6 research outputs found
Implication of thioredoxin system in human chondrocytes subjected to high glucose stress, under hypoxia and normoxia : effects of Resveratrol
Lâarthrose est une maladie dĂ©gĂ©nĂ©rative de lâarticulation caractĂ©risĂ©e par une dĂ©gradation du cartilage, une inflammation de la membrane synoviale et un remodelage de lâos sous-chondral. En conditions physiologiques, les chondrocytes, seul type cellulaire du cartilage, sont en hypoxie (â 2% dâoxygĂšne). Le cartilage Ă©tant un tissu avascularisĂ©, il existe un gradient de concentration en oxygĂšne au sein des diffĂ©rentes couches du cartilage. Lors du dĂ©veloppement de lâarthrose, la dĂ©gradation du cartilage provoque une rupture de ce gradient, exposant ainsi les cellules des couches profondes Ă des concentrations en oxygĂšne beaucoup plus Ă©levĂ©es et induisant des modifications de leur mĂ©tabolisme, ce qui induit leur dysfonction. Le syndrome mĂ©tabolique est dĂ©fini par un ensemble de perturbations glucidiques, lipidiques et vasculaires menant au dĂ©veloppement de maladies cardiovasculaires et au diabĂšte de type 2. RĂ©cemment, un lien entre arthrose et syndrome mĂ©tabolique a Ă©tĂ© suggĂ©rĂ©, introduisant une notion dâarthrose mĂ©tabolique. Au cours de cette Ă©tude, nous nous sommes intĂ©ressĂ©s au lien entre arthrose, syndrome mĂ©tabolique et stress oxydant induit par de fortes concentrations de glucose. Dans la premiĂšre partie de ce travail, nous avons Ă©tudiĂ© les effets in vitro de 25 mM de glucose sur une lignĂ©e de chondrocytes humains immortalisĂ©s (T/C28a2), en hypoxie (2% dâoxygĂšne) et en normoxie (21% dâoxygĂšne). Nous avons montrĂ© que le glucose Ă 25 mM induisait la production dâespĂšces rĂ©actives de lâoxygĂšne (ERO) et de lâazote, lâactivation de la caspase 3, la production dâinterleukine 6 (IL-6), la diminution de lâactivitĂ© lysyl oxydase (LOX), qui est impliquĂ©e dans les liaisons de pontage des fibres de collagĂšne et dâĂ©lastine, ainsi que lâactivation du systĂšme thiorĂ©doxine (Trx). Ce dernier est un systĂšme de dĂ©fense anti-oxydant endogĂšne composĂ© de la thiorĂ©doxine, de la thiorĂ©doxine rĂ©ductase (TR) et de Txnip, qui intervient dans le maintien de lâhomĂ©ostasie cellulaire en rĂ©duisant les protĂ©ines oxydĂ©es, contrĂŽlant ainsi lâenvironnement redox des cellules. Les effets du glucose 25 mM ont Ă©tĂ© observĂ©s dans les deux conditions dâoxygĂšne Ă©tudiĂ©es, cependant la rĂ©ponse cellulaire en normoxie Ă©tait plus prĂ©coce quâen hypoxie. Nous avons Ă©galement pu mettre en Ă©vidence un rĂŽle de rĂ©gulateur nĂ©gatif de la Trx-1 sur la production dâIL-6 faisant intervenir la voie de signalisation p38MAPK. Dans la deuxiĂšme partie de ce travail, nous nous sommes intĂ©ressĂ©s aux effets de lâapport exogĂšne de resvĂ©ratrol sur les modifications induites par le glucose Ă 25 mM. Le resvĂ©ratrol (3,4â,5-trihydroxystilbĂšne) est un polyphĂ©nol de la famille des stilbĂšnes, connu pour ses multiples propriĂ©tĂ©s anti-oxydantes, anti-inflammatoires, anti-diabĂ©tiques et anti-cancer. Nous avons pu observer que le resvĂ©ratrol Ă 25 ÎŒM Ă©tait capable de diminuer les effets dĂ©lĂ©tĂšres provoquĂ©s par le glucose Ă 25 mM. Cependant, la biodisponibilitĂ© du resvĂ©ratrol est trĂšs limitĂ©e, empĂȘchant son utilisation en thĂ©rapeutique humaine. Par consĂ©quent, dans la troisiĂšme partie de cette Ă©tude, nous nous sommes intĂ©ressĂ©s au dĂ©veloppement de nouvelles formulations galĂ©niques de resvĂ©ratrol (nano-Ă©mulsions (NE)) et Ă leurs effets sur un modĂšle de cellules endothĂ©liales aortiques bovines (BAEC), sur les T/C28a2 ainsi que sur des chondrocytes humains en culture primaire provenant de cartilage de patients arthrosiques. Nous avons montrĂ© quâune des NE permettait dâaugmenter le passage intracellulaire de resvĂ©ratrol dans les deux modĂšles Ă©tudiĂ©s et dâen potentialiser les effets protecteurs contre un stress oxydant. Cette NE sâest Ă©galement montrĂ©e efficace dans le rĂ©tablissement de lâactivitĂ© LOX dans les cellules de patients arthrosiques. En conclusion, nous avons montrĂ© que le glucose Ă 25 mM avait des effets dĂ©lĂ©tĂšres sur les chondrocytes de la lignĂ©e T/C28a2 et que lâapport exogĂšne de resvĂ©ratrol permettait de lutter contre ses effets. (...)Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation of synovial membrane and subchondral bone remodelling. Under physiological conditions, chondrocytes - the only cell type found in cartilage - are under hypoxia (around 2% of oxygen). As cartilage is an avascular tissue, an oxygen gradient is established from the superficial to the deeper layers. During OA development, cartilage degradation is responsible for a break in this gradient; consequently, cells from the deepest layers are exposed to higher oxygen concentrations inducing modifications in cell metabolism leading to their dysfunction. Metabolic syndrome (MetS) is defined by a cluster of factors (impairment of glucose and lipid metabolism, vascular dysfunctionsâŠ) leading to cardiovascular diseases and type 2 diabetes development. Recently, a link between OA and MetS has been suggested, introducing a notion of metabolic OA. We have focused our study on the link between OA, MetS and oxidative stress induced by high glucose concentrations. In the first part of this study, we have determined the in vitro effects of 25 mM glucose on an immortalized human chondrocyte cell line (T/C28a2), under hypoxia (2% oxygen) and normoxia (21% oxygen). We demonstrated that 25 mM glucose induced radical oxygen species (ROS) and nitric oxide production, caspase 3 activation, interleukin 6 (IL-6) production, decrease in lysyl oxidase (LOX) activity (involved in type II collagen crosslinks), and activation of the thioredoxin (Trx) system. Trx system is an endogenous anti-oxidant system, composed by thioredoxin, thioredoxin reductase (TR) and Txnip; it is involved in cellular homeostasis by reducing oxidized proteins, thereby controlling cellular redox environment. Effects of 25 mM glucose have been observed under both oxygen conditions; nevertheless, cellular response under normoxia underwent earlier than under hypoxia. We have also highlighted Trx-1 as a negative regulator of IL-6 production through p38MAPK signalling pathway. In the second part of this study, we have focused our work on the effects of the addition of an exogenous antioxidant, i.e. resveratrol, on the modifications induced by 25 mM glucose. Indeed, resveratrol (3,4â,5-trihydroxystilbene) is a polyphenol of the stilbene family, known for its multiple anti-inflammatory, anti-oxidative, anti-diabetes and anti-cancer properties. We have observed that 25 ÎŒM resveratrol was able to decrease deleterious effects induced by 25 mM glucose. However, resveratrol bioavailability is very low, avoiding its use in human therapeutic strategy. Consequently, in the third part of this study, we have developed new galenic formulations of resveratrol, i.e. nano-emulsions (NEs) and determined their effects on a bovine aortic endothelial cells (BAEC) model, on T/C28a2 cells and also on primary cultures of human chondrocytes from osteoarthritic cartilages. One of our NEs was able to increase resveratrol intracellular passage in both cellular models, and to increase the protective effects of resveratrol against oxidative stress. This NE was also efficient in the normalization of LOX activity in osteoarthritic chondrocytes. To conclude, we have demonstrated that 25 mM glucose induced deleterious effects on chondrocytes of the T/C28a2 cell line, and that an exogenous supply in resveratrol allowed to counteract these effects. Development of a new galenic formulation of resveratrol opens new interesting prospects in human therapeutic strategy against OA associated with MetS
Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death
Osteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavailability, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, and thus decrease resveratrol intrinsic cellular toxicity, allowing the use of higher concentrations, second, to increase resveratrol uptake in membrane and intracellular fractions, and finally, to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments
Use of Resveratrol Self-Emulsifying Systems in T/C28a2 Cell Line as Beneficial Effectors in Cellular Uptake and Protection Against Oxidative Stress-Mediated Death
