Bibliographic record
Abstract
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
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.002 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".