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Han, J.,Park, S.J.,Thu, V.T.,Lee, S.R.,Long, L.T.,Kim, H.K.,Kim, N.,Park, S.W.,Jeon, E.S.,Kim, E.J.,Yoon, C.H.,Cho, G.Y.,Choi, D.J. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.3
Background: The aim of this study was to investigate the cardioprotective effect of fimasartan, a newly developed angiotensin II receptor type I blocker (ARB), against myocardial ischemia/reperfusion (I/R) injury and to identify the mechanism by which it reduces mitochondrial damage. Methods: Fimasartan was administered intravenously to Sprague-Dawley rats (3mg/kg), cardiomyocytes (50μM), and H9c2 cells (50μM) before ischemia or hypoxia. Myocardial infarction (MI), echocardiograms, DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling, immunoblotting, oxygen consumption, confocal microscopic appearance, and L-type Ca<SUP>2+</SUP> current (I<SUB>Ca,L</SUB>) were then assessed. Results: Fimasartan pretreatment remarkably reduced the rate of MI and improved cardiac performance well after I/R (n=9/group). Fimasartan also reduced apoptotic cell death both in vivo and in hypoxia/reoxygenation (H/R)-treated H9c2 cells (n=5~8/group). H/R-induced mitochondrial O<SUB>2</SUB><SUP>-</SUP> production and collapse of membrane potential were markedly attenuated in fimasartan-treated cardiomyocytes (n=4~6/group). Additionally, mitochondrial Ca<SUP>2+</SUP> overload during reoxygenation was suppressed by fimasartan (n=4~6/group), and this was found to be possibly related to the inhibition of I<SUB>Ca,L</SUB> and mitochondrial Ca<SUP>2+</SUP> uniporter. Furthermore, fimasartan pretreatment increased phosphorylations of Akt and glycogen synthase kinase-3β (n=5~7/group), decreased pro-apoptotic p53 levels, and increased anti-apoptotic Bcl-2 levels (n=4) during reperfusion. Conclusions: Fimasartan preconditioning has the potential to modulate Bcl-2 and suppress I/R-induced Ca<SUP>2+</SUP> overload by inhibiting I<SUB>Ca,L</SUB> and MCU. These beneficial effects could prevent the mitochondrial dysfunction and apoptosis accompanied by I/R.
Son, L.T.,Ko, K.M.,Cho, J.H.,Singaravelu, G.,Chatterjee, I.,Choi, T.W.,Song, H.O.,Yu, J.R.,Park, B.J.,Lee, S.K.,Ahnn, J. North-Holland Pub ; Elsevier Science Ltd 2011 FEBS letters Vol.585 No.9
Dicarbonyl/l-xylulose reductase (DCXR) converts l-xylulose into xylitol, and reduces various α-dicarbonyl compounds, thus performing a dual role in carbohydrate metabolism and detoxification. In this study, we identified DHS-21 as the only DCXR ortholog in Caenorhabditis elegans. The dhs-21 gene is expressed in various tissues including the intestine, gonadal sheath cells, uterine seam (utse) cells, the spermathecal-uterus (sp-ut) valve and on the plasma membrane of spermatids. Recombinant DHS-21 was shown to convert l-xylulose to xylitol using NADPH as a cofactor. Dhs-21 null mutants of C. elegans show defects in longevity, reproduction and egg-laying. Knock-down of daf-16 and elt-2 transcription factors affected dhs-21 expression. These results suggest that DHS-21 is a bona fide DCXR of C. elegans, essential for normal life span and reproduction.
The Expression of Genes Related to Egg Production in the Liver of Taiwan Country Chickens
Ding, S.T.,Ko, Y.H.,Ou, B.R.,Wang, P.H.,Chen, C.L.,Huang, M.C.,Lee, Y.P.,Lin, E.C.,Chen, C.F.,Lin, H.W.,Cheng, Winston Teng Kuei Asian Australasian Association of Animal Productio 2008 Animal Bioscience Vol.21 No.1
The purpose of this study was to detect expression of genes related to egg production in Taiwan Country chickens by suppression subtractive hybridization. Liver samples of mRNA extraction from two Taiwan Country chicken strains (L2 and B), originated from the same population but with very distinct egg production rates after long-term selection for egg and meat production respectively. Two-way subtraction was performed. The hepatic cDNA from the low egg production chickens (B) was subtracted from the hepatic cDNA from the high egg production strain (L2). The reversed subtraction (L2 from B) was also performed. The resulting differentially expressed gene fragments were cloned and sequenced. We sequenced 288 clones from the forward subtraction and 96 clones from the reverse subtraction. These genes were subjected to further screening to confirm the differential expression between the two genetic breeds of chickens. The apolipoprotein B (apoB) was expressed to a greater extent in the liver of the L2 than in the B line chickens. The 5-aminoimidazole- 4-carboxamide ribonucleotide formyltransferase/IMP cyclohydrolase (PURH) was expressed to a greater extent in the liver of the B than in the L2 strain chickens. We demonstrated that both apoB and PURH were more highly expressed in the liver than that in other tissues (muscle, ovary, and oviduct) in laying Taiwan Country chickens. Taken together, these data suggest that after the selection for egg production, expression of apoB and PURH genes were also changed. Whether the changed expression of these genes is directly related to egg production is not known, but these two genes may be useful markers for egg laying performance in Taiwan Country chickens.
