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https://www.readbyqxmd.com/read/30231617/exploring-the-anomalous-cytotoxicity-of-commercially-available-poly-n-isopropyl-acrylamide-substrates
#1
Phuong A H Nguyen, Lyndsay Stapleton, Adrian Ledesma-Mendoza, Darnell L Cuylear, Marta A Cooperstein, Heather E Canavan
Poly( N -isopropyl acrylamide) (pNIPAM) is a stimulus-responsive polymer that has been of great interest to the bioengineering community. When the temperature is lowered below its lower critical solution temperature (∼32 °C), pNIPAM rapidly hydrates, and adherent cells detach as intact cell sheets. This cell-releasing behavior in a physiologically relevant temperature range has led to NIPAM's use for engineered tissues and other devices. In a previous study, however, the authors found that although most techniques used to polymerize NIPAM yield biocompatible films, some formulations from commercially-available NIPAM (cpNIPAM) can be cytotoxic...
September 19, 2018: Biointerphases
https://www.readbyqxmd.com/read/30227347/an-azine-based-carbothioamide-chemosensor-for-selective-and-sensitive-turn-on-off-sequential-detection-of-zn-ii-and-h-2-po-4-live-cell-imaging-and-inhibit-logic-gate
#2
Rakesh Purkait, Ananya Das Mahapatra, Debprasad Chattopadhyay, Chittaranjan Sinha
Hydrazino-carbothioamide, 1, serves as a turn-on fluorescent chemosensor to Zn2+ and the mixture shows green emission (λem 492) in presence of large number of ions with impressive limit of detection (LOD), 0.59 nM. Intense fluorescence of Zn-complex is selectively turn-off upon adding H2 PO4 - only to the limit of detection, 26 μM, while other anions remain silent. The sensing mechanism of 1 is established by suppressing the ESIPT of 1 and complexation with Zn2+ (CHEF) is supported by Job's plot, 1 H NMR, and HR-MS data...
September 11, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/30220831/thiazoles-with-cyclopropyl-fragment-as-antifungal-anticonvulsant-and-anti-toxoplasma-gondii-agents-synthesis-toxicity-evaluation-and-molecular-docking-study
#3
Krzysztof Z Łączkowski, Natalia Konklewska, Anna Biernasiuk, Anna Malm, Kinga Sałat, Anna Furgała, Katarzyna Dzitko, Adrian Bekier, Angelika Baranowska-Łączkowska, Agata Paneth
Synthesis and investigation of antifungal, anticonvulsant and anti- Toxoplasma gondii activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole 3a - 3j are presented. Among the derivatives, compounds 3a - 3d and 3f - 3j possess very high activity against Candida spp. ATCC with MIC = 0.015-7.81 µg/ml. Compounds 3a - 3d and 3f - 3j possess also very high activity towards most of strains of Candida spp. isolated from clinical materials with MIC = 0.015-7.81 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control...
2018: Medicinal Chemistry Research
https://www.readbyqxmd.com/read/30219365/rapid-quantification-of-vesicular-stomatitis-virus-in-vero-cells-using-laser-force-cytology
#4
Colin G Hebert, Nicole DiNardo, Zachary L Evans, Sean J Hart, Anna-Barbara Hachmann
The ability to rapidly and accurately determine viral infectivity can help improve the speed of vaccine product development and manufacturing. Current methods to determine infectious viral titers, such as the end-point dilution (50% tissue culture infective dose, TCID50) and plaque assays are slow, labor intensive, and often subjective. In order to accelerate virus quantification, Laser Force Cytology (LFC) was used to monitor vesicular stomatitis virus (VSV) infection in Vero (African green monkey kidney) cells...
