Irradiation (IR)-induced xerostomia is the most common side effect of radiation therapy in patients with head and neck cancer (HNC). Xerostomia diagnosis is mainly based on the patient\'s medical history and symptoms. Currently, no direct biomarkers are available for the early prediction of IR-induced xerostomia. Here, we identified PIEZO1 as a novel predictive tissue biomarker for xerostomia. Our data demonstrate that PIEZO1 is significantly upregulated at the gene and protein levels during IR-induced salivary gland (SG) hypofunction. Notably, PIEZO1 upregulation coincided with that of inflammatory (F4/80) and fibrotic markers (fibronectin and collagen fibers accumulation). These findings suggest that PIEZO1 upregulation in SG tissue may serve as a novel predictive marker for IR-induced xerostomia.

OBJECTIVE: Head and Neck Cancer (HNC) patients receiving radiotherapy (RT) often suffer from xerostomia and/or hyposalivation. As saliva plays an important antimicrobial and cleansing roles, these patients are at higher risks of opportunistic infections. This narrative review aims to provide an overview of current evidence on oral Candida colonisation and infection in these patients.
METHODS: A literature review of clinical studies on oral Candida colonisation and candidiasis in HNC patients receiving radiotherapy/chemoradiotherapy was conducted.
RESULTS: Many clinical studies found high levels of Candida colonisation and a substantial proportion of post-RT HNC patients suffering from oropharyngeal candidiasis (OPC). Importantly, oral Candida could be a reservoir for life-threatening systemic infection in immunocompromised patients. The rising prevalence of non-albicans Candida species and drug-resistant infections has made identification of Candida species and antifungal susceptibility more important. Recent advances in oral microbiome and its interactions with Candida are discussed. This review also offers perspectives on limitations of current evidence and suggestions for future research.
CONCLUSIONS: Further research to better understand Candida carriage, microbiome, OPC, and xerostomia/hyposalivation post-RT would aid in devising a more comprehensive long-term management plan and novel therapeutic approaches for HNC patients to achieve the full benefits of RT while minimising side effects.

OBJECTIVE: Xerostomia, a common complication of type 2 diabetes, leads to an increased risk of caries, dysphagia, and dysgeusia. Although anti-vascular endothelial growth factor (VEGF) antibodies, such as ranibizumab (RBZ), have been used to treat diabetic retinopathy, their effects on the salivary glands are unknown. This study evaluated the effects of RBZ on salivary glands to reduce inflammation and restore salivary function in a mouse model of type 2 diabetes.
METHODS: Male KK-Ay mice with type 2 diabetes (10-12 weeks old) were used. The diabetes mellitus (DM) group received phosphate-buffered saline, while the DM + RBZ group received an intraperitoneal administration of RBZ (100 μg/kg) 24 h before the experiment.
RESULTS: Ex vivo perfusion experiments showed a substantial increase in salivary secretion from the submandibular gland (SMG) in the DM + RBZ group. In addition, the mRNA expression levels of TNF-α and IL-1β were considerably lower in this group. In contrast, those of aquaporin 5 were substantially higher in the DM + RBZ group, as revealed by quantitative reverse transcription PCR. Furthermore, the number of lymphocyte infiltration spots in the SMG was notably lower in the DM + RBZ group. Finally, intracellular Ca2+ signaling in acinar cells was considerably higher in the DM + RBZ group than that in the DM group.
CONCLUSIONS: Treating a type 2 diabetic mouse model with RBZ restored salivary secretion through its anti-inflammatory effects.

Salivary gland biofabrication represents a promising avenue in regenerative medicine, aiming to address the challenges of salivary gland dysfunction caused by various factors such as autoimmune diseases and radiotherapy. This review examines the current state of bioprinting technology, biomaterials, and tissue engineering strategies in the context of creating functional, implantable salivary gland constructs. Key considerations include achieving vascularization for proper nutrient supply, maintaining cell viability and functionality during printing, and promoting tissue maturation and integration with surrounding tissues. Despite the existing challenges, recent advancements offer significant potential for the development of personalized therapeutic options to treat salivary gland disorders. Continued research and innovation in this field hold the potential to revolutionize the management of salivary gland conditions, improving patient outcomes and quality of life. This systematic review covers publications from 2018 to April 2024 and was conducted on four databases: Google Scholar, PubMed, EBSCOhost, and Web of Science. The key features necessary for the successful creation, implantation and functioning of bioprinted salivary glands are addressed.

