Although SARS-CoV-2 induces mucin hypersecretion in the respiratory tract, hyposalivation/xerostomia has been reported by COVID-19 patients. We evaluate the submandibular gland (SMGs) pathogenesis in SARS-CoV-2-infected K18-hACE2 mice, focusing on the impact of infection on the mucin production and structural integrity of acini, ductal system, myoepithelial cells (MECs) and telocytes. The spike protein, the nucleocapsid protein, hACE2, actin, EGF, TNF-α and IL-1β were detected by immunofluorescence, and the Egfr and Muc5b expression was evaluated. In the infected animals, significant acinar hypertrophy was observed in contrast to ductal atrophy. Nucleocapsid proteins and/or viral particles were detected in the SMG cells, mainly in the nuclear membrane-derived vesicles, confirming the nuclear role in the viral formation. The acinar cells showed intense TNF-α and IL-1β immunoexpression, and the EGF-EGFR signaling increased, together with Muc5b upregulation. This finding explains mucin hypersecretion and acinar hypertrophy, which compress the ducts. Dying MECs and actin reduction were also observed, indicating failure of contraction and acinar support, favoring acinar hypertrophy. Viral assembly was found in the dying telocytes, pointing to these intercommunicating cells as viral transmitters in SMGs. Therefore, EGF-EGFR-induced mucin hypersecretion was triggered by SARS-CoV-2 in acinar cells, likely mediated by cytokines. The damage to telocytes and MECs may have favored the acinar hypertrophy, leading to ductal obstruction, explaining xerostomia in COVID-19 patients. Thus, acinar cells, telocytes and MECs may be viral targets, which favor replication and cell-to-cell viral transmission in the SMG, corroborating the high viral load in saliva of infected individuals.

Radiotherapy in patients with head and neck cancer fairly leads to xerostomia, profoundly affecting their quality of life. With limited effective preventive and therapeutic methods, attention has turned to exploring alternatives. This article outlines how intraglandular injection of mitochondria-boosting agents can serve as a potential strategy to reduce salivary acinar damage. This method can contribute to the thoughtful development of study protocols or medications to reduce radiation-induced salivary glands damage.

OBJECTIVE: Gargling mouthwash is a safe and convenient oral care intervention; it rinses the mouth and increases salivary flow rate. The effectiveness of lemon mouthwash in relieving xerostomia and increasing the salivary flow rate among hemodialysis patients has not been studied. Our study sought to analyze the effectiveness of varying concentrations of lemon in mouthwash solutions on xerostomia and salivary flow rate.
METHODS: A multi-concentration test was used to assess lemon mouthwash at 20%, 15%, 10%, 5%, and 2.5% concentrations to determine the optimal concentration for relieving dry mouth and increasing salivary flow rate. Generalized estimating equations were used to analyze the differences between various concentrations of lemon mouthwash and bassline values.
RESULTS: In total, 44 patients were recruited. The 10% lemon concentration mouthwash was the most effective for increasing salivary flow rate, but the 5% and 2.5% were better accepted by the participants. Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients.
CONCLUSIONS: Our findings can help establish intervention guidelines to relieve xerostomia among hemodialysis patients.

