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https://www.readbyqxmd.com/read/28629980/polymer-nanoassemblies-with-hydrophobic-pendant-groups-in-the-core-induce-false-positive-sirna-transfection-in-luciferase-reporter-assays
#1
Steven Rheiner, Derek Reichel, Piotr Rychahou, Tadahide Izumi, Hsin-Sheng Yang, Younsoo Bae
Poly(ethylene glycol)-conjugated polyethylenimine (PEG-PEI) is a widely studied cationic polymer used to develop non-viral vectors for siRNA therapy of genetic disorders including cancer. Cell lines stably expressing luciferase reporter protein typically evaluate the transfection efficacy of siRNA/PEG-PEI complexes, however recent findings revealed that PEG-PEI can reduce luciferase expression independent of siRNA. This study elucidates a cause of the false positive effect in luciferase assays by using polymer nanoassemblies (PNAs) made from PEG, PEI, poly-(L-lysine) (PLL), palmitate (PAL), and deoxycholate (DOC): PEG-PEI (2P), PEG-PEI-PAL (3P), PEG-PLL (2P'), PEG-PLL-PAL (3P'), and PEG-PEI-DOC (2PD)...
June 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28624242/facile-access-to-modified-and-functionalized-pnas-through-ugi-based-solid-phase-oligomerization
#2
Jacques Saarbach, Daniela Masi, Claudio Zambaldo, Nicolas Winssinger
Peptide nucleic acids (PNAs) derivatized with functional molecules are increasingly used in diverse biosupramolecular applications. PNAs have proven to be highly tolerant to modifications and different applications benefit from the use of modified PNAs, in particular modifications at the γ position. Herein we report simple protocols to access modified PNAs from iterative Ugi couplings which allow modular modifications at the α, β or γ position of the PNA backbone from simple starting materials. We demonstrate the utility of the method with the synthesis of several bioactive small molecules (a peptide ligand, a kinase inhibitor and a glycan)-PNA conjugates...
June 14, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28617037/quantitative-determination-of-a-sirna-ad00370-in-rat-plasma-using-peptide-nucleic-acid-probe-and-hplc-with-fluorescence-detection
#3
Qingguo Tian, Juan Rogness, Min Meng, Zheng Li
AIM: Toxicokinetic and pharmacokinetic studies of therapeutic oligonucleotides require validated bioanalytical methods for sensitive and specific quantification of oligonucleotide drug candidates in biological samples. RESULTS: A peptide nucleic acid (PNA) hybridization-based HPLC-fluorescence assay was developed and validated for quantification of Arrowhead Pharmaceuticals' proprietary siRNA in rat plasma samples via hybridization and anion-exchange-HPLC (AEX-HPLC) with fluorescence detection...
June 15, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28610975/pna-monomers-fully-compatible-with-standard-fmoc-based-solid-phase-synthesis-of-pseudocomplementary-pna
#4
Toru Sugiyama, Genki Hasegawa, Chie Niikura, Keiko Kuwata, Yasutada Imamura, Yosuke Demizu, Masaaki Kurihara, Atsushi Kittaka
Here we report the synthesis of new PNA monomers for pseudocomplementary PNA (pcPNA) that are fully compatible with standard Fmoc chemistry. The thiocarbonyl group of the 2-thiouracil (sU) monomer was protected with the 4-methoxy-2-methybenzyl group (MMPM), while the exocyclic amino groups of diaminopurine (D) were protected with Boc groups. The newly synthesized monomers were incorporated into a 10-mer PNA oligomer using standard Fmoc chemistry for solid-phase synthesis. Oligomerization proceeded smoothly and the HPLC and MALDI-TOF MS analyses indicated that there was no remaining MMPM on the sU nucleobase...
