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https://www.readbyqxmd.com/read/29577951/interaction-of-porcine-reproductive-and-respiratory-syndrome-virus-major-envelope-proteins-gp5-and-m-with-the-cellular-protein-snapin
#1
Julie A Hicks, Dongwan Yoo, Hsiao-Ching Liu
BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is characterized by abortions in pregnant sows and respiratory disease, particularly in young pigs. The causative agent is porcine reproductive and respiratory syndrome virus (PRRSV), a member of the arterivirus family. GP5 and M are the major envelope proteins encoded by PRRSV. To further characterize these two viral proteins, a yeast two-hybrid approach was utilized to identify interacting partners of PRRSV GP5 and M proteins...
March 22, 2018: Virus Research
https://www.readbyqxmd.com/read/29574193/nonclinical-assessments-of-the-potential-biosimilar-pf-06439535-and-bevacizumab
#2
Marjorie A Peraza, Karen E Rule, Michael H I Shiue, Gregory L Finch, Stéphane Thibault, Paul R Brown, David W Clarke, Michael W Leach
Bevacizumab, a recombinant humanized monoclonal antibody targeting vascular endothelial growth factor (VEGF), is approved for treatment of metastatic colorectal cancer, nonsquamous non-small-cell lung cancer, metastatic kidney cancer, and glioblastoma. To support clinical development of the potential bevacizumab biosimilar PF-06439535, nonclinical studies evaluated structural, functional, toxicological, and toxicokinetic similarity to bevacizumab sourced from the European Union (bevacizumab-EU) and United States (bevacizumab-US)...
March 21, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29548747/replacement-of-primary-monkey-kidney-cells-by-l20b-cell-line-in-the-test-for-effective-inactivation-of-inactivated-poliovirus-vaccine
#3
Cynthia Chapel, Nathalie Rocher-Hélion, Nathalie Mantel, Sandy Imbert, Eric Deshaies, Véronique Barban, Alain Sabouraud, Jean-Philippe Barbe, Laurent Mallet
Absence of 'live' residual poliovirus in Inactivated Poliovirus Vaccine (IPV) is routinely checked using Primary Monkey Kidney Cells (PMKC). However, the increasing demand for IPV and the ethical, technical and safety issues associated with the use of non-human primates in research and quality control, has made the replacement of primary cells with an established cell line a priority, in line with the principles of the 3Rs (Replacement, Reduction and Refinement in animal testing). As an alternative to PMKC, we evaluated the L20B cell line; a mouse cell-line genetically engineered to express human poliovirus receptor, CD155...
June 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29541364/mitigating-the-metabolic-liability-of-carbonyl-reduction-novel-calpain-inhibitors-with-p1-extension
#4
Andreas Kling, Katja Jantos, Helmut Mack, Wilfried Hornberger, Gisela Backfisch, Yanbin Lao, Marjoleen Nijsen, Beatrice Rendenbach-Mueller, Achim Moeller
Dysregulation of calpains 1 and 2 has been implicated in a variety of pathological disorders including ischemia/reperfusion injuries, kidney diseases, cataract formation, and neurodegenerative diseases such as Alzheimer's disease (AD). 2-(3-Phenyl-1 H )-pyrazol-1-yl)nicotinamides represent a series of novel and potent calpain inhibitors with high selectivity and in vivo efficacy. However, carbonyl reduction leading to the formation of the inactive hydroxyamide was identified as major metabolic liability in monkey and human, a pathway not reflected by routine absorption, distribution, metabolism, and excretion (ADME) assays...
