20,859 research outputs found

    Identification of Hindbrain Neural Substrates for Motor Initiation in the hatchling Xenopus laevis Tadpole

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    Animal survival profoundly depends on the ability to detect stimuli in the environment, process them and respond accordingly. In this respect, motor responses to a sensory stimulation evolved into a variety of coordinated movements, which involve the control of brain centres over spinal locomotor circuits. The hatchling Xenopus tadpole, even in its embryonic stage, is able to detect external sensory information and to swim away if the stimulus is considered noxious. To do so, the tadpole relies on well-known ascending sensory pathway, which carries the sensory information to the brain. When the stimulus is strong enough, descending interneurons are activated, leading to the excitation of spinal CPG neurons, which causes the undulatory movement of swimming. However, the activation of descending interneurons that marks the initiation of motor response appears after a long delay from the sensory stimulation. Furthermore, the long-latency response is variable in time, as observed in the slow-summating excitation measured in descending interneurons. These two features, i.e. long-latency and variability, cannot be explained by the firing time and pattern of the ascending sensory pathway of the Xenopus tadpole. Therefore, a novel neuronal population has been proposed to lie in the hindbrain of the tadpole, and being able to 'hold' the sensory information, thus accounting for the long and variable delay of swim initiation. In this work, the role of the hindbrain in the maintenance of the long and variable response to trunk skin stimulation is investigated in the Xenopustadpole at developmental stage 37/38. A multifaceted approach has been used to unravel the neuronal mechanisms underlying the delayed motor response, including behavioural experiments, electrophysiology analysis of fictive swimming, hindbrain extracellular recordings and imaging experiments. Two novel neuronal populations have been identified in the tadpole's hindbrain, which exhibit activation patterns compatible with the role of delaying the excitation of the spinal locomotor circuit. Future work on cellular properties and synaptic connections of these newly discovered populations might shed light on the mechanism of descending control active at embryonic stage. Identifying supraspinal neuronal populations in an embryonic organism could aid in understanding mechanisms of descending motor control in more complex vertebrates

    Uso de las histonas circulantes y sus modificaciones post-traduccionales como biomarcadores en sepsis y shock s茅ptico