October 1, 2018: Vaccine
https://www.readbyqxmd.com/read/30214457/4-phenyl-1-3-thiazole-2-amines-as-scaffolds-for-new-antileishmanial-agents
#5
Carina Agostinho Rodrigues, Paloma Freire Dos Santos, Marcela Oliveira Legramanti da Costa, Thais Fernanda Amorim Pavani, Patrícia Xander, Mariana Marques Geraldo, Ana Mengarda, Josué de Moraes, Daniela Gonçales Galasse Rando
Background: There is still a need for new alternatives in pharmacological therapy for neglected diseases, as the drugs available show high toxicity and parenteral administration. That is the case for the treatment of leishmaniasis, particularly to the cutaneous clinical form of the disease. In this study, we present the synthesis and biological screening of eight 4-phenyl-1,3-thiazol-2-amines assayed against Leishmania amazonensis . Herein we propose that these compounds are good starting points for the search of new antileishmanial drugs by demonstrating some of the structural aspects which could interfere with the observed activity, as well as suggesting potential macromolecular targets...
2018: Journal of Venomous Animals and Toxins Including Tropical Diseases
https://www.readbyqxmd.com/read/30213846/evaluation-of-a-novel-pet-radioligand-to-image-o-glcnacase-in-brain-and-periphery-of-rhesus-monkey-and-knock-out-mouse
#6
Soumen Paul, Mohammad B Haskali, Jeih-San Liow, Sami S Zoghbi, Vanessa N Barth, Marcy Comly Kolodrubetz, Michelle R Bond, Cheryl L Morse, Robert L Gladding, Michael P Frankland, Nancy Kant, Lawrence Slieker, Sergey Shcherbinin, Hugh N Nuthall, Paolo Zanotti-Fregonara, John A Hanover, Cynthia Jesudason, Victor W Pike, Robert B Innis
Accumulation of hyper-phosphorylated tau, a microtubule-associated protein, plays an important role in the progression of Alzheimer's disease (AD). Animal studies suggest that one strategy for treating AD and related tauopathies may be inhibition of O-GlcNAcase (OGA), which may subsequently decrease pathological tau phosphorylation Here, we report the pharmacokinetics of a novel positron emission tomography (PET) radioligand, 18 F-LSN3316612, which binds with high affinity and selectivity to OGA. Methods: PET imaging was performed in rhesus monkeys at baseline and after administration of either thiamet G, a potent OGA inhibitor, or nonradioactive LSN3316612...
September 13, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/30198266/effects-of-decavanadate-salts-with-organic-and-inorganic-cations-on-escherichia-coli-giardia-intestinalis-and-vero-cells
#7
Juliana M Missina, Bruno Gavinho, Kahoana Postal, Francielli S Santana, Glaucio Valdameri, Emanuel M de Souza, David L Hughes, Marcel I Ramirez, Jaísa F Soares, Giovana G Nunes
Decavanadate salts with nicotinamide (3-pyridinecarboxamide, 3-pca) and isonicotinamide (4-pyridinecarboxamide, 4-pca) in both neutral and protonated forms, (3-Hpca)4 [H2 V10 O28 ]·2H2 O·2(3-pca) (complex I) and (4-Hpca)4 [H2 V10 O28 ]·2(4-pca) (complex II), have been synthesized and characterized by vibrational spectroscopy (infrared and Raman), thermogravimetric analysis (TGA), 51 V NMR, and single-crystal X-ray diffraction analysis. The effects of sodium decavanadate (henceforth called NaV10 ) and compounds I and II on Escherichia coli, Giardia intestinalis, and Vero (African green monkey epithelial kidney) cells were evaluated...
