Potent Suppressive Effects of 1-Piperidinylimidazole Based Novel P2X7 Receptor Antagonists on Cancer Cell Migration and Invasion

Park, Jin-Hee,Williams, Darren R.,Lee, Ji-Hyung,Lee, So-Deok,Lee, Je-Heon,Ko, Hyojin,Lee, Ga-Eun,Kim, Sujin,Lee, Jeong-Min,Abdelrahman, Aliaa,Mü,ller, Christa E.,Jung, Da-Woon,Kim, Yong-Chul American Chemical Society 2016 Journal of medicinal chemistry Vol.59 No.16

<P>The P2X7 receptor (P2X7R) has been reported as a key mediator in inflammatory processes and cancer invasion/metastasis. In this study, we report the discovery of novel P2X7R antagonists and their functional activities as potential antimetastatic agents. Modifications of the hydantoin core-skeleton and the side chain substituents of the P2X7R antagonist 7 were performed. The structure activity relationships (SAR) and optimization demonstrated the importance of the sulfonyl group at the R-1 position and the substituted position and overall size of R-2 for P2X7R antagonism. The optimized novel analogues displayed potent P2X7 receptor antagonism (IC50 = 0.11-112 nM) along with significant suppressive effects on IL-1 beta release (IC50 = 0.32-210 nM). Moreover, representative antagonists (12g, 13k, and 17d) with imidazole and uracil core skeletons significantly inhibited the invasion of MDA-MB-231 triple negative breast cancer cells and cancer cell migration in a zebrafish xenograft model, suggesting the potential therapeutic application of these novel P2X7 antagonists to block metastatic cancer.</P>

EPRI의 사용후연료 저장방안

Williams, R. F.,Lambert, R. W.,Stahlkopf, K. E. 한국원자력산업회의 1992 원자력산업 Vol.12 No.1

An objective assessment of the impact of tendon retraction on sleep efficiency in patients with full-thickness rotator cuff tears: a prospective cohort study

Ashley E. MacConnell,William Davis,Rebecca Burr,Andrew Schneider,Lara R Dugas,Cara Joyce,Dane H. Salazar,Nickolas G. Garbis 대한견주관절의학회 2023 대한견주관절의학회지 Vol.26 No.2

Background: Sleep quality, quantity, and efficiency have all been demonstrated to be adversely affected by rotator cuff pathology. Previous measures of assessing the impact of rotator cuff pathology on sleep have been largely subjective in nature. This study was undertaken to objectively analyze this relationship through the use of activity monitors. Methods: Patients with full-thickness rotator cuff tears at a single institution were prospectively enrolled between 2018 and 2020. Waist-worn accelerometers were provided for the patients to use each night for 14 days. Sleep efficiency was calculated using the ratio of the time spent sleeping to the total amount of time that was spent in bed. Retraction of the rotator cuff tear was classified using the Patte staging system. Results: This study included 36 patients: 18 with Patte stage 1 disease, 14 with Patte stage 2 disease, and 4 patients with Patte stage 3 disease. During the study, 25 participants wore the monitor on multiple nights, and ultimately their data was used for the analysis. No difference in the median sleep efficiency was appreciated amongst these groups (P>0.1), with each cohort of patients demonstrating a generally high sleep efficiency. Conclusions: The severity of retraction of the rotator cuff tear did not appear to correlate with changes in sleep efficiency for patients (P>0.1). These findings can better inform providers on how to counsel their patients who present with complaints of poor sleep in the setting of full-thickness rotator cuff tears.

Synthesis of Host Polymers and Guests for Electrophosphorescence

Scott E. Watkins,Khai Leok Chan,Sung Yong Cho,Nicholas R. Evans,Andrew C. Grimsdale,Andrew B. Holmes,Chris S. K. Mak,Albertus J. Sandee,Charlotte K. Williams 한국고분자학회 2007 Macromolecular Research Vol.15 No.2

Consequences of a Linear Two-Coordinate Geometry for the Orbital Magnetism and Jahn−Teller Distortion Behavior of the High Spin Iron(II) Complex Fe[N(<i>t</i>-Bu)₂]₂

Reiff, William M.,Schulz, Charles E.,Whangbo, Myung-Hwan,Seo, Jung In,Lee, Yoon Sup,Potratz, Gregory R.,Spicer, Charles W.,Girolami, Gregory S. American Chemical Society 2009 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.131 No.2

<P>Mossbauer, EPR, magnetic susceptibility, and DFT studies of the unusual two-coordinate iron(II) amide Fe[N(t-Bu)(2)](2) show that it retains a linear N-Fe-N framework due to the nonbonding delta nature of the (xy, x(2)-y(2)) orbitals. The resulting near-degenerate ground state gives rise to a large magnetic moment and a remarkably large internal hyperfine field. The results confirm that extraordinary orbital magnetic effects can arise in linear transition metal complexes in which orbital degeneracies are not broken by Jahn-Teller or Renner-Teller distortions.</P>

NMR and X-ray Study Revealing the Rigidity of Zeolitic Imidazolate Frameworks

Morris, William,Stevens, Caitlin J.,Taylor, R. E.,Dybowski, C.,Yaghi, Omar M.,Garcia-Garibay, Miguel A. American Chemical Society 2012 The Journal of Physical Chemistry Part C Vol.116 No.24