COVID-19, a respiratory illness with a global impact on millions, has recently been linked to manifestations affecting various bodily systems, including the oral cavity. Studies highlight oral issues, like ulcers, blisters, and white patches, alongside olfactory and gustatory dysfunction, influencing an individual\'s quality of life. In this context, our study aimed to assess the frequency of oral lesions, olfactory and gustatory disorders, and xerostomia resulting from COVID-19. An observational study was conducted with 414 patients to evaluate the frequency of oral symptoms resulting from COVID-19. Patients were diagnosed with mild symptoms and evaluated through clinical examination of the oral cavity and a questionnaire to assess functional alterations. The findings showed that 139 out of 414 patients presented clinical manifestations, with oral lesions being the most prevalent (19.1%), followed by gustatory disorders (18.1%), xerostomia (14.2%), and olfactory dysfunction (14%). The most prevalent oral lesions were ulcerations (n = 51), candidiasis (n = 8), and erythema or red plaques (n = 7). Unfortunately, 50 (12.1%) patients died during this study. Therefore, oral lesions, olfactory and gustatory dysfunctions, and xerostomia are common symptoms associated with COVID-19.

Xerostomia emerges as a consequence of salivary gland hypofunction, and seriously compromises the integrity of hard and soft oral tissues, whileperiodontitis is an infectious disease characterized by biofilm accumulation, inflammation and alveolar bone resorption.
OBJECTIVE: The aim this study was to compare the deleterious effects caused by experimental hyposalivation, periodontitis, and the combination of both on periodontal tissues and mandibular biomechanics in rats.
METHODS: Hyposalivation (group H) was induced through bilateral submandibulectomy. Periodontitis (group EP) was induced by injecting LPS (1 mg/ml) into the gingiva of the first lower molars. A third group was subjected to both conditions (group H+EP). Alveolar bone loss was evaluated by micro-computed tomography and histomorphometric analysis, and gingival inflammatory mediators were assessed by specific techniques. Biomechanical properties were evaluated in mandible.
RESULTS: Alveolar bone loss increased similarly in groups H, EP and H+EP compared to control. Metalloproteinase (MMP2 and MMP9) activity was similar in H and control, but higher in groups EP and H+EP (MMP2: C 9644+2214, EP 34441+3336, H 5818+1532, H+EP 42673+3184; MMP9: C 5792+961, EP 14807+861, H 9295+520, H+EP 4838+1531). The rest of the inflammatory mediators evaluated increased in groups H, EP and H+EP to a greater or lesser extent with respect to the control, although in most cases, they were higher in groups EP and H+EP than in group H. The biomechanical properties of the mandible increased in group H compared to the other three groups.
CONCLUSIONS: Both hyposalivation and periodontitis cause periodontal damage, but hyposalivation also produces biomechanical alterations, causing more extensive deleterious effects than periodontitis.
La xerostomía surge como consecuencia de la hipofunción de las glándulas salivales y compromete seriamente la integridad de los tejidos orales duros y blandos, mientras que la periodontitis es una enfermedad infecciosa caracterizada por la acumulación de biofilm, inflamación y reabsorción ósea alveolar.
OBJECTIVE: El objetivo del presente estudio fue comparar los efectos deletéreos causados por la hiposalivación y la periodontitis experimental, y la combinación de ambas sobre los tejidos periodontales y la biomecánica mandibular en ratas.
UNASSIGNED: La hiposalivación (H) se indujo mediante una submandibulectomía bilateral. Por otra parte, la periodontitis (PE) se indujo mediante la inyección de LPS (1 mg/ml) en la encía de los primeros molares inferiores. Otro grupo se sometió a ambas condiciones (H+PE). La pérdida ósea alveolar se evaluó mediante tomografia microcomputarizada y análisis histomorfométrico, mientras que los mediadores inflamatorios gingivales fueron determinados mediante técnicas específicas. Se evaluaron las propiedades biomecánicas en la mandíbula.
RESULTS: La hiposalivación aumentó la pérdida ósea alveolar en comparación con el control de forma similar a la PE y H+PE. La actividad de las metaloproteinasas (MMP2 y MMP9) fue similar en los grupos H y control, pero resultó mayor en los grupos PE y H+PE (MMP2: C 9644+2214, PE 34441+3336, H 5818+1532, H+PE 42673+3184; MMP9: C 5792+961, PE 14807+861, H 9295+520, H+PE 24838+1531). El resto de los mediadores inflamatorios evaluados aumentaron en mayor o menor medida en los grupos H, PE y H+PE respecto al control, aunque en la mayoría de los casos fueron superiores en los grupos PE y H+PE respecto al grupo H. Sin embargo, las propiedades biomecánicas de la mandíbula aumentaron en el grupo H con respecto a los otros grupos.
CONCLUSIONS: Tanto la hiposalivación como la periodontitis causan daño periodontal, pero la hiposalivación también produce alteraciones biomecánicas, provocando efectos deletéreos más extensos que la periodontitis.

