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41.
Nadezhda A. Evtushenko Arkadii K. Beilin Erdem B. Dashinimaev Rustam H. Ziganshin Anastasiya V. Kosykh Maxim M. Perfilov Alexandra L. Rippa Elena V. Alpeeva Andrey V. Vasiliev Ekaterina A. Vorotelyak Nadya G. Gurskaya 《International journal of molecular sciences》2021,22(8)
The recessive form of dystrophic epidermolysis bullosa (RDEB) is a crippling disease caused by impairments in the junctions of the dermis and the basement membrane of the epidermis. Using ectopic expression of hTERT/hTERT + BMI-1 in primary cells, we developed expansible cultures of RDEB fibroblasts and keratinocytes. We showed that they display the properties of their founders, including morphology, contraction ability and expression of the respective specific markers including reduced secretion of type VII collagen (C7). The immortalized keratinocytes retained normal stratification in 3D skin equivalents. The comparison of secreted protein patterns from immortalized RDEB and healthy keratinocytes revealed the differences in the contents of the extracellular matrix that were earlier observed specifically for RDEB. We demonstrated the possibility to reverse the genotype of immortalized cells to the state closer to the progenitors by the Cre-dependent hTERT switch off. Increased β-galactosidase activity and reduced proliferation of fibroblasts were shown after splitting out of transgenes. We anticipate our cell lines to be tractable models for studying RDEB from the level of single-cell changes to the evaluation of 3D skin equivalents. Our approach permits the creation of standardized and expandable models of RDEB that can be compared with the models based on primary cell cultures. 相似文献
42.
Patrizia Marchese Maria Lombardi Maria Elena Mantione Domenico Baccellieri David Ferrara Roberto Chiesa Ottavio Alfieri Chiara Foglieni 《International journal of molecular sciences》2021,22(8)
Atherothrombosis exposes vascular components to blood. Currently, new antithrombotic therapies are emerging. Herein we investigated thrombogenesis of human arteries with/without atherosclerosis, and the interaction of coagulation and vascular components, we and explored the anti-thrombogenic efficacy of blockade of the P2X purinoceptor 7 (P2X7). A confocal blood flow videomicroscopy system was performed on cryosections of internal mammary artery (IMA) or carotid plaque (CPL) determining/localizing platelets and fibrin. Blood from healthy donors elicited thrombi over arterial layers. Confocal microscopy associated thrombus with tissue presence of collagen type I, laminin, fibrin(ogen) and tissue factor (TF). The addition of antibodies blocking TF (aTF) or factor XI (aFXI) to blood significantly reduced fibrin deposition, variable platelet aggregation and aTF + aFXI almost abolished thrombus formation, showing synergy between coagulation pathways. A scarce effect of aTF over sub-endothelial regions, more abundant in tissue TF and bundles of laminin and collagen type I than deep intima, may suggest tissue thrombogenicity as molecular structure-related. Consistently with TF-related vascular function and expression of P2X7, the sections from CPL but not IMA tissue cultures pre-treated with the P2X7 antagonist A740003 demonstrated poor thrombogenesis in flow experiments. These data hint to local targeting studies on P2X7 modulation for atherothrombosis prevention/therapy. 相似文献
43.
Lorena Cuenca-Bermejo Elisa Pizzichini Valeria C. Gonalves María Guilln-Díaz Elena Aguilar-Moino Consuelo Snchez-Rodrigo Ana-María Gonzlez-Cuello Emiliano Fernndez-Villalba María Trinidad Herrero 《International journal of molecular sciences》2021,22(9)
The diurnal rodent Octodon degus (O. degus) is considered an attractive natural model for Alzheimer’s disease and other human age-related features. However, it has not been explored so far if the O. degus could be used as a model to study Parkinson’s disease. To test this idea, 10 adult male O. degus were divided into control group and MPTP-intoxicated animals. Motor condition and cognition were examined. Dopaminergic degeneration was studied in the ventral mesencephalon and in the striatum. Neuroinflammation was also evaluated in the ventral mesencephalon, in the striatum and in the dorsal hippocampus. MPTP animals showed significant alterations in motor activity and in visuospatial memory. Postmortem analysis revealed a significant decrease in the number of dopaminergic neurons in the ventral mesencephalon of MPTP animals, although no differences were found in their striatal terminals. We observed a significant increase in neuroinflammatory responses in the mesencephalon, in the striatum and in the hippocampus of MPTP-intoxicated animals. Additionally, changes in the subcellular expression of the calcium-binding protein S100β were found in the astrocytes in the nigrostriatal pathway. These findings prove for the first time that O. degus are sensitive to MPTP intoxication and, therefore, is a suitable model for experimental Parkinsonism in the context of aging. 相似文献
44.
