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Rory D de Vries, Arwen F Altenburg, Nella J Nieuwkoop, Erwin de Bruin, Stella E van Trierum, Mark R Pronk, Mart M Lamers, Mathilde Richard, David F Nieuwenhuijse, Marion P G Koopmans, Joost H C M Kreijtz, Ron A M Fouchier, Albert D M E Osterhaus, Gerd Sutter, Guus F Rimmelzwaan
Background: Highly pathogenic avian influenza viruses continue to circulate in poultry and wild birds and occasionally infect humans, sometimes with fatal outcome. Development of vaccines is a priority to prepare for potential pandemics, however complicated by antigenic variation of the surface glycoprotein hemagglutinin. We report the immunological profile induced by human immunization with Modified Vaccinia virus Ankara expressing the hemagglutinin gene of H5N1 virus A/Vietnam/1194/04 (rMVA-H5)...
April 18, 2018: Journal of Infectious Diseases
Radu-Cristian Moldovan, Ede Bodoki, Anne-Catherine Servais, Bezhan Chankvetadze, Jacques Crommen, Radu Oprean, Marianne Fillet
A targeted CE-MS approach was developed for the chiral analysis of biologically relevant amino acids in artificial cerebrospinal fluid (aCSF). In order to achieve chiral resolution, the five amino acids (Ser, Asn, Asp, Gln and Glu) were derivatized with (+)-1-(9-fluorenyl)ethyl chloroformate ((+)-FLEC). The diastereoselectivity was found to be highly dependent on pH for all analytes and the optimized background electrolyte (BGE) consisted of 150 mM acetic acid, adjusted to pH 3.7 with NH4 OH. Furthermore, a reversal of the migration order of Asp derivatives was observed...
June 13, 2018: Journal of Chromatography. A
Shengping Wen, Yu Su, Rong Wu, Shiwei Zhou, Qianhao Min, Gao-Chao Fan, Li-Ping Jiang, Rong-Bin Song, Jun-Jie Zhu
The accurate therapeutic evaluation for chronic myeloid leukemia (CML) drug is of great importance to minimize side effects and enhance efficacy. Herein, a facile and precise surface-enhanced scattering (SERS) approach based on coupled plasmonic field has been introduced to evaluate the therapeutic outcomes of antileukemia drug through ultrasensitive assay of caspase-3 activity in apoptotic cells. Caspase-3 as an apoptosis indicator could specifically cleave the N-terminus of biotinylated DEVD-peptide (biotin-Gly-Asp-Gly-Asp-Glu-Val-Asp-Gly-Cys) immobilized on the Au nanoparticle-decorated TiO2 nanotube arrays (TiO2 /Au NTAs) substrate...
June 2, 2018: Biosensors & Bioelectronics
Haiwu Cao, Xiaohong Zhao, Shiyun Lu, Zhi Wang
The aim of the current study was to measure the expression of acetyl-N-Ser-Asp-Lys-Pro (ACSDKP) in patients with acute myeloid leukemia (AML) and the effect of prolyl oligopeptidase inhibitor (POPi) on the bone marrow stromal cells of these patients. Serum and bone marrow stromal cell samples were collected from 33 patients with AML admitted to Wuxi Second People's Hospital, Nanjing Medical University between September 2011 and August 2016. ACSDKP levels were measured using a highly specific competitive enzyme immunoassay (EIA)...
June 2018: Experimental and Therapeutic Medicine
Puay-Wah Phuan, Jung-Ho Son, Joseph-Anthony Tan, Clarabella Li, Ilaria Musante, Lorna Zlock, Dennis W Nielson, Walter E Finkbeiner, Mark J Kurth, Luis J Galietta, Peter M Haggie, Alan S Verkman
BACKGROUND: Current modulator therapies for some cystic fibrosis-causing CFTR mutants, including N1303K, have limited efficacy. We provide evidence here to support combination potentiator (co-potentiator) therapy for mutant CFTRs that are poorly responsive to single potentiators. METHODS: Functional synergy screens done on N1303K and W1282X CFTR, in which small molecules were tested with VX-770, identified arylsulfonamide-pyrrolopyridine, phenoxy-benzimidazole and flavone co-potentiators...
