Upregulated microRNA‐193a‐3p is responsible for cisplatin resistance in CD 44(+) gastric cancer cells

Lee, So D.,Yu, Dayeon,Lee, Do Y.,Shin, Hyun&#x2010,Soo,Jo, Jeong&#x2010,Hyeon,Lee, Yong C. John Wiley and Sons Inc. 2019 Cancer Science Vol.110 No.2

<P>Cisplatin is a well‐known anticancer drug used to treat various cancers. However, development of cisplatin resistance has hindered the efficiency of this drug in cancer treatment. Development of chemoresistance is known to involve many signaling pathways. Recent attention has focused on microRNAs (miRNAs) as potentially important upstream regulators in the development of chemoresistance. CD44 is one of the gastric cancer stem cell markers and plays a role in regulating self‐renewal, tumor initiation, metastasis and chemoresistance. The purpose of the present study was to examine the mechanism of miRNA‐mediated chemoresistance to cisplatin in CD44‐positive gastric cancer stem cells. We sorted gastric cancer cells according to level of CD44 expression by FACS and analyzed their miRNA expression profiles by microarray analysis. We found that miR‐193a‐3p was significantly upregulated in CD44(+) cells compared with CD44(−) cells. Moreover, SRSF2 of miR‐193a‐3p target gene was downregulated in CD44(+) cells. We studied the modulation of Bcl‐X and caspase 9 mRNA splicing by SRSF2 and found that more pro‐apoptotic variants of these genes were generated. We also found that downstream anti‐apoptotic genes such as Bcl‐2 were upregulated, whereas pro‐apoptotic genes such as Bax and cytochrome C were downregulated in CD44(+) cells compared to CD44(−) cells. In addition, we found that an elevated level of miR‐193a‐3p triggered the development of cisplatin resistance in CD44(+) cells. Inhibition of miR‐193a‐3p in CD44(+) cells increased SRSF2 expression and also altered the levels of multiple apoptotic genes. Furthermore, inhibition of miR‐193a‐3p reduced cell viability and increased the number of apoptotic cells. Therefore, miR‐193a‐3p may be implicated in the development of cisplatin resistance through regulation of the mitochondrial apoptosis pathway. miR‐193a‐3p could be a promising target for cancer therapy in cisplatin‐resistant gastric cancer.</P>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.&#x2010,S.,Choi, K.&#x2010,M.,Choi, M.&#x2010,H.,Ji, S.&#x2010,Y.,Lee, S.,Sin, D.&#x2010,M.,Oh, K.&#x2010,W.,Lee, Y.&#x2010,M.,Hong, J.&#x2010,T.,Yun, Y.&#x2010,P.,Yoo, H.&#x2010,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis

Yu, K&#x2010,H.,Hong, K&#x2010,S.,Lee, B&#x2010,C.,Oh, M&#x2010,S.,Cho, Y&#x2010,J.,Koo, J&#x2010,S.,Park, J&#x2010,M.,Bae, H&#x2010,J.,Han, M&#x2010,K.,Ju, Y&#x2010,S.,Kang, D&#x2010,W.,Appelros, P. Blackwell Publishing Ltd 2011 Acta neurologica Scandinavica Vol.123 No.5

