22 research outputs found

    The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

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    Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases

    Sedimentation field-flow fractionation separation of proliferative and differentiated subpopulations during Ca2+-induced differentiation in HaCaT cells.

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    International audienceThe spontaneously immortalized human keratinocyte cell line HaCaT is widely used as a human keratinocyte model. In a previous comparative study between normal human keratinocytes (NHKs) and HaCaT, we reported that Ca2+ concentrations greater than 1mM induced differentiation in vitro in both cell types, notably characterized by increased expression of differentiation markers keratins 1 (K1), 10 (K10) and involucrin. Surprisingly, cells had a higher proliferative activity than those cultured with low Ca2+ levels. These results raised many questions; in particular concerning the emergence of HaCaT cells subpopulation which would have different differentiation states and/or proliferation rates throughout Ca2+-induced differentiation. To isolate these subpopulations, we used sedimentation field-flow fractionation (SdFFF). Results demonstrated that the most differentiated cells (HC-F1), characterized by the highest expression of keratinocyte differentiation markers, had the lowest proliferative activity. In contrast, less differentiated cells (HC-F2) maintained a higher proliferative activity. SdFFF is a tool to sort differentiated and/or proliferating cells from a total pool previously treated with a Ca2+ concentration inducing differentiation, and can be use to prepare biological models necessary for studying HaCaT cell proliferation after Ca2+-induced differentiation treatment

    Impact of a person-centered bowel program on the frequency of nights with bowel movement in dependent elderly people in nursing home: A single-centre randomized controlled trial

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    Introduction: Bowel movements and sleep disturbances in the elderly impact their quality of life and dignity.The management of bowel movements is one of carers' main activities in nursing homes. This activity isunder-recognized. It is routinely managed with laxatives or anti-diarrhea treatments, rather than being targetedat each resident's habits. We hypothesized that the implementation of a daytime person-centered bowelprogram in dependent elderly nursing-home residents could reduce nocturnal bowel movements and sleepdisturbance due to night-time care activities. Our study evaluated the impact of a bowel program on thefrequency of nights with bowel movement.Method: We conducted a single-center randomized controlled trial in two parallel groups: a control groupwith usual management versus an experimental group with the implementation of the person-centeredbowel program.Results: Fifty dependent elderly residents of nursing homes for over one month were included. The imple-mentation of the person-centered bowel program significantly impacted the frequency of nights withbowel movement: 12.0 (7.0; 15.5) in the control group versus 3.7 (2.0; 6.0) in the experimental group(p < 0.000). The strategy had no significant impact on laxative intake (p = 0.470).Conclusions: The introduction of a daytime person-centered bowel program significantly reduces the fre-quency of nights with bowel movements for dependent nursing-home residents. This person-centeredstrategy restores a key role to this basic need care. Further studies could explore the impact of this programon respect, dignity, comfort and night-time rest. It also offers carers new perspectives on care, with respectto the human being.Study registration: The study was registered in ClinicalTrials N°NCT03118401.Tweetable abstract: A daytime bowel program significantly reduces the number of nights with bowelmovements for dependent nursing-home residents.© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    MET Genetic Abnormalities Unreliable for Patient Selection for Therapeutic Intervention in Oropharyngeal Squamous Cell Carcinoma

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    Background: Identification of MET genetic alteration, mutation, or amplification in oropharyngeal squamous cell carcinoma (OPSCC) could lead to development of MET selective kinase inhibitors. The aim of this study was to assess the frequency and prognostic value of MET gene mutation, amplification, and protein expression in primary OPSCC. Methods: A retrospective chart review was conducted of patients treated for single primary OPSCC between January 2007 and December 2009. Pre-treatment OPSCC tissue samples were analyzed for MET mutations, gene amplification, and overexpression using Sanger sequencing, FISH analysis, and immunohistochemistry respectively. Univariate and multivariate analyses were used to analyze correlations between molecular abnormalities and patient survival. Results: 143 patients were included in this study. Six cases (4%) were identified that had a genetic variation, but previously described mutations such as p. Tyr1235Asp (Y1235D) or p.Tyr1230Cys (Y1230C) were not detected. There were 15 high polysomy cases, and only 3 cases met the criteria for true MET amplification, with >= 10% amplified cells per case. Immunohistochemistry evaluation showed 43% of cases were c-MET negative and in 57% c-MET was observed at the tumor cell level. Multivariate analysis showed no significant association between MET mutation, amplification, or expression and survival. Conclusions: Our study shows a low frequency of MET mutations and amplification in this cohort of OPSCC. There was no significant correlation between MET mutations, amplification, or expression and patient survival. These results suggest that patient selection based on these MET genetic abnormalities may not be a reliable strategy for therapeutic intervention in OPSCC
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