March 8, 2018: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29502404/increases-of-phenolics-fatty-acids-phytosterols-and-anticancer-activity-of-sweet-potato-after-fermented-by-lactobacillus-acidophilus
#5
Yixiao Shen, Haiyan Sun, Haiying Zeng, Witoon Prinyawiwatkul, Wenqing Xu, Zhimin Xu
Changes of phenolics, fatty acids, and phytosterols in the sweet potato (SP) fermented by Lactobacillus acidophilus were evaluated and compared with its raw and boiled SPs. The differences of profiles and levels of phenolics between raw and boiled SPs were not as significant as their differences from fermented SP. The level of caffeic acid or 3,5-dicaffeoylquinic acids in fermented SP increased to more than 4 times higher than raw or boiled SP. Two phenolics, p-coumaric acid and ferulic acid which were not detected in either raw or boiled SP were found in fermented SP...
March 3, 2018: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/29479135/circulating-liver-specific-micrornas-in-cynomolgus-monkeys
#6
REVIEW
Takuma Iguchi, Ken Sakurai, Satoshi Tamai, Kazuhiko Mori
Circulating microRNAs (miRNAs) can potentially be used as sensitive and specific biomarkers for tissue injury. However, the usefulness of circulating miRNAs as safety biomarkers in nonclinical toxicological studies using nonhuman primates is debatable owing to the limited information on organ-specific miRNAs. Therefore, a systematic investigation was performed to address this point. We identified organ-specific miRNAs from cynomolgus monkeys by next-generation sequencing analysis, which revealed that miR-122 was only abundant in the liver, whereas miR-192 was abundant in the liver, stomach, intestines, and kidney...
January 2018: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/29471777/spontaneous-and-drug-induced-arteritis-polyarteritis-in-the-g%C3%A3-ttingen-minipig-review
#7
Zuhal Dincer, Virginie Piccicuto, Ursula Junker Walker, Andreas Mahl, Sean McKeag
Arteritis/polyarteritis occurs spontaneously in many species used in preclinical toxicology studies. In Göttingen minipigs, arteritis/polyarteritis is an occasionally observed background change. In the minipig, this finding differs in frequency and nature from age-related polyarteritis nodosa in rats or monkeys, and Beagle pain syndrome in dogs. In minipigs, it can be present in a single small- or medium-sized artery of an organ or a few organs and is most commonly recorded in the cardiac and extracardiac blood vessels, vagina, oviduct, rectum, epididymis, spinal cord, pancreas, urinary bladder, kidneys, and stomach...
February 2018: Toxicologic Pathology
https://www.readbyqxmd.com/read/29461464/protective-effects-of-the-complement-inhibitor-compstatin-cp40-in-hemorrhagic-shock
#8
Martijn van Griensven, Daniel Ricklin, Stephanie Denk, Rebecca Halbgebauer, Christian K Braun, Anke Schultze, Felix Hönes, Sofia Koutsogiannaki, Alexandra Primikyri, Edimara Reis, David Messerer, Sebastian Hafner, Peter Radermacher, Ali-Reza Biglarnia, Ranillo R G Resuello, Joel V Tuplano, Benjamin Mayer, Kristina Nilsson, Bo Nilsson, John D Lambris, Markus Huber-Lang
Trauma-induced hemorrhagic shock (HS) plays a decisive role in the development of immune, coagulation, and organ dysfunction often resulting in a poor clinical outcome. Imbalanced complement activation is intricately associated with the molecular danger response and organ damage after HS. Thus, inhibition of the central complement component C3 as turnstile of both inflammation and coagulation is hypothesized as a rational strategy to improve the clinical course after HS.Applying intensive care conditions, anaesthetized, monitored, and protectively ventilated non-human primates (NHP; cynomolgus monkeys) received a pressure-controlled severe HS (60 min at MAP 30 mmHg) with subsequent volume resuscitation...
