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https://www.readbyqxmd.com/read/28351000/targeted-superparamagnetic-nanoparticles-coated-with-2-deoxy-d-gloucose-and-doxorubicin-more-sensitize-breast-cancer-cells-to-ionizing-radiation
#1
Jalil Pirayesh Islamian, Milad Hatamian, Negar Abbasi Aval, Mohammad Reza Rashidi, Asghar Mesbahi, Mohammad Mohammadzadeh, Mohammad Asghari Jafarabadi
INTRODUCTION: Nanoparticles are promising as a new approach to enhance chemo- radiotherapy efficiency in breast cancer mainly via targeted therapy. MATERIALS & METHODS: SKBR3 and T47D breast cancer cells were treated with superparamagnetic mesoporous hydroxyapatite nanocomposites (SPmHANs)conjugated with 1 μM doxorubicin and 0.5 mM 2-Deoxy-d-Glucose and irradiated with 1 and 2 Gy gamma rays in vitro. The treatment toxicity and also the apoptosis/necrosis ratio were measured by MTT assay and also ELISA cell death detection PLUS, respectively...
March 25, 2017: Breast: Official Journal of the European Society of Mastology
https://www.readbyqxmd.com/read/28350998/anticancer-copper-ii-phosphorus-dendrimers-are-potent-proapoptotic-bax-activators
#2
Serge Mignani, Nabil El Brahmi, Laure Eloy, Joel Poupon, Valérie Nicolas, Anke Steinmetz, Said El Kazzouli, Mosto M Bousmina, Mireille Blanchard-Desce, Anne-Marie Caminade, Jean-Pierre Majoral, Thierry Cresteil
A multivalent phosphorus dendrimer 1G3 and its corresponding Cu-complex, 1G3-Cu have been recently identified as agents retaining high antiproliferative potency. This antiproliferative capacity was preserved in cell lines overexpressing the efflux pump ABC B1, whereas cross-resistance was observed in ovarian cancer cell lines resistant to cisplatin. Theoretical 3D models were constructed: the dendrimers appear as irregularly shaped disk-like nano-objects of about 22 Å thickness and 49 Å diameter, which accumulated in cells after penetration by endocytosis...
March 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28350997/synthesis-and-biological-evaluation-of-hypoxia-activated-prodrugs-of-sn-38
#3
Chen Jin, Qiumeng Zhang, Wei Lu
We designed new hypoxia-activated prodrugs by conjugating (1-methyl-2-nitro-1H-imidazol-5-yl)methanol with 7-ethyl-10-hydroxy camptothecin (SN-38). Initially, we improved the method of multi-gram scale synthesis of (1-methyl-2-nitro-1H-imidazol-5-yl)methanol, which increased the yield to 42% compared to 8% by the original synthesis method. The improved method was used to synthesize evofosfamide (TH-302) and hypoxia-activated prodrugs of SN-38. Two different linkages between (1-methyl-2-nitro-1H-imidazol-5-yl)methanol and SN-38 were evaluated that afforded different hypoxia-selectivity and toxicity...
March 22, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28350958/photo-controlled-sirna-delivery-and-biomarker-triggered-aiegen-emission-by-upconversion-nayf4-yb-3-tm-3-sio2-nanoparticles-for-inducing-and-monitoring-stem-cell-differentiation
#4
Jinming Li, Chris Wai Tung Leung, Dexter Siu Hong Wong, Jianbin Xu, Rui Li, Yueyue Zhao, Chris Yu Yee Yung, Engui Zhao, Benzhong Tang, Liming Bian
Controlling differentiation of stem cell and monitoring the cell differentiation has attracted much research interest since the discovery of stem cells. In this regard, a novel and personalized near-infrared (NIR) light-activated nanoplatform is obtained by encapsulating the photoactivated caged compound (DMNPE/siRNA) and combining a MMP13 cleavaged imaging peptide-tetrapheny-lethene (TPE) unit conjugated with the mesoporous silica coated upconversion nanoparticles (UCNPs) for the remote control of cell differentiation and simultaneously for real-time monitoring of differentiation...
March 28, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28350467/relating-chromophoric-and-structural-disorder-in-conjugated-polymers
#5
Lena Simine, Peter J Rossky
The optoelectronic properties of amorphous conjugated polymers are sensitive to the details of the conformational disorder and spectroscopy provides the means for structural characterization of the fragments of the chain which interact with light - "chromophores". A faithful interpretation of spectroscopic conformational signatures, however, presents a theoretical challenge. Here we investigate the relationship between the ground state optical gaps, the properties of the excited states, and the structural features of chromophores of a single molecule poly(3-hexyl)-thiophene (P3HT), using quantum-classical atomistic simulations...