Olga Shilova Elena Shramova Galina Proshkina Sergey Deyev 《International journal of molecular sciences》2021,22(9)
Cancer cells frequently overexpress specific surface receptors providing tumor growth and survival which can be used for precise therapy. Targeting cancer cell receptors with protein toxins is an attractive approach widely used in contemporary experimental oncology and preclinical studies. Methods of targeted delivery of toxins to cancer cells, different drug carriers based on nanosized materials (liposomes, nanoparticles, polymers), the most promising designed light-activated toxins, as well as mechanisms of the cytotoxic action of the main natural toxins used in modern experimental oncology, are discussed in this review. The prospects of the combined therapy of tumors based on multimodal nanostructures are also discussed. 相似文献
45.
Yana Y. Toporkova Elena O. Smirnova Natalia V. Lantsova Lucia S. Mukhtarova Alexander N. Grechkin 《International journal of molecular sciences》2021,22(9)
The CYP74 clan cytochromes (P450) are key enzymes of oxidative metabolism of polyunsaturated fatty acids in plants, some Proteobacteria, brown and green algae, and Metazoa. The CYP74 enzymes, including the allene oxide synthases (AOSs), hydroperoxide lyases, divinyl ether synthases, and epoxyalcohol synthases (EASs) transform the fatty acid hydroperoxides to bioactive oxylipins. A novel CYP74 clan enzyme CYP440A18 of the Asian (Belcher’s) lancelet (Branchiostoma belcheri, Chordata) was biochemically characterized in the present work. The recombinant CYP440A18 enzyme was active towards all substrates used: linoleate and α-linolenate 9- and 13-hydroperoxides, as well as with eicosatetraenoate and eicosapentaenoate 15-hydroperoxides. The enzyme specifically converted α-linolenate 13-hydroperoxide (13-HPOT) to the oxiranyl carbinol (9Z,11R,12R,13S,15Z)-11-hydroxy-12,13-epoxy-9,15-octadecadienoic acid (EAS product), α-ketol, 12-oxo-13-hydroxy-9,15-octadecadienoic acid (AOS product), and cis-12-oxo-10,15-phytodienoic acid (AOS product) at a ratio of around 35:5:1. Other hydroperoxides were converted by this enzyme to the analogous products. In contrast to other substrates, the 13-HPOT and 15-HPEPE yielded higher proportions of α-ketols, as well as the small amounts of cyclopentenones, cis-12-oxo-10,15-phytodienoic acid and its higher homologue, dihomo-cis-12-oxo-3,6,10,15-phytotetraenoic acid, respectively. Thus, the CYP440A18 enzyme exhibited dual EAS/AOS activity. The obtained results allowed us to ascribe a name “B. belcheri EAS/AOS” (BbEAS/AOS) to this enzyme. BbEAS/AOS is a first CYP74 clan enzyme of Chordata species possessing AOS activity. 相似文献
46.
Olga V. Balberova Evgeny V. Bykov Natalia A. Shnayder Marina M. Petrova Oksana A. Gavrilyuk Daria S. Kaskaeva Irina A. Soloveva Kirill V. Petrov Elena Y. Mozheyko German V. Medvedev Regina F. Nasyrova 《International journal of molecular sciences》2021,22(12)
Regular physical activity in cyclic sports can influence the so-called “angiogenic switch”, which is considered as an imbalance between proangiogenic and anti-angiogenic molecules. Disruption of the synthesis of angiogenic molecules can be caused by local changes in tissues under the influence of excessive physical exertion and its consequences, such as chronic oxidative stress and associated hypoxia, metabolic acidosis, sports injuries, etc. A review of publications on signaling pathways that activate and inhibit angiogenesis in skeletal muscles, myocardium, lung, and nervous tissue under the influence of intense physical activity in cyclic sports. Materials: We searched PubMed, SCOPUS, Web of Science, Google Scholar, Clinical keys, and e-LIBRARY databases for full-text articles published from 2000 to 2020, using keywords and their combinations. Results: An important aspect of adaptation to training loads in cyclic sports is an increase in the number of capillaries in muscle fibers, which improves the metabolism of skeletal muscles and myocardium, as well as nervous and lung tissue. Recent studies have shown that myocardial endothelial cells not only respond to hemodynamic forces and paracrine signals from neighboring cells, but also take an active part in heart remodeling processes, stimulating the growth and contractility of cardiomyocytes or the production of extracellular matrix proteins in myofibroblasts. As myocardial vascularization plays a central role in the transition from adaptive heart hypertrophy to heart failure, further study of the signaling mechanisms involved in the regulation of angiogenesis in the myocardium is important in sports practice. The study of the “angiogenic switch” problem in the cerebrovascular and cardiovascular systems allows us to claim that the formation of new vessels is mediated by a complex interaction of all growth factors. Although the lungs are one of the limiting systems of the body in cyclic sports, their response to high-intensity loads and other environmental stresses is often overlooked. Airway epithelial cells are the predominant source of several growth factors throughout lung organogenesis and appear to be critical for normal alveolarization, rapid alveolar proliferation, and normal vascular development. There are many controversial questions about the role of growth factors in the physiology and pathology of the lungs. The presented review has demonstrated that when doing sports, it is necessary to give a careful consideration to the possible positive and negative effects of growth factors on muscles, myocardium, lung tissue, and brain. Primarily, the “angiogenic switch” is important in aerobic sports (long distance running). Conclusions: Angiogenesis is a physiological process of the formation of new blood capillaries, which play an important role in the functioning of skeletal muscles, myocardium, lung, and nervous tissue in athletes. Violation of the “angiogenic switch” as a balance between proangiogenic and anti-angiogenic molecules can lead to a decrease in the functional resources of the nervous, musculoskeletal, cardiovascular, and respiratory systems in athletes and, as a consequence, to a decrease in sports performance. 相似文献
47.