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    La sepsis es una afecci贸n potencialmente mortal causada por una respuesta anormal del hu茅sped a una infecci贸n, produciendo respuestas fisiol贸gicas alteradas que da帽an los propios tejidos del paciente y pueden provocar disfunci贸n org谩nica e incluso la muerte. Asimismo, algunos pacientes s茅pticos progresan a shock s茅ptico, caracterizado por alteraciones circulatorias, celulares y metab贸licas sustanciales que aumentan el riesgo de mortalidad. A pesar de que la sepsis se caracteriza por un mal funcionamiento del sistema inmunol贸gico, lo que a su vez conduce a una respuesta inmune alterada e inmunosupresi贸n, la alta complejidad de la fisiopatolog铆a de la sepsis requiere una mayor investigaci贸n para comprender las respuestas inmunes que ocurren durante la sepsis. Asimismo, las histonas extracelulares circulantes han ganado relevancia como mediadores citot贸xicos en la sepsis, ya que act煤an como patrones moleculares asociados a da帽o, que inducen estr茅s oxidativo y activan el inflamasoma NLRP3. Estos mecanismos median la activaci贸n de la piroptosis, un mecanismo de muerte celular programada que produce inflamaci贸n mediante la expresi贸n de IL-18, IL-1尾 and IL-1伪. Sin embargo, a pesar de la evidencia de activaci贸n del inflamasoma en las c茅lulas inmunes durante la sepsis, se desconoce si las histonas extracelulares son capaces de activar los inflamasomas endoteliales y sus consecuencias. En este trabajo destacamos el papel previamente desconocido de las histonas extracelulares, mediando la activaci贸n del inflamasoma NLRP3 y la piroptosis en las c茅lulas endoteliales, contribuyendo a la disfunci贸n endotelial y la desregulaci贸n de la respuesta inmune mediada por el endotelio. Asimismo, tambi茅n demostramos c贸mo la acetilaci贸n de histonas disminuye la activaci贸n de la piroptosis. Adem谩s, demostramos que la piroptosis se produce en pacientes con shock s茅ptico y los niveles de histonas circulantes se correlacionan con la expresi贸n de citoquinas proinflamatorias y citoquinas piropt贸ticas, la liberaci贸n de factores de adhesi贸n endotelial y la gravedad de la enfermedad. Proponemos la piroptosis mediada por histonas como un nuevo objetivo para desarrollar intervenciones cl铆nicas. De manera similar, hemos analizado las respuestas inmunorelacionadas que ocurren durante las primeras etapas de la sepsis con el objetivo de proporcionar nuevos datos comparando las cantidades de citoquinas, inmunomoduladores y otros mediadores endoteliales en pacientes cr铆ticamente enfermos no s茅pticos, s茅pticos y de shock s茅ptico. Nuestro enfoque ayudar谩 a caracterizar r谩pidamente las respuestas inmunes alteradas en pacientes s茅pticos y de shock s茅ptico ingresados en la Unidad de Cuidados Intensivos. Finalmente analizamos el papel de la metilaci贸n del ADN en el control del sistema inmune s茅ptico. Nuestros resultados demostraron el papel central de la metilaci贸n del ADN modulando la respuesta molecular en los pacientes de shock s茅ptico y contribuyendo a la inmunosupresi贸n, a trav茅s de la alteraci贸n de los patrones de metilaci贸n de los promotores de IL-10 y TREM-2.Sepsis is a life-threatening condition caused by an abnormal host response to an infection that produce altered physiological responses which damages own tissues of the patient and can result in organ dysfunction and in some cases death. Likewise, a subset of septic patients progresses to septic shock, characterized by substantial circulatory, cellular and metabolic abnormalities, which substantially increase the risk of mortality. Sepsis is characterized by a malfunction of the immune system and it can lead to an altered immune response and immunosuppression. Moreover, the high complexity of the pathophysiology of sepsis requires of further investigation to characterize the immune responses in sepsis and septic shock. Likewise, circulating extracellular histones have gained relevance as cytotoxic mediators in sepsis pathophysiology, since they act as damage-associated molecular patterns, which induce oxidative stress and activate NLRP3 inflammasome. Subsequently, inflammasome mediates pyroptosis activation, a programmed cell death mechanism that produces inflammation through the release of IL-18, IL-1尾 and IL-1伪. However, despite inflammasome activation may occur in immune cells during sepsis, it is unknown if this process also takes place in endothelial cells and particularly whether extracellular histones are capable of activating endothelial inflammasomes and their consequences. In this work we highlight a previously unknown role for extracellular histones, that mediates the activation of NLRP3 inflammasome and pyroptosis in endothelial cells by contributing to endothelial dysfunction and the dysregulation of the immune response mediated by endothelium. Likewise, we demonstrated how histone acetylation decreases pyroptosis activation. Furthermore, we show how pyroptosis occurs in septic shock patients and how circulating histone levels correlate with the expression of pro-inflammatory and pyroptotic cytokines, the release of endothelial adhesion factors and septic shock severity. We propose histone-mediated pyroptosis as a new target to develop clinical interventions. Similarly, we have analyzed the immune-related responses occurring during the early stages of sepsis with the aim of providing new data by comparing the amounts of cytokines, immune modulators and other endothelial mediators in critically-ill non-septic patients, septic and septic shock patients. Our approach will help to rapidly characterize the altered immune responses in septic and septic shock patients admitted in the Intensive Care Unit. Finally, we also analyzed the role of DNA methylation in the control of septic immune system. Our results demonstrated the central role of DNA methylation modulating the molecular response in septic shock patients and contributing to immunosuppression, through the alteration of DNA methylation patterns of IL-10 and TREM2 promoters

    Food for thought! Inulin-type fructans: does the food matrix matter?

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    Food matrices can be described as the final composition of a food product which results from complex interactions between compounds found within different ingredients and the processing parameters used in production. These factors, not only impact on the final structure of a product, but also have the potential to alter both the structural integrity and bioavailability of potentially beneficial compounds present, for example, dietary fibres. As a result, there is growing curiosity amongst the scientific community on whether the food matrix may impact on the prebiotic efficacy of inulin-type fructans. Therefore, the purpose of this review is to explore previous food-based inulin-type fructan supplementation studies to determine whether the food matrix directly impacts on their prebiotic efficacy. Our working hypothesis is that other potentially prebiotic ingredients and components present within the food may alter inulin-type fructans prebiotic effect

    Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder.

