Therapeutic Potential of Mesenchymal Stem Cells for Cancer Therapy

Mesenchymal stem cells (MSCs) are among the most frequently used cell type for regenerative medicine. A large number of studies have shown the beneficial effects of MSC-based therapies to treat different pathologies, including neurological disorders, cardiac ischemia, diabetes, and bone and cartilage diseases. However, the therapeutic potential of MSCs in cancer is still controversial. While some studies indicate that MSCs may contribute to cancer pathogenesis, emerging data reported the suppressive effects of MSCs on cancer cells. Because of this reality, a sustained effort to understand when MSCs promote or suppress tumor development is needed before planning a MSC-based therapy for cancer. Herein, we provide an overview on the therapeutic application of MSCs for regenerative medicine and the processes that orchestrates tissue repair, with a special emphasis placed on cancer, including central nervous system tumors. Furthermore, we will discuss the current evidence regarding the double-edged sword of MSCs in oncological treatment and the latest advances in MSC-based anti-cancer agent delivery systems.Junta de Andalucía PI-0272-2017Ministerio de Ciencia, Innovación y Universdad CD16/00118, CP19/00046, PI16/00259, BFU2017-83588-P, CP14/00105, PI18/01590, PI17/02104, PIC18/0010, IC19/0052Juvenile Diabetes Research Foundation (USA) 2-SRA-2019-837-S-BFundación Española para la Ciencia y la Tecnología 2018-00023

La relation texte/scène en phase de reconfiguration : propositions théoriques autour de Terre océane de Daniel Danis

Avec la publication du «Théâtre postdramatique» d’Hans-Thies Lehmann et la montée de la performance dans la représentation théâtrale contemporaine, le drame, et avec lui le texte dramatique, semblent une fois de plus mis à mal. Or, la propension de certains ouvrages critiques à présenter comme cataclysmique l’avènement d’un théâtre postdramatique laisse en plan de nombreuses questions, notamment celle de la dynamique texte/scène qui, plutôt que d’en évacuer la première constituante, semble en métamorphoser les deux parties. Ce mémoire entend creuser la question du texte au sein de cette dynamique afin d’interroger ses mutations et les techniques d’approche qui permettent de l’intégrer dans une praxis théâtrale.With Hans-Thies Lehmann’s ''Postdramatic Theater'' and the growing presence of performance in the contemporary theater scene, the notion of drama, and the text itself, seems once again to suffer a terrible blow. Unfortunately, some critics’ tendencies to present new ways of making theater as if it were a violent upheaval, overshadow some phenomena, for one the dynamic between text and scene, in which instead of its first constituant disapearing, both of them seem to metamorphose under mutual influence. This thesis will investigate that phenomenom and its consequences on the dramatic text, as well as how we understand it as praxis of contemporary theater

L'insertion professionnelle des jeunes n'ayant pas complété leurs études secondaires

Dans les recherches québécoises sur l’insertion en emploi des jeunes et dans les considérations de la population en général, il est bien ancré que le fait de décrocher du secondaire sans avoir obtenu de diplôme mène éventuellement et inévitablement à des difficultés d’insertion dans le marché du travail. Toutefois, lorsque l’on entreprend de vérifier l’origine de cette considération, on ne trouve que très peu de réponses, puisque les enquêtes sur l’insertion des jeunes au Québec et au Canada ont presque toujours ignoré les jeunes sans diplômes et les recherches traitant du sujet citent souvent des sources non probantes. Dans ce mémoire, nous avons utilisé une enquête récente qui n’est pas restreinte aux seuls diplômés pour étudier l’insertion des jeunes, en faisant l’hypothèse que les jeunes décrocheurs du secondaire du Québec et du reste du Canada n’ont pas significativement plus de chances de connaître des insertions en emploi difficiles que les jeunes n’ayant que ce niveau de diplôme à leur actif. Nos résultats ne nous permettent pas d’affirmer que les décrocheurs ne connaissent pas plus de problèmes d’insertion que les diplômés du secondaire, mais ils montrent tout de même que d’autres variables sont bien plus déterminantes. L’intérêt de ce mémoire ne s’arrête pas à la comparaison statistique entre les deux groupes de jeunes à l’étude, il se veut être une réflexion théorique sur la notion d’insertion, sur les raisons qui expliquent son caractère restrictif, et sur les paradigmes qui inspirent ce champ de recherche.In Quebec’s researches on the young people’s entry into the adulthood and in the beliefs of the population in general, it is well anchored that the fact of dropping out from high school without obtaining diploma leads eventually and inevitably to difficulties of entry on the labour market. However, when one undertakes to check the origin of this belief, one finds only very few answers, since the investigations into the insertion of the young people in Quebec and Canada almost always ignored the young people without diplomas and research treating of the subject often quotes nonconvincing sources. In this analysis, we used a recent investigation which is not restricted to the only graduates to study insertion of the young people, by making the assumption that the young high school dropouts of Quebec and the remainder of Canada are not likely significantly more to know difficult insertions in employment than the young people not having but this level of diploma to their credit. Our results do not enable us to affirm that the dropouts do not know more problems of insertion than the high school graduates, but they show all the same that other variables are much more determining. The interest of this analysis does not stop with the statistical comparison between the two groups of young people being studied, it wants to be a theoretical reflexion on the notion of insertion, on the reasons which explain its restrictive character, and on the paradigms which inspire this field of research

