Философия символа Вячеслава Иванова и Павла Флоренского

The paper analyzes the philosophic and artistic principles of the theory of symbol developed by two prominent personalities of Russian Silver Age: poet, Vyacheslav Ivanov and philosopher, Pavel Florensky. The role of the symbol as a link between empiric and noumenal worlds is shown as being fundamental for both thinkers.В статье анализируются философские и художественные принципы теории символа, развитые двумя выдающимися представителями русского Серебряного века: поэтом Вячеславом Ивановым и философом о. Павлом Флоренским. Показана фундаментальная роль символа для обоих мыслителей как связующего звена между эмпирическим и ноуменальным мирами

Real-time ratiometric imaging of micelles assembly state in a microfluidic cancer-on-a-chip

The performance of supramolecular nanocarriers as drug delivery systems depends on their stability in the complex and dynamic biological media. After administration, nanocarriers are challenged by physiological barriers such as shear stress and proteins present in blood, endothelial wall, extracellular matrix, and eventually cancer cell membrane. While early disassembly will result in a premature drug release, extreme stability of the nanocarriers can lead to poor drug release and low efficiency. Therefore, comprehensive understanding of the stability and assembly state of supramolecular carriers in each stage of delivery is the key factor for the rational design of these systems. One of the main challenges is that current 2D in vitro models do not provide exhaustive information, as they fail to recapitulate the 3D tumor microenvironment. This deficiency in the 2D model complexity is the main reason for the differences observed in vivo when testing the performance of supramolecular nanocarriers. Herein, we present a real-time monitoring study of self-assembled micelles stability and extravasation, combining spectral confocal microscopy and a microfluidic cancer-on-a-chip. The combination of advanced imaging and a reliable 3D model allows tracking of micelle disassembly by following the spectral properties of the amphiphiles in space and time during the crucial steps of drug delivery. The spectrally active micelles were introduced under flow and their position and conformation continuously followed by spectral imaging during the crossing of barriers, revealing the interplay between carrier structure, micellar stability, and extravasation. Integrating the ability of the micelles to change their fluorescent properties when disassembled, spectral confocal imaging and 3D microfluidic tumor blood vessel-on-a-chip resulted in the establishment of a robust testing platform suitable for real-time imaging and evaluation of supramolecular drug delivery carrier's stability

Secretome of Undifferentiated Neural Progenitor Cells Induces Histological and Motor Improvements in a Rat Model of Parkinson's Disease

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that results from the death of dopamine (DA) neurons. Over recent years, differentiated or undifferentiated neural stem cells (NSCs) transplantation has been widely used as a means of cell replacement therapy. However, compelling evidence has brought attention to the array of bioactive molecules produced by stem cells, defined as secretome. As described in the literature, other cell populations have a high-neurotrophic activity, but little is known about NSCs. Moreover, the exploration of the stem cell secretome is only in its initial stages, particularly as applied to neurodegenerative diseases. Thus, we have characterized the secretome of human neural progenitor cells (hNPCs) through proteomic analysis and investigated its effects in a 6-hydroxidopamine (6-OHDA) rat model of PD in comparison with undifferentiated hNPCs transplantation. Results revealed that the injection of hNPCs secretome potentiated the histological recovery of DA neurons when compared to the untreated group 6-OHDA and those transplanted with cells (hNPCs), thereby supporting the functional motor amelioration of 6-OHDA PD animals. Additionally, hNPCs secretome proteomic characterization has revealed that these cells have the capacity to secrete a wide range of important molecules with neuroregulatory actions, which are most likely support the effects observed. Overall, we have concluded that the use of hNPCs secretome partially modulate DA neurons cell survival and ameliorate PD animals' motor deficits, disclosing improved results when compared to cell transplantation approaches, indicating that the secretome itself could represent a route for new therapeutic options for PD regenerative medicine. Stem Cells Translational Medicine 2018;7:829-838.Portuguese Foundation for Science and Technology: Ciência 2007 Program and IF Development Grant (IF/00111/2013) to A.J.S., Ph.D. scholarships to S.I.A. (SFRH/BD/81495/ 2011); Canada Research Chair in Biomedical Engineering (LAB). This article has been developed under the scope of the project NORTE‐01‐0145‐FEDER‐000013 and NORTE‐01‐0145‐FEDER‐000023, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the projects POCI‐01‐0145‐FEDER‐007038, PTDC/NEU‐NMC/0205/2012, UID/NEU/04539/2013, and POCI‐01‐0145‐FEDER‐007440 cofunded by the Programa Operacional Factores de Competitividade, QREN, the European Union (FEDER), and by the National Mass Spectrometry Network under the contract REDE/1506/REM/2005info:eu-repo/semantics/publishedVersio