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    Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome

    Modificaciones de la variabilidad de la frecuencia card铆aca producidas en un modelo experimental de s铆ndrome metab贸lico

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    Antecedentes: El s铆ndrome metab贸lico (SM) se define como el conjunto de al menos tres de las siguientes condiciones: obesidad central, elevaci贸n de triglic茅ridos, disminuci贸n de lipoprote铆nas de alta densidad, hipertensi贸n sist茅mica e intolerancia a la glucosa. El SM est谩 relacionado con una alta prevalencia de enfermedades cardiovasculares, muerte s煤bita card铆aca y arritmias auriculares, eventos que pueden ser consecuencia de cambios relacionados con la estructura, funci贸n y control del coraz贸n. Uno de los mecanismos subyacentes podr铆a ser la alteraci贸n de la automaticidad del nodo sinusal por alteraciones del sistema nervioso aut贸nomo qu茅 pueden evaluarse analizando los componentes de la variabilidad de la frecuencia card铆aca (VFC). Objetivo: Examinar las modificaciones de la VFC, su evoluci贸n y su posible relaci贸n con los diferentes componentes del s铆ndrome metab贸lico en un modelo experimental en conejo, inducido por la administraci贸n de una dieta alta en grasa y az煤car. M茅todos: Se asignaron al azar conejos machos NZW al grupo control (n = 10) o al grupo SM (n = 10), alimentados con una dieta rica en grasas (10% de aceite de coco y 5% de manteca de cerdo) y alta en sacarosa (15% disuelta en agua). durante 28 semanas. Se registr贸 un ECG durante 15 minutos antes de la administraci贸n de la dieta, en las semanas 14 y 28. En la semana 28, se realiz贸 un registro de ECG de 24 horas (eMotion Faros 180, Mega Electronics庐, 1 kHz). Luego se aislaron estos corazones, se estabilizaron durante 15 minutos y se registraron electrogramas de 15 minutos de duraci贸n en un sistema de tipo Languendorff. Analizamos las oscilaciones RR in vivo de corta y larga duraci贸n, y en coraz贸n aislado, en los dominios del tiempo, la frecuencia y el an谩lisis no lineal. Para el an谩lisis estad铆stico se utiliz贸 el an谩lisis multivariado de varianza (MANOVA, modelo factorial) (p <0,05). Resultados an谩lisis de corta duraci贸n: El an谩lisis del dominio de la frecuencia de la VFC mostr贸 un aumento en el componente de HF en los animales con SM en la semana 28 (p 0,05) en MSE m铆nimo y m谩ximo, as铆 como en el CI1-20 con predominio en la semana 14. Los dem谩s par谩metros del an谩lisis no lineal no mostraron cambios estad铆sticamente significativos. Resultados an谩lisis de larga duraci贸n: El an谩lisis en el dominio del tiempo mostr贸 una disminuci贸n en el intervalo RR y el Ti geom茅trico (p>0,005) en animales con SM, indicativo de un aumento de la FC. El resto de par谩metros en el dominio del tiempo analizados no se modificaron. En el dominio de la frecuencia en el espectro FFT, encontramos una disminuci贸n significativa en la banda LF (p = 0.032) en animales SM. El resto de los par谩metros del dominio de la frecuencia (铆ndice VLF, HF y LF / HF) se mantuvo sin cambios. El an谩lisis de Poincar茅 mostr贸 un aumento del 铆ndice SD1 / SD2 en animales con SM durante el d铆a y la noche en comparaci贸n con los controles (p = 0.043). Adem谩s, encontramos una disminuci贸n de DFA伪1 (p = 0.021) y DFA伪2 (p = 0.002) en animales SM. Se encontr贸 la misma tendencia en MSEmax (p = 0.014) para el grupo SM. No se observaron cambios significativos en el resto de componentes de los an谩lisis no lineales. Resultados an谩lisis en coraz贸n aislado: En el dominio de la frecuencia, encontramos un aumento en el componente LF de VFC en animales con SM y la relaci贸n LF / HF (p <0.05), pero el resto de los par谩metros del dominio de la frecuencia permanecieron sin cambios. Con respecto al an谩lisis no lineal, la ApEn; (p <0.05) y el m铆nimo de entrop铆a multiescala (p <0.05) disminuy贸 en grupo SM. No se encontraron diferencias en ninguno de los par谩metros est谩ndar del dominio del tiempo. Conclusiones: El SM produjo cambios significativos en el an谩lisis de la VFC de corta duraci贸n, en el dominio del tiempo y la frecuencia, lo que sugiere aumento de la actividad simp谩tica y alteraci贸n barorefleja respectivamente, aspectos que podr铆an predisponer a un mayor riesgo cardiometabolico y muerte s煤bita. Con respecto al an谩lisis de larga duraci贸n observamos aumentos de la FC tanto en el dia como en la noche, lo que indica la perdida del equilibrio auton贸mico y se asocia a patrones arr铆tmicos. Adem谩s, el an谩lisis no lineal muestra una coactivaci贸n aleatoria y perdida del equilibrio simp谩tico-vagal, reflejado en el descenso de DFA伪-1, DFA伪-2, y la entrop铆a. Finalmente, el an谩lisis de la VFC en el coraz贸n aislado mostr贸 un descenso de la concentraci贸n espectral, indicativo de una mayor heterogeneidad de altas y bajas frecuencias y permiti贸 observar el aumento de la entrop铆a que apunta a una mayor irregularidad del control intr铆nseco cardiaco