September 10, 2018: Inorganic Chemistry
https://www.readbyqxmd.com/read/30179610/tp0463518-a-novel-inhibitor-for-hypoxia-inducible-factor-prolyl-hydroxylases-increases-erythropoietin-in-rodents-and-monkeys-with-a-good-pharmacokinetics-pharmacodynamics-correlation
#8
Sota Kato, Noriko Takayama, Hiroki Takano, Hiroko Koretsune, Chie Koizumi, Ei-Ichi Kunioka, Saeko Uchida, Teisuke Takahashi, Koji Yamamoto
Hypoxia-inducible factor prolyl hydroxylases (PHDs) inhibitor stabilizes hypoxia inducible factor alpha, which increases erythropoietin (EPO) expression via the hypoxia response element. Therefore, PHDs inhibitors have been developed as novel therapeutic agents for anemia. Here, we characterize the in vitro and in vivo pharmacological profiles of TP0463518, 2-[[1-[[6-(4-chlorophenoxy)pyridin-3-yl]methyl]-4-hydroxy-6-oxo-2,3-dihydropyridine-5-carbonyl]amino]acetic acid, a novel potent PHDs inhibitor. TP0463518 competitively inhibited human PHD2 with a Ki value of 5...
September 1, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/30155487/renal-ischemia-reperfusion-injury-in-a-diabetic-monkey-model-and-therapeutic-testing-of-human-bone-marrow-derived-mesenchymal-stem-cells
#9
Kyo Won Lee, Tae Min Kim, Kyeong Sik Kim, Seunghwan Lee, Junhun Cho, Jae Berm Park, Ghee Young Kwon, Sung Joo Kim
Clinically, acute kidney injury (AKI) episodes in diabetes mellitus (DM) patients are associated with a cumulative risk of developing end-stage renal disease. In this study, we asked whether the severity of AKI induced by renal ischemia-reperfusion injury (IRI) is more prominent in DM than in non-DM control using a cynomolgus monkey ( Macaca fascicularis) model. We also investigated whether human bone marrow-derived mesenchymal stem cells (hBM-MSCs) infused via the renal artery could ameliorate renal IRI in DM monkeys...
2018: Journal of Diabetes Research
https://www.readbyqxmd.com/read/30139307/the-nonclinical-safety-profile-of-galnac-conjugated-rnai-therapeutics-in-subacute-studies
#10
Maja M Janas, Carole E Harbison, Victoria K Perry, Brenda Carito, Jessica E Sutherland, Akshay K Vaishnaw, Natalie D Keirstead, Garvin Warner
Short interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) are the most clinically advanced oligonucleotide-based platforms. A number of N-acetylgalactosamine (GalNAc)-conjugated siRNAs (GalNAc-siRNAs), also referred to as RNA interference (RNAi) therapeutics, are currently in various stages of development, though none is yet approved. While the safety of ASOs has been the subject of extensive review, the nonclinical safety profiles of GalNAc-siRNAs have not been reported. With the exception of sequence differences that confer target RNA specificity, GalNAc-siRNAs are largely chemically uniform, containing limited number of phosphorothioate linkages, and 2'-O-methyl and 2'-deoxy-2'-fluoro ribose modifications...
August 23, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/30114400/conserved-transcriptional-activity-and-ligand-responsiveness-of-avian-ppars-potential-role-in-regulating-lipid-metabolism-in-mirgratory-birds
#11
Angelica Hamilton, Jennifer Ly, Jasmine R Robinson, Keely R Corder, Kristen J DeMoranville, Paul J Schaeffer, Janice M Huss
Migratory birds undergo metabolic remodeling in tissues, including increased lipid storage in white adipose and fatty acid uptake and oxidation in skeletal muscle, to optimize energy substrate availability and utilization in preparation for long-distance flight. Different tissues undergo gene expression changes in keeping with their specialized functions and driven by tissue specific transcriptional pathways. Peroxisome proliferator-activated receptors (PPARs) are lipid-activated nuclear receptors that regulate metabolic pathways involved in lipid and glucose utilization or storage in mammals...
