Notice bibliographique
Résumé
ABSTRACTSalivary hypofunction, also known as xerostomia, is a major side effect of radiotherapy for head and neck cancer patients. Current treatments of irradiation (IR)-injured salivary glands (SGs) remain palliative. Our previous studies showed that mouse bone marrow cell extract (BMCE) could restore the secretory function of IR-injured SGs and that native proteins in BMCE were the main effective ingredients for the treatment. However, BMCE therapy requires multiple injections and protein denaturation is a concern during BMCE storage. The first aim of this thesis was to preserve, by lyophilization (freeze-drying), the bioactive factors in BMCE. We developed a method to freeze-dry BMCE and then to analyze its ingredients and functions in vivo. Results showed that the presence of angiogenesis-related factors and cytokines in freeze-dried (FD) BMCE remained comparable to those found in fresh BMCE. Both fresh and FD-BMCE restored comparably saliva production, protected salivary acinar cells, parasympathetic nerves, and blood vessels, increased cell proliferation, upregulated regenerative/repair genes in the irradiation-damaged salivary glands. Lyophilization of BMCE maintained its bioactivity and therapeutic effect on irradiation-injured salivary glands. A mouse bone marrow cell extract could restore salivary secretory function to irradiation-injured mice. However, the components and therapeutic effects of human BMCE remain unknown. In addition, the whole bone marrow consists of heterogeneous cells, including red blood cells (RBCs), granulocytes (GCs), and mononuclear cells (MCs). This increases the complexity of the cell extract and consequently, increases the difficulties in identifying and analyzing the effective proteins in the cell extract. The second aim of this thesis was to test the therapeutic effect of the cell extract from human bone marrow (BMCE) and to test whether the effect observed could be from a specific cell sub-population on IR-injured SGs. Results showed that BMCE and cell extract of RBCs, GCs and MCs (RBCE, GCE, MCE) contained various proteins/growth factors. MCE treatment provided the best therapeutic effect, and BMCE therapy could also restore the function of SGs, while RBCE treatment did not improve the secretory production when compared with the negative control group. Studies suggest that tissue-specific cells may be more suitable for treating their original tissues/organs. Furthermore, the procedure of BM cell harvesting remains invasive and in severe cases, could even lead to life-threatening complications. Therefore, the third objective of this thesis was to test if human labial gland stem cells (LSCs) could be used as an alternate source of cell extract for the repair of IR-injured SGs. Results demonstrated that several angiogenesis-related factors were detected in LSCE. LSCE treatment restored 50%-60% of saliva secretion, protected acinar cells, blood vessels and parasympathetic nerves, promoted cell proliferation, and up-regulated the expression of tissue repair/regeneration proteins and genes. In summary, lyophilization is a reliable approach to preserve the bioactive ingredients of BMCE in a powder form for long-term storage. Human BMCE, GCE and MCE successfully restored IR- induced salivary hypofunction and MCE provided the best therapeutic effect. LSCE was also an effective treatment in repairing irradiated-SG in the mouse model. These treatments showed the clinical potential to mitigate irradiated SGs
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».