Toreh, K.R.N.,Kim, D.H.,Dash, U.,Phan, T.L.,Lee, B.W.,Jin, H.W.,Lee, S.,Park, B.H.,Park, J.Y.,Cho, M.R.,Park, Y.D.,Acharya, S.K.,Yoo, W.,Jung, M.H.,Jung, C.U. Elsevier Sequoia 2016 Journal of alloys and compounds Vol.657 No.-
SrRu<SUB>1-x</SUB>Fe<SUB>x</SUB>O<SUB>3-δ</SUB> (x = 0.00, 0.05, 0.10, and 0.20) thin films were fabricated to study the intrinsic aspects of a ''self spin valve''. Using epitaxial strain and high oxygen partial pressure during thin film growth, single phase thin films with negligible oxygen vacancies were successfully grown, and problems related to A-site disorder and grain boundaries were minimized. Under application of an external magnetic field of up to 9 T, the resistivity of all films decreased, resulting in large negative magnetoresistance (up to ~14.4%), which was stronger at temperatures in the range 10-30 K. An abrupt metal-insulator transition at T~ 43 K was found in the x = 0.20 film, which was explained using a two-fluid model related to electron-electron interactions. From the model, two fitting parameters were found to be necessary for in-situ and homogenous defects, while three or unphysical fitting parameters were necessary for ex-situ and inhomogeneous defects.
The X-ray counterpart to the gravitational-wave event GW170817
Troja, E.,Piro, L.,van Eerten, H.,Wollaeger, R. T.,Im, M.,Fox, O. D.,Butler, N. R.,Cenko, S. B.,Sakamoto, T.,Fryer, C. L.,Ricci, R.,Lien, A.,Ryan Jr, R. E.,Korobkin, O.,Lee, S.-K.,Burgess, J. M.,Lee, Nature Publishing Group 2017 Nature Vol. No.
A long-standing paradigm in astrophysics is that collisions—or mergers—of two neutron stars form highly relativistic and collimated outflows (jets) that power γ-ray bursts of short (less than two seconds) duration. The observational support for this model, however, is only indirect. A hitherto outstanding prediction is that gravitational-wave events from such mergers should be associated with γ-ray bursts, and that a majority of these bursts should be seen off-axis, that is, they should point away from Earth. Here we report the discovery observations of the X-ray counterpart associated with the gravitational-wave event GW170817. Although the electromagnetic counterpart at optical and infrared frequencies is dominated by the radioactive glow (known as a ‘kilonova’) from freshly synthesized rapid neutron capture (r-process) material in the merger ejecta, observations at X-ray and, later, radio frequencies are consistent with a short γ-ray burst viewed off-axis. Our detection of X-ray emission at a location coincident with the kilonova transient provides the missing observational link between short γ-ray bursts and gravitational waves from neutron-star mergers, and gives independent confirmation of the collimated nature of the γ-ray-burst emission.
Sundar, R,Huang, K K,Qamra, A,Kim, K -M,Kim, S T,Kang, W K,Tan, A L K,Lee, J,Tan, P Oxford University Press 2019 Annals of oncology Vol.30 No.3
<P><B>Abstract</B></P><P><B>Background</B></P><P>Utilization of alternative transcription start sites through alterations in epigenetic promoter regions causes reduced expression of immunogenic N-terminal peptides, which may facilitate immune evasion in early gastric cancer. We hypothesized that tumors with high alternate promoter utilization would be resistant to immune checkpoint inhibition in metastatic gastric cancer.</P><P><B>Patients and methods</B></P><P>Two cohorts of patients with metastatic gastric cancer treated with immunotherapy were analyzed. The first cohort (<I>N </I>=<I> </I>24) included patients treated with either nivolumab or pembrolizumab. Alternate promoter utilization was measured using the NanoString<SUP>®</SUP> (NanoString Technologies, Seattle, WA, USA) platform on archival tissue samples. The second cohort was a phase II clinical trial of patients uniformly treated with pembrolizumab (<I>N </I>=<I> </I>37). Fresh tumor biopsies were obtained, and transcriptomic analysis was carried out on RNAseq data. Alternate promoter utilization was correlated to T-cell cytolytic activity, objective response rate and survival.</P><P><B>Results</B></P><P>In the first cohort 8 of 24 (33%) tumors were identified to have high alternate promoter utilization (AP<SUB>high</SUB>), and this was used to define the AP<SUB>high</SUB> tertile of the second cohort (13 AP<SUB>high</SUB> of 37). AP<SUB>high</SUB> tumors exhibited decreased markers of T-cell cytolytic activity and lower response rates (8% versus 42%, <I>P </I>=<I> </I>0.03). Median progression-free survival was lower in the AP<SUB>high</SUB> group (55 versus 180 days, <I>P </I>=<I> </I>0.0076). In multivariate analysis, alternative promoter utilization was an independent predictor of immunotherapy survival [hazard ratio 0.29, 95% confidence interval 0.099–0.85, <I>P </I>=<I> </I>0.024). Analyzing tumoral evolution through paired pre-treatment and post-treatment biopsies, we observed consistent shifts in alternative promoter utilization rate associated with clinical response.</P><P><B>Conclusion</B></P><P>A substantial proportion of metastatic gastric cancers utilize alternate promoters as a mechanism of immune evasion, and these tumors may be resistant to anti-PD1 immune checkpoint inhibition. Alternate promoter utilization is thus a potential mechanism of resistance to immune checkpoint inhibition, and a novel predictive biomarker for immunotherapy.</P><P><B>Trial Registration</B></P><P>ClinicalTrials.gov Identifier: NCT#02589496</P>