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Katarzyna Szczepańska Tadeusz Karcz Magdalena Kotańska Agata Siwek Kamil J. Kuder Gniewomir Latacz Szczepan Mogilski Stefanie Hagenow Annamaria Lubelska Michał Sobolewski Holger Stark Katarzyna Kieć-Kononowicz 《Bioorganic & medicinal chemistry》2018,26(23-24):6056-6066
As a continuation of our search for novel histamine H3 receptor ligands, a series of new acetyl and propionyl phenoxyalkylamine derivatives (2–25) was synthesized. Compounds with three to four carbon atoms alkyl chain spacer, composed of six various 4N-substituted piperazine moieties were evaluated for their binding properties at human histamine H3 receptors (hH3R). In vitro test results proved the 4-pyridylpiperazine moiety as crucial element for high hH3R affinity (hH3R Ki?=?5.2–115?nM). Moreover introduction of carbonyl group containing residues in the lipophilic part of molecules instead of branched alkyl substituents resulted in increased affinity in correlation to previously described series, whereas propionyl derivatives showed slightly higher affinities than those of acetyl (16 and 22vs.4 and 10; hH3R Ki?=?5.2 and 15.4?nM vs. 10.2 and 115?nM, respectively). These findings were confirmed by molecular modelling studies, demonstrating multiple ligand-receptor interactions. Furthermore, pharmacological in vivo test results of compound 4 clearly indicate that it may affect the amount of calories consumed, thus act as an anorectic compound. Likewise, its protective action against hyperglycemia and the development of overweight has been shown. In order to estimate drug-likeness of compound 4, in silico and experimental evaluation of metabolic stability in human liver microsomes was performed. 相似文献
135.
Marta Michalczuk Beata Urban Tadeusz Porowski Anna Wasilewska Alina Bakunowicz-Łazarczyk 《Metabolomics : Official journal of the Metabolomic Society》2018,14(6):82
Introduction
Citrate is an old metabolite which is best known for the role in the Krebs cycle. Citrate is widely used in many branches of medicine. In ophthalmology citrate is considered as a therapeutic agent and an useful diagnostic tool—biomarker.Objectives
To summarize the published literature on citrate usage in the leading causes of blindness and highlight the new possibilities for this old metabolite.Methods
We conducted a systematic search of the scientific literature about citrate usage in ophthalmology up to January 2018. The reference lists of identified articles were searched for providing in-depth information.Results
This systematic review included 30 articles. The role of citrate in the leading causes of blindness is presented.Conclusions
Citrate might help inhibit cataract progression, in case of questions confirm glaucoma diagnosis or improve cornea repair treatment as adjuvant agent (therapy of ulcerating cornea after alkali injury, crosslinking procedure). However, the knowledge about possible citrate usage in ophthalmology is not widely known. Promoting recent scientific knowledge about citrate usage in ophthalmology may not only benefit of medical improvement but may also limit economic costs caused by leading causes of blindness. Further studies on citrate usage in ophthalmology should continuously be the field of scientific interest.136.
137.
Blood parasites shape extreme major histocompatibility complex diversity in a migratory passerine
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Aleksandra Biedrzycka Wojciech Bielański Adam Ćmiel Wojciech Solarz Tadeusz Zając Magdalena Migalska Alvaro Sebastian Helena Westerdahl Jacek Radwan 《Molecular ecology》2018,27(11):2594-2603
Pathogens are one of the main forces driving the evolution and maintenance of the highly polymorphic genes of the vertebrate major histocompatibility complex (MHC). Although MHC proteins are crucial in pathogen recognition, it is still poorly understood how pathogen‐mediated selection promotes and maintains MHC diversity, and especially so in host species with highly duplicated MHC genes. Sedge warblers (Acrocephalus schoenobaenus) have highly duplicated MHC genes, and using data from high‐throughput MHC genotyping, we were able to investigate to what extent avian malaria parasites explain temporal MHC class I supertype fluctuations in a long‐term study population. We investigated infection status and infection intensities of two different strains of Haemoproteus, that is avian malaria parasites that are known to have significant fitness consequences in sedge warblers. We found that prevalence of avian malaria in carriers of specific MHC class I supertypes was a significant predictor of their frequency changes between years. This finding suggests that avian malaria infections partly drive the temporal fluctuations of the MHC class I supertypes. Furthermore, we found that individuals with a large number of different supertypes had higher resistance to avian malaria, but there was no evidence for an optimal MHC class I diversity. Thus, the two studied malaria parasite strains appear to select for a high MHC class I supertype diversity. Such selection may explain the maintenance of the extremely high number of MHC class I gene copies in sedge warblers and possibly also in other passerines where avian malaria is a common disease. 相似文献
138.