June 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28607435/preferential-suppression-of-anopheles-gambiae-host-sequences-allows-detection-of-the-mosquito-eukaryotic-microbiome
#5
Eugeni Belda, Boubacar Coulibaly, Abdrahamane Fofana, Abdoul H Beavogui, Sekou F Traore, Daryl M Gohl, Kenneth D Vernick, Michelle M Riehle
Anopheles mosquitoes are vectors of the human malaria parasite, Plasmodium falciparum. The vector microbiota is a likely factor influencing parasite transmission. The prokaryotic microbiota of mosquitoes is efficiently surveyed by sequencing of hypervariable regions of the 16s ribosomal RNA (rRNA) gene. However, identification of the eukaryotic microbiota by targeting the 18s rRNA gene is challenging due to simultaneous amplification of the abundant 18s rRNA gene target in the mosquito host. Consequently, the eukaryotic microbial diversity of mosquitoes is vastly underexplored...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28605126/tin-sulfide-based-nanohybrid-for-high-performance-anode-of-sodium-ion-batteries
#6
Jaewon Choi, Na Rae Kim, Kyungmi Lim, Kyojin Ku, Hyeon Ji Yoon, Jin Gu Kang, Kisuk Kang, Paul V Braun, Hyoung-Joon Jin, Young Soo Yun
Nanohybrid anode materials for Na-ion batteries (NIBs) based on conversion and/or alloying reactions can provide significantly improved energy and power characteristics, while suffering from low Coulombic efficiency and unfavorable voltage properties. An NIB paper-type nanohybrid anode (PNA) based on tin sulfide nanoparticles and acid-treated multiwalled carbon nanotubes is reported. In 1 m NaPF6 dissolved in diethylene glycol dimethyl ether as an electrolyte, the above PNA shows a high reversible capacity of ≈1200 mAh g(-1) and a large voltage plateau corresponding to a capacity of ≈550 mAh g(-1) in the low-voltage region of ≈0...
June 12, 2017: Small
https://www.readbyqxmd.com/read/28601017/effect-of-substituted-phenylamine-antioxidants-on-three-life-stages-of-the-freshwater-mussel-lampsilis-siliquoidea
#7
R S Prosser, P L Gillis, E A M Holman, D Schissler, H Ikert, J Toito, E Gilroy, S Campbell, A J Bartlett, D Milani, J L Parrott, V K Balakrishnan
Substituted phenylamines (SPAs) are incorporated into a variety of consumer products (e.g., polymers, lubricants) in order to increase the lifespan of the products by acting as a primary antioxidant. Based on their physicochemical properties, if SPAs were to enter the aquatic environment, they would likely partition into sediment. No studies to date have investigated the effect of sediment-associated SPAs on aquatic organisms. The current study examined the effect of four SPAs (diphenylamine (DPA); N-phenyl-1-napthylamine (PNA); N-(1,3-dimethylbutyl)-N'-phenyl-1,4-phenylenediamine (DPPDA); 4,4'-methylene-bis[N-sec-butylaniline] (MBA)) on three different life stages of the freshwater mussel, Lampsilis siliquoidea...
June 7, 2017: Environmental Pollution
https://www.readbyqxmd.com/read/28600771/multiplex-peptide-nucleic-acid-fluorescence-in-situ-hybridization-pna-fish-for-diagnosis-of-bacterial-vaginosis
#8
Antonio Machado, Nuno Cerca
Fluorescence in situ hybridization (FISH) is a molecular method used to identify and quantify microorganisms in a wide range of samples. This technique combines the simplicity of microscopic observation and the specificity of DNA/rRNA hybridization, allowing detection of selected bacterial species and morphologic visualization. Here, we describe a quantitative molecular diagnosis of bacterial vaginosis, based on the classical Nugent score. Our probes are able to differentiate Lactobacillus spp. and Gardnerella vaginalis from the other undefined bacterial species considered in the Nugent score...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28600208/purification-and-partial-characterization-of-a-low-molecular-fibrinolytic-serine-metalloprotease-c142-from-the-culture-supernatant-of-bacillus-subtilis-c142
#9
Jun-Hui Choi, Jung-Eun Kim, Seung Kim, Jae-Woo Yoon, Dae-Hun Park, Hyun-Jae Shin, Hyo-Jeong Lee, Seung-Sik Cho
Novel serine metalloprotease-like enzyme, C142 was purified from the culture supernatant of Bacillus subtilis C142. The C142 was purified to homogeneity by a two-step procedure with a 20.7-fold increase in specific activity and 0.9% recovery. The molecular mass of C142 was approximately 23.5kDa based on SDS-PAGE. The N-terminal amino acid sequence of the first 21 amino acids of C142 was AQSVPYGISQIKAPALHSQGY. Its optimum pH, optimum temperature, pH stability, and thermal stability were pH 6, 40°C, pH 6-8, and 20-35°C, respectively...
