOCVD. The as-grown samples were characterized in situ with OES and RGA and ex situ with XRD, XPS, and SEM. The mechanical and oxidation-resistant properties have been checked. The optimum SiC film was obtained at 85$0^{\circ}C$ and RF power of 200W. The maximum deposition rate and microhardness are 2$mu extrm{m}$/h and 4,336kg/mm2 Hv, respectively. The hardness was strongly influenced with the stoichiometry of SiC protective layers.
Kim, Jong-Hee;Bae, Ju-Hyeon;Lee, Yong-Seop;Kim, Sang-Dal
한국지구과학회:학술대회논문집
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2004.02a
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pp.2-12
/
2004
The purpose for this study is to inquire into the effects of teaching methods in the class on the conceptual change of atmospheric pressure for middle school students. After analyzing the concept of atmospheric pressure in the middle school science textbooks on the present 7th Curriculum, classes were performed adopting classified Method A and Method B. For Method A, the textbook used that explains the concept in the view of weight. For Method B, the textbook used approaching to the concept in the views of molecular movement as well as of weight. This study consists of four classes in the third grade students of middle school in Busan, which were divided into the Method A group and the Method B group. The result of the study carried out pre-post each of these classes on the learning achievement and on the conceptual change of atmospheric pressure. The result of this study were as follows: First, the effect on the learning achievement was displayed the average score of the Method B was showing meaningful difference comparing to the Method A. Second, the effect on the conceptual change measured by verifying the score for the difference among the averages for each sub-scale three out of four conceptual factors, 'the direction of atmospheric influence and the reason', 'the principle of atmospheric action' and 'the atmospheric changes by the temperature rise on the surface of the earth and the reason', showed meaningful improvement. But, the one left factor, 'the distribution of atmospheric pressure by altitudes and the reason', displayed no meaningful difference. Third, The concept of atmospheric pressure is better defined as the pressure created by the movement of air particles, in the view of kinetic theory of gas, rather than explained by the notion of the weight of air.
Park, Sang-Joong;Ryu, Kang;Suh, Chang-Woo;Chai, Young-Gyu;Kwon, Oh-Byung;Park, Seung-Kook;Lee, Eun-Kyu
KSBB Journal
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v.17
no.2
/
pp.153-157
/
2002
A fusion protein, consisting of a human epidermal growth factor as the recognition domain and human angiogenin as the toxin domain, can be used as a targeted therapeutic against breast cancer cells among others. The fusion protein was expressed as an inclusion body in recombinant E. coli, yet when the conventional solution-phase refolding process was used the refolding yield was very low due to severe aggregation, probably because of the opposite surface charge resulting from the vastly different pl values of each domain. Accordingly the solid-phase refolding process, which exploits the ionic interactions between a solid matrix and the protein, was tried, however the ionic binding yield was also very low regardless of the resins and pH conditions used. Therefore, to provide a higher affinity toward the solid matrix, six Iysine residues were tagged to the N-terminus of the hEGF domain. When cation exchange resins, such as heparin- or CM-Sepharose, were used as the matrix, the adsorption capacity increased 2.5~3-fold and the subsequent refolding yield increased nearly 15-fold compared to the conventional process. A similat result was also obtained when an Ni-NTA metal affinity resin was used.
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