Dense suspension of solid particles as a new heat transfer fluid for concentrated solar thermal plants: on-sun proof of concept

This paper demonstrates the capacity of dense suspensions of solid particles to transfer concentrated solar power from a tubular receiver to an energy conversion process by acting as a heat transfer fluid. Contrary to a circulating fluidized bed, the dense suspension of particles’ flows operates at low gas velocity and large solid fraction. A single-tube solar receiver was tested with 64 µm mean diameter silicon carbide particles for solar flux densities in the range 200–250 kW/m2, resulting in a solid particle temperature increase ranging between 50 °C and 150 °C. The mean wall-to-suspension heat transfer coefficient was calculated from experimental data. It is very sensitive to the particle volume fraction of the suspension, which was varied from 26 to 35%, and to the mean particle velocity. Heat transfer coefficients ranging from 140 W/m2 K to 500 W/m2 K have been obtained, thus corresponding to a 400 W/m2 K mean value for standard operating conditions (high solid fraction) at low temperature. A higher heat transfer coefficient may be expected at high temperatures because the wall-to-suspension heat transfer coefficient increases drastically with temperature. The suspension has a heat capacity similar to a liquid heat transfer fluid, with no temperature limitation but the working temperature limit of the receiver tube. Suspension temperatures of up to 750 °C are expected for metallic tubes, thus opening new opportunities for high efficiency thermodynamic cycles such as supercritical steam and supercritical carbon dioxide

Suivi scientifique de vingt-sept régénérations naturelles de chêne sessile et de hêtre en Ardenne: retour d'expérience

National audienceRégénérer naturellement le chêne apparaît très délicat en Ardenne et cela se traduit déjà par un déficit marqué de jeunes chênes au niveau régional. Afin de rechercher des solutions sylvicoles à ce problème, vingt-sept régénérations naturelles de hêtre et de chêne ont été suivies entre 2007 et 2011. L’analyse montre clairement les besoins en lumière des chênes par rapport aux hêtres et, surtout, l’importance d’effectuer des nettoiements afin de réduire les effets de la compétition des hêtres sur les chênes

Transcriptional response of pancreatic beta cells to metabolic stimulation: large scale identification of immediate-early and secondary response genes

<p>Abstract</p> <p>Background</p> <p>Physiological long term adaptation of pancreatic beta cells is driven by stimuli such as glucose and incretin hormones acting via cAMP (e.g. GLP-1) and involves regulated gene expression. Several rapidly inducible immediate-early genes (IEGs) have been identified in beta cells. Many of these IEGs code for transcription factors and have the potential to control the transcription of downstream <it>target </it>genes likely involved in long term cellular adaptation. The identity of these <it>target </it>genes has not been determined, and the sequence of events occurring during beta cell adaptation is still unclear.</p> <p>Results</p> <p>We have developed a microarray-based strategy for the systematic search of <it>targets</it>. In Min6 insulin-secreting cells, we identified 592 <it>targets </it>and 1278 IEGs responding to a co-stimulation with glucose and cAMP. Both IEGs and <it>targets </it>were involved in a large panel of functions, including those important to beta cell physiology (metabolism, secretion). Nearly 200 IEGs were involved in signaling and transcriptional regulation. To find specific examples of the regulatory link between IEGs and <it>targets</it>, <it>target </it>promoter sequences were analyzed <it>in silico</it>. Statistically significant over-representation of AP-1 response elements notably suggested an important role for this transcription factor, which was experimentally verified. Indeed, cell stimulation altered expression of IEG-encoded components of the AP-1 complex, activating AP-1-dependent transcription. Loss and gain-of-function experiments furthermore allowed to validate a new AP-1 regulated gene (<it>sulfiredoxin</it>) among the <it>targets</it>. AP-1 and <it>sulfiredoxin </it>are sequentially induced also in primary cells from rat islets of Langerhans.</p> <p>Conclusion</p> <p>By identifying IEGs and their downstream <it>targets</it>, this study brings a comprehensive description of the transcriptional response occurring after beta cell stimulation, as well as new mechanistic insights concerning the AP-1 transcription factor.</p