Expression of Stem Cell Markers in the Human Fetal Kidney

In the human fetal kidney (HFK) self-renewing stem cells residing in the metanephric mesenchyme (MM)/blastema are induced to form all cell types of the nephron till 34th week of gestation. Definition of useful markers is crucial for the identification of HFK stem cells. Because wilms' tumor, a pediatric renal cancer, initiates from retention of renal stem cells, we hypothesized that surface antigens previously up-regulated in microarrays of both HFK and blastema-enriched stem-like wilms' tumor xenografts (NCAM, ACVRIIB, DLK1/PREF, GPR39, FZD7, FZD2, NTRK2) are likely to be relevant markers. Comprehensive profiling of these putative and of additional stem cell markers (CD34, CD133, c-Kit, CD90, CD105, CD24) in mid-gestation HFK was performed using immunostaining and FACS in conjunction with EpCAM, an epithelial surface marker that is absent from the MM and increases along nephron differentiation and hence can be separated into negative, dim or bright fractions. No marker was specifically localized to the MM. Nevertheless, FZD7 and NTRK2 were preferentially localized to the MM and emerging tubules (<10% of HFK cells) and were mostly present within the EpCAMneg and EpCAMdim fractions, indicating putative stem/progenitor markers. In contrast, single markers such as CD24 and CD133 as well as double-positive CD24+CD133+ cells comprise >50% of HFK cells and predominantly co-express EpCAMbright, indicating they are mostly markers of differentiation. Furthermore, localization of NCAM exclusively in the MM and in its nephron progenitor derivatives but also in stroma and the expression pattern of significantly elevated renal stem/progenitor genes Six2, Wt1, Cited1, and Sall1 in NCAM+EpCAM- and to a lesser extent in NCAM+EpCAM+ fractions confirmed regional identity of cells and assisted us in pinpointing the presence of subpopulations that are putative MM-derived progenitor cells (NCAM+EpCAM+FZD7+), MM stem cells (NCAM+EpCAM-FZD7+) or both (NCAM+FZD7+). These results and concepts provide a framework for developing cell selection strategies for human renal cell-based therapies

The ethical conception of Leo Tolstoy in the interpretation of Maximilian Voloshin

The article examines the interpretation of Leo Tolstoy’s ethical conception provided by a Russian poet Maximilian Voloshin. A brief exposition of Tolstoy’s ethical conception position of a person’s concern for their soul is provided. In this regard, the requirements of love and nonviolence are not of value in and of themselves but are subordinate to the main cause of salvation, the improvement of a person’s soul. This is the point on which Voloshin focuses his criticism reproaching Tolstoy for selfishness. Non-resistance to evil by violence is paradoxically interpreted by Voloshin as evasion from evil. Voloshin emphasizes that Tolstoy’s understanding of evil is simplified due to his failure to understand the sinful nature of mankind. Voloshin opposes Tolstoy’s ethics interpreted by him in this manner with his own ethical conception suggesting that it is necessary to not move away from evil in the world but, on the contrary, take it into oneself and strive to transform it with the internal forces of good. In conclusion, it is examined that despite their differences both thinkers agreed that responding with evil to evil is unacceptable from the point of ethics. Both Tolstoy and Voloshin were also characterized by the implementation of their ethical provisions in their personal lives

“Theurgic creativity” in philosophical conceptions of F. Nietzsche, Vl. Solovyov, and N. Berdyaev

The article presents a comparative analysis of theurgic activity in the works of three thinkers from the point of the generic understanding of theurgy as a “complete transformation of reality”. Despite the literal meaning of the term “theurgy”, according to all three thinkers, the indicated transforming influence is carried out by man and not by God. Although F. Nietzsche himself does not utilize the concept of theurgy, his theory of the Übermensch does fit into the framework of radical theurgic creativity since it presupposes a complete transformation of man carried out by himself, a change in his ontological nature. What is noted as a substantial similarity of the understanding of the transforming human activity by V. Solovyov and F. Nietzsche is that both thinkers view man as a product and the highest link of nature from which it follows that the highest calling of man is the transformation of not only himself but also nature. The difference lies in the fact that in Nietzsche’s view, the theurgic transformation is carried out by a person alone, through heroic effort. According to Solovyov, the main path of transformation of man and the world – the path of love – begins with a combination of two individuals and leads to conciliarity. In contrast, N. Berdyaev’s conception of theurgic creativity is distinguished by its radical transcendence, opposition to nature

Philosophy of symbol by Vyacheslav Ivanov and Pavel Florensky

The paper analyzes the philosophic and artistic principles of the theory of symbol developed by two prominent personalities of Russian Silver Age: poet, Vyacheslav Ivanov and philosopher, Pavel Florensky. The role of the symbol as a link between empiric and noumenal worlds is shown as being fundamental for both thinkers