March 28, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28350458/immobilization-to-positively-charged-cellulose-nanocrystals-enhances-the-antibacterial-activity-and-stability-of-hen-egg-white-and-t4-lysozyme
#6
Adel Abouhmad, Tarek Dishisha, Magdy A Amin, Rajni Hatti-Kaul
Antibacterial bionanostructures were produced from cellulose nanocrystals (CNC) with immobilized lysozyme from hen egg white (HEW) and T4 bacteriophage, respectively. The nanocrystals were prepared from microcrystalline cellulose by ammonium persulfate oxidation with a yield of 68% and having an average size of 250 nm and low polydispersity index. HEW lysozyme (HEWL) and T4 lysozyme (T4L) were immobilized to CNC by different mechanisms including adsorption, and covalent coupling to carbodiimide-activated carboxylate groups, and to glutaraldehyde-activated aminated CNC (Am-CNC), respectively...
March 28, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28350451/ros-switchable-polymeric-nanoplatform-with-stimuli-responsive-release-for-active-targeted-drug-delivery-to-breast-cancer
#7
Yu Zhang, Qin Guo, Sai An, Yifei Lu, Jianfeng Li, Xi He, Lisha Liu, Yujie Zhang, Tao Sun, Chen Jiang
Tumor microenvironment plays a vital role in the process of tumor development, proliferation, invasion, and metastasis. It is well acknowledged that reduction in pH, reactive oxygen species (ROS), and increased level of glucose transporter 1 (GLUT1) have become featured intracellular and extracellular biochemical markers of cancer owing to oncogenic transformation and abnormal metabolism. To establish a distinctive drug delivery system directed against the tumor microenvironment features, we develop a newly engineered polymeric nanoplatform for efficient doxorubicin (DOX) delivery with reduced systemic toxicity and high antitumor efficiency...
March 28, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28350442/engineered-polymer-transferrin-conjugates-as-self-assembling-targeted-drug-delivery-systems
#8
Hiteshri Makwana, Francesca Mastrotto, Johannes Pall Magnusson, Darrell Sleep, Joanna Hay, Karl J Nicholls, Stephanie Allen, Cameron Alexander
Polymer-protein conjugates can be engineered to self-assemble into discrete and well-defined drug delivery systems which combine the advantages of receptor targeting and controlled drug release. We designed specific conjugates of the iron-binding and transport protein, transferrin (Tf), to combine the advantages of this serum-stable protein as a targeting agent for cancer cells with self-assembling polymers to act as carriers of cytotoxic drugs. Tf variants were expressed with cysteine residues at sites spanning different regions of the protein surface and the polymer conjugates grown from these variants were compared with polymer conjugates grown from non-selectively derivatised sites on native Tf...
March 28, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28346811/improved-soluble-scfv-elisa-screening-approach-for-antibody-discovery-using-phage-display-technology
#9
Mohammad R Tohidkia, Maryam Sepehri, Shirin Khajeh, Jaleh Barar, Yadollah Omidi
Phage display technology (PDT) is a powerful tool for the isolation of recombinant antibody (Ab) fragments. Using PDT, target molecule-specific phage-Ab clones are enriched through the "biopanning" process. The individual specific binders are screened by the monoclonal scFv enzyme-linked immunosorbent assay (ELISA) that may associate with inevitable false-negative results. Thus, in this study, three strategies were investigated for optimization of the scFvs screening using Tomlinson I and J libraries, including (1) optimizing the expression of functional scFvs, (2) improving the sensitivity of ELISA, and (3) preparing different samples containing scFvs...
March 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346750/intuitive-understanding-of-%C3%AF-delocalization-in-loose-and-%C3%AF-localization-in-tight-helical-conformations-of-an-oligosilane-chain
#10
Milena Jovanovic, Dean Antic, David Rooklin, Annika Bande, Josef Michl
Conformational effects on σ-electron delocalization in oligosilanes are addressed by Hartree-Fock and time-dependent density functional theory (B3LYP, 6-311G**) at MP2 optimized geometries of permethylated uniformly helical linear oligosilanes (all-ω-SinR2n+2) up to n = 16 and for backbone dihedral angles ω = 55 - 180̊. The extent of σ delocalization is judged by the partition ratio of the highest occupied molecular orbital and is reflected in the dependence of its shape and energy and of UV absorption spectra on n...