Kamil Dobrzyn Nina Smolinska Marta Kiezun Karol Szeszko Edyta Rytelewska Katarzyna Kisielewska Marlena Gudelska Tadeusz Kaminski 《Acta veterinaria Scandinavica》2018,60(1):76
Background
Orexin A (OXA) and orexin B (OXB) are hypothalamic-derived peptides that participate in the regulation of energy metabolism, food intake and reproductive function by influencing the hypothalamic-pituitary-ovarian axis. Orexins are also produced in the endometrium, myometrium and placenta, which suggests that they could act as a link between energy metabolism and the reproductive system. Changes in the expression of orexin and the orexin receptor genes and proteins during the oestrous cycle and early gestation in pigs imply that orexin activity may be regulated by local factors within the uterus. The aim of this study was to investigate the influence of progesterone (P4) on the expression of orexin system genes, and proteins in the porcine uterus during early gestation. Gene expression was analyzed by real-time PCR. Adiponectin secretion was determined by ELISA, and the receptors proteins content was defined using western blot analysis.Results
In the endometrium, P4 enhanced OXA secretion on days 10 to 11 of gestation and OXB secretion on days 12 to 13. In the myometrium, P4 inhibited the secretion of both orexins on days 15 to 16 and OXB secretion also on days 12 to 13. In the endometrium, P4 inhibited the expression of orexin receptor 1 (OX1R) protein at nearly all times analyzed, whereas the expression of orexin receptor 2 (OX2R) protein was inhibited only on days 15 to 16 of gestation. In the myometrium, P4 stimulated OX1R protein expression on days 12 to 13 and 15 to 16 of gestation and inhibited OX1R protein expression on days 27 to 28. The expression of OX2R protein in the myometrium increased on days 12 to 13 and decreased on days 10 to 11 and 15 to 16.Conclusions
The results indicate that P4 could regulate the expression of the orexin system in the porcine uterus during early pregnancy, which suggests the presence of a local feedback loop that could play an important role in the regulation of maternal metabolism during pregnancy. The findings may contribute to the existing knowledge of the mechanisms linking maternal energy metabolism with the regulation of the reproductive system during pregnancy.139.
Ca2+-dependent influence of excess Cu2+ on the photosynthetic akpparatus monitored through chlorophyll fluorescence measurements was investigated in runner bean plants (Phaseolus coccineus L. cv. Pie kny Ja?) at three different growth stages. It was observed that the toxic effect of excess Cu2+ on plants depends both on their growth stages and the Ca2+ content in the medium. Increased Ca2+ content limits Cu2+ action on plants at their initial growth stage (I) through: stabilization of the PSII complex (increase of the ratio of variable to minimal fluorescence [Fv/F0]), improved electron flow and reoxidative processes of the quinone primary electron acceptor of PSII (QA) (increase of quantum yield of PSII electron transport [φe] and photochemical quenching of fluorescence [qP] values) and elimination of nonphotochemical energy dissipation (decrease of nonphotochemical fluorescence quenching from the Stern-Volmer equation [NPQ] and fraction of the absorbed light energy not used for photochemistry [LNU] values). At this growth stage excess Cu2+ decreases the rates of QA reduction as a result of decreased PSII activity at its donor side only at lower Ca2+ level. At the intermediate growth stage (II) the plants were less sensitive to Cu2+ treatment and also to changed Ca2+ content. A weakening of some photochemical processes by excess Cu2+ could be observed only at a higher Ca2+ dose. At the final growth stage of plants (III) Ca2+ ions exerted a decisively different effect on the mechanism of excess Cu2+ action on bean plants, visualized by decreased PSII stabilization and utilization of absorbed light energy at increased Ca2+ content in the medium. 相似文献
140.
Rami N Khayat Tadeusz Przybylowski Keith C Meyer James B Skatrud Barbara J Morgan 《Journal of applied physiology》2004,97(2):635-640
We reasoned that, if the lung inflation reflex contributes importantly to apnea-induced sympathetic activation, such activation would be attenuated in bilateral lung transplant recipients (LTX). We measured muscle sympathetic nerve activity (MSNA; intraneural electrodes), heart rate, mean arterial pressure, tidal volume, end-tidal Pco(2), and arterial oxygen saturation in seven LTX and seven healthy control subjects (Con) before, during, and after 20-s end-expiratory breath holds. Our evidence for denervation in LTX was 1) greatly attenuated respiratory sinus arrhythmia and 2) absence of cough reflex below the level of the carina. During apnea, the temporal pattern and the peak increase in MSNA were virtually identical in LTX and Con (347 +/- 99 and 359 +/- 46% of baseline, respectively; P > 0.05). In contrast, the amount of MSNA present in the first 5 s after resumption of breathing was greater in LTX vs. Con (101 +/- 4 vs. 38 +/- 7% of baseline, respectively; P < 0.05). There were no between-group differences in apnea-induced hypoxemia or hypercapnia, hemodynamic, or ventilatory responses. Thus cessation of the rhythmic sympathoinhibitory feedback that normally accompanies eupneic breathing does not contribute importantly to sympathetic excitation during apnea. In contrast, vagal afferent input elicited by hyperventilation-induced lung stretch plays an important role in the profound, rapid sympathetic inhibition that occurs after resumption of breathing after apnea. 相似文献