June 11, 2018: Journal of Cystic Fibrosis: Official Journal of the European Cystic Fibrosis Society
Warintra Pitsawong, Vanessa Buosi, Renee Otten, Roman V Agafonov, Adelajda Zorba, Nadja Kern, Steffen Kutter, Gunther Kern, Ricardo Ap Pádua, Xavier Meniche, Dorothee Kern
Protein kinases are major drug targets, but the development of highly-selective inhibitors has been challenging due to the similarity of their active sites. The observation of distinct structural states of the fully-conserved Asp-Phe-Gly (DFG) loop has put the concept of conformational selection for the DFG-state at the center of kinase drug discovery. Recently, it was shown that Gleevec selectivity for the Tyr-kinases Abl was instead rooted in conformational changes after drug binding. Here, we investigate whether protein dynamics after binding is a more general paradigm for drug selectivity by characterizing the binding of several approved drugs to the Ser/Thr-kinase Aurora A...
June 14, 2018: ELife
C Ledesma, C Rosario, J Gracia-Mora, G Tapia, L Gutiérrez, H Sumano
The interaction of 3 water sanitizers (sodium hypochlorite, iodine-polyvinylpyrrolidone, and citrate) utilized in poultry production on antibacterial activity and bioavailability of amoxicillin trihydrate (AMX) were studied. Sanitizers were mixed with AMX in prepared water, the resulting substances were regarded as amoxicillin-sanitizer products (ASP). First, the in vitro antibacterial activity of each ASP was compared to that of AMX. Then, pharmacokinetics (PK) of ASP and AMX diluted in prepared water, were carried out in broiler-chickens...
April 20, 2018: Poultry Science
Katrin Schwarze, Andreas Kribben, Oliver Ritter, Gerhard A Müller, Daniel Patschan
BACKGROUND: AKI (Acute Kidney Injury) occurs frequently in hospitals worldwide, the therapeutic options are limited. Diabetes mellitus (DM) affects more and more people around the globe, the disease worsens the prognosis of AKI even further. In recent years, cell-based therapies have increasingly been applied in experimental AKI. Aim of the study was to utilize two established autophagy inducers for pharmacological preconditioning of so-called proangiogenic cells (PACs) in PAC treatment of diabetic AKI...
June 13, 2018: American Journal of Physiology. Renal Physiology
Maximilian Klingler, Clemens Decristoforo, Christine Rangger, Dominik Summer, Julie Foster, Jane K Sosabowski, Elisabeth von Guggenberg
Minigastrin (MG) analogs show high affinity to the cholecystokinin-2 receptor (CCK2R) and have therefore been intensively studied to find a suitable analog for imaging and treatment of CCK2R-expressing tumors. The clinical translation of the radioligands developed thus far has been hampered by high kidney uptake or low enzymatic stability. In this study, we aimed to develop new MG analogs with improved targeting properties stabilized against degradation through site-specific amino acid modifications. Method: Based on the lead structure of a truncated MG analog, four new MG derivatives with substitutions in the C -terminal part of the peptide (Trp-Met-Asp-Phe-NH2 ) were synthesized and derivatized with DOTA at the N -terminus for radiolabeling with trivalent radiometals...
2018: Theranostics
Yihebali Chi, Zhiwei Fang, Xiao-Nan Hong, Yang Yao, Ping Sun, Guowen Wang, Feng Du, Yongkun Sun, Qiong Wu, Guofan Qu, Shusen Wang, Jianmin Song, Jianchun Yu, Yongkui Lu, Xia Zhu, Xiaohui Niu, Zhiyong He, Jinwan Wang, Hao Yu, Jianqiang Cai
PURPOSE: The prognosis for patients with refractory soft-tissue sarcoma (STS) is dismal. Anlotinib has previously shown antitumor activity on STS in preclinical and phase I studies. EXPERIMENTAL DESIGN: Patients 18 years and older, progressing after anthracycline-based chemotherapy, naïve from angiogenesis inhibitors, with at least one measurable lesion according to RECIST 1.1, were enrolled. The main subtypes eligible were: undifferentiated pleomorphic sarcoma (UPS), liposarcoma (LPS), leiomyosarcoma (LMS), synovial sarcoma (SS), fibrosarcoma (FS), alveolar soft part sarcoma (ASPS) and clear cell sarcoma (CCS)...
