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81.
Marian L. Kruzel Jeffrey K. Actor Michał Zimecki Jasen Wise Paulina Płoszaj Shaper Mirza Mark Kruzel Shen-An Hwang Xueqing Ba Istvan Boldogh 《Journal of biotechnology》2013
Lactoferrin, an iron-binding protein found in high concentrations in mammalian exocrine secretions, is an important component of the host defense system. It is also a major protein of the secondary granules of neutrophils from which is released upon activation. Due to its potential clinical utility, recombinant human lactoferrin (rhLF) has been produced in various eukaryotic expression systems; however, none of these are fully compatible with humans. Most of the biopharmaceuticals approved by the FDA for use in humans are produced in mammalian expression systems. The Chinese hamster ovary cells (CHO) have become the system of choice for proteins that require post-translational modifications, such as glycoproteins. 相似文献
82.
Biotransformation of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide,a novel potent 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties: In vitro and in silico approach
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Karolina Słoczyńska Katarzyna Wójcik‐Pszczoła Vittorio Canale Paweł Żmudzki Paweł Zajdel Elżbieta Pękala 《Journal of biochemical and molecular toxicology》2018,32(5)
The aim of the study was to investigate the metabolism of 4‐fluoro‐N‐(1‐{2‐[(propan‐2‐yl)phenoxy]ethyl}‐8‐azabicyclo[3.2.1]octan‐3‐yl)‐benzenesulfonamide (PZ‐1150), a novel 5‐HT7 receptor antagonist with antidepressant‐like and anxiolytic properties, by the following three ways: in vitro with microsomes; in vitro employing Cunninghamella echinulata, and in silico using MetaSite. Biotransformation of PZ‐1150 with microsomes resulted in five metabolites, while transformation with C. echinulata afforded two metabolites. In both models, the predominant metabolite occurred due to hydroxylation of benzene ring. In silico data coincide with in vitro experiments, as three MetaSite metabolites matched compounds identified in microsomal samples. In human liver microsomes PZ‐1150 exhibited in vitro half‐life of 64 min, with microsomal intrinsic clearance of 54.1 μL/min/mg and intrinsic clearance of 48.7 mL/min/kg. Therefore, PZ‐1150 is predicted to be a high‐clearance agent. The study demonstrated the applicability of using microsomal model coupled with microbial model to elucidate the metabolic pathways of compounds and comparison with in silico metabolite predictions. 相似文献
83.
Adeno-associated viruses (AAV) 总被引:1,自引:0,他引:1
Recombinant adeno-associated virus derived vectors (rAAV) a thought to be a most promising candidates for gene therapy applications. Their nonpathogenic nature as well as the encouraging capability to infect both proliferating and non proliferating cells are advantages for gene therapy applications. Here, we summarize the potential mechanisms responsible for AAV maintenance and site-specific integration to human genome. The role of Rep proteins, inverted terminal repeats and p5 promotor sequences for chromosomal incorporation of AAV are discussed. Making the site-specific integrative recombinant AAV vectors for gene therapy seems to be closely dependent on the development of viral vectorology. 相似文献
84.
Marianna Małek Bożena Bogusz Paulina Mrowiec Mariusz Szuta Maciej Opach Iwona Skiba-Kurek Paweł Nowak Karolina Klesiewicz Alicja Budak Elżbieta Karczewska 《Revista iberoamericana de micología》2018,35(3):140-146
Background
Fungal rhinosinusitis has become an increasingly recognized disease, being Aspergillus species responsible for most of the cases. Its diagnosis is quite difficult because of the non-specific symptoms and low sensitivity of the current diagnostic methods.Aims
An Aspergillus-specific nested polymerase chain reaction (PCR) assay using biopsy specimens taken from the maxillary sinuses was performed in order to assess its usefulness. Conventional diagnostic methods (histology and culture) were also carried out.Methods
A case–control study was performed in the Institute of Stomatology, Jagiellonian University in Kraków, between 2011 and 2014. The case group consisted of 21 patients with suspected rhinosinusal mycetoma while the control group included 46 patients with no suspicion of fungal rhinosinusitis. The two-step PCR assay amplified an Aspergillus specific portion of the 18S rRNA gene. Interval estimation of sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated to assess the diagnostic test performance. The agreement between the PCR and the other tests was evaluated using the Kappa coefficient (k).Results
Ninety percent of the samples obtained from patients diagnosed with mycetoma yielded positive PCR results. The PCR showed almost perfect concordance with histology (k = 0.88). Sensitivity, specificity, PPV and NPV estimates were 90%; 95% CI: (55.5–99.7%), 98.3%; 95% CI: (90.9–100%), 90%; 95% CI: (55.5–99.7%) and 98.3%; 95% CI: (90.9–100%), respectively. One clinical sample showed growth of Aspergillus fumigatus and positive PCR despite the negative histological examination.Conclusions
Nested PCR assay is a promising diagnostic tool to evaluate the presence of Aspergillus in the tissue of maxillary sinus from patients with suspicion of sinus aspergillosis. 相似文献85.
