The effects of celastrol on endothelial cells survival and proliferation

Introduction: Coronary artery bypass grafts are most commonly performed using saphenous vein grafts to complement the internal thoracic artery. The saphenous vein will remain popular despite its lower patency rate because it is easily accessible and lengthy enough to perform multiple bypasses. Therefore, several approaches have been studied, with the common goal of finding the optimal conditions that reduce graft failure. They include novel harvest techniques, new preservation preparations, innovative genetic therapies and experimental drugs. We believe a pharmacological pre-conditioning with an anti-oxidative and anti-inflammatory drug during the crucial time of harvest may spark beneficial survival response from the endothelial cells. One particular compound is Celastrol, an HSP90 inhibitor, which displays those antioxidant and anti-inflammatory properties. Methods: Human umbilical vein endothelial cells (HUVEC) were pretreated with various concentrations of Celastrol (10-10M, 10-8M and 10-6M). In order to reproduce oxidative stress found in ischemia/reperfusion, cells were exposed to hydrogen peroxide for a short and extended period (1h and 24h). To mimic storage condition encountered in clinical settings, cells were also exposed in heparinized normal saline. The viability was assessed by LIVE/DEAD assay. As for migrative and proliferative properties, scratch tests were performed. Finally, various protective intracellular pathways were evaluated by Western blot. Results: This study shows that pre-treatment with Celastrol promotes survival in HUVEC submitted to oxidative stress. Notable improvement in cellular viability was detected as early as 1 hour after oxidative stress (H2O2 4 mM), 76.6% vs 66.1% (p=0.005). Significant survival benefits are also reported after prolonged oxidative stress (H2O2 0.5 mM for 24 hours); viability was 93.7% vs 76.9% (p=0.001) for Cel 10- 8 M and 96.6% vs 76.9% (p=0.002) for Celastrol 10-10M when compared to the vehicle. Celastrol, however, did not significantly affect viability of HUVEC stored in heparinized normal saline. Celastrol at 10-6 M promotes faster and more complete wound closure compared to the vehicle or to lower dosages. Celastrol triggers early activation of the RISK pathway, inducing activation of both Akt and ERK1/2 within the first 15 minutes of treatment. Celastrol also induces the expression of HSP70 and HO-1, effectors of the Heat Shock Response and the anti-oxidative response respectively. Conclusion: Pre-treatment by Celastrol provides survival benefits in endothelial cells under oxidative stress. It also stimulates endothelial cell proliferation and migration, promoting faster and more complete re-endothelialisation. Celastrol can potentially be used as an additive to storage solutions to limit endothelial injury and promote graft protection.Introduction: La chirurgie de pontage coronarien requiert, dans la grande majorité des cas, l’utilisation de l’artère mammaire interne en combinaison avec un ou des greffons provenant de la grande veine saphène. Malgré le taux de perméabilité inférieur aux artères, la veine saphène reste un choix populaire de conduit en raison de son accessibilité et de sa longueur. De ce fait, le greffon veineux devient la cible de multiples approches et le sujet de nombreuses études visant à optimiser sa perméabilité. Celles-ci incluent le raffinement des techniques de prélèvement, les solutions de préservations, les agents pharmacologiques ainsi que la thérapie génique. Il est davantage intéressant de combiner les approches afin de joindre leurs bénéfices, comme, par exemple, ajouter un agent pharmacologique à une solution de préservation. Un agent potentiel serait le Celastrol, connu pour être un inhibiteur du HSP90 et possède des propriétés antioxydantes et anti-inflammatoires. Méthodologie: Des cellules endothéliales humaines provenant de la veine ombilicale (HUVEC) sont pré-conditionnées à de multiples concentrations de Celastrol (10-10M, 10-8M and 10-6M) pendant une heure avant d’être soumises aux conditions de stress. Pour reproduire les conditions per-opératoires de prélèvement, les cellules endothéliales ont été préservées dans du salin (NS) héparinisé. Pour mimer le stress secondaire à l’ischémie/reperfusion, les cellules ont aussi été soumises à diverses concentrations de H2O2. Une analyse de la viabilité cellulaire fut conduite par le test de LIVE/DEAD. La capacité de ré-endothélialisation est étudiée grâce à l’épreuve de scratch test. Les voies intracellulaires de survie telles que le RISK pathway (Akt, ERK1/2), le Heat shock response (HSP70) et la réponse anti-oxydante (via l’activité de HO-1) ont été examinées par immunoblot. Résultats: Les résultats démontrent que la préservation des cellules endothéliales dans du NS héparinisé est associée à une augmentation de la mortalité comparativement au milieu de culture (20.4% vs 1.9%, p=0.004). Toutefois, un traitement au Celastrol n’affecte pas significativement la survie des cellules endothéliales dans le NS héparinisé. Le stress oxydatif induit aussi une augmentation de la mortalité, et ce à dose-dépendante. Suivant un court stress 6 oxydatif (H2O2 4 mM), un pré-traitement au Celastrol 10-10M est associé à une meilleure viabilité comparativement au véhicule (76.6% vs 66.1%, p=0.005). Lorsque soumises à un stress oxydatif prolongé (H2O2 0.5 mM pendant 24h), les HUVEC pré-traitées au Celastrol à 10-8M et 10-10M démontrent une amélioration significative de la viabilité, 93.7% vs 76.9% (p=0.001) et 93.6% vs 76.9% (p=0.002) respectivement. Quant à la ré-endothélialisation, un traitement au Celastrol 10- 6M est associé à une fermeture plus rapide et complète comparativement au véhicule. Un court traitement au Celastrol active précocement les kinases de la voie de RISK (Akt et ERK). Le traitement induit aussi l’expression de HSP70 et HO-1 qui reste soutenue jusqu’à 48 heures posttraitement. Conclusion: Le Celastrol active plusieurs voies de protection intracellulaire tels que le RISK pathway, le Heat Shock Response et la réponse antioxydante via l’activité de HO-1. En corrélation avec cette réponse, il améliore la survie des cellules endothéliales dans un milieu oxydatif. Le Celastrol promeut aussi une ré-endothélialisation plus complète et rapide. Cette étude met en valeur les bénéfices potentiels du Celastrol sur les cellules endothéliales. Afin d’optimiser la protection du greffon, le Celastrol pourrait donc être considéré comme agent adjuvant à une solution de préservation