February 14, 2018: Shock
https://www.readbyqxmd.com/read/29407773/preclinical-evaluation-of-the-mono-pegylated-recombinant-human-interleukin-11-in-cynomolgus-monkeys
#9
Kuo-Ming Yu, Johnson Yiu-Nam Lau, Manson Fok, Yuk-Keung Yeung, Siu-Ping Fok, Suxing Zhang, Peizhen Ye, Kezhi Zhang, Xiaobo Li, Juan Li, Qin Xu, Wing-Tak Wong, Qui-Lim Choo
The mono-PEGylated recombinant human interleukin-11 (rhIL-11) was evaluated for its pharmacology and toxicology profile in non-human primates. This PEGylated IL-11 (PEG-IL11) showed a much prolonged circulating half-life of 67h in cynomolgus monkeys as compared to its un-PEGylated counterpart (~3h) through subcutaneous administration, implicating that a single injection of the recommended dose will effectively enhance thrombopoiesis in humans for a much longer period of time compared to rhIL-11 in humans (t1/2=6...
February 2, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29395533/immunization-with-phage-virus-like-particles-displaying-zika-virus-potential-b-cell-epitopes-neutralizes-zika-virus-infection-of-monkey-kidney-cells
#10
Rupsa Basu, Lukai Zhai, Alice Contreras, Ebenezer Tumban
Zika virus (ZIKV) is a mosquito-borne flavivirus that has re-emerged and is associated with many debilitating clinical manifestations. Research is currently being conducted to develop a prophylactic vaccine against the virus; however, there has not been any licensed ZIKV vaccine. Recent studies have identified potential B-cell epitopes (amino acids 241-259, 294-315, 317-327, 346-361, 377-388 and 421-437) on the envelope protein of ZIKV, which could be explored to develop peptide vaccines against ZIKV infection...
January 30, 2018: Vaccine
https://www.readbyqxmd.com/read/29348125/metabolism-and-disposition-of-a-novel-selective-%C3%AE-7-neuronal-acetylcholine-receptor-agonist-abt-126-in-humans-characterization-of-the-major-roles-for-flavin-containing-monooxygenases-and-udp-glucuronosyl-transferase-1a4-and-2b10-in-catalysis
#11
Hong Liu, David M Stresser, Melissa J Michmerhuizen, Xiaofeng Li, Ahmed A Othman, Aimee D Reed, Michael R Schrimpf, Jens Sydor, Anthony J Lee
Mass balance, metabolism, and excretion of ABT-126, an α 7 neuronal acetylcholine receptor agonist, were characterized in healthy male subjects ( n = 4) after a single 100-mg (100 μ Ci) oral dose. The total recovery of the administered radioactivity was 94.0% (±2.09%), with 81.5% (±10.2%) in urine and 12.4% (±9.3%) in feces. Metabolite profiling indicated that ABT-126 had been extensively metabolized, with 6.6% of the dose remaining as unchanged parent drug in urine. Parent drug accounted for 12.2% of the administered radioactivity in feces...
April 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29348093/antifungal-and-cytotoxic-activities-of-selected-medicinal-plants-from-malaysia
#12
Yik Sin Chan, Yit Hong Cheah, Poh Zen Chong, Hui Lai Khor, Wen Siang Teh, Kong Soo Khoo, Hean Chooi Ong, Nam Weng Sit
This study was conducted to investigate the antifungal potential and cytotoxicity of selected medicinal plants from Malaysia. The extracts from the stem of Cissus quadrangularis and the leaves of Asplenium nidus, Pereskia bleo, Persicaria odorata and Sauropus androgynus were assayed against six fungi using p-iodonitrotetrazolium-based on colorimetric broth microdilution method. All the plant extracts were found to be fungicidal against at least one type of fungus. The strongest fungicidal activity (minimum fungicidal concentration=0...
January 2018: Pakistan Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29342972/the-effect-of-combining-natural-terpenes-and-antituberculous-agents-against-reference-and-clinical-mycobacterium-tuberculosis-strains
#13
Elwira Sieniawska, Rafal Sawicki, Marta Swatko-Ossor, Agnieszka Napiorkowska, Agata Przekora, Grazyna Ginalska, Ewa Augustynowicz-Kopec
Background: On account of emergence of multi- and extensively drug-resistant Mycobacterium tuberculosis (Mtb) strains, combinations of drugs with natural compounds were tested to search for antibiotic activity enhancers. In this work we studied terpenes (α-pinene, bisabolol, β-elemene, (R)-limonene, (S)-limonene, myrcene, sabinene), which are the main constituents of essential oil obtained from Mutellina purpurea L., a plant with described antitubercular activity, to investigate their interactions with antibiotics against reference Mtb strains and multidrug-resistant clinical isolates...
