Appareil digestif

Résumé

Le système digestif, appelé aussi appareil digestif, est l'ensemble des organes qui chez les êtres vivants a pour rôle d'assurer l'ingestion et la digestion des aliments pour en extraire l'énergie et les nutriments nécessaires à la survie de l'organisme qui sont ensuite absorbés par l'organisme. Ce système est essentiel à la vie des animaux et se retrouve nécessairement pour toutes les espèces. Le rôle de ce système biologique est également d'assurer l'excrétion des matières alimentaires qui n'ont pu être absorbées par l'organisme. Le système digestif varie de manière plus ou moins importante d'un animal à un autre. Ainsi il peut être très simple pour les organismes unicellulaires et les éponges où il n'y a pas de système digestif différencié et où la digestion des aliments se fait au sein même de leurs cellules, ou bien être différencié mais sans spécialisation comme chez les cnidaires et les vers plats où la digestion est assurée au sein de la cavité gastrovasculaire et où la bouch

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https://fr.wikipedia.org/wiki/Appareil_digestif

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Chargement

A new non-toxic chemically cross-linked ELP hydrogel for in situ protein delivery

Karine Ciapala

Proteins play an essential role in all biological processes and have been attracting more and more attention as drug candidates due to their high specificity and activity. However, their use as therapeutics has been seriously held back given that their ability to be effectively and conveniently delivered is problematic. Indeed, simple oral administration is ineffective since proteins are degraded in the digestive tract. Until now, these therapeutic agents were delivered by infusions or frequent injections. But this causes serious problems, as the compound does not get delivered in a prolonged continuous manner. Additionally, injections are also problematic as patients are reluctant to use needles unless there illness is life threatening. That is why focus has grown over the last years on developing novel delivery systems for proteins. Amongst the various types of delivery systems that exist, hydrogel based ones are very promising, as they possess remarkable biomimetic properties. The hydrogels that are chemically cross-linked are stronger than their counterparts, the physical hydrogels. An appealing approach to protein delivery that is more and more sought is to form the hydrogel in situ from an injected aqueous polymer solution and to use the formed gel as a depot for the sustained release of the protein. Oxygen sensitive gellation is an interesting stimulus to form these gels, but has not been successfully developed, as the gelling kinetics are too slow. Therefore, research groups have turned to the use of toxic chemicals to speed up the reaction. Elastin-like poylpeptides (ELP) are artificial biopolymers that are composed of a pentapeptide repeat. This repeat consists of Val-Pro-Gly-Xaa-Gly, where Xaa denotes a guest residue. An interesting characteristic of ELPs is that they are thermally responsive. Meaning, that when in solution they go through a lower critical solution temperature (LCST) transition. Below their LCST they are soluble in water and above their LCST they are insoluble. ELPs are well suited for drug delivery applications for many reasons such as their biocompatibility. The ELP that is studied is ELP9 Gel. Its guest residues are Val, Ala and Cys in a ratio of 1:14:1 respectively. As this ELP has cysteines it has the capacity to form a gel via cross-linking of the thiols groups by oxidation. The rheological tests that were carried out showed that this ELP9 Gel has all the characteristics of a gel. Furthermore, its gelling kinetics were greatly increased by heating it, but still remain too long for in situ applications. This suggests that the LCST behaviour of ELPs seems to play some role in favouring the cross-linking. But further controls remain to be done to confirm this hypothesized tandem process. A delivery strategy that involved this ELP9 Gel and Blue Fluorescent Proteins (BFP) with added cysteines was not successful as the molecular biology to obtain the modified proteins failed. However, the elaboration of a fusion peptide between Glucagon-Like-Peptide-1 (GLP-1) and ELP9 Gel was accomplished. The preliminary activity assay showed a reduced activity in comparison to the GLP-1 peptide alone. Unfortunately this ELP9 Gel has a setback due to its slow gelling time. Therefore, before continuing the research on the delivery strategies, it would be wiser to create a better ELP. If a new ELP with a higher cysteine concentration and lower transition temperature can be created, its gelling kinetics may be favourable for in situ protein delivery applications and thus, a chemically cross-linked hydrogel that does not require any toxic cross-linker would be available. This would be a big step in creating a very robust hydrogel for protein delivery applications but also for tissue regeneration

2009

Chargement

Table d'alimentation à induction- Gestion d'énergie

Alexis Heraïef

Le présent projet porte sur la réalisation de l'alimentation et des interrupteurs. La détection des charges est le cadre d'un autre projet . Le dimensionnement du circuit magnétique du transformateur n'a pas encore été abordé.

2008

Chargement

Bile acids (BAs) are small molecules synthesized by the host and chemically modified by the microorganisms inhabiting the intestinal tract. The microbial transformation of BAs in the gut is critical to BA-mediated signaling as it modifies their amount and affinity for specific BA receptors. Bile acid 7-dehydroxylating bacteria are intestinal commensals of particular importance as they catalyze the dehydroxylation of liver-derived (primary) bile acids at the C7 position (i.e., 7-dehydroxylation) and produce secondary bile acids. One of the major receptors for secondary BAs is Takeda G-protein receptor 5 (TGR5), and it is associated with regulation of energy expenditure and glucose management, protection from liver steatosis and inflammation. In addition, 7-dehydroxylated bile acids are also associated with protection from infection by specific intestinal pathogens (i.e., Clostridioides difficile). Thus, through their action on primary BAs, 7-dehydroxylating (7-DH-ing) bacteria play an important role in health promotion and in the functioning of major physiological processes in the body such as insulin secretion, thermogenesis and immune responses. Despite these potentially important roles in the mammalian host, bile acid 7-dehydroxylating bacteria are poorly studied and much remains to be deciphered regarding their metabolism, diversity, abundance in the gut, and colonization dynamics in the host. Here, we use Clostridium scindens, as model organism to study bile acid 7-dehydroxylation in vitro and in gnotobiotic mice. We found that C. scindens metabolize only human primary bile acids (CA and CDCA). We uncovered the formation of a novel intermediate during CA 7-dehydroxylation by C. scindens in vitro: 12-oxoLCA. In vivo, using NanoSIMS and metabolomic analysis, we demonstrated that the large intestine constitutes C. scindens primary ecological niche in gnotobiotic mice. Following up on the discovery of the 12oxoLCA, we hypothesized the existence of another 7-dehydroxylation pathway for cholic acid. We postulated that it may involve the B and C rings of the steroid structure and may entail the oxidation/reduction of the C12- hydroxyl group. Thus, it was dubbed the putative vertical pathway. Conducting in vitro enzymatic assays with purified enzymes, we confirmed the existence of this novel vertical biosynthetic 7-dehydroxylation pathway for cholic acid, the most abundant primary bile acid in humans, and identified the core of enzymes necessary and sufficient for CA 7-dehydroxylation. Furthermore, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Additionnally, we also considered the bile acid profile in mice with more complex microbiota or with no microbiota. By comparing the bile acid profile of the different mice models along with expression of key genes of bile acid synthesis, we emphasized the profound influence of the gut microbial community on BA pool homeostasis. Altogether, our data provides a significant contribution to our collective understanding of the microbiology of bile acid 7-dehydroxylating bacteria, a group of gut commensals highly relevant to host health but that remains poorly characterized. The discovery of a novel 7-dehydroxylation pathway is a major scientific achievement of this thesis.

EPFL2020

Chargement

A new non-toxic chemically cross-linked ELP hydrogel for in situ protein delivery

Karine Ciapala

2009

EPFL2020