Ewa Szczurowska  Eszter Sznti-Pintr  Alena Randkov  Jan Jakubík  Eva Kudova 《International journal of molecular sciences》2022,23(21)

Muscarinic acetylcholine receptors are membrane receptors involved in many physiological processes. Malfunction of muscarinic signaling is a cause of various internal diseases, as well as psychiatric and neurologic conditions. Cholesterol, neurosteroids, neuroactive steroids, and steroid hormones are molecules of steroid origin that, besides having well-known genomic effects, also modulate membrane proteins including muscarinic acetylcholine receptors. Here, we review current knowledge on the allosteric modulation of muscarinic receptors by these steroids. We give a perspective on the research on the non-genomic effects of steroidal compounds on muscarinic receptors and drug development, with an aim to ultimately exploit such knowledge.  相似文献   

    

Mariapompea Cutroneo  Lorenzo Torrisi  Letteria Silipigni  Alena Michalcova  Vladimir Havranek  Anna Mackova  Petr Malinsky  Vasily Lavrentiev  Pavol Noga  Jozef Dobrovodsky  Petr Slepicka  Dominik Fajstavr  Lucio And  Vaclav Holy 《International journal of molecular sciences》2022,23(20)

In the present study, graphene oxide foils 10 μm thick have been irradiated in vacuum using same charge state (one charge state) ions, such as protons, helium and oxygen ions, at the same energies (3 MeV) and fluences (from 5 × 10¹¹ ion/cm² to 5 × 10¹⁴ ion/cm²). The structural changes generated by the ion energy deposition and investigated by X-ray diffraction have suggested the generation of new phases, as reduced GO, GO quantum dots and graphitic nanofibers, carbon nanotubes, amorphous carbon and stacked-cup carbon nanofibers. Further analyses, based on Rutherford Backscattering Spectrometry and Elastic Recoil Detection Analysis, have indicated a reduction of GO connected to the atomic number of implanted ions. The morphological changes in the ion irradiated GO foils have been monitored by Transmission Electron, Atomic Force and Scanning Electron microscopies. The present study aims to better structurally, compositionally and morphologically characterize the GO foils irradiated by different ions at the same conditions and at very low ion fluencies to validate the use of GO for radiation detection and propose it as a promising dosimeter. It has been observed that GO quantum dots are produced on the GO foil when it is irradiated by proton, helium and oxygen ions and their number increases with the atomic number of beam gaseous ion.  相似文献   

    

Christopher L. Moore  Alena V. Savenka  Alexei G. Basnakian 《International journal of molecular sciences》2021,22(1)

Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay is a long-established assay used to detect cell death-associated DNA fragmentation (3’-OH DNA termini) by endonucleases. Because these enzymes are particularly active in the kidney, TUNEL is widely used to identify and quantify DNA fragmentation and cell death in cultured kidney cells and animal and human kidneys resulting from toxic or hypoxic injury. The early characterization of TUNEL as an apoptotic assay has led to numerous misinterpretations of the mechanisms of kidney cell injury. Nevertheless, TUNEL is becoming increasingly popular for kidney injury assessment because it can be used universally in cultured and tissue cells and for all mechanisms of cell death. Furthermore, it is sensitive, accurate, quantitative, easily linked to particular cells or tissue compartments, and can be combined with immunohistochemistry to allow reliable identification of cell types or likely mechanisms of cell death. Traditionally, TUNEL analysis has been limited to the presence or absence of a TUNEL signal. However, additional information on the mechanism of cell death can be obtained from the analysis of TUNEL patterns.  相似文献   

    

Alena S. Tsvetkova  Olesya G. Bernikova  Natalya J. Mikhaleva  Darya S. Khramova  Alexey O. Ovechkin  Marina M. Demidova  Pyotr G. Platonov  Jan E. Azarov 《International journal of molecular sciences》2021,22(1)