Claudio Alimonti Mara Lombardi Monica Cardarilli Elena Soldo 《Water Resources Management》2017,31(6):1745-1758
The quantification of soil variability is one of the most important aspects in the geo-engineering context. The uncertainty analysis is the main part of the reliability assessment for which a quantitative evaluation was performed in this study. The Reliability Index and the Probability of Failure using the First-Order Reliability Method (FORM) represents both, an effective method which is easy to implement at the same time. This work analyzes possible effects of compaction induced into the aquifer of the Scarlino Plain, caused by the extension of the hydraulic barrier for groundwater remediation. The currently implemented vertical barrier is composed of 12 wells which reach the depth of 10 m. The improvement of the project involves the construction of a further 40 clusters, each consisting of a doublet which intercepts different depths (10 and 18 m). The models of the subsoil stratigraphy and of the groundwater were built using a numerical model. The groundwater flow and the piezometric surface in the current configuration of the barrier were studied and the project configuration was evaluated. Using the Aquitard drainage model, the land subsidence was estimated to calculate the maximum admissible displacement related to exhibited goods, the so called territorial vulnerability. The evaluation analysis was performed using a traditional deterministic approach, followed by a reliability method based on probabilistic models. Finally, the respective results were reported in a soil mapping with overlapping layers. 相似文献
48.
Elena R. Andrievskaya Lidiya M. Lopato 《Journal of the American Ceramic Society》1992,75(11):3026-3032
Phase equilibria in the system HfO2 –Y2 O3 –CaO were studied in the temperature range 1250° to 2850°C by both experimental methods (X-ray phase analysis at 20° to 2000°C, petrography, annealing and quenching, differential thermal analysis in He at temperatures to 2500°C, thermal analysis in air using a solar furnace at temperatures to 3000°C, and electron microprobe X-ray analysis) and theoretical means (development of a mathematical model for the liquidus surface by means of the reduced polynomial method). Phase equilibria were determined by the structure of the restricting binary systems. No ternary compounds were found. The liquidus was characterized by the presence of six four-phase, invariant equilibria. Solid solutions were based on monoclinic (M), tetragonal (T), and cubic (F) modifications of HfO2 ; C and H forms of Y2 O3 ; CaO; and CaHfO3 that crystallized in two polymorphous modifications, namely, the cubic and rhombic perovskite-type structure. 相似文献
49.
Sanja Dogramadzi Maria Elena Giannaccini Christopher Harper Mohammad Sobhani Roger Woodman Jiyeon Choung 《Journal of Intelligent and Robotic Systems》2014,76(1):73-117
Robot manufacturers will be required to demonstrate objectively that all reasonably foreseeable hazards have been identified in any robotic product design that is to be marketed commercially. This is problematic for autonomous mobile robots because conventional methods, which have been developed for automatic systems do not assist safety analysts in identifying non-mission interactions with environmental features that are not directly associated with the robot’s design mission, and which may comprise the majority of the required tasks of autonomous robots. In this paper we develop a new variant of preliminary hazard analysis that is explicitly aimed at identifying non-mission interactions by means of new sets of guidewords not normally found in existing variants. We develop the required features of the method and describe its application to several small trials conducted at Bristol Robotics Laboratory in the 2011–2012 period. 相似文献
50.
Thin films, in the range of tens of micrometers thickness, have been prepared by casting onto glass plates the chloroform or N‐methylpyrrolidone solutions of polyimides or poly(imide‐amide)s containing silicon and phenylquinoxaline units in the main chain. The polymers have been synthesized by solution polycondensation reaction of aromatic diamines having preformed phenylquinoxaline rings with bis(3,4‐dicarboxyphenyl)dimethylsilane dianhydride or with a diacid chloride resulting from the reaction of this dianhydride with p‐aminobenzoic acid. The polymers were easily soluble in polar aprotic solvents and showed high thermal stability. The free‐standing films exhibited good mechanical properties with tensile strengths in the range of 48–86 MPa, tensile modulus in the range of 1.25–2.22 GPa and elongation at break in the range of 3–37%. Electrical insulating properties of some polymer films were evaluated on the basis of dielectric constant and dielectric loss and their variation with frequency and temperature. The values of the dielectric constant at 10 kHz were in the range of 2.94–3.08 for polyimides and 3.89–4.49 for poly(imide‐amide)s. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 3062–3068, 2006 相似文献