Étude de médicaments botaniques de la médecine traditionnelle chinoise pour la croissance des cellules endothéliales et l'angiogenèse

Les médicaments botaniques, y compris ceux utilisés en médecine traditionnelle chinoise (MTC), traitent depuis longtemps les maladies cardiovasculaires où la dysfonction endothéliale est un facteur de risque bien établi. Dans la littérature, il existe de nombreux rapports sur les avantages dans la clinique et la santé des médicaments ou des préparations botaniques pour le système cardiovasculaire. Il a été indiqué que des médicaments botaniques, en particulier ceux ayant une capacité antioxydante puissante, protègent les cellules endothéliales (CE) en culture contre les radicaux libres et les oxydants. Cependant, il y a peu de recherches sur les médicaments botaniques dans le contexte de la cicatrisation et de la régénération tissulaire. Cette thèse a étudié quatre médicaments botaniques enregistrés dans la MTC pour explorer leurs effets sur la croissance des CE vasculaires et l'angiogenèse, deux événements activement impliqués dans la cicatrisation et la régénération tissulaire. Dans la première partie de la thèse, des cellules endothéliales ombilicales humaines (HUVEC) ont été cultivées en présence de différentes doses d'extrait d'astragale en forme de poudre, d'injection d'astragale, d'injection de puerarin et de proanthocyanidine. Parmi les quatre médicaments, la proanthocyanidine a montré un effet puissant sur la viabilité cellulaire et stimulé la croissance cellulaire d'une manière dépendante de la dose. En dehors de la gamme de doses efficaces, la proanthocyanidine était inefficace ou cytotoxique. Fait important, la proanthocyanidine testée était capable de maintenir une viabilité cellulaire comparable aux cellules supplémentées avec le milieu spécifique pour les CE avec un niveau bas ou normal de sérum, ce qui suggère le potentiel de la proanthocyanidine en tant que stimulateur de croissance et réactif angiogénique. Dans la seconde partie de la thèse, des études mécanistiques ont été réalisées en bloquant à la fois les récepteurs du facteur de croissance des cellules endothéliales (VEGFR) et les récepteurs du facteur de croissance des cellules épithéliales (EGFR). Cependant, les bloqueurs ont été inefficaces pour réduire l'effet stimulant de la proanthocyanidine sur les CE. En conséquence, il est conclu que la proanthocyanidine stimule probablement la croissance des CE à travers des récepteurs membranaires autres que VEGFR et EGFR. Dans la troisième partie de la thèse, il a été montré que la proanthocyanidine pouvait être chargée dans un cryogel d'alcool polyvinylique, puis libérée du gel à une concentration dans la gamme de la dose efficace. Ceci a démontré la faisabilité d'une libération lente de proanthocyanidine à partir d'un support polymérique. Enfin, la propriété angiogénique de la proanthocyanidine a été testée sur un modèle de membrane chorioallantoïque d'embryon de poulet (CAM), montrant que ce médicament botanique était capable de stimuler le développement du système vasculaire. Cette thèse a donc démontré pour la première fois que la proanthocyanidine est capable de moduler l'activité des CE humaines, particulièrement de réguler positivement l'activité et la croissance des CE en l'absence de facteurs de croissance, et que la proanthocyanidine peut être utilisée comme réactif angiogénique et libérée d'un support de médicament synthétique. En somme, cette thèse a démontré que les médicaments botaniques en médecine traditionnelle chinoise peuvent être utilisés comme substituts pour produits protéiques pour maintenir les cellules en culture et induire l'angiogenèse pour la cicatrisation et la régénération tissulaire.Botanic drugs including those used in traditional Chinese medicine (TCM) have a long history of treating cardiovascular diseases, of which endothelial dysfunction is well established as a risk factor. In literature there exist extensive reports about the clinic and healthy benefits of botanic drugs or preparations to the cardiovascular system. Botanic drugs particularly those with potent antioxidative capacity have also been reported to protect endothelial cells (EC) in culture against free radicals and oxidants. However, there is little research about botanic drugs in the context of wound healing and tissue regeneration. This thesis studied four botanic drugs recorded in TCM to explore their effects on vascular EC growth and angiogenesis, two events actively involved in wound healing and tissue regeneration. In the first part of the thesis, human umbilical endothelial cells (HUVEC) were cultured in the presence of different doses of astragalus powder extract, astragalus injection, puerarin injection, and proanthocyanidin. Among the four drugs, proanthocyanidin showed a potent effect on cell viability and stimulated cell growth in a dose dependent manner. Outside the effective dose range proanthocyanidin was either ineffective or cytotoxic. Importantly, the proanthocyanidin under test was able to maintain a cell viability comparable with the cells supplemented with the commercially available EC growth medium at both low and normal serum conditions, which suggests the potential of proanthocyanidin as an EC growth stimulator and an angiogenic reagent. In the second part of the thesis, mechanistic studies were performed by blocking both endothelial cell growth factor receptors (VEGFR) and epithelial cell growth factor receptors (EGFR). However, the blockers were ineffective in reducing the stimulatory effect of proanthocyanidin on EC. Therefore it is concluded that proanthocyanidin stimulates EC growth through membrane receptors other than VEGFR and EGFR. In the third part of the thesis, it was shown that proanthocyanidin could be loaded into polyvinyl alcohol cryogel and then released from the gel at a concentration within the effective dose window. This demonstrated the feasibility of drug releasing of proanthocyanidin. Finally, the angiogenic property of proanthocyanidin was tested in chick embryo chorioallantoic membrane (CAM) model, showing that this botanic drug was capable of stimulating vasculature development. Preliminary data in rat subcutaneous model also support the angiogenic potential of proanthocyanidin. This thesis therefore demonstrated for the first time that proanthocyanidin was capable of modulating the activity of human EC and in particular upregulating EC activity and growth in the absence of growth factors, and that proanthocyanidin may be used as an angiogenic reagent and released from a synthetic drug carrier. Consequently, this thesis has demonstrated that botanic drugs in traditional medicine may be used as substitutes of protein products to maintain cells in culture and to induce angiogenesis for wound healing and tissue regeneration