January 15, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29319621/selective-cd28-inhibition-modulates-alloimmunity-and-cardiac-allograft-vasculopathy-in-anti-cd154-treated-monkeys
#14
Tianshu Zhang, Agnes M Azimzadeh, Wenji Sun, Natalie A O'Neill, Evelyn Sievert, Emily Bergbower, Gheorghe Braileanu, Lars Burdorf, Xiangfei Cheng, Thomas Monahan, Siamak Dahi, Donald G Harris, Elana Rybak, Emily Welty, Anthony Kronfli, Chris Avon, Richard N Pierson
BACKGROUND: Selective CD28 inhibition is actively pursued as an alternative to B7 blockade using cytotoxic T lymphocyte antigen 4 Ig based on the hypothesis that the checkpoint immune regulators cytotoxic T lymphocyte antigen 4 and programmed death ligand 1 will induce tolerogenic immune signals. We previously showed that blocking CD28 using a monovalent nonactivating reagent (single-chain anti-CD28 Fv fragment linked to alpha-1 antitrypsin [sc28AT]) synergizes with calcineurin inhibitors in nonhuman primate (NHP) kidney and heart transplantation...
March 2018: Transplantation
https://www.readbyqxmd.com/read/29318455/4-6-dimethoxyisoflavone-7-o-%C3%AE-d-glucopyranoside-wistin-is-a-peroxisome-proliferator-activated-receptor-%C3%AE-ppar%C3%AE-agonist-in-mouse-hepatocytes
#15
Misato Suzuki, Fumiya Nakamura, Emi Taguchi, Maho Nakata, Fumi Wada, Momoka Takihi, Tomoyo Inoue, Shinji Ohta, Hiroyuki Kawachi
Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that regulate lipid and glucose metabolism. PPARα mainly affects fatty acid metabolism, and its activation lowers lipid levels. PPARγ is involved in the regulation of adipogenesis, insulin sensitivity, energy balance, and lipid biosynthesis. We have previously reported that 4',6-dimethoxyisoflavone-7-O-β-D-glucopyranoside (wistin) can activate PPARγ. The purpose of the present study is to investigate the PPARα agonist activity of wistin...
January 9, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29300231/long-term-nonhuman-primate-renal-allograft-survival-without-ongoing-immunosuppression-in-recipients-of-delayed-donor-bone-marrow-transplantation
#16
Kiyohiko Hotta, Tetsu Oura, Abbas Dehnadi, Svjetlan Boskovic, Masatoshi Matsunami, Ivy Rosales, Rex N Smith, Robert B Colvin, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We have previously reported successful induction of renal allograft tolerance in nonhuman primates (NHP) after an initial posttransplant period of conventional immunosuppression (delayed tolerance) using a nonmyeloablative conditioning regimen consisting of anti-CD154 and anti-CD8 mAbs plus equine antithymocyte globulin (Atgam) and donor bone marrow transplantation (DBMT). Because these reagents are not currently clinically available, the protocol was revised to be applicable to human recipients of deceased donor allografts...