High solar flux heating of upflow bubbling fluidized bed circulating in opaque vertical tube - 3d numerical simulation

Current solar Heat Transfer Fluids (HTF) have a limited working temperature (\u3c 600 °C) and present operational risks. We proposed to use air-fluidized Dense Particle Suspensions (DPS), also called Upflow Bubbling Fluidized Bed (UBFB), in tubes as a new HTF and storage medium in the frame of the so-called CSP2 FP7 European project (http://www.csp2-project.eu/). UBFB can operate up to the solid sintering temperature, thus improving the plant efficiency, it has no lower temperature limitation and is riskless. The DPS capacity to extract heat from a tube absorber exposed to concentrated solar radiation was demonstrated on a single-tube experimental receiver that was tested at the focus of the CNRS 1 MW solar furnace in Odeillo. The DPS flowed upward through the absorber tube (i.d. 3.6 cm) that passed through a 50 cm high cavity where it was exposed to concentrated solar flux that heated the DPS. The tube wall-to-DPS Heat Transfer Coefficient (HTC) first values were calculated by Flamant et al. (1). A stable outlet temperature of 750 °C was reached with a metallic tube and a particle reflux in the near tube wall region was evidenced by Benoit et al. (2). In this paper, the UBFB behavior is studied using the multiphase flow code NEPTUNE_CFD (3). Hydrodynamics of SiC Geldart A-type particles (40 µm Sauter diameter) and heat transfer imposed by a thermal flux at the wall are coupled in 3D numerical simulations. The convective/diffusive heat transfer between the gas and dispersed phase, and the inter-particle radiative transfer (Rosseland approximation) are accounted for. The numerical and experimental results are compared in order to validate the model. The heat exchange between the particles close to the tube wall and those in the tube center is characterized. Please click Additional Files below to see the full abstract

Restriction of cytosolic Acetyl-CoA to promote healthy aging

Motivation: During the last century humans have reached the longest lifespan in History. However, the increase on lifespan is associated to the development of age-related diseases that limit the quality of life of aged individuals (1). Therefore, there is a current need to determine the molecular mechanisms underlining age-related pathologies and to develop novel effective therapies for these diseases. Acetyl-CoA (Ac-CoA) is a central metabolite in energy metabolism involved in protein acetylation, fatty acid synthesis and cholesterol synthesis (2,3), which may play a significant role modulating the intrinsic processes of aging. In this work, we studied the effects of 4 cytosolic Ac-CoA reducing agents; two inhibitors of the ATP citrate lyase; SB-204990 (SB) and hydroxycitric acid (HCA), an inhibitor of Ac-CoA synthase; allicin, and a inhibitor of the citrate isocitrate carrier; 1,2,3-benzenetricarboxylic acid (BTC).Methods: Mice were fed a Standard Diet (STD) or a High Fat Diet (HFD) supplemented with SB for 15 weeks. After in vivo studies, we performed WB on metabolic tissues. In liver tissue we performed a proteomic analysis by iTRAQ (Isobaric tags for relative and absolute quantification). In parallel, we have initiated a longevity assay using HCA. Necropsies have been performed to determine the cause of death. Finally, we are currently investigating the effects of BTC and allicin in murine physiology using three experimental approaches; a healthy STD, a prophylactic treatment using an obesogenic/diabetogenic HFD and a therapeutic treatment used in obese mice.Results: Preliminary in vivo results have shown improvements in metabolic health on mice treated with SB. Ex vivo analyses have indicated that SB modulates lipid metabolism. Proteomic analyses revealed a decrease in the expression of proinflammatory proteins in SB-treated and HFD-fed mice. HCA supplementation in healthy STD-fed mice has resulted in delayed early mortality in mice. Additionally, HCA treatment revealed potential benefits in muscle strength in wirehang test. Our research using BTC and allicin will generate results in the nearly future.Conclusions: Results of SB-treated and HFD-fed mice show a robust modulation in lipid metabolism and in inflammatory pathways, suggesting that the intervention could rescue the phenotype associated to a metabolic deregulation. The improvements observed in HCA-treated mice suggest that HCA could have geroprotective effects in early mortality