In this study, we analysed the modulation of keratinocyte growth factor (KGF) mRNA expression in human dermal fibroblasts cultured either in monolayer or within a collagen matrix (dermal equivalent). ...In monolayer cultures, KGF expression by quiescent fibroblasts was stimulated by different growth substances such as serum, epidermal growth factor and basic fibroblast growth factor. Moreover, we demonstrated that the induction of this gene was mediated by at least 2 different signalling pathways involving protein kinase C (PKC) and cAMP. In dermal equivalents, we observed that the collagen matrix negatively modulated KGF mRNA expression. Indeed, among the growth substances used, only the serum slightly stimulated KGF expression. Nevertheless, as in monolayers, this induction involved at least PKC and cAMP signalling pathways. As the collagen matrix can modulate fibroblast growth, we also studied KGF expression in growing fibroblasts from either monolayer cultures or dermal equivalents. We then showed that this collagen matrix negatively influenced KGF expression independently of the proliferative state of fibroblasts. All these results underline the fact that KGF mRNA expression by human dermal fibroblasts is induced by different substances; however this expression can be modulated by fibroblast-matrix interactions.
We report the pharmacologic effects of retinoids in a human skin-equivalent model. This sophisticated culture system is composed, as in vivo, of a dermis and epidermis, and provides a unique in vitro ...system for studying dermal-epidermal interactions and thus, whether normal dermal fibroblasts influence the effects of retinoids on epidermal growth. Epidermalization was initiated on collagen substrates in which fibroblasts were either viable or lysed by osmotic shock. Retinoic acid, isotretinoin, and acitretin at 10-6 M or 10-7 M were added to the cultures just after epidermalization, then every two days. Epidermal growth was determined after 2 weeks in terms of the surface area, DNA content, and tritiated thymidine incorporation during the last 24 h of culture. In the absence of viable fibroblasts, retinoic acid and isotretinoin increased epidermal growth, whereas etretin inhibited it. In contrast, in the presence of viable fibroblasts, retinoic acid and isotretinoin inhibited epidermal growth, whereas etretin had no effect. Thus, retinoic acid and isotretinoin had a similar effect on keratinocyte proliferation that contrasted with that of etretin. Taken as a whole, these results show that fibroblasts, present within a collagen substrate, can modulate the pharmacologic effects of retinoids on epidermal growth.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In this work, we have studied the modulation of fibroblast-extracellular matrix interactions by physiological doses of ultraviolet A (UV-A) radiation using an adhesion assay on collagen. We have ...shown that low doses of UV-A (20 kJ/m
2) stimulate fibroblast adhesion while higher doses (100 and 200 kJ/m
2) inhibit it. By measurement of the thiobarbituric acid reactive substances (TBARS) and use of the chainbreaking antioxidant vitamin E, no role of lipid peroxidation can be detected in these effects. By incubating fibroblasts with a specific protein kinase C (PKC) inhibitor, GF109203X, we have demonstrated that the stimulation of the adhesion by low doses of UV-A involves, at least in part, a PKC-dependent mechanism. In addition, using function-blocking antibodies of α1, α2 or α5 integrin chains involved in extracellular matrix anchorage, we have shown that they decrease the stimulation of adhesion following low doses of UV-A radiation, demonstrating the involvement of these three integrin chains in this UV-A effect. In parallel, 20 kJ/m
2 of UV-A are found to rapidly stimulate membrane expression of α1, α2 and α5 integrin chains. This work, which underlines the involvement of integrins in UV-A effects, contributes to the evaluation of the mechanisms by which cell-matrix interactions modulate cell behaviour.
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IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Veno-venous (VV) extracorporeal membrane oxygenation (ECMO) is increasingly used in Coronavirus disease-19 (COVID-19) patients with the most severe forms of acute respiratory distress syndrome ...(ARDS). Its use is associated with a significant hemostatic challenge, especially in COVID- 19 patients who have been demonstrated to otherwise present a COVID-19-associated coagulopathy. The systematic use of unfractionated heparin therapy to prevent circuit thrombosis is warranted during ECMO support. The clinical presentation and management of heparin-induced thrombocytopenia, which is a rare but life-threatening complication of heparin therapy, has not been described in those patients yet. We report herein two cases of laboratory-confirmed HIT in COVID-19 patients with severe ARDS admitted to our intensive care unit for VV-ECMO support and the successful use of argatroban as an alternative therapy. We also provide a brief literature review of best evidence for managing such patients. The diagnosis and management of HIT is particularly challenging in COVID-19 patients receiving ECMO support. An increased awareness is warranted in those patients who already present a procoagulant state leading to higher rates of thrombotic events which can confuse the issues. Argatroban seems to be an appropriate and safe therapeutic option in COVID-19 patients with HIT while on VV-ECMO.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Context
. The origin of the fossil magnetic fields detected in 5 to 10% of intermediate-mass main sequence stars is still highly debated.
Aims
. We want to bring observational constraints to a large ...population of intermediate-mass pre-main sequence (PMS) stars in order to test the theory that convective-dynamo fields generated during the PMS phases of stellar evolution can occasionally relax into fossil fields on the main sequence.
Methods
. Using distance estimations, photometric measurements, and spectropolarimetric data from HARPSpol and ESPaDOnS of 38 intermediate-mass PMS stars, we determined fundamental stellar parameters (
T
eff
,
L
and
v
sin
i
) and measured surface magnetic field characteristics (including detection limits for non-detections, and longitudinal fields and basic topologies for positive detections). Using PMS evolutionary models, we determined the mass, radius, and internal structure of these stars. We compared different PMS models to check that our determinations were not model-dependant. We then compared the magnetic characteristics of our sample accounting for their stellar parameters and internal structures.
Results
. We detect magnetic fields in about half of our sample. About 90% of the magnetic stars have outer convective envelopes larger than ∼25% of the stellar radii, and heavier than ∼2% of the stellar mass. Going to higher mass, we find that the magnetic incidence in intermediate-mass stars drops very quickly, within a timescale on the order of few times 0.1 Myr. Finally, we propose that intermediate-mass T Tauri stars with large convective envelopes, close to the fully convective limit, have complex fields and that their dipole component strengths may decrease as the sizes of their convective envelopes decrease, similar to lower-mass T Tauri stars.
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FMFMET, NUK, UL, UM, UPUK
Cet article présente la Base de Données (BDD) développée dans le cadre du projet ERC Mapping Ancient Polytheisms (MAP), qui vise à étudier les systèmes religieux des mondes grecs et ouest-sémitiques ...dans la longue durée (ca. 1000 av. – 400 ap. J.-C.) à travers le prisme des « attributs onomastiques divins ». On entend par là les noms, épithètes, formes verbales, et autres appellations que les Anciens attribuaient à leurs dieux. La construction d’un tel outil, qui n’est pas sans précédents mais qui s’efforce de franchir un seuil quantitatif et qualitatif, répond à un double impératif : permettre le traitement exhaustif des myriades de dénominations divines en prenant en compte la diversité de contextes dans lesquels elles apparaissent ; utiliser ces dénominations comme les révélateurs des configurations divines et de l’agentivité humaine. La complexité inhérente aux séquences onomastiques divines nécessite l’élaboration d’une base de données soigneusement structurée, souple et précise à la fois. Ainsi, à la suite d’une mise au point terminologique et historiographique, on présente ici la structure de la BDD MAP, et notamment le dispositif d’analyse des formules qui permet la modélisation des séquences onomastiques divines.
Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose ...strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients.
The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers.
This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation.
NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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