International audienceOsteoarthritis (OA) is the most prevalent rheumatic disease in the world. Although its etiology is still unknown, one of the key processes in OA progression and development is oxidative stress. In this context, resveratrol, a well-known anti-oxidant from the stilbene family, could be of particular interest in future OA therapeutic strategies. However, currently, because of its low bioavaiIabiIity, use of resveratrol in human health is very limited. In this study, we tested two resveratrol self-emulsifying systems previously developed in our laboratory in order to determine if they could improve cellular uptake of resveratrol in a human immortalized chondrocytic cell line (T/C28a2) and enhance protection against oxidative stress. Our results showed that resveratrol self-emulsifying systems were able first to increase cellular tolerance towards resveratrol, and thus decrease resveratrol intrinsic cellular toxicity, allowing the use of higher concentrations, second, to increase resveratrol uptake in membrane and intracellular fractions, and finally, to improve protection against oxidative stress-mediated death in human immortalized chondrocytic cell line T/C28a2. These data suggest that new formulations of resveratrol could be considered as potential beneficial effectors in future OA treatments
Penetration of resveratrol into bovine aortic endothelial cells (BAEC): A possible passive diffusion
Cancer de la vessie localement avancé ou métastatique : identification des freins et leviers du parcours des patients en France
International audienceIntroduction: Bladder cancer is currently ranked as the 8th most common cancer in France. However, the patient care pathway for this cancer is still not well known.Methods: A telephone survey was conducted with fifteen healthcare professionals, ten patients, and five family caregivers between November 2020 and March 2021. The objectives of this survey were to identify the major steps in the care pathway according to the medical, emotional and societal dimensions, for patients with locally advanced or metastatic bladder cancer, the associated barriers, and the initiatives to be implemented to improve it.Results: Several barriers were identified at different stages of the overall care pathway, including lack of knowledge of risk factors and warning signs of the disease by the general population and some healthcare professionals, difficulties linked to the announcement consultation, lack of psychological support for patients and their caregivers, and lack of information given about the disease and supportive care.Discussion: These results allowed us to identify three major initiatives which could improve the overall care pathway and the quality of life of patients and their caregivers: 1/implementation of a public awareness campaign on bladder cancer; 2/creation of booklets for patients and their caregivers to provide them with a source of reliable information; and 3/the creation of communication tools between healthcare professionals and patients to facilitate exchanges during consultations.Introduction > Le cancer de la vessie est aujourd'hui classĂ© en huitiĂšme position des cancers lesplus frĂ©quents en France. Le parcours de soins de ce cancer est, cependant, mal connu.MĂ©thodes > Une enquĂȘte tĂ©lĂ©phonique a Ă©tĂ© menĂ©e en France auprĂšs de quinze professionnels desantĂ©, dix patients et cinq aidants entre novembre 2020 et mars 2021. Les objectifs de cetteenquĂȘte Ă©taient d'identifier les grandes Ă©tapes du parcours de soins des patients atteints d'uncancer de la vessie localement avancĂ© ou mĂ©tastatique, selon l'angle mĂ©dical, Ă©motionnel etsociĂ©tal, les freins y Ă©tant associĂ©s et les initiatives Ă mettre en place pour l'amĂ©liorer. IntroductionLe cancer d'origine vĂ©sicale est dans 90 % des cas un carcinomeurothĂ©lial, dont l'incidence est de 13 000 nouveaux cas diag-nostiquĂ©s chaque annĂ©e en France [1], le plaçant en huitiĂšmeposition des cancers les plus frĂ©quents. Il arrive au quatriĂšmerang des cancers masculins et au quatorziĂšme rang des cancersfĂ©minins et est responsable d'environ 5000 dĂ©cĂšs par an enFrance (3778 dĂ©cĂšs