August 13, 2018: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/30089413/drug-induced-glomerulonephritis-the-spectre-of-biotherapeutic-and-antisense-oligonucleotide-immune-activation-in-the-kidney
#12
Kendall S Frazier, Leslie A Obert
Prevalence of immune-mediated glomerulonephritis has increased in preclinical toxicity studies, with more frequent use of biotherapeutic agents (especially antigenic humanized molecules) and antisense oligonucleotide (ASO) therapies. Immune complex disease affects a small number of study monkeys, often correlates with antidrug antibody (ADA) titers, and occurs at a dose that favors immune complex formation or impedes clearance. While preclinical glomerulonephritis often fails to correlate with evidence of glomerular or vascular injury in human clinical trials and is not considered predictive, additional animal investigative immunohistochemical work may be performed to substantiate evidence for immune complex pathogenesis...
August 8, 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/30066121/characterization-of-11-c-pxt012253-as-a-pet-radioligand-for-mglu-4-allosteric-modulators-in-nonhuman-primates
#13
Akihiro Takano, Sangram Nag, Zhisheng Jia, Mahabuba Jahan, Anton Forsberg, Ryosuke Arakawa, Per Grybäck, Guillaume Duvey, Christer Halldin, Delphine Charvin
PURPOSE: Modulation of presynaptic metabotropic glutamate receptor 4 (mGlu4 ) by an allosteric ligand has been proposed as a promising therapeutic target in Parkinson's disease and levodopa-induced dyskinesia. A positron emission tomography (PET) ligand for an allosteric site of mGlu4 may provide evidence that a clinical drug candidate reaches and binds the target. A carbon-11-labeled PET radioligand binding an allosteric site of mGlu4 , [11 C]PXT012253, has been recently developed. Here, we describe the detailed characterization of this novel radiolabeled mGlu4 ligand in nonhuman primates...
July 31, 2018: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/30060991/in-vitro-antidermatophytic-activity-and-cytotoxicity-of-extracts-derived-from-medicinal-plants-and-marine-algae
#14
N W Sit, Y S Chan, S C Lai, L N Lim, G T Looi, P L Tay, Y T Tee, Y Y Woon, K S Khoo, H C Ong
OBJECTIVES: This study was conducted to evaluate the antidermatophytic activity of 48 extracts obtained from medicinal plants (Cibotium barometz, Melastoma malabathricum, Meuhlenbeckia platyclada, Rhapis excelsa, Syzygium myrtifolium, Vernonia amygdalina) and marine algae (Caulerpa sertularioides, Kappaphycus alvarezii) against Trichophyton rubrum and Trichophyton interdigitale (ATCC reference strains), and the cytotoxicity using African monkey kidney epithelial (Vero) cells. Active plant extracts were screened for the presence of phytochemicals and tested against clinical isolates of Trichophyton tonsurans...
September 2018: Journal de Mycologie Médicale
https://www.readbyqxmd.com/read/30054149/non-clinical-evaluation-of-jr-051-as-a-biosimilar-to-agalsidase-beta-for-the-treatment-of-fabry-disease
#15
Hideto Morimoto, Yae Ito, Eiji Yoden, Masato Horie, Noboru Tanaka, Yoshikazu Komurasaki, Ryuji Yamamoto, Kazutoshi Mihara, Kohtaro Minami, Tohru Hirato
Fabry disease (FD) is an X-linked lysosomal storage disease. It is caused by deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to excessive deposition of neutral glycosphingolipids, especially globotriaosylceramide (GL-3), in cells throughout the body. Progressive accumulation of GL-3 causes life-threatening complications in several tissues and organs, including the vasculature, heart, and kidney. Currently available enzyme replacement therapy for FD employs recombinant α-Gal A in two formulations, namely agalsidase alfa and agalsidase beta...