June 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Andrea Angeli, Sonia Del Prete, Fatmah A S Alasmary, Linah S Alqahtani, Zeid AlOthman, William A Donald, Clemente Capasso, Claudiu T Supuran
The first activation study of a η-class carbonic anhydrase (CAs, EC is reported. A panel of 24 natural and non-natural amino acids and amines was used to explore the activation profile of Plasmodium falciparum CA (PfACA). The most effective activators belonged to the amino acid chemotype, with d-Glu, l-Asp, l-/d-Phe and l-/d-DOPA possessing activation constant in the range of 82 nM-0.75 µM, whereas l-/d-His, l-Tyr, 4-amino-l-Phe and l-Gln were slightly less effective (KA in the range of 1.00-2...
June 4, 2018: Bioorganic Chemistry
Yonghong Tao, Yanan Niu, Yun Wang, Tianxiao Chen, Shahzad Amir Naveed, Jian Zhang, Jianlong Xu, Zhikang Li
Aluminum (Al) stress is becoming the major limiting factor in crop production in acidic soils. Rice has been reported as the most Al-tolerant crop and the capacity of Al toxicity tolerance is generally evaluated by comparing root growth under Al stress. Here, we performed an association mapping of Al toxicity tolerance using a core collection of 211 indica rice accessions with 700 K high quality SNP data. A total of 21 putative QTL affecting shoot height (SH), root length (RL), shoot fresh weight (SFW), shoot dry weight (SDW), root dry weight (RDW) and shoot water content (SWC) were identified at seedling stage, including three QTL detected only under control condition, eight detected only under Al stress condition, ten simultaneously detected in both control and Al stress conditions, and seven were identified by stress tolerance index of their corresponding traits...
2018: PloS One
Bradley J Langford, Julie Hui-Chih Wu, Kevin A Brown, Xuesong Wang, Valerie Leung, Charlie Tan, Gary Garber, Nick Daneman
OBJECTIVES: Antibiotic use varies widely between hospitals, but the influence of antimicrobial stewardship programs (ASPs) on this variability is not known. We aimed to determine the key structural and strategic aspects of ASPs associated with differences in risk-adjusted antibiotic utilization across facilities. DESIGN: Observational study of acute-care hospitals in Ontario, Canada METHODS: A survey was sent to hospitals asking about both structural (8 elements) and strategic (32 elements) components of their ASP...
June 12, 2018: Infection Control and Hospital Epidemiology
Zhan He, Hang Wang, Xiao Han, Tiantian Ma, Yi Hang, Huifei Yu, Fangfang Wei, Jing Sun, Yongchun Yang, Changyong Cheng, Houhui Song
We aimed to obtain the recombinant aminopeptidase encoded by Listeria monocytogenes (L. monocytogenes) gene lmo1711, and characterized the enzyme. First, the amino acid sequences of Lmo1711 from L. monocytogenes EGD-e and its homologues in other microbial species were aligned and the putative active sites were analyzed. The putative model of Lmo1711 was constructed through the SWISS-MODEL Workspace. Then, the plasmid pET30a-Lmo1711 was constructed and transformed into E. coli for expression of the recombinant Lmo1711...
