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https://www.readbyqxmd.com/read/28651330/rosiglitazone-improves-insulin-resistance-mediated-by-10-12-conjugated-linoleic-acid-in-a-male-mouse-model-of-metabolic-syndrome
#1
Shari Wang, Leela Goodspeed, Katherine E Turk, Barbara Houston, Laura J den Hartigh
Trans-10, cis-12 conjugated linoleic acid (10,12 CLA) is a dietary fatty acid that promotes weight loss and disproportionate fat loss. Obese mice fed a high fat high sucrose (HFHS) diet containing 10,12 CLA are resistant to weight gain and contain markedly reduced subcutaneous fat and adiponectin, with a concurrent lack of improvement in insulin sensitivity despite significant weight loss. Taken together, 10,12 CLA promotes a phenotype resembling PPARγ antagonism. Since thiazolidinediones such as rosiglitazone (Rosi) are used clinically to improve insulin sensitivity by activating PPARγ, with particular efficacy in subcutaneous white adipose tissue, we hypothesized that Rosi would improve glucose metabolism in mice losing weight with 10,12 CLA...
June 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28651154/new-comprehensive-studies-of-a-gold-iii-dithiocarbamate-complex-with-proven-anticancer-properties-aqueous-dissolution-with-cyclodextrins-pharmacokinetics-and-upstream-inhibition-of-the-ubiquitin-proteasome-pathway
#2
Marianna F Tomasello, Chiara Nardon, Valeria Lanza, Giuseppe Di Natale, Nicolò Pettenuzzo, Stefano Salmaso, Danilo Milardi, Paolo Caliceti, Giuseppe Pappalardo, Dolores Fregona
The gold(III)-dithiocarbamate complex AuL12 (dibromo [ethyl-N-(dithiocarboxy-kS,kS')-N-methylglycinate] gold(III)), is endowed with promising in vitro/in vivo antitumor activity and toxicological profile. Here, we report our recent strategies to improve its water solubility and stability under physiological conditions along with our efforts for unravelling its tangled mechanism of action. We used three types of α-cyclodextrins (CDs), namely β-CD, Me-β-CD and HP-β-CD to prepare aqueous solutions of AuL12...
June 19, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28650646/catalytic-conjugate-addition-of-electron-rich-heteroarenes-to-%C3%AE-%C3%AE-disubstituted-enones
#3
Tanner L Metz, Joshua Evans, Levi M Stanley
Catalytic conjugate additions of heteroarenes to β,β-disubstituted enones are reported. Additions of a range of heteroarene nucleophiles, including furans, indoles, a pyrrole, and a thiophene, to a variety of β,β-disubstituted enones occur to form the corresponding ketone products containing heteroarylated, all-carbon quaternary centers in up to 90% yield. These reactions occur under mild reaction conditions in the presence of low loadings of bismuth triflate.
June 26, 2017: Organic Letters
https://www.readbyqxmd.com/read/28650633/two-photon-spectroscopy-of-a-series-of-platinum-acetylides-conformation-induced-ground-state-symmetry-breaking
#4
Thomas M Cooper, Joy E Haley, Douglas M Krein, Aaron R Burke, Jonathan E Slagle, Aleksandr Mikhailov, Aleksander Rebane
With the goal of elucidating electronic and conformational effects on structure-spectroscopic property relationships in platinum acetylides, we synthesized a series of nominally centrosymmetric chromophores trans-Pt(PBu3)2(CC-Phenyl-X)2, where X = diphenylamino(DPA), NH2, OCH3, t-Bu, CH3, H, F, benzothiazole(BTH), CF3, CN and NO2. We collected one- and two-photon absorption spectra and also performed DFT and TDDFT calculations on the ground and excited state properties of these compounds. The DFT calculations revealed facile rotation between the two ligands, suggesting that the compounds exhibit nonplanar ground state conformations in solution...
June 26, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/28650621/novel-cdta-based-bifunctional-chelators-for-stable-and-inert-mn-ii-complexation-synthesis-and-physicochemical-characterization
#5
Christian Vanasschen, Enikő Molnár, Gyula Tircsó, Ferenc K Kálmán, Éva Tóth, Marie Brandt, Heinz H Coenen, Bernd Neumaier
In the search for Mn(II) MR and PET/MR imaging agents with optimal balance between thermodynamic stability, kinetic inertness, and relaxivity, two novel bifunctional Mn(II) chelators (BFMnCs) based on CDTA (trans-1,2-diaminocyclohexane-N,N,N',N'-tetraacetic acid) were synthesized. A six-step synthesis, involving the buildup of a functionalized trans-1,2-diaminocyclohexane core, provided CuAAC-reactive 6a and 6b bearing an alkyne or azide substituent on the cyclohexane ring, respectively (CuAAC = Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition)...