Nowak R Baranowska-Bosiacka I Stefańska B Machaliński B Hłyńczak AJ Tarasiuk J 《Acta biochimica Polonica》2005,52(4):953-957
Multidrug resistance (MDR) of tumour cells is related to the overexpression of ATP-dependent pumps responsible for the active efflux of antitumour agents out of resistant cells. Benzoperimidine and anthrapyridone compounds exhibit comparable cytotoxic activity against sensitive and MDR tumour cells. They diffuse extremely rapidly across the plasma membrane and render the ATP-dependent efflux inefficient. Such uptake could disturb an energy metabolism of normal cells possessing an elevated level of ATP-dependent proteins, especially erythrocytes having a high level of the MRP1, MRP4 and MRP5 proteins. In this study the effect of five antitumour agents: benzoperimidine (BP1), anthrapyridones (CO1, CO7) and reference drugs used in the clinic: doxorubicin (DOX) and pirarubicin (PIRA), on the energetic state in human erythrocytes has been examined. These compounds have various types of structure and kinetics of cellular uptake (slow--DOX, CO7, moderate--PIRA, fast--BP1, CO1) resulting in their different ability to saturate ATP-dependent transporters. The energetic state of erythrocytes was examined by determination of purine nucleotide contents (ATP, ADP, AMP), NAD(+) and values of adenylate energy charge (AEC) using an HPLC method. It was found that the level of nucleotides as well as the AEC value of erythrocytes were not changed during 24 h of incubation with these agents independently of their structure and ability to saturate ATP-dependent pumps. This is a very promising result in view of their potential use in the clinic as antitumour drugs against multidrug resistant cancers. 相似文献
86.
Perła J Undas A Twardowski T Jakubowski H 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2004,807(2):257-261
Modification with homocysteine (Hcy)-thiolactone leads to the formation of N-Hcy-Lys-protein. Although N-Hcy-Lys-proteins are immunogenic, pure antibodies have not yet been obtained. Here we describe synthesis and application of Nomega-homocysteinyl-aminohexyl-Agarose for affinity purification of anti-N-Hcy-Lys-protein antibodies. Nomega-homocysteinyl-aminohexyl-Agarose was prepared by N-homocysteinylation of omega-aminohexyl-Agarose with Hcy-thiolactone. Immune serum was obtained from rabbits inoculated with N-Hcy-Lys-keyhole limpet hemocyanine and IgG fraction prepared by chromatography on protein A-Agarose. Anti-N-Hcy-Lys-protein IgG was adsorbed on Nomega-homocysteinyl-aminohexyl-Agarose column at pH 8.6 and eluted with a pH 2.3 buffer. Enzyme-linked immunosorbent assays demonstrate that the antibody recognizes specifically N-homocysteinylated variants of hemoglobin, albumin, transferrin, and antitrypsin. 相似文献
87.
88.
