Physciosporin suppresses the proliferation, motility and tumourigenesis of colorectal cancer cells

Taf,, İ,sa,Han, Jin,Park, So-Yeon,Yang, Yi,Zhou, Rui,Gamage, Chathurika D.B.,Van Nguyen, Tru,Lee, Ji-Yoon,Choi, Yong Jae,Yu, Young Hyun,Moon, Kyung-Sub,Kim, Kyung Keun,Ha, Hyung-Ho,Kim, Sang Elsevier 2019 Phytomedicine Vol.56 No.-

<P><B>Abstract</B></P> <P><B>Background</B></P> <P>Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms.</P> <P><B>Purpose</B></P> <P>The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells.</P> <P><B>Methods</B></P> <P>PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array <I>in vitro</I> as well as tumorigenicity study <I>in vivo</I>.</P> <P><B>Results</B></P> <P>PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated β-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity.</P> <P><B>Conclusion</B></P> <P>PHY suppresses the growth and motility of CRC cells via novel mechanisms.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Complex chromosomal rearrangements by single catastrophic pathogenesis in NUT midline carcinoma

Lee, J.-K.,Louzada, S.,An, Y.,Kim, S. Y.,Kim, S.,Youk, J.,Park, S.,Koo, S. H.,Keam, B.,Jeon, Y. K.,Ku, J.-L.,Yang, F.,Kim, T. M.,Ju, Y. S. Oxford University Press 2017 Annals of Oncology Vol.28 No.4

<P><B>Background</B></P><P>Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare aggressive malignancy often occurring in the tissues of midline anatomical structures. Except for the pathognomonic <I>BRD3/4–NUT</I> rearrangement, the comprehensive landscape of genomic alterations in NMCs has been unexplored.</P><P><B>Patients and methods</B></P><P>We investigated three NMC cases, including two newly diagnosed NMC patients in Seoul National University Hospital, and a previously reported cell line (Ty-82). Whole-genome and transcriptome sequencing were carried out for these cases, and findings were validated by multiplex fluorescence <I>in situ</I> hybridization and using individual fluorescence probes.</P><P><B>Results</B></P><P>Here, we present the first integrative analysis of whole-genome sequencing, transcriptome sequencing and cytogenetic characterization of NUT midline carcinomas. By whole-genome sequencing, we identified a remarkably similar pattern of highly complex genomic rearrangements (previously denominated as chromoplexy) involving the <I>BRD3/4–NUT</I> oncogenic rearrangements in two newly diagnosed NMC cases. Transcriptome sequencing revealed that these complex rearrangements were transcribed as very simple <I>BRD3/4–NUT</I> fusion transcripts. In Ty-82 cells, we also identified a complex genomic rearrangement involving the <I>BRD4–NUT</I> rearrangement underlying the simple t(15;19) karyotype. Careful inspections of rearrangement breakpoints indicated that these rearrangements were likely attributable to single catastrophic events. Although the NMC genomes had >3000 somatic point mutations, canonical oncogenes or tumor suppressor genes were rarely affected, indicating that they were largely passenger events. Mutational signature analysis showed predominant molecular clock-like signatures in all three cases (accounting for 54%−75% of all base substitutions), suggesting that NMCs may arise from actively proliferating normal cells.</P><P><B>Conclusion</B></P><P>Taken together, our findings suggest that a single catastrophic event in proliferating normal cells could be sufficient for neoplastic transformation into NMCs.</P>

Association of genetic variation in <i>FTO</i> with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians

Li, H.,Kilpelä,inen, T. O.,Liu, C.,Zhu, J.,Liu, Y.,Hu, C.,Yang, Z.,Zhang, W.,Bao, W.,Cha, S.,Wu, Y.,Yang, T.,Sekine, A.,Choi, B. Y.,Yajnik, C. S.,Zhou, D.,Takeuchi, F.,Yamamoto, K.,Chan, J. C.,Man Springer-Verlag 2012 Diabetologia Vol.55 No.4