    Vagus Nerve Stimulation in Medically- Resistant Epilepsy: Efficacy and Tolerance

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    Background: Epilepsy is a common neurological disease that affects 1% of the population. One third of patients with epilepsy will not respond to antiseizure medications. The most effective treatment when a patient has medically resistant epilepsy is epilepsy surgery. Unfortunately, in many cases surgery is not possible. Neuromodulation is a therapy used in those patients and Vagus Nerve Stimulation (VNS) is the most common type. There are many studies focusing on seizure reduction using VNS, it is still unclear which patients will obtain the greatest benefits. Objective: To define the seizure response post-VNS implantation, to determine predictive factors associated with good outcomes after VNS implantation and to evaluate complications and side effects. Analysis will be completed in the total sample of VNS cases, in the paediatric subgroup, in medically resistant generalized epilepsy and pregnant women implanted with VNS. Patients & Methods: Patients with medically resistant epilepsy implanted with VNS at the London Health Science Centre-Western University, from 1997 to July 2018. Results: 1) VNS in epilepsy: 114 patients were included. Median seizure rate reduction was - 67.8% and 55.6% (n=41) had a 鈮50% seizure reduction. There was a reduction of hospitalization after VNS implantation from 89.5% (n=102) to 45.6% (n=52). 5.3% (n=6) developed side effects associated with the implantation; and side effects were reported in 63.2% (n=72). 2) Paediatric Group: 22 patients were included. The median age when the VNS was implanted was 13. A 鈮50% seizure reduction was achieved in 50% (n=11) and the median seizure reduction was -75%. Side effects were detected in 54.5% (n=12). 3) 46 patients were included in this study with a history of medically resistant generalized epilepsy. The mean age at implantation was 24 years-old. Of the LGS group 41.7% (n=12) of patients had an overall seizure reduction of 鈮50%, and in the GGE group 64.7% (n=11) had a seizure reduction of 鈮50%. There was a significant reduction of seizure-related hospital admissions. 4) Four patients and seven pregnancies were included. The median duration since implantation was 3.17 years. Three required c-sections, one related to failure to progress, the second due to pre-eclampsia and the third due to breach presentation. All babies were healthy, except one with developmental delay of unclear severity. Conclusion: 1) VNS can reduce the number of seizures by 50% in more than half of the patients implanted. VNS has shown a reduction in hospitalization. It is a safe therapy with frequent mild side effects. 2) The paediatric population obtained similar results compared to the total sample. 3) VNS should be considered as a treatment in patients with therapy resistant generalized epilepsy, especially in cases with GGE. 4) Our small sample suggests VNS is a relatively safe therapy during pregnancy, however, larger sample series should be collected

