Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Park, Nam&#x2010,Sook,Park, Yu&#x2010,Kyoung,Ramalingam, Mahesh,Yadav, Anil Kumar,Cho, Hyo&#x2010,Rim,Hong, Victor Sukbong,More, Kunal N.,Bae, Jae&#x2010,Hoon,Bishop&#x2010,Bailey, David,Kano, Junko,N John Wiley and Sons Inc. 2018 Journal of cellular and molecular medicine Vol.22 No.12

<P><B>Abstract</B></P><P>Meridianin C is a marine natural product known for its anti‐cancer activity. At present, the anti‐tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, YD‐8, YD‐10B, YD‐38 and HSC‐3. Among the cells tested, meridianin C most strongly reduced the growth of YD‐10B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the YD‐10B cells; confirmed by the microscopic and TEM analysis as well as the entry of FITC‐dextran, which was sensitive to the macropinocytosis inhibitor amiloride. SEM data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of YD‐10B cells treated with meridianin C, pointing out that meridianin C‐induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf‐related protein‐3 (DKK‐3), a known negative regulator of macropinocytosis. A role for DKK‐3 in regulating macropinocytosis in the YD‐10B cells was confirmed by siRNA knockdown of endogenous DKK‐3, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous DKK‐3 overexpression, which resulted in a considerable inhibition of the meridianin C‐induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti‐proliferative effects via macropinocytosis in the highly tumorigenic YD‐10B cell line and the effects are mediated in part through down‐regulation of DKK‐3.</P>

Influence of Cr Doping on the Critical Behavior of Amorphous Alloy Ribbons Fe_{78–<i>x</i>}Cr_<i>x</i>Si₄Nb₅B₁₂Cu₁

Phan, T. L.,Thanh, P. Q.,Chau, N.,Huu, C. X.,Ngo, D.-T,Ho, T. A.,Thanh, T. D.,Yu, S. C. IEEE 2014 IEEE transactions on magnetics Vol.50 No.11

<P>Though many previous works focused on studying Cr-doped Fe-Si-Nb-B-Cu amorphous alloys, magnetic-interaction mechanisms in these materials have not been carefully investigated yet. Dealing with these issues, we have prepared the amorphous alloy ribbons Fe<SUB>78-x</SUB>Cr<SUB>x</SUB>Si<SUB>4</SUB>Nb<SUB>5</SUB>B<SUB>12</SUB>Cu<SUB>1</SUB> with x= 1, 3, and 6, and then studied their magnetic and critical properties. Magnetization versus temperature and magnetic-field measurements, MHT, performed on a vibrating sample magnetometer reveal that the Cr-content increase in Fe<SUB>78-x</SUB>Cr<SUB>x</SUB>Si<SUB>4</SUB>Nb<SUB>5</SUB>B<SUB>12</SUB>Cu<SUB>1</SUB> reduces the T<SUB>C</SUB> from 430 K for x= 1 to about 322 K (for x= 6). This indicates the decline of ferromagnetic (FM) exchange interactions between Fe atoms when there is the presence of Cr atoms. We have also analyzed the M(H) data at the temperatures in the vicinity of the T<SUB>C</SUB> using the modified Arrott plot method and the scaling hypothesis, and determined the values of the critical exponents β = 0.367-0.376 and γ = 1.315-1.338. These values are close to those expected for the 3-D Heisenberg model with β = 0.365 and γ = 1.336, proving the existence of short-range FM order in the amorphous alloy ribbons.</P>

Large‐Deformation Behavior of Honeycomb‐Structured Polymer Sheets as a Function of Polar Angle

Jin, Kwang&#x2010,Yong,Kim, Dae&#x2010,Yoon,Kim, So&#x2010,Eun,Kuo, Shiao&#x2010,Wei,Lee, Joong Hee,Lyu, Min&#x2010,Young,Hwang, Seok&#x2010,Ho,Gent, Alan N.,Nah, Changwoon,Jeong, Kwang&#x2010,Un WILEY‐VCH Verlag 2011 Macromolecular chemistry and physics Vol.212 No.9

<P><B>Abstract</B></P><P>To construct the structure/property relationships of patterned polymer architectures depending on symmetry, the large‐deformation behavior of 2D HSPS with respect to the polar angle was studied. Holes aligned along the HSPS apex were more effective in decreasing tensile force and reducing stress concentration than those located along the plane. On varying the polar angle from 0 to 30°, the tensile force fluctuated up and down like an undamped negative sinusoidal wave with a wavelength of 15°. Additionally, molecular orientations of HSPS were monitored in situ. By comparing experimental measurements with computer simulations, it was concluded that the tensile force depends on the number of holes as well as the orientation of the axes of the honeycomb structure. </P>

Association of thromboxane A2 receptor (<i>TBXA2R</i>) gene polymorphism in patients with aspirin‐intolerant acute urticaria

Palikhe, N. S.,Kim, S.&#x2010,H.,Lee, H.&#x2010,Y.,Kim, J.&#x2010,H.,Ye, Y.&#x2010,M.,Park, H.&#x2010,S. Blackwell Publishing Ltd 2011 Clinical and experimental allergy Vol.41 No.2