May 25, 2018: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
Jie Yang, Zhonghua Liu, Chuanping Wang, Rui Yang, Joseph K Rathkey, Otis W Pinkard, Wuxian Shi, Yinghua Chen, George R Dubyak, Derek W Abbott, Tsan Sam Xiao
The inflammasomes are signaling platforms that promote the activation of inflammatory caspases such as caspases-1, -4, -5, and -11. Recent studies identified gasdermin D (GSDMD) as an effector for pyroptosis downstream of the inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases allows its N-terminal domain to associate with membrane lipids and form pores that induce pyroptotic cell death. Despite the important role of GSDMD in pyroptosis, the molecular mechanisms of GSDMD recognition and cleavage by inflammatory caspases that trigger pyroptosis are poorly understood...
June 11, 2018: Proceedings of the National Academy of Sciences of the United States of America
Beatriz Helena Dias Panariello, Marlise I Klein, Ewerton Garcia De Oliveira Mima, Ana Cláudia Pavarina
Background : Fluconazole (FLZ) is a drug commonly used for the treatment of Candida infections. However, β-glucans in the extracellular matrices (ECMs) hinder FLZ penetration into Candida biofilms, while extracellular DNA (eDNA) contributes to the biofilm architecture and resistance. Methods : This study characterized biofilms of FLZ-sensitive (S) and -resistant (R) Candida albicans and Candida glabrata in the presence or absence of FLZ focusing on the ECM traits. Biofilms of C. albicans American Type Culture Collection (ATCC) 90028 (CaS), C...
2018: Journal of Oral Microbiology
Yumeng Jiang, Tao Li, Meiling Lu, Dan Li, Fazheng Ren, Huiying Zhao, Yuan Li
There is an urgent need for developing nanocarrier of excellent biocompatibility which can selectively release drugs at desired locations that can increase intratumoral drug concentration and reduce side effects. Herein, we developed a highly biocompatible nanocarrier made of oxidized starch in delivering doxorubicin (DOX) for enhanced anti-cancer therapy. The 30% oxidized starch can spontaneously self-assemble into 30-50 nm spherical nanoassemblies under physiological concentrations. DO30 nanoassemblies possessed negligible toxicity in several cell lines and ICR mice, in contrast to severe toxicity of synthetic polyacrylic acid (PAA), both of which are carboxyl-abundant polymers...
June 7, 2018: International Journal of Pharmaceutics
Guangyan Wu, Xue Yang, Yuequan Shen
Transient receptor potential mucolipin subfamily 1 (TRPML1) is a non-selective cation channel mainly located in late endosomes and lysosomes. Mutations of the gene encoding human TRPML1 can cause severe lysosomal diseases. The activity of TRPML1 is regulated by both Ca2+ and H+ , which are important for its critical physiological functions in membrane trafficking, exocytosis, autophagy, and intracellular signal transduction. However, the molecular mechanism of its dual regulation by Ca2+ and H+ remains elusive...
June 8, 2018: Journal of Biological Chemistry
Philip J Sandoval, Kimberely M Zorn, Alex M Clark, Sean Ekins, Stephen H Wright
The organic cation transporter OCT2 mediates the entry step for organic cation secretion by renal proximal tubule cells and is a site of unwanted drug-drug interactions (DDIs). But reliance on decision tree-based predictions of DDIs at OCT2 that depend on IC50 values can be suspect because they can be influenced by choice of transported substrate; for example, IC50 s for inhibition of metformin vs MPP transport can vary by 5 to 10-fold. However, it is not clear if substrate-dependence of ligand interaction is common among OCT2 substrates...
June 8, 2018: Molecular Pharmacology
Gun Woo Lee, Ji-Hoon Shin
OBJECTIVE: To present a minimally-invasive surgical technique using cortical bone trajectory-pedicle screw (cortical screw, CS) for adjacent segment pathology (ASP) after lumbar fusion surgery, and to thoroughly compare postoperative outcomes of the two surgical techniques with either CS or conventional pedicle screw (PS) for ASP in one year follow-up time. METHODS: Among 59 patients who underwent surgical treatment for proximal ASP after lumbar fusion surgery, 53 patients who met the study criteria (group A, 31 patients with conventional technique using PS; group B, 22 patients with minimally-invasive technique using CS) were enrolled in the study...
June 5, 2018: World Neurosurgery
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