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981.
Aminothiazoles inhibit RANKL‐ and LPS‐mediated osteoclastogenesis and PGE2 production in RAW 264.7 cells
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Anna Kats Maria Norgård Zenebech Wondimu Catalin Koro Hernán Concha Quezada Göran Andersson Tülay Yucel‐Lindberg 《Journal of cellular and molecular medicine》2016,20(6):1128-1138
Periodontitis is characterized by chronic inflammation and osteoclast‐mediated bone loss regulated by the receptor activator of nuclear factor‐κB (RANK), RANK ligand (RANKL) and osteoprotegerin (OPG). The aim of this study was to investigate the effect of aminothiazoles targeting prostaglandin E synthase‐1 (mPGES‐1) on RANKL‐ and lipopolysaccharide (LPS)‐mediated osteoclastogenesis and prostaglandin E2 (PGE2) production in vitro using the osteoclast precursor RAW 264.7 cells. RAW 264.7 cells were treated with RANKL or LPS alone or in combination with the aminothiazoles 4‐([4‐(2‐naphthyl)‐1,3‐thiazol‐2‐yl]amino)phenol (TH‐848) or 4‐(3‐fluoro‐4‐methoxyphenyl)‐N‐(4‐phenoxyphenyl)‐1,3‐thiazol‐2‐amine (TH‐644). Aminothiazoles significantly decreased the number of multinucleated tartrate‐resistant acid phosphatase (TRAP)‐positive osteoclast‐like cells in cultures of RANKL‐ and LPS‐stimulated RAW 264.7 cells, as well as reduced the production of PGE2 in culture supernatants. LPS‐treatment induced mPGES‐1 mRNA expression at 16 hrs and the subsequent PGE2 production at 72 hrs. Conversely, RANKL did not affect PGE2 secretion but markedly reduced mPGES‐1 at mRNA level. Furthermore, mRNA expression of TRAP and cathepsin K (CTSK) was reduced by aminothiazoles in RAW 264.7 cells activated by LPS, whereas RANK, OPG or tumour necrosis factor α mRNA expression was not significantly affected. In RANKL‐activated RAW 264.7 cells, TH‐848 and TH‐644 down‐regulated CTSK but not TRAP mRNA expression. Moreover, the inhibitory effect of aminothiazoles on PGE2 production was also confirmed in LPS‐stimulated human peripheral blood mononuclear cell cultures. In conclusion, the aminothiazoles reduced both LPS‐ and RANKL‐mediated osteoclastogenesis and PGE2 production in RAW 264.7 cells, suggesting these compounds as potential inhibitors for treatment of chronic inflammatory bone resorption, such as periodontitis. 相似文献
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983.
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985.
Pedro M. Martin-Sanchez Anna A. Gorbushina Hans-Jörg Kunte Jörg Toepel 《Biofouling》2016,32(6):635-644
A wide variety of fungi and bacteria are known to contaminate fuels and fuel systems. These microbial contaminants have been linked to fuel system fouling and corrosion. The fungus Hormoconis resinae, a common jet fuel contaminant, is used in this study as a model for developing innovative risk assessment methods. A novel qPCR protocol to detect and quantify H. resinae in, and together with, total fungal contamination of fuel systems is reported. Two primer sets, targeting the markers RPB2 and ITS, were selected for their remarkable specificity and sensitivity. These primers were successfully applied on fungal cultures and diesel samples demonstrating the validity and reliability of the established qPCR protocol. This novel tool allows clarification of the current role of H. resinae in fuel contamination cases, as well as providing a technique to detect fungal outbreaks in fuel systems. This tool can be expanded to other well-known fuel-deteriorating microorganisms. 相似文献
986.
987.