<P>Yu K‐H, Hong K‐S, Lee B‐C, Oh M‐S, Cho Y‐J, Koo J‐S, Park J‐M, Bae H‐J, Han M‐K, Ju Y‐S, Kang D‐W, Appelros P, Norrving B, Terent A. Comparison of 90‐day case‐fatality after ischemic stroke between two different stroke outcome registries using propensity score matching analysis. 
Acta Neurol Scand: 2011: 123: 325–331. 
© 2010 John Wiley & Sons A/S.</P><P><B>Background – </B> It has not been clarified whether the disparity in ischemic stroke outcome between populations is caused by ethnic and geographic differences or by variations in case mix. Propensity score matching (PSM) analysis can overcome some analytical problems but is rarely used in stroke outcome research. This study was to compare the ischemic stroke case‐fatality between two PSM cohorts of Sweden and Korea.</P><P><B>Methods – </B> Prognostic variables related to baseline characteristics and stroke care were included in our PSM model. Then, we selected 7675 Swedish and 1220 Korean patients with ischemic stroke from each stroke registers and performed one‐to‐one matching based on propensity scores of each patient.</P><P><B>Results – </B> After PSM, all measured variables were well balanced in 1163 matched subjects, and the 90‐day case‐fatality was identical 6.2% (HR 0.997, 95%CI 0.905–1.099) in Sweden and Korea.</P><P><B>Conclusions – </B> No difference is found in the 90‐day case‐fatality in propensity score‐matched Swedish and Korean patients with ischemic stroke.</P>

Epidermal regeneration by <i>ent</i>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid isolated from <i>Siegesbeckia pubescens</i>

Sung, S.&#x2010,H.,Park, S.&#x2010,H.,Song, S.&#x2010,Y.,Lee, S.&#x2010,J.,Lee, H.&#x2010,W.,Kim, S.&#x2010,H.,A Lee, M.,Yoon, I.&#x2010,S.,Kim, D.&#x2010,D.,Kang, S.,Sung, J.&#x2010,H. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.6

<P><B>Abstract</B></P><P><B>Objectives: </B> Keratinocyte stem/progenitor cells (KSCs) are known to regenerate epidermal tissue which they perform through to their great regenerative capacity.</P><P><B>Materials and methods: </B> Because stimulation of resident KSCs may regenerate epidermal tissue, we devised a strategy to find an appropriate KSC activator from natural products and to develop it as a skin‐rejuvenating agent.</P><P><B>Results: </B> <I>Ent</I>‐16α, 17‐dihydroxy‐kauran‐19‐oic acid (DHK) isolated from <I>Siegesbeckia pubescens</I> exhibited a KSC‐stimulating effect during screening of natural products. DHK increased proliferation and migration of KSCs using the Akt/ERK pathway. We further examined the mechanism of KSC stimulation and found that phosphorylation of Y1068 epithelial growth factor receptor (EGFR) was significantly increased. Functional inhibition of EGFR using neutralizing antibody and a chemical inhibitor, AG1478, attenuated DHK‐induced KSC stimulation. In a 3D culture model of KSCs, DHK treatment significantly induced establishment of fully stratified epidermis and increased numbers of p63‐positive cells. Likewise, DHK treatment significantly accelerated healing of epidermal wounds created by laser and dermatome, and increased p63‐positive cells, in animal models.</P><P><B>Conclusion: </B> Collectively, these results indicate that DHK regenerates epidermal tissue mainly through EGFR phosphorylation. As DHK has diverse advantages over recombinant growth factors for commercialization (that is long‐term stability and skin permeability), DHK might be applied to wound‐healing agents and to a basic materials used in cosmetics.</P>

HLA‐DQB1*05:06, a novel HLA‐DQB1*05 allele identified by sequence‐based typing

Cho, M.&#x2010,C.,Ko, S.&#x2010,Y.,Oh, H.&#x2010,B.,Heo, Y.&#x2010,S.,Kwon, O.&#x2010,J. Blackwell Publishing Ltd 2011 Tissue antigens Vol.77 No.4

<P>The new allele DQB1*05:06 showed one nucleotide difference with DQB1*05:03:01 at codon 40 (TTC/TTG).</P>

Investigation of Optical and Structural Stability of Localized Surface Plasmon Mediated Light‐Emitting Diodes by Ag and Ag/SiO₂ Nanoparticles

Jang, Lee&#x2010,Woon,Jeon, Dae&#x2010,Woo,Kim, Myoung,Jeon, Ju&#x2010,Won,Polyakov, Alexander Y.,Ju, Jin&#x2010,Woo,Lee, Seung&#x2010,Jae,Baek, Jong&#x2010,Hyeob,Yang, Jin&#x2010,Kyu,Lee, In&#x2010,H WILEY‐VCH Verlag 2012 Advanced functional materials Vol.22 No.13