<P><B>Aims/hypothesis</B></P><P><I>FTO</I> harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for <I>FTO</I> in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the <I>FTO</I> locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.</P><P><B>Methods</B></P><P>All studies published on the association between <I>FTO</I>-rs9939609 (or proxy [<I>r</I><SUP>2</SUP> > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.</P><P><B>Results</B></P><P>The <I>FTO</I>-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (<I>p</I> = 9.0 × 10<SUP>−19</SUP>), overweight by 1.13-fold/allele (<I>p</I> = 1.0 × 10<SUP>−11</SUP>) and type 2 diabetes by 1.15-fold/allele (<I>p</I> = 5.5 × 10<SUP>−8</SUP>). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, <I>p</I> = 6.6 × 10<SUP>−5</SUP>). The <I>FTO</I>-rs9939609 minor allele increased BMI by 0.26 kg/m<SUP>2</SUP> per allele (<I>p</I> = 2.8 × 10<SUP>−17</SUP>), WHR by 0.003/allele (<I>p</I> = 1.2 × 10<SUP>−6</SUP>), and body fat percentage by 0.31%/allele (<I>p</I> = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12–20%) than South Asians (30–33%), the effect of <I>FTO</I> variation on obesity-related traits and type 2 diabetes was similar in the two populations.</P><P><B>Conclusions/interpretation</B></P><P><I>FTO</I> is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, <I>FTO</I> is also associated with type 2 diabetes independently of BMI.</P><P><B>Electronic supplementary material</B></P><P>The online version of this article (doi:10.1007/s00125-011-2370-7) contains peer-reviewed but unedited supplementary material, which is available to authorised users.</P>

CHF enhancement by vessel coating for external reactor vessel cooling

Yang, J.,Dizon, M.B.,Cheung, F.B.,Rempe, J.L.,Suh, K.Y.,Kim, S.B. Elsevier 2006 Nuclear engineering and design Vol.236 No.10

<P><B>Abstract</B></P><P>In-vessel retention (IVR) is a key severe accident management (SAM) strategy that has been adopted by some operating nuclear power plants and proposed for some advanced light water reactors (ALWRs). One viable means for IVR is the method of external reactor vessel cooling (ERVC) by flooding the reactor cavity during a severe accident. As part of a joint Korean–United States International Nuclear Energy Research Initiative (K-INERI), an experimental study has been conducted to investigate the viability of using an appropriate vessel coating to enhance the critical heat flux (CHF) limits during ERVC. Toward this end, transient quenching and steady-state boiling experiments were performed in the subscale boundary layer boiling (SBLB) facility at the Pennsylvania State University using test vessels with micro-porous aluminum coatings. Local boiling curves and CHF limits were obtained in these experiments. When compared to the corresponding data without coatings, substantial enhancement in the local CHF limits for the case with surface coatings was observed. Results of the steady-state boiling experiments showed that micro-porous aluminum coatings were very durable. Even after many cycles of steady-state boiling, the vessel coatings remained rather intact, with no apparent changes in color or structure. Moreover, the heat transfer performance of the coatings was found to be highly desirable with an appreciable CHF enhancement in all locations on the vessel outer surface but with very little effect of aging.</P>

Hytramycins V and I, Anti-<i>Mycobacterium tuberculosis</i> Hexapeptides from a <i>Streptomyces hygroscopicus</i> Strain

Cai, Geping,Napolitano, José,G.,McAlpine, James B.,Wang, Yuehong,Jaki, Birgit U.,Suh, Joo-Won,Yang, Seung Hwan,Lee, In-Ae,Franzblau, Scott G.,Pauli, Guido F.,Cho, Sanghyun American Chemical Society and American Society of 2013 Journal of natural products Vol.76 No.11