<P>Cite this as: N. S. Palikhe, S.‐H. Kim,H.‐Y. Lee, J.‐H. Kim, Y.‐M. Ye and H.‐S. Park, Clinical & Experimental Allergy, 2011 (41) 179–185.</P><P><B>Summary</B></P><P><B>Background </B> The thromboxane A2 receptor (<I>TBXA2R</I>) is a potent broncho‐ and vaso‐constrictor and is associated with leukotriene synthesis. Polymorphisms in the <I>TBXA2R</I> gene have been linked to atopy, asthma, and atopic dermatitis. This study evaluated the association between genetic <I>TBXA2R</I> variants and the development of acetyl salicylic acid (ASA)‐intolerant acute urticaria (AIAU).</P><P><B>Methods </B> AIAU patients (<I>n</I>=167), ASA‐intolerant chronic urticaria (AICU) patients (<I>n</I>=149), and healthy controls (NC) (<I>n</I>=265) were included. All patients were enrolled at Ajou University Hospital in Suwon, Korea. Two <I>TBXA2R</I> polymorphisms (−4684T>C and 795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer extension kit. Luciferase activity was measured using a dual‐luciferase reporter assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a nuclear extract from a human mast cell line (HMC‐1).</P><P><B>Results </B> Genetic association data demonstrated that compared with NC subjects, AIAU patients had a significantly higher frequency of the homozygous TT genotype of <I>TBXA2R</I>−4684T>C (<I>P=</I>0.005, <I>P</I><SUB>corr</SUB>=0.03). No differences were identified between the AICU and the NC groups. Luciferase activity, reflecting promoter activity, was significantly lower with the <I>TBXA2R</I>−4684T‐containing construct than with the −4684C‐containing construct (<I>P</I><0.001); the activity decreased further upon co‐transfection with ETS‐like gene transcription factor‐1 (ELK‐1) (<I>P=</I>0.012). EMSA revealed that the −4684T allele produced a specific shifted band, with a greater affinity than that produced by the −4684C allele.</P><P><B>Conclusion and clinical relevance </B> These results suggest that the <I>TBXA2R</I>−4684T allele may be associated with lower TBXA2R expression, which may contribute to the development of the AIAU phenotype.</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>

Hypoxic resistance to articular chondrocyte apoptosis – a possible mechanism of maintaining homeostasis of normal articular cartilage

Seol, J.&#x2010,W.,Lee, H.&#x2010,B.,Lee, Y.&#x2010,J.,Lee, Y.&#x2010,H.,Kang, H.&#x2010,s.,Kim, I.&#x2010,s.,Kim, N.&#x2010,S.,Park, S.&#x2010,Y. Blackwell Publishing Ltd 2009 FEBS JOURNAL Vol.276 No.24

<P>Hypoxia and hypoxia‐related genes are important factors in articular chondrocytes during cartilage homeostasis and osteoarthritis. We have investigated the various apoptotic factors that show significance in synovial fluid obtained from normal and experimental osteoarthritic animal models and have evaluated the effect of hypoxia on articular chondrocyte apoptosis induced by these apoptotic factors. Mature beagle dogs underwent surgical transections of ligaments and medial meniscectomies to explore the underlying mechanisms of osteoarthritis. Cartilage and synovial fluid obtained from normal animals and those with osteoarthritis were evaluated via proteasome inhibition, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) protein expression, mitochondrial transmembrane potential and levels of reactive oxygen species. Canine chondrocytes were exposed to the proteasome inhibitor <I>N</I>‐acetyl‐Leu‐Leu‐Norleu‐al and treated with recombinant TRAIL protein under normoxic and hypoxic conditions, measuring chondrocyte cell viability, proteasome activity and levels of apoptotic factors. TRAIL protein expression and ubiquitinated proteins were increased significantly, but the proteasome activity in the synovial fluid of osteoarthritic joints relative to that in normal joints was not. Primary cultured articular chondrocytes cotreated with the proteasome inhibitor and TRAIL progressed to severe apoptosis under normoxic conditions, but the sensitization caused by the combined treatment was suppressed by exposure to hypoxia. Caspase‐8 activation, c‐Jun N‐terminal kinase phosphorylation, the mitochondrial transmembrane potential and the generation of reactive oxygen species involved in cell death regulation were significantly inhibited under hypoxic conditions. These findings suggest that proteasome inhibition and TRAIL may be possible mechanisms in cartilage degradation and joint‐related diseases. Furthermore, the maintenance of hypoxic conditions or therapy with hypoxia‐related genes in the joint may be successful for the treatment of joint‐related diseases, including osteoarthritis.</P>

Production of recombinant human acid α-glucosidase with high-mannose glycans in gnt1 rice for the treatment of Pompe disease

Jung, J.W.,Huy, N.X.,Kim, H.B.,Kim, N.S.,Van Giap, D.,Yang, M.S. Elsevier Science Publishers 2017 Journal of biotechnology Vol.249 No.-