<P>NMR relaxation studies and spectroscopic measurements of zeolitic imidazolate framework-8 (ZIF-8) are reported. The dominant nuclear spin–lattice relaxation (<I>T</I><SUB>1</SUB>) mechanism for ZIF-8 in air arises from atmospheric paramagnetic molecular oxygen. The <SUP>13</SUP>C <I>T</I><SUB>1</SUB> measurements indicate that the oxygen interacts primarily with the imidazolate ring rather than the methyl substituent. Similar relaxation behavior was also observed in a ZIF with an unsubstituted ring, ZIF-4. Single-crystal X-ray diffraction was used to provide data for the study of the thermal ellipsoids of ZIF-8 at variable temperatures from 100 to 298 K, which further confirmed the rigid nature of this ZIF framework. These results highlight a rigid ZIF framework and are in contrast with dynamic metal–organic frameworks based on benzenedicarboxylate linking groups, for which the relaxation reflects the dynamics of the benzenedicarboxylate moiety.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jpccck/2012/jpccck.2012.116.issue-24/jp303907p/production/images/medium/jp-2012-03907p_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/jp303907p'>ACS Electronic Supporting Info</A></P>

Dynamic Expansion of Gastric Mucosal Doublecortin-Like Kinase 1-Expressing Cells in Response to Parietal Cell Loss Is Regulated by Gastrin

Choi, E.,Petersen, C.P.,Lapierre, L.A.,Williams, J.A.,Weis, V.G.,Goldenring, J.R.,Nam, K.T. American Association of Pathologists and Bacteriol 2015 The American journal of pathology Vol.185 No.8

Doublecortin-like kinase 1 (Dclk1) is considered a reliable marker for tuft cells in the gastrointestinal tract. We investigated the dynamic changes of tuft cells associated with mouse models of oxyntic atrophy and metaplasia in the stomach. Increases in the numbers of Dclk1-positive tuft cells were observed in several models of parietal cell loss. However, the expanded population of Dclk1-expressing cells showed a morphologically distinct structure in apical microvilli and acetylated microtubules, which was not seen in the tuft cells present in the normal gastric mucosa. These microvillar sensory cells (MVSCs) showed no evidence of proliferation. The expansion of the MVSCs induced by oxyntic atrophy was reversible after the return of parietal cells. More important, expansion of MVSCs after induced parietal cell loss was not observed in Gast<SUP>-/-</SUP> mice. Although the Dclk1-expressing cells in the normal gastric mucosa were in part derived from Lrig1-expressing stem cells, the Lrig1-lineaged cells did not produce the expanded Dclk1-expressing cells associated with oxyntic atrophy. These studies indicate that loss of parietal cells leads to the reversible emergence of a novel Dclk1-expressing sensory cell population in the gastric mucosa.

2,000년대의 콘크리이트 (상)

Kesler Clyde E.,Maples William A.,Anderson Arthur R.,Bates A. Allan,Burnett G.E.,Hognestad Eivind,Hudson W.R.,Khan Fazlur,Mather Bryant,Muenow Richard,Schmid Emil,Valore Jr. R.C. 한국시멘트협회 1973 시멘트 Vol.50 No.-

Synthesis of Host Polymers and Guests for Electrophosphorescence

Watkins Scott E.,Chan, Khai Leok,Cho, Sung-Yong,Evans Nicholas R.,Grimsdale Andrew C.,Holmes Andrew B.,Mak Chris S.K.,Sandee Albertus J.,Williams Charlotte K. The Polymer Society of Korea 2007 Macromolecular Research Vol.15 No.2

Significant progress has been realized in the design and synthesis of light emitting polymers that emit over the entire visible spectrum. However, up to seventy-five percent of charge recombination events can lead to triplet states that decay non-radiatively. Following the pioneering work in the field of small molecule organic light emitting devices, it has been found that solution processible iridium polymer complexes can be used to harness the wasted triplet energy. In this paper, new results with respect to the electrophosphorescence of solution processible tethered iridium polymer derivatives are presented. Furthermore, our approaches to the design of new high triplet energy conjugated polymer hosts are also reported.

Acute toxicity of aqueous extract of Ambrosia arborescens Mill. on biochemical and histopathological parameters in rats

Silva-Correa Carmen R.,Villarreal-La Torre Víctor E.,González-Siccha Anabel D.,Cruzado-Razco José L.,González-Blas María V.,Sagástegui-Guarniz William Antonio,Calderón-Peña Abhel A.,Aspajo-Villalaz Ci 한국독성학회 2022 Toxicological Research Vol.38 No.2

Medicinal plants play an important role in the management of various diseases, so their use has become widespread. However, in some cases the population uses plant species regardless of the toxicity they may possess. The objective of this study was to evaluate the acute toxicity of aqueous extract from the leaves of Ambrosia arborescens Mill. on the biochemical and histopathological parameters of albino Holtzman rats. To do this, the leaves of A. arborescens were collected in the province of Julcan, La Libertad Region—Peru. OECD (Organisation for Economic Cooperation and Development) guideline 423 was conducted, forming experimental groups of 10 animals each one (5 males and 5 females): Group I (Control), which received 2 mL physiological saline solution (SSF 0.9%), Groups II and III (A. arborescens-300 and A. arborescens-2000), which were given the aqueous extract leaves of A. arborescens in a single dose of 300 and 2000 mg/kg/day, respectively. On the 14th day of exposure, biochemical (creatinine, ALT and AST) and histopathological parameters were measured. The results show that the aqueous extract of A. arborescens at the dose of 2000 mg/kg produces an increase in biochemical parameters which is related to histopathological analysis of liver and renal tissue with mild congestion. The study concludes that the aqueous extract leaves of A. arborescens has a LD50 greater than 2000 mg/kg and produces mild congestion in kidneys and liver, but showed no significant toxicological changes in the other albino Holtzman rats organs.