July 23, 2018: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/30048323/xenoantigen-deletion-and-chemical-immunosuppression-can-prolong-renal-xenograft-survival
#16
Andrew B Adams, Steven C Kim, Gregory R Martens, Joseph M Ladowski, Jose L Estrada, Luz M Reyes, Cindy Breeden, Allison Stephenson, Devin E Eckhoff, Matt Tector, Alfred Joseph Tector
OBJECTIVE: Xenotransplantation using pig organs could end the donor organ shortage for transplantation, but humans have xenoreactive antibodies that cause early graft rejection. Genome editing can eliminate xenoantigens in donor pigs to minimize the impact of these xenoantibodies. Here we determine whether an improved cross-match and chemical immunosuppression could result in prolonged kidney xenograft survival in a pig-to-rhesus preclinical model. METHODS: Double xenoantigen (Gal and Sda) knockout (DKO) pigs were created using CRISPR/Cas...
October 2018: Annals of Surgery
https://www.readbyqxmd.com/read/30045989/bovine-herpesvirus-1-entry-by-a-low-ph-endosomal-pathway
#17
Gabrielle Pastenkos, Becky Lee, Suzanne M Pritchard, Anthony V Nicola
Bovine herpesvirus (BoHV-1) is an alphaherpesvirus that poses a significant challenge to health and welfare in the cattle industry. We investigated the cellular entry route utilized by BoHV-1. We report that BoHV-1 enters Madin Darby bovine kidney (MDBK) cells, bovine turbinate cells, and African green monkey kidney (Vero) cells via a low pH-mediated endocytosis pathway. Treatment of MDBK cells with hypertonic medium, which inhibits receptor-mediated endocytosis, prevented infection as measured by a beta-galactosidase reporter assay...
July 25, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30041149/predicting-response-to-sepantronium-bromide-ym155-a-survivin-suppressant-by-pet-imaging-with-11-c-ym155
#18
Keisuke Mitsuoka, Aya Kita, Yoshihiro Murakami, Kenna Shirasuna, Akihiro Noda, Kentaro Yamanaka, Naoki Kaneko, Sosuke Miyoshi
INTRODUCTION: Sepantronium bromide (YM155) is a survivin suppressant that induces apoptosis in tumor cells. Although YM155 induces tumor regression in various tumor types in vivo, phase I and II studies demonstrated responding and non-responding patient populations. We investigated 11 C-labeled YM155 ([11 C]YM155) used as a positron emission tomography (PET) tracer to assess whether tumor uptake of [11 C]YM155 correlated with its anti-tumor effect, thereby allowing identification of patients who would respond to YM155 treatment...
June 27, 2018: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/30023713/fluorenyl-loaded-quatsome-nanostructured-fluorescent-probes
#19
Xinglei Liu, Antonio Ardizzone, Binglin Sui, Mattia Anzola, Nora Ventosa, Taihong Liu, Jaume Veciana, Kevin D Belfield
Delivery of hydrophobic materials in biological systems, for example, contrast agents or drugs, is an obdurate challenge, severely restricting the use of materials with otherwise advantageous properties. The synthesis and characterization of a highly stable and water-soluble nanovesicle, referred to as a quatsome (QS, vesicle prepared from cholesterol and amphiphilic quaternary amines), that allowed the nanostructuration of a nonwater soluble fluorene-based probe are reported. Photophysical properties of fluorenyl-quatsome nanovesicles were investigated via ultraviolet-visible absorption and fluorescence spectroscopy in various solvents...
August 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/29988799/application-of-tetracycline-hydrochloride-loaded-fungal-chitosan-and-aloe-vera-extract-based-composite-sponges-for-wound-dressing
#20
Sathiyaseelan Anbazhagan, Kalaichelvan Puthupalayam Thangavelu
Chitosan composite material has been used as an efficient drug carrier for potential drug delivery systems in specific cases of wound dressing management. In the present study, 0.5 g/L of the antibiotic tetracycline hydrochloride (TCH) was loaded into 1% fungal chitosan (FCS) incorporated with 0.2% of Aloe vera extract (AVE). Two types of sponges were prepared, with and without AVE, such as FCS-AVE-TCH and FCS-TCH, respectively. They were characterized by UV-Visible spectrophotometer, attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and scanning electron microscopy (SEM)...
November 2018: Journal of Advanced Research
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