Fansubbing in China:Technology-facilitated activism in translation

This paper seeks to explore the socio-political tensions between freedom and constraints in the Chinese fansubbing networks. It approaches the development of fansubbing in China as a process of technology democratisation with the potential to liberate ordinary citizens from authoritarian and commercial imperatives, enabling them to contest official state domination. The paper draws on the strategies adopted by fansubbing groups to organise their working practices and interactive social activities with a view to engaging target audiences. Both facets complement each other and bring to the fore the ‘gamified’ system of fansubbing networks. Gamification enables ordinary citizens to translate, distribute and consume foreign audiovisual products in a strategic move that pits collective activism against government dominance.</jats:p

Ideological Manipulation of Controversial Information:The Unusual Case of the Chinese-subtitled Version of House of Cards

In recent years, owing to the spread of cultural and economic globalisation, Western values and ideologies have become increasingly accessible via media products to the general public in the People’s Republic of China (Mainland China, or China). Although translation enables the exchange of socio-cultural values and ideas across different languages and cultures, it is susceptible to manipulation in terms of political and ideological control. This paper examines interventions by Chinese authorities in the online distribution of foreign audio-visual products. Such interventions are undertaken to secure broadcasting and distribution rights of the government which also encompass more conventional media from other countries, such as television, in promoting mainstream ideological values and political agendas.  Censorship institutions supervise the selection of specific media products to be imported and translated for the Chinese market not only to ensure ease of comprehension but also for political correctness, with a view to avoid any clashes of cultures and ideologies. In the last decade, Chinese audiences have the rise of new media facilitating the wide-spread online viewing of foreign TV and thereby changing the dynamic of access and dissemination of foreign entertainment media in China. We argue that censorship institutions in China opt to adopt alternative strategies, or in many cases more relaxed criteria, in appraising foreign audiovisual products, in order to cater the demands of the new generation of Chinese audiences in those officially supervised media rather than suppressing their needs outright. We will dwell into the Chinese-subtitled version of the second season of the American political drama House of Cards (Netflix 2014), as released by Sohu, the largest online franchise in China. We consider the outcome of subtitling "honest" in terms of the exposure of sensitive information and controversial cultural and political allusions to the reality in contemporary China. By analysing possible reasons behind such “honest” exposure, we argue that an attempt at ideological manipulation has been made in this subtitled version, serving rather than subverting the political objectives of the Chinese government.

Astragaloside IV, a Novel Antioxidant, Prevents Glucose-Induced Podocyte Apoptosis In Vitro and In Vivo

Glucose-induced reactive oxygen species (ROS) production initiates podocyte apoptosis, which represents a novel early mechanism leading to diabetic nephropathy (DN). Here, we tested the hypothesis that Astragaloside IV(AS-IV) exerts antioxidant and antiapoptotic effects on podocytes under diabetic conditions. Apoptosis, albuminuria, ROS generation, caspase-3 activity and cleavage, as well as Bax and Bcl-2 mRNA and protein expression were measured in vitro and in vivo. Cultured podocytes were exposed to high glucose (HG) with 50, 100 and 200 µg/ml of AS-IV for 24 h. AS-IV significantly attenuated HG-induced podocyte apoptosis and ROS production. This antiapoptotic effect was associated with restoration of Bax and Bcl-2 expression, as well as inhibition of caspase-3 activation and overexpression. In streptozotocin (STZ)-induced diabetic rats, severe hyperglycemia and albuminuria were developed. Increased apoptosis, Bax expression, caspase-3 activity and cleavage while decreased Bcl-2 expression were detected in diabetic rats. However, pretreatment with AS-IV (2.5, 5, 10 mg·kg−1·d−1) for 14 weeks ameliorated podocyte apoptosis, caspase-3 activation, renal histopathology, podocyte foot process effacement, albuminuria and oxidative stress. Expression of Bax and Bcl-2 mRNA and protein in kidney cortex was partially restored by AS-IV pretreatment. These findings suggested AS-IV, a novel antioxidant, to prevent Glucose-Induced podocyte apoptosis partly through restoring the balance of Bax and Bcl-2 expression and inhibiting caspase-3 activation