UNASSIGNED: Psychiatric patients suffer from oral diseases and side effects of antipsychotic medication. In particular, the typical antipsychotic drugs may cause severe hyposalivation with subsequent oral symptoms. We therefore aimed to compare oral health behavior and oral side effects of in-hospital patients taking typical vs. atypical antipsychotic drugs with the hypothesis that the former drugs cause more oral pain than the newer drugs.
UNASSIGNED: This cross-sectional questionnaire and interview study investigated subjective oral symptoms and their health behavior in 170 hospitalized psychiatric patients, comparing those taking typical vs. atypical antipsychotic drugs. Cross-tabulations and chi-square tests were used for analyses.
UNASSIGNED: Persistent oral pain lasting throughout the day was reported by 46% in the typical, and 5% in the atypical antipsychotic group patients, respectively. In both groups, the pain was mainly in the tongue and buccal mucosa and was described as a burning sensation. A significantly higher prevalence of xerostomia was reported in the typical antipsychotic medication group (66%) compared with the atypical antipsychotic medication group (53%, p<0.01). Self-assessed dental health was assessed as poor by two-thirds of the patients of whom 69% reported toothbrushing once daily. Approximately half of them reported having had a visit to a dentist within the previous year. Of the women 28%, and of the men 17%, respectively, had received professional consultations for oral symptoms.
UNASSIGNED: The current results on psychiatrically hospitalized patients emphasize the need for awareness of oral discomfort and its subsequent effects on the quality of life in this challenging patient group. Focus should also be placed on a wide range of support encouraging the patients to maintain good daily oral hygiene and seek professional dental help when needed.

UNASSIGNED: Diabetes Mellitus is a chronic disease characterized by uncontrolled blood sugar levels, which lead to end-organ damage. While the diagnosis and treatment of its complications have been extensively studied, the effect of Hyperbaric Oxygen Therapy (HBO2) on diabetes-related oral complications remains unexplored.
UNASSIGNED: This prospective clinical study aims to investigate the effect of HBO2 on diabetes-related oral complications.
UNASSIGNED: Twenty patients diagnosed with diabetic foot ulcers and scheduled for HBO2 were included in this study. We recorded stimulated and unstimulated saliva pH, buffering capacity, flow rate, and subjective symptoms such as dry mouth, halitosis, taste loss, difficulty swallowing, and clinical examination findings before HBO2 and after the 21st session.
UNASSIGNED: Upon comparing the findings, we observed a significant decrease in dry mouth and halitosis, periodontal disease severity, and healing of candida-related stomatitis and angular cheilitis. Despite not reaching statistical significance for other saliva parameters, the unstimulated salivary flow rate increased to normal limits (0.3-0.4 ml/min) in 6 out of 8 patients with a flow rate of less than 0.25 ml/min.
UNASSIGNED: Our study investigated the effect of HBO2 on diabetes-related oral complications for the first time, highlighting symptomatic relief for dry mouth and halitosis. Although our results are insufficient to report a definitive benefit, they underscore the need for further research on the oral health effects of HBO2.

BACKGROUND: Oral health problems have increased among older adults. Oral hypofunction is characterized by seven signs and symptoms: oral uncleanness, oral dryness, decline in occlusal force, decline in the movement function of the tongue and lips, decline in tongue pressure, decline in masticatory function, and decline in swallowing function, the latter being a significant risk factors for oral frailty. Recent research has suggested that salivary biomarkers can be used to assess not only oral diseases, including dental caries and periodontitis, but also systemic diseases, such as cancer and diabetes mellitus. This cross-sectional study investigated the relationship between oral hypofunction and the levels of salivary biomarkers.
METHODS: In total, 116 patients, aged 65 years or older, were included in this cross-sectional study. If three or more signs or symptoms in seven kinds of tests met the criteria of each test, oral hypofunction was diagnosed. The levels of biomarkers in the saliva collected from the patients were analyzed using an enzyme-linked immunosorbent assay.
RESULTS: In total, 63.8% of patients were diagnosed with oral hypofunction. Multivariable linear regression analysis showed that calprotectin levels in the saliva were significantly related to oral moisture and masticatory function. Furthermore, 8-OHdG levels in saliva were associated with the movement function of the tongue and lips and oral hygiene level, and salivary AGE correlated only with the movement function of the tongue and lips. Multiple logistic regression analysis revealed that calprotectin levels in the saliva were significantly correlated with the prevalence of oral hypofunction, even after adjusting for age, sex, and periodontal status. However, none of the biomarker levels in the saliva had a significant relationship with the number of examinations outside the reference range.
CONCLUSIONS: Calprotectin, 8-OHdG, and AGE levels are associated with oral hypofunction in older adults.

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.