chez les hommes et 1235 dĂ©cĂšs chez lesfemmes, observĂ©s en 2017). Il est ainsi le septiĂšme cancer leplus mortel en France [1].Les principaux facteurs de risque du cancer de la vessie sontl'Ăąge, avec une moyenne d'Ăąge au diagnostic de 73 ans chezl'homme et 78 ans chez la femme [2], et le tabagisme [3]. Unfumeur a, en effet, environ 5,5 fois plus de risque de dĂ©velopperla maladie par rapport Ă un non-fumeur. En France, le tabagismeserait responsable de 53 % des cas de tumeurs de la vessie chezles hommes et de 39 % chez les femmes [4]. Les autres facteursde risque sont l'exposition professionnelle Ă des substances,comme les amines aromatiques, Ă des agents infectieux (ex :schistosome), ou Ă certains mĂ©dicaments (ex : traitement antĂ©-rieur Ă base de cyclophosphamide). Les facteurs de risqueassociĂ©s au carcinome urothĂ©lial en font historiquement uncancer principalement masculin [5].Le diagnostic de ce cancer peut ĂȘtre retardĂ©, Ă cause de symp-tĂŽmes cliniques non spĂ©cifiques pouvant laisser penser, notam-ment, Ă une infection urinaire, tels qu'une augmentation de lafrĂ©quence urinaire, de l'urgence mictionnelle et une dysurie, quiRĂ©sultats > Plusieurs freins ont Ă©tĂ© identifiĂ©s Ă diffĂ©rentes Ă©tapes du parcours, notamment lemanque de connaissance des facteurs de risque et signes d'alerte de la maladie par le grand publicet certains professionnels de santĂ©, les difficultĂ©s liĂ©es Ă la consultation d'annonce, le manqued'accompagnement psychologique pour les patients et aidants, le manque d'informations don-nĂ©es sur la maladie et les soins de support.Discussion > Ces rĂ©sultats ont permis d'identifier ainsi trois grandes initiatives qui permettraientd'amĂ©liorer le parcours de soins dans sa globalitĂ© et la qualitĂ© de vie des patients et de leursaidants : 1/mise en place d'une campagne de sensibilisation du grand public sur le cancer de lavessie ; 2/crĂ©ation de livrets Ă destination des patients et de leurs aidants pour leur fournir unesource d'informations fiables ; et 3/la crĂ©ation d'outils de communication entre soignants etpatients pour faciliter les Ă©changes lors des consultations
Teleconsultation in rheumatology: a literature review and opinion paper
In this article, we review published literature on âtelerheumatologyâ, a term describing the use of telemedicine in rheumatology. This field has received considerable recent attention through the development of efficient digital technologies, resulting in a good level of satisfaction among patients and health care professionals. In 2020, the social distancing constraints during the COVID-19 pandemic accelerated more widespread adoption worldwide. Telerheumatology is particularly suited for patients with rheumatoid arthritis who have achieved a sustained therapeutic target of remission or low disease activity. To facilitate remote consultations and meet expectations of rheumatologists and patients, international and national guidelines have recently been proposed and existing tools, such as Patient-Reported Outcomes questionnaires, have had to be digitally adapted. In addition, telerheumatology toolkits are proposed by the Arab League of Associations for Rheumatology (ArLAR), the Association of American Medical College (AAMC), and the American College of Rheumatology (ACR) for all learners, from medical students to practicing clinicians, encouraging the acquisition of telehealth skills and facilitating their integration into their routine clinical practice. The main benefits reported for this mode of health care are greater access to specialty care, flexibility, reduced rates of missed appointments, as well as improved patient engagement and autonomy. Limitations include the absence of physical examination. However, to implement telerheumatology effectively and widely in daily clinical practice, some barriers still need to be addressed. These include training of health care professionals, technological restrictions and reimbursement mechanisms. Despite the advantages of telerheumatology, it is not intended to replace face-to-face visits, but rather as a way to enhance access to care, service delivery and health care support for patients