Influence of Heat Treatment on the Morphologies of Copper Nanoparticles Based Films by a Spin Coating Method

We have investigated the influence of heat treatment on the morphologies of copper nanoparticles based films on glass slides by a spin coating method. The experiments show that heat treatment can modify the sizes and morphologies of copper nanoparticles based films on glass slides. We suggest that through changing the parameters of heat treatment process may be helpful to vary the scattering and absorbing intensity of copper nanoparticles when used in energy harvesting/conversion and optical devices

Ex Vivo Assay of Electrical Stimulation to Rat Sciatic Nerves: Cell Behaviors and Growth Factor Expression

Neurite outgrowth and axon regeneration are known to benefit from electrical stimulation. However, how neuritis and their surroundings react to electrical field is difficult to replicate by monolayer cell culture. In this work freshly harvested rat sciatic nerves were cultured and exposed to two types of electrical field, after which time the nerve tissues were immunohistologically stained and the expression of neurotrophic factors and cytokines were evaluated. ELISA assay was used to confirm the production of specific proteins. All cell populations survived the 48 h culture with little necrosis. Electrical stimulation was found to accelerate Wallerian degeneration and help Schwann cells to switch into migratory phenotype. Inductive electrical stimulation was shown to upregulate the secretion of multiple neurotrophic factors. Cellular distribution in nerve tissue was altered upon the application of an electrical field. This work thus presents an ex vivo model to study denervated axon in well controlled electrical field, bridging monolayer cell culture and animal experiment. It also demonstrated the critical role of electrical field distribution in regulating cellular activities

Magnolin Protects against Contrast-Induced Nephropathy in Rats via Antioxidation and Antiapoptosis

BACKGROUND: Magnolin is the major active ingredient of the herb Magnolia fargesii which has anti-inflammatory and antioxidative effects. Oxidative stress and apoptosis are involved in the pathogenesis of contrast-induced nephropathy (CIN). We hypothesize that Magnolin could protect against CIN through antioxidative and antiapoptotic properties. METHODS: To test whether Magnolin could attenuate CIN, oxidative stress and apoptosis, in vivo and in vitro, we utilized a rat model of ioversol-induced CIN and a cell model of oxidative stress in which HK2 cells were treated with H2O2. Rats were assigned to 4 groups (n = 6 per group): control group, ioversol group (ioversol-induced CIN), vehicle group (CIN rats pretreated with vehicle), and Magnolin group (CIN rats pretreated with 1 mg/kg Magnolin). RESULTS: The results showed that magnolin ameliorated the renal tubular necrosis, apoptosis, and the deterioration of renal function (P < 0.05). Furthermore, Magnolin reduced the renal oxidative stress, suppressed caspase-3 activity, and increased Bcl-2 expression in vivo and in vitro. CONCLUSION: Magnolin might protect CIN in rats through antioxidation and antiapoptosis

Effect of molecular distillation on the anti-inflammatory activity and neurotoxicity of Asarum essential oil

Asarum essential oil (AEO) has been shown to have good pharmacological activities for the anti-inflammatory and analgesic effects, but increasing the dose may cause toxicity. Therefore, we studied the toxic and pharmacodynamic components of AEO by molecular distillation (MD). Anti-inflammatory activity was assessed using RAW264.7 cells. Neurotoxicity was assessed in PC12 cells and the overall toxicity of AEO was evaluated in the mouse acute toxicity assay. The results showed that AEO is primarily composed of safrole, methyl eugenol, and 3,5-dimethoxytoluene. After MD, three fractions were obtained and contained different proportions of volatile compounds relative to the original oil. The heavy fraction had high concentrations of safrole and methyl eugenol, while the light fraction contained high concentrations of α-pinene and β- pinene. The original oil and all three fractions exhibited anti-inflammatory effects, but the light fraction demonstrated more excellent anti-inflammatory activity than the other fractions. Asarum virgin oil and MD products are all neurotoxic. The exposure of PC12 cells to high concentrations of AEO resulted in abnormal nuclei, an increased number of apoptotic cells, increased ROS formation, and decreased SOD levels. Moreover, the results of acute toxicity tests in mice revealed that the light fractions were less toxic than virgin oils and other fractions. In summary, the data suggest that the MD technology enables the enrichment and separation of essential oil components and contributes to the selection of safe concentrations of AEO