Antiarrhythmic effects of melatonin have been demonstrated ex vivo and in rodent models, but its action in a clinically relevant large mammalian model remains largely unknown. Objectives of the present study were to evaluate electrophysiological and antiarrhythmic effects of melatonin in a porcine model of acute myocardial infarction. Myocardial ischemia was induced by 40-min coronary occlusion in 25 anesthetized pigs. After ischemia onset, 12 animals received melatonin (4 mg/kg). 48 intramyocardial electrograms were recorded from left ventricular wall and interventricular septum (IVS). In each lead, activation time (AT) and repolarization time (RT) were determined. During ischemia, ATs and dispersion of repolarization (DOR = RTmax − RTmin) increased reaching maximal values by 3–5 and 20–25 min, respectively. Ventricular fibrillation (VF) incidence demonstrated no relations to redox state markers and was associated with increased DOR and delayed ATs (specifically, in an IVS base, an area adjacent to the ischemic zone) (p = 0.031). Melatonin prevented AT increase in the IVS base, (p < 0.001) precluding development of early VF (1–5 min, p = 0.016). VF occurrence in the delayed phase (17–40 min) where DOR was maximal was not modified by melatonin. Thus, melatonin-related enhancement of activation prevented development of early VF in the myocardial infarction model.  相似文献   

    

Alena Nprstkov  Kate&#x;ina Malínsk  Lenka Zvesk Drbkov  Elodie Billey  Dagmar Nprstkov  Eva Sýkorov  Ccile Bousquet-Antonelli  David Honys 《International journal of molecular sciences》2021,22(4)

ALBA DNA/RNA-binding proteins form an ancient family, which in eukaryotes diversified into two Rpp25-like and Rpp20-like subfamilies. In most studied model organisms, their function remains unclear, but they are usually associated with RNA metabolism, mRNA translatability and stress response. In plants, the enriched number of ALBA family members remains poorly understood. Here, we studied ALBA dynamics during reproductive development in Arabidopsis at the levels of gene expression and protein localization, both under standard conditions and following heat stress. In generative tissues, ALBA proteins showed the strongest signal in mature pollen where they localized predominantly in cytoplasmic foci, particularly in regions surrounding the vegetative nucleus and sperm cells. Finally, we demonstrated the involvement of two Rpp25-like subfamily members ALBA4 and ALBA6 in RNA metabolism in mature pollen supported by their co-localization with poly(A)-binding protein 3 (PABP3). Collectively, we demonstrated the engagement of ALBA proteins in male reproductive development and the heat stress response, highlighting the involvement of ALBA4 and ALBA6 in RNA metabolism, storage and/or translational control in pollen upon heat stress. Such dynamic re-localization of ALBA proteins in a controlled, developmentally and environmentally regulated manner, likely reflects not only their redundancy but also their possible functional diversification in plants.  相似文献   

    

Elena Chugunova  Gabriele Micheletti  Dario Telese  Carla Boga  Daut Islamov  Konstantin Usachev  Alexander Burilov  Alena Tulesinova  Alexandra Voloshina  Anna Lyubina  Syumbelya Amerhanova  Tatiana Gerasimova  Aisylu Gilfanova  Victor Syakaev 《International journal of molecular sciences》2021,22(14)

A series of novel hybrid compounds containing benzofuroxan and 2-aminothiazole moieties are synthesized via aromatic nucleophilic substitution reaction. Possible reaction pathways have been considered quantum-chemically, which allowed us to suggest the most probable products. The quantum chemical results have been proved by X-ray data on one compound belonging to the synthesized series. It was shown that the introduction of substituents to both the thiazole and amine moieties of the compounds under study strongly influences their UV/Vis spectra. Initial substances and obtained hybrid compounds have been tested in vitro as anticancer agents. Target compounds showed selectivity towards M-HeLa tumor cell lines and were found to be more active than starting benzofuroxan and aminothiazoles. Furthermore, they are considerably less toxic to normal liver cells compared to Tamoxifen. The mechanism of action of the studied compounds can be associated with the induction of apoptosis, which proceeds along the mitochondrial pathway. Thus, new hybrids of benzofuroxan are promising candidates for further development as anticancer agents.  相似文献   

    

Sylva Prerostova  Petre I. Dobrev  Vojtech Knirsch  Jana Jarosova  Alena Gaudinova  Barbara Zupkova  Ilja T. Pr&#x;il  Tibor Janda  B&#x;etislav Brzobohatý  Jan Skalk  Radomira Vankova 《International journal of molecular sciences》2021,22(5)