<P>Thirty-five thousand actinomycete extracts were screened for anti-<I>Mycobacterium tuberculosis</I> (<I>M. tb</I>) activity, followed by C<SUB>18</SUB> cartridge fractionation of 37 prioritized extracts. Based on MICs against replicating and nonreplicating <I>M. tb</I>, and IC<SUB>50</SUB> values against Vero cells to generate selectivity indices, seven fractions from seven different strains were selected for further examination. When cultured in G.S.S. media and extracted with ethyl acetate, the <I>Streptomyces hygroscopicus</I> strain ECUM 14046 yielded an extract with promising anti-<I>M. tb</I> activity and a well-defined chromatographic profile. Fractionation by preparative HPLC and subsequent structure elucidation of two active fractions using 1D- and 2D-NMR and MS methods revealed the presence of two cyclohexapeptides, hytramycins V and I, each containing three unusual piperazic acid moieties. The use of <SUP>1</SUP>H iterative full spin analysis (HiFSA) on both hytramycins confirmed that quantum mechanics-simulated spectra match the experimental data, and all <I>J</I><SUB>H,H</SUB> and δ<SUB>H</SUB> values are consistent with the proposed structures. The absolute configuration of each amino acid moiety was determined by Marfey’s method. The MICs against replicating and, more importantly, nonreplicating <I>M. tb</I> fall into the range of some existing second-line anti-TB drugs, such as streptomycin and capreomycin, respectively. The activities were maintained against <I>M. tb</I> strains that represent the major global clades, as well as H<SUB>37</SUB>Rv-isogenic strains that are resistant to individual clinical anti-TB drugs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2013/jnprdf.2013.76.issue-11/np400145u/production/images/medium/np-2013-00145u_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np400145u'>ACS Electronic Supporting Info</A></P>

Magnetic domain tuning and the emergence of bubble domains in the bilayer manganiteLa2−2xSr1+2xMn2O7(x=0.32)

Jeong, Juyoung,Yang, Ilkyu,Yang, Jinho,Ayala-Valenzuela, Oscar E.,Wulferding, Dirk,Zhou, J.-S.,Goodenough, John B.,de Lozanne, Alex,Mitchell, J. F.,Leon, Neliza,Movshovich, Roman,Jeong, Yoon Hee,Yeom, American Physical Society 2015 Physical review. B, Condensed matter and materials Vol.92 No.5

Protecting nickel with graphene spin-filtering membranes: A single layer is enough (4 pages)

Martin, M.-B.,Dlubak, B.,Weatherup, R. S.,Piquemal-Banci, M.,Yang, H.,Blume, R.,Schloegl, R.,Collin, S.,Petroff, F.,Hofmann, S. American Institute of Physics 2015 Applied Physics Letters Vol.107 No.1

Variation and Correlation of Shearing Force with Feed Nutritional Characteristics of Wheat Straw

Cui, X.M.,Yang, Z.B.,Yang, W.R.,Jiang, S.Z.,Zhang, G.G.,Liu, L.,Wu, B.R.,Wang, Z.F. Asian Australasian Association of Animal Productio 2013 Animal Bioscience Vol.26 No.10

This experiment was conducted to study the variation laws and correlations of shearing force and feed characteristics including morphological characteristic, chemical composition and in situ degradability of wheat straw. Feasibility of evaluating the nutritional value of wheat straws with shearing force values was analyzed in this study. Six hundred wheat straw plants (Jimai 22) were randomly selected and placed in a cool and ventilated place. Samples were collected in the 1st, 15th, 30th, 45th, 60th d after harvest to measure shearing force, morphological characteristic, nutritional composition. Rumen degradation of dry matter (DM), neutral detergent fiber (NDF) and acid detergent fiber (ADF) of wheat straws were determined by the nylon bags method. The results demonstrated that linear and quadratic effects of storage time on all the tested morphological characteristics were significantly correlative (p<0.01). As storage time goes on, all the tested nutrients and their rumen degradations of wheat straw was linearly (p<0.01) and quadratic (p<0.01) correlative except ADF content and rumen degradation of ADF. Significant correlations were determined in linear effect of shearing force on morphological characteristics (p<0.01), and linear density and diameter were a more sensitive predictor than stem thickness for shearing force. There were strong correlations between storage time and all the measured physical characteristics (shearing force, morphological characteristics and shearing force standardized by morphological characteristics) (p<0.01). Nutrition compositions were linearly correlative with shearing force and standardized shearing force (p<0.01). The linear correlation between rumen degradation of DM and NDF and shearing force and standardized shearing force were evident (p<0.01). In conclusion, shearing force, nutrition compositions and their rumen degradation of wheat straw were still dynamic with storage time after harvest. Correlation could be found between shearing force and nutritional characteristics of wheat straw. Nutrient content, morphological index and rumen degradation of DM and NDF could be predicted by changes in shearing force. Shearing force should be applied according to a standardized storage time when it is used to forecast the feed value of wheat straws.

