Radiotherapy is commonly used in patients with head and neck cancer, and usually results in irreversible salivary glands damage and hypofunction. It is therefore important to manage such irradiation to prevent damage to the salivary glands. A previous study showed that Lactoferrin (LF) has a radioprotective effect, but the mechanism was not determined in salivary glands. In the present study, we investigated the detailed radioprotective effect of LF using both ex vivo submandibular salivary gland organ culture and ICR male mice in vivo. We found that LF had effects on both cell proliferation and CyclinD1-mediated cell-cycle progression which were regulated via the ERK1/2 and AKT signal transduction pathways. In addition, LF affected acinar cell structure and function after irradiation. These findings suggest that LF may be a useful agent to prevent irradiation effects in salivary glands.

Summary Background Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of partial or complete upper airway collapse during sleep and is highly prevalent in the general population. The nasopharyngeal airway stent (Nastent) is a specifically designed, preformed silicone tube that intends to maintain the upper airway patency during sleep and reduce snoring and sleep apnoea. Objective(s) The purpose of this study was to determine the efficacy of Nastent treatment and examine predictors for Nastent treatment outcomes in patients with OSA. Methods Consecutive thirty patients were enrolled in this study. Cephalometric radiographs were obtained to analyse the pharyngeal and craniofacial morphology. Before and after Nastent treatment, we evaluated OSA using a portable sleep study. Results Twenty‐nine subjects completed this study. There were significant decreases in the respiratory event index (REI) (22.4 ± 14.1 to 15.7 ± 10.4, P < 0.01) and a significant increase in the lowest SpO2 (81.9 ± 7.5 to 86.6 ± 4.8, P < 0.01) by Nastent treatment. Subjects were divided into responders and non‐responders based on reduction in REI of >50% compared with baseline REI. We evaluated the ratio of inferior airway width and middle airway width (IAW/MAW) on cephalograms as the index of the narrowest airway site. The IAW/MAW was significantly higher in responders than in non‐responders (1.4 ± 0.9 vs 0.9 ± 0.4, P < 0.01) and predicted treatment responders with high accuracy (sensitivity: 90.9%, specificity: 88.9%, when IAW/MAW was set at 1.10). Conclusions The Nastent device improved OSA, and a narrower velopharynx than hypopharynx predicted treatment response with a good sensitivity and specificity.

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Development of the salivary gland is characterized by extensive branching morphogenesis. Although various molecules have been implicated in salivary gland development, the role of the mammalian target of rapamycin (mTOR) signalling pathway, including both mTOR complexes 1 and 2 (mTORC1 and 2), in salivary gland development is unknown. Here, we examined protein expression levels related to the mTOR signalling pathway using an ex vivo submandibular salivary gland (SMG) organ culture. We showed that branching buds in the salivary glands were substantially decreased and phosphorylation of mTORC1 signalling pathway related proteins (mTOR, p70 ribosomal protein S6 kinase 1 and eukaryotic initiation factor 4E‐binding protein 1) was inhibited by rapamycin (an mTOR inhibitor). In addition, AKT, which is an upstream protein kinase of mTORC1 and is downstream of mTORC2, is inhibited by LY294002 (a phosphatidylinositol 3‐kinase inhibitor), but not by rapamycin. Moreover, rapamycin‐treated ICR neonatal mice exhibited a reduction in both body weight and salivary glands compared with vehicle‐treated neonatal mice. The present data indicate that the mTOR signalling pathway, including both mTORC1 and mTORC2, plays a critical role in salivary gland development both in ex vivo SMG organ culture and ICR neonatal mice in vivo.

The transcription factor p63, a component of the p53 family, has important functions in development, homeostasis, and regeneration of epithelial tissues. However, the role of p63 in the regeneration of exocrine glands, including the salivary glands (SGs), has not been fully investigated. We investigated p63 expression in SG regeneration induced by duct ligation and irradiation. The expression of DNp63, a p63 isoform, increased and was colocalized with keratin 5 positive cells were myoepithelial cells. Furthermore, DNp63 expression was regulated by FGF7 stimulation via p38 MAPK phosphorylation and affected SG morphogenesis. These results suggest that DNp63 is essential for SG regeneration and may be a new target for regenerative treatment.