    3D printed Microneedles for Transdermal Drug Delivery

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    3D printing is a revolutionary manufacturing and prototyping technology that has altered the outlooks of numerous industrial and scientific fields since its introduction. Recently, it has attracted attention for its potential as a manufacturing tool for transdermal microneedles for drug delivery. In the present thesis, the 3D printability of solid and hollow microneedles via photopolymerisation-based 3D printing was investigated, aiming at establishing robust manufacturing strategies for reproducible, mechanically strong and versatile microneedles. The developed microneedles were employed as drug delivery systems for the treatment of diabetes via insulin administration. Solid microneedles featuring different geometries were designed and 3D printed. It was demonstrated that the printing and post-printing parameters affected the printed quality, a finding that was employed to optimise the manufacturing strategy. Microneedle geometry was also found to have an impact on the piercing and fracture behaviour; however all microneedle designs were found to be mechanically safe upon application. The solid microneedles were subsequently coated with insulin-polymer films, using a 2D inkjet printing technology. The coating process achieved spatial control of the drug deposition, with quantitative accuracy. The microneedle geometry was shown to influence the morphology of the coating film, an effect that was pronounced during in the in vitro delivery studies of insulin to porcine skin. Furthermore, hollow microneedles were designed and 3D printed, featuring different heights. Two photopolymerisation-based technologies were studied, and their performance was compared. The key influential parameters of the printing outcome and microneedle quality were identified to be the printing angle and the size of the microneedle opening. The hollow microneedles were found to be effective in piercing porcine skin without structural damaging. The hollow microneedles were incorporated into complex patches with internal microfluidic structures for the provision and distribution of drug-containing solutions. The developed complex hollow microneedle patches were coupled with a microelectromechanical system to create a novel platform device for controlled, personalised transdermal drug delivery. Advanced imaging techniques revealed that the device achieved distribution of the liquid within porcine skin tissue without the creation of depots that would delay absorption. The device was evaluated for its efficacy to transdermally deliver a model dye and insulin in vitro. In vivo trials were also conducted using diabetic rodents, with the device achieving faster onset of insulin action and sustained glycemic control, in comparison to subcutaneous injections. Overall, the findings of the present research are anticipated to elucidate key problematic areas associated with the application of 3D printing for microneedle manufacturing and propose feasible solutions. The outermost goal of this work is to contribute to the advancement of knowledge in the field of 3D printed transdermal drug delivery systems, in order to bring them one step closer to their adoption in the clinical setting

    The Role of the GATA Transcription Factor Gaf1 in Nutrient Responses and Cellular Ageing

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    The discovery of the biological bases of ageing continues to be one of the most fascinating challenges in modern science. Current efforts have narrowed the complexity of such task by focusing on mechanisms used by the cell to couple its physiology with environmental stimuli as they are often involved in the regulation of ageing. The Target of Rapamycin (TOR) have been proved to be a rheostat of nutritional status orchestrating cellular growth and homeostasis mainly through the regulation of transcriptional responses that remain to be understood. Recent studies unveiled novel functions of the evolutionarily conserved GATA transcription factor Gaf1 in nutrient sensing pathways and potentially in cellular ageing by regulating transcription downstream of TOR signalling. To elucidate these questions, the robust model organism Schizosaccharomyces pombe was used in this study due to its relevant similarity with higher eukaryotes and thoroughly described genetics. The experimental settings involved a combination of in silico analyses, fitness assessments, revivability assays, transcriptomics, mutagenesis, chemical-genetics, and interactome to further characterise functions of Gaf1. This study also contributed to the identification of candidate genes that promote longevity and mediate the resistance of mutant cells depleted of gaf1 gene to the TOR-kinase inhibitor torin1. The results indicate that upon TOR complex 1 (TORC1) inhibition, Gaf1 represses genes that induce protein translation (anabolism) and upregulates genes required for survival (catabolism) under adverse nutritional conditions downstream of TORC1

    Les cellules m茅soth茅liales et l'ascite influencent la biologie des sph茅ro茂des dans le cancer 茅pith茅lial de l'ovaire