Patients undergoing palliative care often develop debilitating oral conditions, including xerostomia. These conditions may significantly impact patients\' quality of life. Despite the high prevalence and adverse impact of xerostomia, effective management strategies remain unclear. This scoping review was performed to elucidate effective interventions for xerostomia in patients undergoing palliative and end-of-life care. A comprehensive search strategy was employed to identify relevant studies up to August 2023. Full-text primary articles focusing on xerostomia in patients receiving palliative care were included in the review. Eleven articles were selected for analysis, and data were extracted by six reviewers. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Among the 11 studies, interventions ranged from oral care to saliva substitutes and methods to stimulate saliva secretion. The primary method of assessing xerostomia was the performance of subjective evaluations using visual analog scale scores or numerical rating scale scores. Various interventions including oral care regimens, topical treatments, and mixed efficacy outcomes were reported. Notably, only one study directly measured the saliva volume, highlighting a reliance on subjective endpoints in most studies. Although no definitive conclusions can be drawn regarding the most effective intervention, oral care was a preferred option for managing xerostomia in patients undergoing palliative care. Additionally, adjunctive treatments such as ice cubes, saline, and moisturizers showed promise but require further investigation. Objective measures should be incorporated into future intervention trials to complement subjective assessments and provide a comprehensive evaluation of xerostomia management strategies in this patient population.

BACKGROUND: Few studies have examined health related Quality of Life (HR-QoL) during the treatment of head and neck cancer (HNC) with even fewer focusing on the impact of oral mucositis (OM) on HR-QoL. Studies performed during treatment of HNC makes it possible to follow fluctuations in HR-QoL, OM and other treatment related side effects. The aim was to prospectively analyze HR-QoL, changes in clinical variables and the impact of OM on HR-QoL during HNC treatment.
METHODS: Patients were recruited before commencing curative cancer treatment and were given professional oral care weekly during oncologic treatment. HR-QoL was reported before, during (week 2, 4 and 6) and three months after treatment using the EORTC Quality of Life questionnaires C30 and H&N35 and the stimulated whole salivary secretion rate was determined at the same time-points. OM (erythema and ulceration) was registered using the Oral Mucositis Assessment Scale (OMAS), at baseline, weekly during treatment and post treatment. Differences in HR-QoL between different timepoints were analyzed. To analyze the impact of OM on HR-QoL the patients were categorized into two groups: no/mild OM (OMAS ulceration score 0-1) or severe OM (OMAS ulceration score ≥ 2) and HR-QoL was compared between the two OM groups at three timepoints during treatment.
RESULTS: Fifty-seven patients (43 men, 14 women), with a mean age of 58 years were included. Patients reported progressively impaired HR-QoL, with peak issues noted at weeks 4 and 6, particularly in social eating, senses, appetite loss, sticky saliva, and decreasing salivary secretion rates were determined. Patients with severe OM reported worse HR-QoL compared to those with no/mild OM. Persistent problems 3 months post treatment were appetite loss, dry mouth, senses (smell and taste) and problems with social eating.
CONCLUSIONS: Patients experienced exacerbated symptoms and problems weeks 4 and 6 of oncological treatment, especially among those with severe OM, stressing the importance of clinically monitoring the patients to reduce and alleviate their symptoms. Persistent problems three months post treatment are likely associated with the reduced salivary secretion rate indicating that patients should be monitored also after completed oncological treatment.

UNASSIGNED: Previous studies have shown that a calcium prerinse can increase intraoral fluoride retention from a fluoride rinse. To explore the potential of this approach to control root caries, we assessed intraoral fluoride bioavailability after a calcium prerinse in older adults with normal to low salivary flow rates.
UNASSIGNED: In a 2-period crossover trial (NCT04239872), 20 participants (65-80 y old), with low or normal salivary flow rate, rinsed for 1 min with a 0.05% NaF mouth rinse (226 ppm F, F only) or with this rinse immediately after a 1-min rinse with 150 mM calcium lactate (Ca→F). Dental biofilm and saliva samples were collected before and up to 2 h after the rinse(s). Fluoride concentrations in saliva (whole and clarified) and dental biofilm (fluid and solid phases) were blindly determined. Data were statistically analyzed by a mixed-effects model for the effect of treatment, time, and their interaction (α = 5%).
UNASSIGNED: The Ca→F group resulted in significantly higher fluoride concentrations in all variables analyzed, for almost all of the collection time points. The effect was greater in the biofilm solids and whole saliva (compatible with the formation of calcium fluoride deposits) and still significant (P < 0.001) after 2 h in the biofilm fluid and clarified saliva, suggesting that fluoride stored in insoluble particles was released, increasing free fluoride.
UNASSIGNED: The use of a calcium prerinse before a fluoride rinse was able to prolong intraoral fluoride bioavailability in older adults.
UNASSIGNED: A calcium prerinse increased intraoral fluoride bioavailability in older individuals. This approach could be used to improve root caries control without the need to increase the fluoride concentration in dental products.

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