<P><B>Abstract</B></P><P>Localized surface plasmon (LSP) effects due to Ag and Ag/SiO<SUB>2</SUB> nanoparticles (NPs) deposited on GaN/InGaN multiquantum well (MQW) light‐emitting diode (LED) structures are studied. The colloidal NPs are synthesized by a sol‐gel method and drop‐cased on the LED structures. The surface density of NPs its controlled by the concentration of the NP solution. Theoretical modeling is performed for the emission spectrum and the electric field distribution of LSP resonance for Ag/SiO<SUB>2</SUB> NPs. Enhanced photoluminescence (PL) efficiency is observed in the LED structures and the amount of PL enhancement increases with increasing the surface density of Ag and Ag/SiO<SUB>2</SUB> NPs. These effects are attributed to resonance coupling between the MQW and LSP in the NPs. It is also shown that the PL enhancement attainable with Ag NPs and Ag/SiO<SUB>2</SUB> NPs is comparable, but the latter displays a much higher stability with respect to long‐term storage and annealing due to a barrier for NP agglomeration, Ag oxidation, and impurity diffusion provided by the SiO<SUB>2</SUB> shell.</P>

Tensile test of lead zirconate titanate (PZT)/Platinum (Pt) thin film

Park, J.&#x2010,H.,Bae, H.&#x2010,Y.,Oh, Y.&#x2010,R.,Kim, Y.&#x2010,J.,Kim, H.Y.,Huh, Y.&#x2010,H. WILEY‐VCH Verlag 2011 Materialwissenschaft und Werkstofftechnik Vol.42 No.5

<P><B>Abstract</B></P><P>This paper presents the results of tensile tests for lead zirconate titanate (PZT)/Platinum (Pt) thin films of 2.15 μm thickness in atmospheric air at room temperature. An axial loading tester developed by the authors was used for the tests. The tester was equipped with a load cell with a maximum capacity of 0.5 N and a non‐contact position measuring system based on the principle of capacitance micrometry. Furthermore, the tester was equipped with a CCD (charge‐coupled device) system for measuring the displacement of the gage length. Specimens with three different widths (50, 100 and 150 μm) were fabricated to study the size (width of specimen) effects. The elastic moduli of the specimens with 50, 100 and 150 μm width were 72.8 ± 3.7, 75.0 ± 1.3, 73.3 ± 1.8 GPa, respectively. In addition, the ultimate tensile strength of the specimens with 50, 100 and 150 μm width were 263.4 ± 21.1, 238.6 ± 4.5, 221.1 ± 13.9 MPa, respectively. It was observed that the width of specimen has little effect on the elastic modulus of PZT/Pt thin films but has an effect on the ultimate tensile strength of PZT/Pt thin films and the ultimate tensile strength decreases as the width increases. It was assumed that the scatter in the ultimate tensile strength of 50 μm width was attributed to delamination of PZT/Pt layers before the fracture in the tensile test. The 0.2% offset yield strength could not be measured because the PZT/Pt thin film is very brittle.</P>

Color vision in Parkinson’s disease and essential tremor

Oh, Y.&#x2010,S.,Kim, J.&#x2010,S.,Chung, S.&#x2010,W.,Song, I.&#x2010,U.,Kim, Y.&#x2010,D.,Kim, Y.&#x2010,I.,Lee, K.&#x2010,S. Blackwell Publishing Ltd 2011 European Journal of Neurology Vol.18 No.4