Lovisa Wennerström Linda Laikre Nils Ryman Fred M. Utter Nurul Izza Ab Ghani Carl André Jacquelin DeFaveri Daniel Johansson Lena Kautsky Juha Merilä Natalia Mikhailova Ricardo Pereyra Annica Sandström Amber G. F. Teacher Roman Wenne Anti Vasemägi Małgorzata Zbawicka Kerstin Johannesson Craig R. Primmer 《Biodiversity and Conservation》2013,22(13-14):3045-3065
Information on spatial and temporal patterns of genetic diversity is a prerequisite to understanding the demography of populations, and is fundamental to successful management and conservation of species. In the sea, it has been observed that oceanographic and other physical forces can constitute barriers to gene flow that may result in similar population genetic structures in different species. Such similarities among species would greatly simplify management of genetic biodiversity. Here, we tested for shared genetic patterns in a complex marine area, the Baltic Sea. We assessed spatial patterns of intraspecific genetic diversity and differentiation in seven ecologically important species of the Baltic ecosystem—Atlantic herring (Clupea harengus), northern pike (Esox lucius), European whitefish (Coregonus lavaretus), three-spined stickleback (Gasterosteus aculeatus), nine-spined stickleback (Pungitius pungitius), blue mussel (Mytilus spp.), and bladderwrack (Fucus vesiculosus). We used nuclear genetic data of putatively neutral microsatellite and SNP loci from samples collected from seven regions throughout the Baltic Sea, and reference samples from North Atlantic areas. Overall, patterns of genetic diversity and differentiation among sampling regions were unique for each species, although all six species with Atlantic samples indicated strong resistence to Atlantic-Baltic gene-flow. Major genetic barriers were not shared among species within the Baltic Sea; most species show genetic heterogeneity, but significant isolation by distance was only detected in pike and whitefish. These species-specific patterns of genetic structure preclude generalizations and emphasize the need to undertake genetic surveys for species separately, and to design management plans taking into consideration the specific structures of each species. 相似文献
89.
Persistence of Mhc heterozygosity in homozygous clonal killifish,Rivulus marmoratus: implications for the origin of hermaphroditism 总被引:1,自引:0,他引:1
Sato A Satta Y Figueroa F Mayer WE Zaleska-Rutczynska Z Toyosawa S Travis J Klein J 《Genetics》2002,162(4):1791-1803
The mangrove killifish Rivulus marmoratus, a neotropical fish in the order Cyprinodontiformes, is the only known obligatorily selfing, synchronous hermaphroditic vertebrate. To shed light on its population structure and the origin of hermaphroditism, major histocompatibility complex (Mhc) class I genes of the killifish from seven different localities in Florida, Belize, and the Bahamas were cloned and sequenced. Thirteen loci and their alleles were identified and classified into eight groups. The loci apparently arose approximately 20 million years ago (MYA) by gene duplications from a single common progenitor in the ancestors of R. marmoratus and its closest relatives. Distinct loci were found to be restricted to different populations and different individuals in the same population. Up to 44% of the fish were heterozygotes at Mhc loci, as compared to near homozygosity at non-Mhc loci. Large genetic distances between some of the Mhc alleles revealed the presence of ancestral allelic lineages. Computer simulation designed to explain these findings indicated that selfing is incomplete in R. marmoratus populations, that Mhc allelic lineages must have diverged before the onset of selfing, and that the hermaphroditism arose in a population containing multiple ancestral Mhc lineages. A model is proposed in which hermaphroditism arose stage-wise by mutations, each of which spread through the entire population and was fixed independently in the emerging clones. 相似文献
90.
N-(m-Nitrophenyl)-beta-D-glucopyranosylamine (Gln), N-(N-methylphenyl)-beta-D-glucopyranosylamine (Glm), N-beta-D-glucopyranosylpyrazole (Glp), and N-beta-D-glucopyranosylimidazole (Gli) have been synthesized. Their basicity constants, pKb, determined in methanol were, respectively, 14.99, 14.36, 15.04, and 9.74. The derivatives of secondary amines (Glm, Glp, and Gli) did not mutarotate in methanol in the presence of 3,5-dinitrobenzoic acid and hydrochloric acid. The heats of formation and entropies were calculated by the AM1 and PM3 methods for the glucosylamines and their cations under consideration of two plausible protonation centers. Thermodynamic parameters for the proton transfer in the reaction: glucosylamine + CH3OH2+ = glucosylamineH+ + CH3OH were determined and the protonation center in the glucosylamine molecule was identified. The mechanism of mutarotation of the glucosylamines is discussed and the conclusion made that formation of an acyclic immonium cation is not a satisfactory condition for the reaction to proceed. 相似文献