DEVELOPMENT OF ELECTROACTIVE POLYMETHYLTHIOPHENE BASED DOPAMINE SENSOR

Joint Research on Environmental Science and Technology for the Eart

EfficientRec an unlimited user-item scale recommendation system based on clustering and users interaction embedding profile

Recommendation systems are highly interested in technology companies nowadays. The businesses are constantly growing users and products, causing the number of users and items to continuously increase over time, to very large numbers. Traditional recommendation algorithms with complexity dependent on the number of users and items make them difficult to adapt to the industrial environment. In this paper, we introduce a new method applying graph neural networks with a contrastive learning framework in extracting user preferences. We incorporate a soft clustering architecture that significantly reduces the computational cost of the inference process. Experiments show that the model is able to learn user preferences with low computational cost in both training and prediction phases. At the same time, the model gives a very good accuracy. We call this architecture EfficientRec with the implication of model compactness and the ability to scale to unlimited users and products.Comment: Published in 14th Asian Conference on Intelligent Information and Database Systems (ACIIDS), 202

Using YouTube Videos to Promote Universities : A Content Analysis

In today’s global higher education environment, international students represent not only an important source of external income for universities: the degree of cross-border student mobility also reflects the internationalization of higher education sector. Universities have engaged in efforts to sell themselves to prospective students and promotional videos are among the most widely used marketing tools for this purpose. This study reports the results of a study analyzing the content of 140 higher education promotional videos from 14 countries available on YouTube. The results reveal that while the pattern of use of YouTube for two-waycommunication with viewers, information contents and appeal messages among sampled universities is fairly homogenous, some marked differences emerge when cultural background and global position ranking of the university are taken into account. The implications of these findings are that, although, transnational higher education has been profoundly globalized, culture still plays a significant role in marketing practice for the recruitment of mobile students. In addition, different universities have various student-targeted segments. These findings provide the basis of a series of recommendations for universities looking to optimize their use of YouTube and promotional video design to market to international students

On how religions could accidentally incite lies and violence: Folktales as a cultural transmitter

This research employs the Bayesian network modeling approach, and the Markov chain Monte Carlo technique, to learn about the role of lies and violence in teachings of major religions, using a unique dataset extracted from long-standing Vietnamese folktales. The results indicate that, although lying and violent acts augur negative consequences for those who commit them, their associations with core religious values diverge in the final outcome for the folktale characters. Lying that serves a religious mission of either Confucianism or Taoism (but not Buddhism) brings a positive outcome to a character (βT_and_Lie_O= 2.23; βC_and_Lie_O= 1.47; βT_and_Lie_O= 2.23). A violent act committed to serving Buddhist missions results in a happy ending for the committer (βB_and_Viol_O= 2.55). What is highlighted here is a glaring double standard in the interpretation and practice of the three teachings: the very virtuous outcomes being preached, whether that be compassion and meditation in Buddhism, societal order in Confucianism, or natural harmony in Taoism, appear to accommodate two universal vices—violence in Buddhism and lying in the latter two. These findings contribute to a host of studies aimed at making sense of contradictory human behaviors, adding the role of religious teachings in addition to cognition in belief maintenance and motivated reasoning in discounting counterargument

Does the informal economy mitigate poverty and how does it work? : the case of Vietnam

Countries with lower quality institutions or heavier burden of regulation are associated with a larger informal sector. In addition, other studies show that low startup costs are a key determinant in entering the informal economy. The paper investigates the linkage between the informal economy and poverty reduction based on the 2010 Vietnam Household Living Standard Surveys. Among low income households, those with members involved in informal economic activities have a higher per capita income than those with no members in the informal economy, and informal wage workers earn more than informal self-employed workers on average. Meanwhile, among non-poor households an inverse trend is observed

Impact of various essential oils and plant extracts on the characterization of the composite seaweed hydrocolloid and gac pulp (Momordica cochinchinensis) edible film

Edible films and coatings have currently received increasing interest because of their potential in food applications. This study examined the effect of incorporated essential oils and natural plant extracts on the characteristics of the composite seaweed hydrocolloid and gac pulp films. Films were prepared by a casting technique, followed by measurement of physical, optical, barrier, mechanical, and structural properties. The results showed that adding plant oils and extracts significantly affected the physical, optical, mechanical, and structural properties of the composite films. Incorporation of the essential oils resulted in a reduction in moisture content and opacity while increasing values for Hue angle and elongation at break of the composite films. Besides, incorporation of the plant extracts showed increases in thickness, opacity, Delta E, Chroma, and elongation at the break, while there is a decrease in the Hue angle values of the composite films. In conclusion, incorporating plant essential oils and extracts into composite seaweed hydrocolloid and gac pulp films can enhance film properties, which can potentially be applied in food products