June 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28650616/cucurbit-6-uril-promoted-click-chemistry-for-protein-modification
#6
Joel A Finbloom, Kenneth Han, Clancy C Slack, Ariel L Furst, Matthew B Francis
Azide-alkyne cycloaddition is a powerful reaction for the formation of bioconjugates. When catalyzed by Cu(I) or strain promotion, this cycloaddition is considered to be a "click" reaction with many applications in chemical biology and materials science. We report a new type of azide-alkyne click chemistry for the synthesis of protein conjugates using cucurbit[6]uril (CB6) supramolecular chemistry. CB6-promoted azide-alkyne cycloaddition has been previously used for the synthesis of rotaxanes, but has not been applied to the development of complex bioconjugates...
June 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28650467/genome-wide-loss-of-function-genetic-screening-identifies-opioid-receptor-%C3%AE-1-as-a-key-regulator-of-l-asparaginase-resistance-in-pediatric-acute-lymphoblastic-leukemia
#7
S M Kang, J L Rosales, V Meier-Stephenson, S Kim, K Y Lee, A Narendran
L-asparaginase is a critical chemotherapeutic agent for acute lymphoblastic leukemia (ALL). It hydrolyzes plasma asparagine into aspartate and NH3, causing asparagine deficit and inhibition of protein synthesis and eventually, leukemic cell death. However, patient relapse often occurs due to development of resistance. The molecular mechanism by which ALL cells acquire resistance to L-asparaginase is unknown. Therefore, we sought to identify genes that are involved in L-asparaginase resistance in primary leukemic cells...
June 26, 2017: Oncogene
https://www.readbyqxmd.com/read/28650416/redistribution-of-streptococcus-pneumoniae-serotypes-after-nationwide-13-valent-pneumococcal-conjugate-vaccine-program-in-children-in-northern-taiwan
#8
Ying-Chun Cho, Nan-Chang Chiu, Chun-Yi Lu, Daniel Tsung-Ning Huang, Fu-Yuan Huang, Luan-Yin Chang, Li-Min Huang, Hsin Chi
BACKGROUND: After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of non-vaccine serotypes in children with invasive pneumococcal disease (IPD). A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy...
June 22, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28650317/serine-adp-ribosylation-reversal-by-the-hydrolase-arh3
#9
Ivan Ahel, Pietro Fontana, Juan José Bonfiglio, Luca Palazzo, Edward Bartlett, Ivan Matic
ADP-ribosylation (ADPr) is a posttranslational modification (PTM) of proteins that controls many cellular processes, including DNA repair, transcription, chromatin regulation and mitosis. A number of proteins catalyse the transfer and hydrolysis of ADPr, and also specify how and when the modification is conjugated to the targets. We recently discovered a new form of ADPr that is attached to serine residues in target proteins (Ser-ADPr) and showed that this PTM is specifically made by PARP1/HPF1 and PARP2/HPF1 complexes...
June 26, 2017: ELife
https://www.readbyqxmd.com/read/28650139/a-strategy-to-boost-the-efficiency-of-rhodanine-electron-acceptor-for-organic-dye-from-nonconjugation-to-conjugation
#10
Zhongquan Wan, Chunyang Jia, Yan Wang, Xiao-Jun Yao
Rhodanine-3-acetic acid is a very important and common electron acceptor of organic dye for dye-sensitized solar cells (DSSCs). However, the photovoltaic performances of organic dyes with rhodanine-3-acetic acid are relatively poor in the great majority of cases due to its nonconjugated structure between rhodanine ring and carboxyl anchoring group. Herein, a rhodanine derivative with conjugated structure between rhodanine ring and anchoring group is first employed as electron acceptor for TiO2-based DSSCs. Organic dye with this conjugated electron acceptor can not only maintain wide absorption spectrum, but also greatly improve the electronic structure and adsorption geometry on TiO2, which significantly enhances the electron injection and slows the charge recombination...
