Development of double porous poly (ε - caprolactone)/chitosan polymer as tissue engineering scaffold

Polymer blend made from poly( - caprolactone)/chitosan (PCL/CHT) offers interesting opportunities for biological applications. The paper presents a new way to fabricate PCL/CHT double-porosity (macrovoids with interconnected microporosity) membrane materials from a chemical optimization of the solvent and non-solvent phases and from a modified phase inversion technique. By varying the PCL/CHT proportion, it is shown that it is possible to improve the chemical and physical properties of the CHT carbohydrate polymer. The PCL/CHT membranes are fully characterized in term of physico-chemical properties (ATR-FTIR, XRD and DSC) to understand the miscibility of the two-polymer blend. Morphological characterization by SEM shows that by increasing CHT wt% in the blend, the size of the macrovoids was increasing. Rapid enzymatic degradation of PCL from all the blend was found by using lipase (from P. cepacia). The mechanisms at the origin of the morphological structuration of the material is also discussed. To test the ability to operate these materials as small diameter vascular scaffolds, cell culture with human umbilical vein endothelial cells (HUVECs) were carried out on the membrane and the results analyzed with laser scanning confocal microscopy (LSCM). Data suggest that the blend membrane with higher concentration of CHT polymer wt% have suitable properties that promote high number of cells on the surface by maintaining cellular cytoskeleton integrity within 3 days. The blend membrane with a double porous morphology could be potentially applicable in future for small diameter vascular graft application. The surface macrovoids (20–90 μm) could be useful for three-dimensional cellular adhesion and proliferation and interconnected microporous spongy network (7–20 μm) is expected to transfer essential nutrients, oxygen, growth factor between the macrovoids and the supernatant

Artificial membranes tuning for lymphatic wall repair

Chylothorax is an uncommon form of pleural effusion, which generally occurs after cardiac surgery and almost any surgical operation in the chest. The aim of this project is to develop a bioresorbable vascular patch for lymphatic wall repair [1]. Here, we project to develop new materials (i.e. membranes) having two different levels of porosity [2]. First short tests made with Polycaprolactone (PCL) membranes and PCL was blended with different biocompatible, bioresorbable membranes. It shows that human dermal lymphatic endothelial (HDLEC) cells can bind and spread on certain membrane and not on others suggesting that the chemical structure and the morphology of the membranes is important

Hypoxia Induces VEGF-C Expression in Metastatic Tumor Cells via a HIF-1α-Independent Translation-Mediated Mechanism

SummaryVarious tumors metastasize via lymph vessels and lymph nodes to distant organs. Even though tumors are hypoxic, the mechanisms of how hypoxia regulates lymphangiogenesis remain poorly characterized. Here, we show that hypoxia reduced vascular endothelial growth factor C (VEGF-C) transcription and cap-dependent translation via the upregulation of hypophosphorylated 4E-binding protein 1 (4E-BP1). However, initiation of VEGF-C translation was induced by hypoxia through an internal ribosome entry site (IRES)-dependent mechanism. IRES-dependent VEGF-C translation was independent of hypoxia-inducible factor 1α (HIF-1α) signaling. Notably, the VEGF-C IRES activity was higher in metastasizing tumor cells in lymph nodes than in primary tumors, most likely because lymph vessels in these lymph nodes were severely hypoxic. Overall, this transcription-independent but translation-dependent upregulation of VEGF-C in hypoxia stimulates lymphangiogenesis in tumors and lymph nodes and may contribute to lymphatic metastasis

Knockout of Vdac1 activates hypoxia-inducible factor through reactive oxygen species generation and induces tumor growth by promoting metabolic reprogramming and inflammation

BACKGROUND: Mitochondria are more than just the powerhouse of cells; they dictate if a cell dies or survives. Mitochondria are dynamic organelles that constantly undergo fusion and fission in response to environmental conditions. We showed previously that mitochondria of cells in a low oxygen environment (hypoxia) hyperfuse to form enlarged or highly interconnected networks with enhanced metabolic efficacy and resistance to apoptosis. Modifications to the appearance and metabolic capacity of mitochondria have been reported in cancer. However, the precise mechanisms regulating mitochondrial dynamics and metabolism in cancer are unknown. Since hypoxia plays a role in the generation of these abnormal mitochondria, we questioned if it modulates mitochondrial function. The mitochondrial outer-membrane voltage-dependent anion channel 1 (VDAC1) is at center stage in regulating metabolism and apoptosis. We demonstrated previously that VDAC1 was post-translationally C-terminal cleaved not only in various hypoxic cancer cells but also in tumor tissues of patients with lung adenocarcinomas. Cells with enlarged mitochondria and cleaved VDAC1 were also more resistant to chemotherapy-stimulated cell death than normoxic cancer cells. RESULTS: Transcriptome analysis of mouse embryonic fibroblasts (MEF) knocked out for Vdac1 highlighted alterations in not only cancer and inflammatory pathways but also in the activation of the hypoxia-inducible factor-1 (HIF-1) signaling pathway in normoxia. HIF-1α was stable in normoxia due to accumulation of reactive oxygen species (ROS), which decreased respiration and glycolysis and maintained basal apoptosis. However, in hypoxia, activation of extracellular signal-regulated kinase (ERK) in combination with maintenance of respiration and increased glycolysis counterbalanced the deleterious effects of enhanced ROS, thereby allowing Vdac1 (-/-) MEF to proliferate better than wild-type MEF in hypoxia. Allografts of RAS-transformed Vdac1 (-/-) MEF exhibited stabilization of both HIF-1α and HIF-2α, blood vessel destabilization, and a strong inflammatory response. Moreover, expression of Cdkn2a, a HIF-1-target and tumor suppressor gene, was markedly decreased. Consequently, RAS-transformed Vdac1 (-/-) MEF tumors grew faster than wild-type MEF tumors. CONCLUSIONS: Metabolic reprogramming in cancer cells may be regulated by VDAC1 through vascular destabilization and inflammation. These findings provide new perspectives into the understanding of VDAC1 in the function of mitochondria not only in cancer but also in inflammatory diseases

Young children's understanding of disabilities: the influence of development, context and cognition

Throughout Europe, educational support for children with disabilities has moved towards a model of inclusive education. Such policy changes mean that for all children there will be an increased likelihood of working with and encountering children with differing disabilities and difficulties. Previous research had indicated that children had poorly differentiated views of developmental differences. The present study investigated children?s representations of different disabilities. Seventy-nine 8-9 and 10-11 year old Greek children from an urban school and a rural school completed an attitudes toward school inclusion rating scale and a semi-structured interview. Responses to the attitude scale provided generally positive views of educational inclusion. However, children were less positive about activities that might directly reflect upon themselves. Children?s responses in the interviews indicated that they were developing rich representations of differences and diversities. Children had the greatest understanding of sensory and physical disabilities, followed by learning disabilities. There was limited knowledge of dyslexia and hyperactivity and no child was familiar with the term autism. Both groups of children identified a range of developmental difficulties, with older children being more aware of specific learning disabilities, their origin and impact. Results are discussed in terms of children?s developing knowledge systems and the implications for educational practices

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Etude de l'effet de l'Oestradiol sur la migration et la prolifération endothéliale

TOULOUSE3-BU Sciences (315552104) / SudocSudocFranceF

Rôle de l’ARN non codant NEAT1 dans le contrôle de la traduction des ARN messagers par le noyau cellulaire

International audienceNo abstract availabl