Effects of L-tryptophan, Fructan, and Casein on Reducing Ammonia, Hydrogen Sulfide, and Skatole in Fermented Swine Manure

Q.K. Sheng,Z.J. Yang,H.B. Zhao,X.L. Wang,J.F. Guo 아세아·태평양축산학회 2015 Animal Bioscience Vol.28 No.8

The effects of daily dietary Bacillus subtilis (Bs), and adding L-tryptophan, fructan, or casein to fecal fermentation broths were investigated as means to reduce the production of noxious gas during manure fermentation caused by ammonia, hydrogen sulfide (H2S), and 3-methylindole (skatole). Eighty swine (50.0±0.5 kg) were equally apportioned to an experimental group given Bs in daily feed, or a control group without Bs. After 6 weeks, fresh manure was collected from both groups for fermentation studies using a 3×3 orthogonal array, in which tryptophan, casein, and fructan were added at various concentrations. After fermentation, the ammonia, H2S, L-tryptophan, skatole, and microflora were measured. In both groups, L-tryptophan was the principle additive increasing skatole production, with significant correlation (r = 0.9992). L-tryptophan had no effect on the production of ammonia, H2S, or skatole in animals fed Bs. In both groups, fructan was the principle additive that reduced H2S production (r = 0.9981). Fructan and Bs significantly interacted in H2S production (p = 0.014). Casein was the principle additive affecting the concentration of ammonia, only in the control group. Casein and Bs significantly interacted in ammonia production (p = 0.039). The predominant bacteria were Bacillus spp. CWBI B1434 (26%) in the control group, and Streptococcus alactolyticus AF201899 (36%) in the experimental group. In summary, daily dietary Bs reduced ammonia production during fecal fermentation. Lessening L-tryptophan and increasing fructan in the fermentation broth reduced skatole and H2S.

Effect of Corticosterone Administration on Small Intestinal Weight and Expression of Small Intestinal Nutrient Transporter mRNA of Broiler Chickens

Hu, X.F.,Guo, Yuming,Huang, B.Y.,Zhang, L.B.,Bun, S.,Liu, D.,Long, F.Y.,Li, J.H.,Yang, X.,Jiao, P. Asian Australasian Association of Animal Productio 2010 Animal Bioscience Vol.23 No.2

The effects of corticosterone (CORT) administration on the weight of small intestine and the expression of nutrient transporter mRNA in the small intestine of broiler chickens (Gallus gallus domesticus) were investigated. One hundred and eight sevenday-old birds were randomly divided into two equal groups comprising a control group (CTRL) and an experimental group (CORT). CTRL birds were fed a basal diet and the CORT birds were fed a basal diet containing 30 mg corticosterone/kg from d 8 to 21. At 21 d of age, average daily feed intake (ADFI), serum corticosterone level, small intestinal absolute wet weight and relative weight, and relative abundance of SGLT1, CaBP-D28k, PepT1 mRNA in the duodenum and L-FABP mRNA in the jejunum were determined. The results showed that serum corticosterone level, liver weight and small intestinal relative weight (small intestinal wet weight/body weight) of CORT chickens were about 30.15%, 26.72% and 42.20% higher, respectively, than in the CTRL group (p<0.05). CORT birds had relative mRNA abundance of CaBP-D28k and PepT1 in the duodenum, and L-FABP in the jejunum which was 1.77, 1.37 and 1.94 fold higher, respectively, than in the CTRL group (p<0.05); the relative abundance of SGLT1 was 1.67 fold higher than in the CTRL group (p = 0.097). ADFI, small intestinal wet weight and length in CORT-treated broiler chickens was about 29.11%, 31.12% and 12.35% lower, respectively, than in the CTRL group (p<0.05). In conclusion, corticosterone administration lowered the wet weight but increased the relative weight of the small intestine and the expression of intestinal nutrient transporter mRNA of broiler chickens.