June 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28650116/polymeric-drug-delivery-systems-for-intraoral-site-specific-chemoprevention-of-oral-cancer
#11
REVIEW
Kashappa Goud H Desai
Oral cancer is among the most prevalent cancers in the world. Moreover, it is one of the major health problems and causes of death in many regions of the world. The traditional treatment modalities include surgical removal, radiation therapy, systemic chemotherapy, or a combination of these methods. In recent decades, there has been significant interest in intraoral site-specific chemoprevention via local drug delivery using polymeric systems. Because of its easy accessibility and clear visibility, the oral mucosa is amenable for local drug delivery...
June 26, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28650088/two-structurally-characterized-conformational-isomers-with-different-c-p-bonds
#12
Herbert W Roesky, Sudipta Roy, Kartik Chandra Mondal, Bin Li, Subrata Kundu, Christian J Schürmann, Sayan Dutta, Debasis Koley, Dietmar Stalke, Regine Herbst-Irmer
The cyclic alkyl(amino) carbene (cAAC) bonded chlorophosphinidene (cAAC)P-Cl (2/2´) was isolated from the direct reaction between cAAC and phosphorus trichloride (PCl3). Compound 2/2´ has been characterized by NMR and mass spectrometry. 31P NMR investigations [~160 ppm (major) and ~130 ppm (minor)] structural determination reveal that there are two different P environments of P-Cl unit. X-ray single crystal determination suggests a co-crystallization of two conformational isomers of (cAAC)P-Cl (2/2´); the major compound possessing a cAAC-PCl unit with CcAAC-P 1...
June 26, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28650017/a-large-pyrene-fused-n-heteroacene-fifteen-aromatic-six-membered-rings-annulated-in-one-row
#13
Zilong Wang, Peiyang Gu, Guangfeng Liu, Huiying Yao, Yishi Wu, Yongxin Li, Ganguly Rakesh, Jia Zhu, Hongbing Fu, Qichun Zhang
Here, we present our recent progress on the synthesis, crystal structure, physical properties and DFT calculations of a novel large pyrene-fused N-heteroacene (15RINGS) with 15 aromatic six-membered rings linearly fused in one row. The long conjugated backbone (more than 35 Å) of 15RINGS possesses a dual-bending feature (the bending angle is about 13.2°).
June 26, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28649998/uniform-electroactive-fibre-like-micelle-nanowires-for-organic-electronics
#14
Xiaoyu Li, Piotr J Wolanin, Liam R MacFarlane, Robert L Harniman, Jieshu Qian, Oliver E C Gould, Thomas G Dane, John Rudin, Martin J Cryan, Thomas Schmaltz, Holger Frauenrath, Mitchell A Winnik, Charl F J Faul, Ian Manners
Micelles formed by the self-assembly of block copolymers in selective solvents have attracted widespread attention and have uses in a wide variety of fields, whereas applications based on their electronic properties are virtually unexplored. Herein we describe studies of solution-processable, low-dispersity, electroactive fibre-like micelles of controlled length from π-conjugated diblock copolymers containing a crystalline regioregular poly(3-hexylthiophene) core and a solubilizing, amorphous regiosymmetric poly(3-hexylthiophene) or polystyrene corona...
June 26, 2017: Nature Communications
https://www.readbyqxmd.com/read/28649962/biological-sensing-using-hybridization-phase-of-plasmonic-resonances-with-photonic-lattice-modes-in-arrays-of-gold-nanoantennas
#15
Rithvik Reddy Gutha, Seyed M Sadeghi, Christina Sharp, Waylin J Wing
We study biological sensing using the hybridization phase of localized surface plasmon resonances (LSPRs) with diffraction modes (photonic lattice modes) in arrays of gold nanoantennas. We map the degree of the hybridization process using an embedding dielectric material (Si), identifying the critical thicknesses wherein the optical responses of the arrays are mainly governed by pure LSPRs (insignificant hybridization), Fano-type coupling of LSPRs with diffraction orders (hybridization state), and their intermediate state (hybridization phase)...