March 27, 2017: Chemistry, An Asian Journal
https://www.readbyqxmd.com/read/28346714/discrepant-serological-assays-for-pneumococcus-in-renal-transplant-recipients
#11
Jay A Fishman, David N Iklé, Robert A Wilkinson
Vaccine immunoprotection for Streptococcus pneumoniae is mediated by opsonizing antibodies targeting serotype-specific capsular polysaccharides. Quantitative antibody levels (ELISA) and antibody-mediated opsonophagcytic assays (OPA) measure vaccine-induced protection; correlation of these assays in transplantation requires investigation. This study examines the laboratory assessment of antibody titers in vaccinated renal recipients. Streptococcus pneumoniae 19A is common in immunocompromised hosts and is represented in protein-conjugate vaccines (PCV) and polysaccharide vaccines (PSV)...
March 27, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28346357/comparison-of-the-in-vivo-biotransformation-of-two-emerging-estrogenic-contaminants-bp2-and-bps-in-zebrafish-embryos-and-adults
#12
Vincent Le Fol, François Brion, Anne Hillenweck, Elisabeth Perdu, Sandrine Bruel, Selim Aït-Aïssa, Jean-Pierre Cravedi, Daniel Zalko
Zebrafish embryo assays are increasingly used in the toxicological assessment of endocrine disruptors. Among other advantages, these models are 3R-compliant and are fit for screening purposes. Biotransformation processes are well-recognized as a critical factor influencing toxic response, but major gaps of knowledge exist regarding the characterization of functional metabolic capacities expressed in zebrafish. Comparative metabolic studies between embryos and adults are even scarcer. Using ³H-labeled chemicals, we examined the fate of two estrogenic emerging contaminants, benzophenone-2 (BP2) and bisphenol S (BPS), in 4-day embryos and adult zebrafish...
March 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28346350/fast-and-selective-plasmonic-serotonin-detection-with-aptamer-gold-nanoparticle-conjugates
#13
Jorge L Chávez, Joshua A Hagen, Nancy Kelley-Loughnane
Neurotransmitters detection is critical to understanding communication between the brain and peripheral tissue. Serotonin is a key neurotransmitter linked to a number of conditions, but a full understanding of its role in disease is still lacking. The development of fast and selective serotonin detection platforms will provide researchers with tools to monitor serotonin in individuals before and after treatment for the condition of interest. Aptamer-gold nanoparticles conjugates that responded colorimetrically to serotonin with minimal response to its metabolite and other neurotransmitters were designed by simply adsorbing the DNA on the surface of AuNPs...
March 25, 2017: Sensors
https://www.readbyqxmd.com/read/28346226/a-tlr9-dependent-checkpoint-governs-b-cell-responses-to-dna-containing-antigens
#14
Vishal J Sindhava, Michael A Oropallo, Krishna Moody, Martin Naradikian, Lauren E Higdon, Lin Zhou, Arpita Myles, Nathaniel Green, Kerstin Nündel, William Stohl, Amanda M Schmidt, Wei Cao, Stephanie Dorta-Estremera, Taku Kambayashi, Ann Marshak-Rothstein, Michael P Cancro
Mature B cell pools retain a substantial proportion of polyreactive and self-reactive clonotypes, suggesting that activation checkpoints exist to reduce the initiation of autoreactive B cell responses. Here, we have described a relationship among the B cell receptor (BCR), TLR9, and cytokine signals that regulate B cell responses to DNA-containing antigens. In both mouse and human B cells, BCR ligands that deliver a TLR9 agonist induce an initial proliferative burst that is followed by apoptotic death. The latter mechanism involves p38-dependent G1 cell-cycle arrest and subsequent intrinsic mitochondrial apoptosis and is shared by all preimmune murine B cell subsets and CD27- human B cells...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28346192/menopausal-symptom-relief-and-side-effects-experienced-by-women-using-compounded-bioidentical-hormone-replacement-therapy-and-synthetic-conjugated-equine-estrogen-and-or-progestin-hormone-replacement-therapy-part-3
#15
Laura J Deleruyelle
The use of compounded bioidentical hormone replacement therapy by menopausal women has become a popular alternative to traditional synthetic conjugated equine estrogen and progestin hormone replacement therapy due to safety concerns raised by recent studies. However, due to the lack of randomized, large-scale trials to evaluate the efficacy and side-effect profile of compounded bioidentical hormone replacement therapy many healthcare providers are reluctant to prescribe such therapy. The purpose of this study was to compare women's menopausal symptom relief and side effects experienced when using compounded bioidentical hormone replacement therapy and traditional hormone replacement therapy...