April 2018: Transplantation
https://www.readbyqxmd.com/read/29295701/evaluation-of-fibroblasts-cells-viability-and-adhesion-on-six-different-titanium-surfaces-an-in-vitro-experimental-study
#17
Sergio Alexandre Gehrke, Leticia Perez-Diaz, Berenice Anina Dedavid
BACKGROUND: The topographical surficial characteristics and properties of materials can induce different cell reactions regards to the viability and adhesion according to the recent patents. The aim of this in vitro experimental study was to evaluate the viability and adhesion of fibroblastic cells seeded on titanium disks with different surface topography. In addition, we revised all patents relating to sintering process titanium powder surface treatment for a of dental implants. METHODS: Fibroblast cells were cultured on 6 surfaces models: mA disks corresponding to titanium surfaces without additional treatment (machined surface) were compared with mB disks, where surfaces were sandblasting etching using aluminum oxide; mC disks where titanium oxide was used for sandblasting etching; mD disks where triple acid conditioning was used, mE disks with laser treated surface and mF disks which were made of titanium powder by a sintering process...
January 1, 2018: Recent Patents on Biotechnology
https://www.readbyqxmd.com/read/29285901/characterization-of-porcine-sapelovirus-isolated-from-japanese-swine-with-plc-prf-5-cells
#18
H Bai, J Liu, L Fang, M Kataoka, N Takeda, T Wakita, T-C Li
Porcine sapelovirus (PSV) is a causative agent of neurological disorders, fertility disorders and dermal lesions of swine. In this study, we isolated two PSV strains, Jpsv477 and Jpsv1315, from swine faecal specimens using a PLC/PRF/5 cell culture system. The PSV infection of PLC/PRF/5 cells induced a cytopathic effect (CPE). Two types of virus particles with identical diameter (~35 nm) but different densities (1.300 and 1.285 g/cm3 ) were observed in the cell culture supernatants. Analysis of the entire genome sequence of Jpsv477 and Jpsv1315 revealed that both strains possess 7,558 nucleotides and the poly (A) tail and have a typical PSV genome organization consisting of a 5' terminal untranslated region (5'UTR), a large open reading frame (ORF), and a 3' terminal untranslated region (3'UTR)...
December 28, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/29282065/pulmonary-edema-following-central-nervous-system-lesions-induced-by-a-non-mouse-adapted-ev71-strain-in-neonatal-balb-c-mice
#19
Yuefei Jin, Chao Zhang, Rongguang Zhang, Jingchao Ren, Shuaiyin Chen, Meili Sui, Guangyuan Zhou, Dejian Dang, Jiehui Zhu, Huifen Feng, Yuanlin Xi, Haiyan Yang, Guangcai Duan
BACKGROUND: Enterovirus (EV) infection has been a serious health issue in Asia-Pacific region. It has been indicated that the occurrence of fatal hand foot and mouth disease (HFMD) cases following EV71 infection is mainly attributed to pulmonary edema. However, the development of pulmonary disorders after EV71 infection remains largely unknown. To establish an EV71-infected animal model and further explore the underlying association of central nervous system (CNS) invasion with pulmonary edema, we isolated a clinical source EV71 strain (ZZ1350) from a severe case in Henan Province...
December 28, 2017: Virology Journal
https://www.readbyqxmd.com/read/29260328/vivo-morpholino-oligomers-strongly-inhibit-dengue-virus-replication-and-production
#20
Patta Phumesin, Mutita Junking, Aussara Panya, Petlada Yongpitakwattana, Sansanee Noisakran, Thawornchai Limjindaporn, Pa-Thai Yenchitsomanus
Dengue virus (DENV) infection is a worldwide public health problem, which can cause severe dengue hemorrhagic fever (DHF) and life-threatening dengue shock syndrome (DSS). There are currently no anti-DENV drugs available, and there has been an intensive search for effective anti-DENV agents that can inhibit all four DENV serotypes. In this study, we tested whether vivo-morpholino oligomers (vivo-MOs), whose effect on DENV infection has not previously been studied, can inhibit DENV infection. Vivo-MOs were designed to target the top of 3' stem-loop (3' SL) in the 3' UTR of the DENV genome and tested for inhibition of DENV infection in monkey kidney epithelial (Vero) cells and human lung epithelial carcinoma (A549) cells...
April 2018: Archives of Virology
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