June 26, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28649842/lipo-oligomer-nanoformulations-for-targeted-intracellular-protein-delivery
#16
Peng Zhang, Benjamin Steinborn, Ulrich Lächelt, Stefan Zahler, Ernst Wagner
Here, we report novel lipo-oligoaminoamide nanoformulations for targeted intracellular protein delivery. Formulations are generated by first bioreversibly conjugating a sequence-defined amphiphilic lipo-oligomer 728 to the cargo protein via disulfide bonds, followed by formulation of the formed 728-SS-protein conjugate with different helper lipids in various compositions. The triblock oligoaminoamide 728 contains cysteines for reversible covalent protein conjugation and crosslink-stabilization of formed nanoparticles, polyethylene glycol (PEG) for shielding and providing a hydrophilic domain, eight cationizable succinoyl tetraethylene pentamine (Stp) repeats for endosomal buffering and escape into the cytosol, and a tetra-oleic acid block for hydrophobic stabilization...
June 26, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28649772/luminescence-color-tuning-of-stable-luminescent-solid-materials-from-blue-to-nir-based-on-bis-o-carborane-substituted-oligoacenes
#17
Hirofumi Naito, Kenta Nishino, Yasuhiro Morisaki, Kazuo Tanaka, Yoshiki Chujo
It was known that the aryl-substituted o-carboranes showed highly-efficient solid-state emission in the previous studies. To demonstrate color tuning of solid-state emission from aryl-o-carborane-based system, bis-o-carborane-substituted oligoacenes were synthesized and their properties were systematically investigated. Optical and electrochemical measurements revealed efficient decreases in energy band gaps and lowest unoccupied molecular orbital (LUMO) levels by adding the number of fused benzene rings for the extension of π-conjugation...
June 26, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28649747/synthesis-structure-and-biological-evaluation-of-a-platinum-carbazole-conjugate
#18
Young Cheun, Myong-Chul Koag, Youssef W Naguib, Hala Ouzon-Shubeita, Zhengrong Cui, Danaya Pakotiprapha, Seongmin Lee
Cisplatin resistance is caused, in part, by the efficient removal of the helix-distorting cisplatin 1,2-intrastrand crosslinks by nucleotide excision repair (NER) machinery. To make a platinum-DNA adduct that causes less helical distortion than the cisplatin 1,2-intrastrand adduct, we designed and synthesized a monofunctional platinum-carbazole conjugate (carbazoleplatin). The 2.5Å crystal structure of carbazoleplatin-DNA adduct revealed both the monoplatination of the N7 of a guanine (G) base and the intercalation into two G:C base pairs while causing a minor distortion of the DNA helix...
June 26, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28649690/enzymatic-conjugation-using-branched-linkers-for-constructing-homogeneous-antibody-drug-conjugates-with-high-potency
#19
Yasuaki Anami, Wei Xiong, Xun Gui, Mi Deng, Cheng Cheng Zhang, Ningyan Zhang, Zhiqiang An, Kyoji Tsuchikama
Antibody-drug conjugates (ADCs) are emerging therapeutic agents in the treatment of cancer, and various conjugation strategies and chemical linkers have been developed to efficiently construct ADCs. Despite previous extensive efforts for improving conjugation efficiency and ADC homogeneity, most ADC linkers developed to date load only single payloads. Branched linkers that can load multiple payload molecules have yet to be fully explored. It is logical to envisage that a multi-loading strategy allows for increase in drug-to-antibody ratio (DAR) with less chemical or enzymatic modification to the antibody structure compared to traditional linear linkers, leading to efficient ADC construction, minimal destabilization of the antibody structure, and enhanced ADC efficacy...
June 26, 2017: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/28649658/niche-localized-tumor-cells-are-protected-from-her2-targeted-therapy-via-upregulation-of-an-anti-apoptotic-program-in-vivo
#20
Jason J Zoeller, Roderick T Bronson, Laura M Selfors, Gordon B Mills, Joan S Brugge
Several lines of evidence suggest that components of the tumor microenvironment, specifically basement membrane and extracellular matrix proteins, influence drug sensitivities. We previously reported differential drug sensitivity of tumor cells localized adjacent to laminin-rich extracellular matrix in three-dimensional tumor spheroid cultures. To evaluate whether differential intra-tumor responses to targeted therapy occur in vivo, we examined the sensitivity of human epidermal growth factor receptor 2-positive tumors to lapatinib using a previously described ductal carcinoma in situ-like model characterized by tumor cell confinement within ductal structures surrounded by an organized basement membrane...
2017: NPJ Breast Cancer
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