Plant survival in temperate zones requires efficient cold acclimation, which is strongly affected by light and temperature signal crosstalk, which converge in modulation of hormonal responses. Cold under low light conditions affected Arabidopsis responses predominantly in apices, possibly because energy supplies were too limited for requirements of these meristematic tissues, despite a relatively high steady-state quantum yield. Comparing cold responses at optimal light intensity and low light, we found activation of similar defence mechanisms—apart from CBF1–3 and CRF3–4 pathways, also transient stimulation of cytokinin type-A response regulators, accompanied by fast transient increase of trans-zeatin in roots. Upregulated expression of components of strigolactone (and karrikin) signalling pathway indicated involvement of these phytohormones in cold responses. Impaired response of phyA, phyB, cry1 and cry2 mutants reflected participation of these photoreceptors in acquiring freezing tolerance (especially cryptochrome CRY1 at optimal light intensity and phytochrome PHYA at low light). Efficient cold acclimation at optimal light was associated with upregulation of trans-zeatin in leaves and roots, while at low light, cytokinin (except cis-zeatin) content remained diminished. Cold stresses induced elevation of jasmonic acid and salicylic acid (in roots). Low light at optimal conditions resulted in strong suppression of cytokinins, jasmonic and salicylic acid.  相似文献   

    

Mariia Levit  Alena Vdovchenko  Apollinariia Dzhuzha  Natalia Zashikhina  Elena Katernyuk  Alexey Gostev  Eugene Sivtsov  Antonina Lavrentieva  Tatiana Tennikova  Evgenia Korzhikova-Vlakh 《International journal of molecular sciences》2021,22(21)

The self-assembly of amphiphilic block-copolymers is a convenient way to obtain soft nanomaterials of different morphology and scale. In turn, the use of a biomimetic approach makes it possible to synthesize polymers with fragments similar to natural macromolecules but more resistant to biodegradation. In this study, we synthesized the novel bio-inspired amphiphilic block-copolymers consisting of poly(N-methacrylamido-d-glucose) or poly(N-vinyl succinamic acid) as a hydrophilic fragment and poly(O-cholesteryl methacrylate) as a hydrophobic fragment. Block-copolymers were synthesized by radical addition–fragmentation chain-transfer (RAFT) polymerization using dithiobenzoate or trithiocarbonate chain-transfer agent depending on the first monomer, further forming the hydrophilic block. Both homopolymers and copolymers were characterized by ¹H NMR and Fourier transform infrared spectroscopy, as well as thermogravimetric analysis. The obtained copolymers had low dispersity (1.05–1.37) and molecular weights in the range of ~13,000–32,000. The amphiphilic copolymers demonstrated enhanced thermal stability in comparison with hydrophilic precursors. According to dynamic light scattering and nanoparticle tracking analysis, the obtained amphiphilic copolymers were able to self-assemble in aqueous media into nanoparticles with a hydrodynamic diameter of approximately 200 nm. An investigation of nanoparticles by transmission electron microscopy revealed their spherical shape. The obtained nanoparticles did not demonstrate cytotoxicity against human embryonic kidney (HEK293) and bronchial epithelial (BEAS-2B) cells, and they were characterized by a low uptake by macrophages in vitro. Paclitaxel loaded into the developed polymer nanoparticles retained biological activity against lung adenocarcinoma epithelial cells (A549).  相似文献   

    

Alena Akusevich  Ivana Parchovianská  Milan Parchovianský  Anna Prnová  František Lofaj  Marek Vojtko  Róbert Klement 《International Journal of Applied Glass Science》2021,12(4):497-508

Sintering by viscous flow in a “kinetic window” between T_g and T_x temperatures was used to prepare bulk glass/glass-ceramic luminescent materials from rapidly quenched glass microspheres in the system Y₂O₃–Al₂O₃ doped with Ce³⁺ ions. The glass microspheres were prepared from sol–gel synthesized precursor powders in a high-temperature methane-oxygen flame. The crystallization of the glasses was analyzed using differential scanning calorimetry and high-temperature X-ray diffraction. The crystallization behavior of quenched glass microspheres was found to be strongly dependent on glass composition. The glass microspheres were consolidated into bulk material by hot-pressing technique at a temperature of up to 1100℃ with the applied pressure 40MPa. The optimized time-temperature-pressure regime enables the preparation of bulk glass, and glass-ceramic with a high fraction of crystalline Ce³⁺-doped YAG phase embedded in the Al₂O₃-enriched glass matrix. The glass/glass-ceramics emit blue/yellow light with high intensity under excitation in UV and/or blue spectral region.  相似文献   

    

Dieter Ungermann  Alena Patschin  Anja Ptzold  Eva Preckwinkel  Paul Floerke  Sonja Weiß  Mike Gralla  Tim Brandt  Thomas Ummenhofer  Manfred Hermann  Tim Zinke  Christoph Herrmann  Tina Dettmer  Karsten Ulrich Tichelmann  Bastian Ziegler 《Stahlbau》2014,83(7):441-451

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