<P><B>Background and purpose: </B> Decreased visual function is one of the non‐motor dysfunctions of Parkinson’s disease (PD). Recent evidences suggest that essential tremor (ET) is not ‘pure’ motor disorder and there is growing evidence that this disease is a multiple‐system disorder. In some cases, it is difficult to differentiate ET from PD. In addition, there is considerable controversy regarding the relationship between PD and ET. The objective of this study was to compare color discrimination dysfunction amongst patients with PD and ET and to investigate the clinical relevance.</P><P><B>Methods: </B> Case–control comparisons of 54 patients with PD, 36 patients with ET, and 34 age‐matched controls were performed. All cases underwent Farnsworth–Munsell 100 Hue test (FMT) and clinical assessments on medication. In addition, the association between color vision abnormalities and motor handicaps was investigated.</P><P><B>Results: </B> There were significant differences in the total error scores (TES) of the FMT amongst the three groups; patients with the PD had higher TES than the patients with ET and the controls after adjustments for age. In addition, the motor symptom severity in PD correlated with the FMT abnormalities, especially with regard to the axial symptoms.</P><P><B>Conclusion: </B> The results of this study suggest that color vision abnormalities may be one of the non‐motor clinical characteristics of PD‐related dysfunction in contrast to ET. In addition, the severity of axial motor symptoms was closely related to visual dysfunction. Confirmation of these findings as well as the mechanisms underlying these results requires further study.</P>

Advances in <i>J</i>‐integral estimation of circumferentially surface cracked pipes

CHO, D.&#x2010,H.,SEO, H.&#x2010,B.,KIM, Y.&#x2010,J.,CHANG, Y.&#x2010,S.,JHUNG, M.&#x2010,J.,CHOI, Y.&#x2010,H. Blackwell Publishing Ltd 2011 Fatigue & Fracture of Engineering Materials and St Vol.34 No.9

<P><B>ABSTRACT</B></P><P>This paper describes enhanced <I>J</I>‐integral estimation schemes for pipes with circumferential semi‐elliptical cracks subjected to tensile loading, global bending and internal pressure. These schemes are given in two different forms to cover the wide ranges of geometries and material parameters; the modified GE/EPRI method and the modified reference stress method. In the former method, new plastic influence functions for fully plastic <I>J</I>‐integral estimation are developed based on extensive three‐dimensional finite element calculations. In the latter method, new optimized reference loads are suggested and utilized to predict the <I>J</I> values. To verify the feasibility of these two schemes, <I>J</I>‐integral values obtained from further detailed FE analyses are compared to those from the proposed schemes. Because the estimated <I>J</I>‐integrals agree fairly well with the detailed FE analysis results, the new solutions can be applied for accurate structural integrity assessment of different size pipes with a circumferential surface crack.</P>

Molecular genetic diversity and population structure of a selected core set in garlic and its relatives using novel SSR markers

Zhao, W.&#x2010,G.,Chung, J.&#x2010,W.,Lee, G.&#x2010,A.,Ma, K.&#x2010,H.,Kim, H.&#x2010,H.,Kim, K.&#x2010,T.,Chung, I.&#x2010,M.,Lee, J.&#x2010,K.,Kim, N.&#x2010,S.,Kim, S.&#x2010,M.,Park, Y.&#x2010 Blackwell Publishing Ltd 2011 Plant breeding Vol.130 No.1

<P> <I>With 7 figures and 6 tables</I> </P><P><B>Abstract</B></P><P>Garlic is widely consumed for its culinary and medical benefits. Six hundred and thirteen accessions of garlic and its relatives with diverse origin were evaluated for genetic diversity at eight recently novel simple sequence repeat loci in this study. A total of 113 alleles were detected, the average allelic richness was 14.1 alleles per locus. Using a heuristic approach, a core set of 95 accessions was successfully developed, which showed 100% coverage of alleles with minimum redundancy. The model‐based structure analysis here revealed the presence of four subpopulations in the selected core set, which was basically consistent with clustering based on the genetic distance. The analysis of molecular variance based on this core set showed that between‐population component of genetic variance is <15.6% in contrast to 84.4% for the within population component. Overall <I>F</I><SUB>ST</SUB> value was 0.1560, indicating a moderate differentiation among the four groups. These results will provide an effective aid for future allele mining, association genetics, mapping and cloning gene(s), germplasm conservation, and improvement programs.</P>