Anticonvulsant Activity of Enantiomeric N‐trans‐Cinnamoyl Derivatives of 2‐Aminopropan‐1‐ols and 2‐Aminobutan‐1‐ols
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Agnieszka Gunia‐Krzyżak Ewa Żesławska Wojciech Nitek Justyna Popiół Henryk Marona 《Chirality》2016,28(6):482-488
Epilepsy, one of the most frequent neurological disorders, is still insufficiently treated in about 30% of patients. As a consequence, identification of novel anticonvulsant agents is an important issue in medicinal chemistry. In the present article we report synthesis, physicochemical, and pharmacological evaluation of N‐trans‐cinnamoyl derivatives of R and S‐2‐aminopropan‐1‐ol, as well as R and S‐2‐aminobutan‐1‐ol. The structures were confirmed by spectroscopy and for derivatives of 2‐aminopropan‐1‐ols the configuration was evaluated by means of crystallography. The investigated compounds were tested in rodent models of seizures: maximal electroshock (MES) and subcutaneous pentetrazol test (scPTZ), and also in a rodent model of epileptogenesis: pilocarpine‐induced status prevention. Additionally, derivatives of 2‐aminopropan‐1‐ols were tested in benzodiazepine‐resistant electrographic status epilepticus rat model as well as in vitro for inhibition of isoenzymes of cytochrome P450. All of the tested compounds showed promising anticonvulsant activity in MES. For R(–)‐(2E)‐N‐(1‐hydroxypropan‐2‐yl)‐3‐phenylprop‐2‐enamide pharmacological parameters were found as follows: ED50 = 76.7 (68.2–81.3) mg/kg (MES, mice i.p., time = 0.5 h), ED50 = 127.2 (102.1–157.9) mg/kg (scPTZ, mice i.p., time = 0.25 h), TD50 = 208.3 (151.4–230.6) mg/kg (rotarod, mice i.p., time = 0.25 h). Evaluation in pilocarpine status prevention proved that all of the reported compounds reduced spontaneous seizure activity and act as antiepileptogenic agents. Both enantiomers of 2‐aminopropan‐1‐ols did not influence cytochrome P450 isoenzymes activity in vitro and are likely not to interact with CYP substrates in vivo. Chirality 28:482–488, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
988.
989.
Ultrastructural Impact of Tobacco Rattle Virus on Tobacco and Pepper Ovary and Anther Tissues
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The one‐third of plant viruses are seed transmitted, and this has significant economic consequences. Tobacco rattle virus (TRV), belonging to the genus Tobravirus and family Virgaviridae, has one of the widest host range of any known plant viruses. TRV infects vegetative organ and effects seed and pollen development that results in a decrease in crop yield. The mechanisms by which Tobravirus is transmissible to seeds are still poorly understood. The presence of the virus in pollen grains and inside ovaries is linked with seed transmission and can have effects on virus particles' transport during the pollination and fertilization process. This paper focuses on the significant impact of TRV on pepper and tobacco anthers and ultrastructure changes in ovaries. The presence of two types of TRV particles in ovary wall parenchyma and vascular tissues as well as in placenta cells was demonstrated via ultrastructural analysis. For the first time, the regular inclusion of virus particles was reported in both ovule integuments and nucellus parenchyma cells. Immunolocalization of TRV capsid proteins indicated the deposition of TRV CP epitope in ovary vascular bundles and in placenta cells. Moreover, the presence of virus particles was demonstrated inside pepper seeds in endothelium and integument parenchyma layers as well as on the embryo cell wall. Virus particles were found not only on the surface of pollen grains but also inside pepper pollen protoplasts in mature anthers. Also, this is the first time where TRV particles are reported in both differentiated endothecium cells and the remaining tapetum cells. Moreover, the detection of TRV capsid protein epitope in tobacco and pepper vascular anther tissues as well as in tapetum and endothecium cells was correlated with TRV distribution in infected anthers. Demonstrated analyses indicated that pollen grains and ovaries with ovules as well as could be a natural source of TRV transmission. 相似文献
990.
Tapani Repo Anna Korhonen Tarja Lehto Raimo Silvennoinen 《Trees - Structure and Function》2016,30(2):483-495