June 6, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28583598/detection-of-macrophages-in-rabbit-semen-and-their-relationship-with-semen-quality
#10
Lenka Kuželová, Jaromír Vašíček, Ján Rafay, Peter Chrenek
We aimed at the evaluating the occurrence of macrophages in rabbit semen and finding possible relationship between macrophage concentration and spermatozoa quality. The concentration of macrophages in semen samples from broiler rabbit males of lines M91 and P91 (n = 30) without overt evidence of genital tract infections was determined using monocyte/macrophage lineage antigen CD14 and flow cytometry. Then the rabbits were assigned into three groups according to the macrophage concentration in semen (MΦ1 group with less than 1 × 10(6) macrophages/mL, MΦ2 group with 1...
July 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/28576048/study-on-%C3%AE-cyclodextrin-complexed-nanogels-with-improved-thermal-response-for-anticancer-drug-delivery
#11
Panpan Yi, Yifeng Wang, Peixin He, Yuan Zhan, Zhengguang Sun, Yulin Li, Yuhong Zhang
For achievement of controllability in drug delivery, development of nanocarriers with thermal response is one of the most investigated stimulative strategies for oncological treatment. How to improve the thermosensitivity of the nanocarriers is an important factor for their successful drug delivery applications. In this study, a kind of complexed nanogels (PNACD) was developed by incorporating β-cyclodextrin (β-CD) into the nanogels of copolymers of N-isopropylacrylamide (NIPAM) and acrylic acid (AA) during their polymerization via in situ crosslinking of N,N'-methylenebisacrylamide (MBA) as a crosslinker...
September 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28562823/transcolonic-perirectal-notes-access-pna-a-feasibility-study-with-survival-in-swine-model
#12
André L A Oliveira, Ricardo Zorron, Flavio M M DE Oliveira, Marcelo B Dos Santos, Jussara P Scheffer, Marcelo Rios, Fernanda Antunes
Transrectal access still has some unsolved issues such as spatial orientation, infection, access and site closure. This study presents a simple technique to perform transcolonic access with survival in a swine model series. A new technique for NOTES perirectal access to perform retroperitoneoscopy, peritoneoscopy, liver and lymphnode biopsies was performed in 6 pigs, using Totally NOTES technique. The specimens were extracted transanally. The flexible endoscope was inserted through a posterior transmural incision and the retrorectal space...
May 2017: Anais da Academia Brasileira de Ciências
https://www.readbyqxmd.com/read/28556026/preclinical-pilot-study-monitoring-topical-drug-penetration-and-dermal-bioavailability-of-a-peptidase-inhibitor-from-different-galenic-formulations-into-pig-dermis-using-cutaneous-microdialysis
#13
S R Quist, A Heimburg, U Bank, D Mahnkopf, G Koch, H Gollnick, M Täger, S Ansorge
BACKGROUND: Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body. AIM: To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families. METHODS: Using CM, we tested the penetration and dermal bioavailability of IP10...
May 29, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28555724/population-pharmacokinetics-of-amoxicillin-in-term-neonates-undergoing-moderate-hypothermia
#14
Yuma A Bijleveld, Ron A A Mathôt, Johanna H van der Lee, Floris Groenendaal, Peter H Dijk, Arno van Heijst, Sinno H P Simons, Koen P Dijkman, Henrica L M van Straaten, Monique Rijken, Inge A Zonnenberg, Filip Cools, Alexandra Zecic, Debbie H G M Nuytemans, Anton H van Kaam, Timo R de Haan
The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N=125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3000 g, 2 days PNA (i.e. TEMP 33.5°C), and normal UO, Cl was 0...
May 27, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28551389/mutation-analysis-of-ctnnb1-gene-and-the-ras-pathway-genes-kras-nras-braf-and-pik3ca-in-eyelid-sebaceous-carcinomas
#15
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe
Sebaceous carcinoma (SC) represents a rare, aggressive eyelid malignancy with poor prognosis and is a possible component of Muir-Torre syndrome. However, genetic features as driver mutations or potential therapeutic targets are not fully elucidated. Recent a few studies have shown that SCs have concurrently multiple mutations including RAS/RAF/MAPK and PI3K/Akt pathways via next-generation sequencing in western population. Because we recently demonstrated absence of KRAS mutations in Korean eyelid SCs, we extended our previous study to the analysis of NRAS, BRAF, PIK3CA, and CTNNB1 mutations, and the examination of related protein expressions in 15 eyelid SCs...