January 2017: International Journal of Pharmaceutical Compounding
https://www.readbyqxmd.com/read/28346102/phage-display-derived-ligand-for-mucosal-transcytotic-receptor-gp-2-promotes-antigen-delivery-to-m-cells-and-induces-antigen-specific-immune-response
#16
Inam Ullah Khan, Jiansheng Huang, Rui Liu, Jingbo Wang, Jun Xie, Naishuo Zhu
Successful oral immunization depends on efficient delivery of antigens (Ags) to the mucosal immune induction site. Glycoprotein-2 (GP-2) is an integral membrane protein that is expressed specifically on M cells within follicle-associated epithelium (FAE) and serves as transcytotic receptor for luminal Ags. In this study, we selected peptide ligands against recombinant human GP-2 by screening a phage display library and evaluated their interaction with GP-2 in vitro and ex vivo. Selected peptides were conjugated to the C-terminal of enhanced green fluorescence protein (EGFP) and evaluated for their ability to induce an immune response in mice...
February 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28346086/a-small-molecule-microarray-approach-for-the-identification-of-e2-enzyme-inhibitors-in-ubiquitin-like-conjugation-pathways
#17
Katherine Zlotkowski, William M Hewitt, Ranu S Sinniah, Joseph E Tropea, Danielle Needle, George T Lountos, Joseph J Barchi, David S Waugh, John S Schneekloth
E2 enzymes in ubiquitin-like conjugation pathways are important, highly challenging pharmacological targets, and despite significant efforts, few noncovalent modulators have been discovered. Small-molecule microarray (SMM)-based screening was employed to identify an inhibitor of the "undruggable" small ubiquitin-like modifier (SUMO) E2 enzyme Ubc9. The inhibitor, a degradation product from a commercial screening collection, was chemically synthesized and evaluated in biochemical, mechanistic, and structure-activity relationship studies...
January 1, 2017: SLAS Discov
https://www.readbyqxmd.com/read/28345918/direct-s0%C3%A2-t-excitation-of-a-conjugated-polymer-repeat-unit-unusual-spin-forbidden-transitions-probed-by-time-resolved-electron-paramagnetic-resonance-spectroscopy
#18
Deborah L Meyer, Florian Lombeck, Sven Huettner, Michael Sommer, Till Biskup
A detailed understanding of the electronic structure of semiconducting polymers and their building blocks is essential to develop efficient materials for organic electronics. (Time-resolved) electron paramagnetic resonance (EPR) is particularly suited to address these questions, allowing to directly detect paramagnetic states and to reveal their spin-multiplicity, besides its clearly superior resolution compared to optical meth- ods. We present here evidence for a direct S0→T optical excitation of distinct triplet states in the repeat unit of a conjugated polymer used in organic photovoltaics...
March 27, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28345902/hyaluronate-peanut-agglutinin-conjugates-for-target-specific-bioimaging-of-colon-cancer
#19
Songeun Beack, Minsoo Cho, Young-Eun Kim, G-One Ahn, Sei Kwang Hahn
Colon cancer is one of the most common death-related cancers in the world. For treating the colon cancer, it is crucial to detect and remove malignant lesions in the early time. Here, we developed hyaluronate (HA) - peanut agglutinin (PNA) conjugates for bioimaging of colon cancer. The HA-PNA conjugates were successfully synthesized by the coupling reaction between aldehyde modified HA and the N-terminal amine group of PNA. For diagnostic imaging, rhodamine B (RhoB) was chemically conjugated onto PNA in HA-PNA conjugates...
March 27, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28345882/covalent-allosteric-inactivation-of-ptp1b-by-an-inhibitor-electrophile-conjugate
#20
Puminan Punthasee, Adrian R Laciak, Andrea Hicks Cummings, Kasi Viswanatharaju Ruddraraju, Sarah M Lewis, Roman Hillebrand, Harkewal Singh, John J Tanner, Kent S Gates
Protein tyrosine phosphatase 1B (PTP1B) is a validated drug target but it has proven difficult to develop medicinally-useful, reversible inhibitors of this enzyme. Here we explored covalent strategies for the inactivation of PTP1B using a conjugate composed of an active site-directed 5-aryl-1,2,5-thiadiazolidin-3-one 1,1-dioxide inhibitor connected via a short linker to an electrophilic α-bromoacetamide moiety. The inhibitor-electrophile conjugate 5a caused time-dependent loss of PTP1B activity consistent with a covalent inactivation mechanism...
March 27, 2017: Biochemistry
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