<P>Lysosomal storage diseases are a group of inherited metabolic disorders. Patients are treated with enzyme replacement therapy (ERT), in which the replacement enzymes are required to carry terminal mannose or mannose 6-phosphate residues to allow efficient uptake into target cells and tissues. N-acetylglucosaminyl-transferase-I (GnTI) mediates N-glycosylation in the cis cisternae of the Golgi apparatus by adding N-acetylglucosamine to the exposed terminal mannose residue of core N-glycan structures for further processing. Mutant rice lacking GnTI produces only high mannosylated glycoproteins. In this study, we introduced a gene encoding recombinant human acid alpha-glucosidase (rhGAA), which is used in ERT for Pompe disease, into gnt1 rice callus by particle bombardment. Integration of the target gene into the genome of the gnt1 rice line and its mRNA expression were confirmed by PCR and Northern blot, respectively. Western blot analysis was performed to confirm secretion of the target proteins into the culture media. Using an indirect enzyme linked immunosorbent assay, we determined the maximum expression of rhGAA to be approximately 45 mg/L, 13 days after induction. To assay the enzymatic activity and determine the N-glycan profile of rhGAA, we purified the protein using a 6 x histidine tag. The in vitro alpha-glucosidase activity of rhGAA from gnt1 rice callus (gnt1-GAA) was 3.092 U/mg, similar to the activity of the Chinese hamster ovary cell-derived GAA (3.154 U/mg). N-glycan analysis revealed the presence of high-mannose N-glycans on gnt1-GAA. In addition, the production of high-mannose GAA using gnt1 rice calli as an expression host was characterized, which may aid the future development of therapeutic enzymes for the treatment of Pompe disease.</P>

Crystal structure of the protein A t3g01520, a eukaryotic universal stress protein‐like protein from <i>arabidopsis thaliana</i> in complex with AMP

Kim, Do Jin,Bitto, Eduard,Bingman, Craig A.,Kim, Hyun&#x2010,Jung,Han, Byung Woo,Phillips Jr., George N. John Wiley and Sons Inc. 2015 Proteins Vol.83 No.7

<P><B>ABSTRACT</B></P><P>Members of the universal stress protein (USP) family are conserved in a phylogenetically diverse range of prokaryotes, fungi, protists, and plants and confer abilities to respond to a wide range of environmental stresses. <I>Arabidopsis thaliana</I> contains 44 USP domain‐containing proteins, and USP domain is found either in a small protein with unknown physiological function or in an N‐terminal portion of a multi‐domain protein, usually a protein kinase. Here, we report the first crystal structure of a eukaryotic USP‐like protein encoded from the gene At3g01520. The crystal structure of the protein At3g01520 was determined by the single‐wavelength anomalous dispersion method and refined to an <I>R</I> factor of 21.8% (<I>R</I><SUB>free</SUB> = 26.1%) at 2.5 Å resolution. The crystal structure includes three At3g01520 protein dimers with one AMP molecule bound to each protomer, comprising a Rossmann‐like α/β overall fold. The bound AMP and conservation of residues in the ATP‐binding loop suggest that the protein At3g01520 also belongs to the ATP‐binding USP subfamily members. Proteins 2015; 83:1368–1373. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.</P>

Piezoelectric properties of (1 ? x)Pb(Zr1/2Ti1/2)O3?xPb(Zn1/3Nb2/3)O3 ceramics prepared by the columbite?(wolframite) precursor method

N. Vittayakorn,C. Puchmark,G. Rujijanagul,X. Tan,D.P. Cann 한국물리학회 2006 Current Applied Physics Vol.6 No.3

Solid solutions of the perovskite structure, (1. x)Pb(Zr1/2Ti1/2)O3xPb(Zn1/3Nb 2/3)O3 withx = 0.10.5, were synthesized via the col-umbite(wolframite) precursor method. The phase development of calcined powder precursors was analyzed by X-ray diraction. Phase-pure perovskite of PZNPZT ceramics was obtained over a wide compositional range. The microstructure and piezoelectric propertieswere characterrized by means of scanning electron microscopy (SEM),d33 measurements and impedance analysis. It has been found thatof d33 (690 pC/N) and the highestkp (0.7) were recorded for the compositionx = 0.3 located at the boundary between tetragonal andrhombohedral ferroelectric phases. Furthermore, large values ofd33 (600 pC/N) and kp (0.67) were observed at a compositions ofx = 0.5, which is the boundary between two ferroelectric rhombohedral phases.

Identification of a novel <i>HLA‐B*40</i> null allele, <i>HLAB*40:155N</i>

Ko, S.&#x2010,Y.,Oh, H.&#x2010,B.,Cho, M.&#x2010,C.,Park, N.,Kwon, O.&#x2010,J. Blackwell Publishing Ltd 2011 Tissue antigens Vol.78 No.2

<P>The new allele B*40:155N showed five nucleotide insertion between nucleotide 594 and 595 (codon 174 and 175) compared to B*40:01:01.</P>