June 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28548967/detection-of-activating-and-acquired-resistant-mutation-in-plasma-from-egfr-mutated-nsclc-patients-by-peptide-nucleic-acid-pna-clamping-assisted-fluorescence-melting-curve-analysis
#16
Chang Gon Kim, Hyo Sup Shim, Min Hee Hong, Yoon Jin Cha, Su Jin Heo, Hyung Soon Park, Jee Hung Kim, Jin Gu Lee, Chang Young Lee, Byoung Chul Cho, Hye Ryun Kim
This study was designed to prospectively examine whether peptide nucleic acid clamping-assisted fluorescence melting curve analysis (PANAMutyper™) is feasible for the detection of activating and acquired resistant epidermal growth factor receptor (EGFR) mutation in plasma. Patients with non-small cell lung cancer harboring activating EGFR mutations who were scheduled to undergo EGFR-tyrosine kinase inhibitors (EGFR-TKIs) were enrolled between September 2011 and March 2015. A total of 102 patients with EGFR-mutated lung cancer were enrolled, 53 had available plasma samples at disease progression, and 28 underwent serial plasma sampling during EGFR-TKI treatment...
May 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28539717/caspase-mediated-apoptotic-effects-of-ebenus-boissieri-barbey-extracts-on-human-cervical-cancer-cell-line-hela
#17
Ece Simsek, Nilufer Imir, Esra Arslan Aydemir, Ramazan Suleyman Gokturk, Erdem Yesilada, Kayahan Fiskin
BACKGROUND: Ebenus boissieri Barbey is an Antalya, Turkey-endemic plant belonging to Fabaceae family. The aerial parts and the roots of E. boissieri Barbey were used in this study. OBJECTIVE: In the present study, we have examined the apoptotic effects of hydroalcoholic extracts of E. boissieri Barbey in human cervical cancer cell line HeLa. MATERIALS AND METHODS: To determine the cytotoxic effect, cells were treated with various concentrations of extracts for 24, 48, and 72 h incubation periods...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28532812/the-occurrence-of-biofilm-in-an-equine-experimental-wound-model-of-healing-by-secondary-intention
#18
E Jørgensen, L Bay, T Bjarnsholt, L Bundgaard, M A Sørensen, S Jacobsen
In humans, biofilm is a well-known cause of delayed healing and low-grade inflammation of chronic wounds. In horses, biofilm formation in wounds has been studied to a very limited degree. The objective of this study was thus to investigate the occurrence of biofilm in equine experimental wounds healing by secondary intention. Tissue biopsies from non-contaminated, experimental excisional shoulder and limb wounds were obtained on day 1-2, day 7-10 and day 14-15 post-wounding. Limb wounds were either un-bandaged or bandaged to induce exuberant granulation tissue (EGT) formation and thereby impaired healing...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28506869/model-based-clinical-dose-optimization-for-phenobarbital-in-neonates-an-illustration-of-the-importance-of-data-sharing-and-external-validation
#19
Swantje Völler, Robert B Flint, Leo M Stolk, Pieter L J Degraeuwe, Sinno H P Simons, Paula Pokorna, David M Burger, Ronald de Groot, Dick Tibboel, Catherijne A J Knibbe
BACKGROUND: Particularly in the pediatric clinical pharmacology field, data-sharing offers the possibility of making the most of all available data. In this study, we utilize previously collected therapeutic drug monitoring (TDM) data of term and preterm newborns to develop a population pharmacokinetic model for phenobarbital. We externally validate the model using prospective phenobarbital data from an ongoing pharmacokinetic study in preterm neonates. METHODS: TDM data from 53 neonates (gestational age (GA): 37 (24-42) weeks, bodyweight: 2...
May 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28504473/dynamic-cooperative-glycan-assembly-blocks-the-binding-of-bacterial-lectins-to-epithelial-cells
#20
Takuya Machida, Alexandre Novoa, Émilie Gillon, Shuangshuang Zheng, Julie Claudinon, Thorsten Eierhoff, Anne Imberty, Winfried Römer, Nicolas Winssinger
Pathogens frequently rely on lectins for adhesion and cellular entry into the host. Since these interactions typically result from multimeric binding of lectins to cell-surface glycans, novel therapeutic strategies are being developed with the use of glycomimetics as competitors of such interactions. Herein we study the benefit of nucleic acid based oligomeric assemblies with PNA-fucose conjugates. We demonstrate that the interactions of a lectin with epithelial cells can be inhibited with conjugates that do not form stable assemblies in solution but benefit from cooperativity between ligand-protein interactions and PNA hybridization to achieve high affinity...
June 6, 2017: Angewandte Chemie
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