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    Le cancer de l鈥檕vaire est le cancer gyn茅cologique le plus meurtrier. Cela est reli茅, du moins en partie, 脿 un diagnostic tardif de la maladie, alors que celle-ci est diss茅min茅e dans la cavit茅 abdominale au moment o霉 les patientes consultent. Malgr茅 l鈥檃vancement des connaissances et des traitements, le cancer de l鈥檕vaire demeure difficile 脿 traiter et 脿 diagnostiquer de fa莽on pr茅coce. L鈥檜ne des caract茅ristiques du cancer de l鈥檕vaire est le d茅veloppement d鈥檌mportants volumes d鈥檃scite dans la cavit茅 p茅riton茅ale. L鈥檃scite constitue un microenvironnement riche en cellules, dont les cellules m茅soth茅liales, et en mol茅cules pouvant interagir avec les cellules tumorales. C鈥檈st, en partie dans ce r茅servoir que peuvent se diss茅miner les cellules canc茅reuses. Lors du processus de diss茅mination, les cellules tumorales se d茅tachent de la tumeur primaire pour se retrouver dans l鈥檃scite et s鈥檃gr茅ger en amas multicellulaires appel茅s sph茅ro茂des. Subs茅quemment, ceux-ci adh猫rent 脿 la paroi p茅riton茅ale pour ensuite envahir les tissus sous-jacents. Bien que l鈥檕n connaisse les m茅canismes g茅n茅raux r茅gissant la formation des m茅tastases, encore plusieurs points demeurent 脿 approfondir, notamment sur la constitution cellulaire des sph茅ro茂des et l鈥檌nfluence de l鈥檃scite sur ces derniers. Afin de mieux comprendre les m茅canismes de formation des sph茅roides et leur composition, ceux-ci ont 茅t茅 isol茅s et caract茅ris茅s d鈥檃scite de patientes atteintes d鈥檜n cancer de l鈥檕vaire s茅reux, l鈥檋istotype le plus commun, 脿 diff茅rents stades de la maladie. La constitution cellulaire a 茅t茅 d茅termin茅e par immunofluorescence et immunohistochimie pour r茅v茅ler que les sph茅ro茂des sont form茅s principalement d鈥檜n centre compos茅 de cellules m茅soth茅liales entour茅 par les cellules tumorales. Suite 脿 nos observations, un mod猫le cellulaire a 茅t茅 茅tabli 脿 partir de la lign茅e cellulaire OVCAR3 et des cellules primaires canc茅reuses COV2 et OVC508a, ainsi qu鈥檃vec les cellules primaires m茅soth茅liales M茅so4 et M茅so7. Il a 茅t茅 remarqu茅 que la compaction des sph茅ro茂des d茅pend du type cellulaire les composant. Par la suite, l鈥檈xpression de diverses prot茅ines dont les int茅grines 尾-1 a 茅t茅 v茅rifi茅e par immunobuvardage de type Western pour comprendre les m茅canismes r茅gissant la formation et la compaction des sph茅ro茂des. Il a 茅t茅 observ茅 que les cellules exprimant fortement les int茅grines 尾-1, telles que les cellules m茅soth茅liales, forment des sph茅ro茂des compacts. Afin d鈥櫭﹖udier les effets de l鈥檃scite sur les sph茅ro茂des, l鈥檈xpression de l鈥橢-cadh茅rine, des cytok茅ratines 8 et 18 et de la vimentine a 茅t茅 茅tudi茅e par immunobuvardage de type Western. La pr茅sence d鈥檃scite chez les sph茅ro茂des COV2 et COV2/M茅so favorise l鈥檃doption d鈥檜n profil migratoire cellulaire en diminuant statistiquement l鈥檈xpression de l鈥橢-cadh茅rine (P=0,0344 pour les COV2 et P=0,0267 pour les COV2/M茅so) en plus de diminuer l鈥檈xpression des cytok茅ratines 8/18 et d鈥檃ugmenter celle de la vimentine. En conclusion, les sph茅ro茂des de l鈥檃scite sont form茅s principalement de deux populations cellulaires, une tumorale et l鈥檃utre m茅soth茅liale. Ces cellules m茅soth茅liales contribuent 脿 la formation de structures compactes par le biais d鈥檌nteractions cellule-matrice. Enfin, l鈥檃scite influence les sph茅ro茂des en favorisant l鈥檃doption d鈥檜n profil migratoire des cellules
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