We evaluated the epidemiological and clinical factors related to the complications and failure of sialoendoscopy.

This retrospective study analyzed the medical records of patients who underwent sialoendoscopy between 2010 and 2019.

Of the 174 sialoendoscopies analyzed, 125 (71.8%) were performed in women, and 114 (65.5%), in the parotid gland. The most prevalent complications described were false path (4.59%) and restenosis (2.30%). Complications in the submandibular gland were 3.43 times more common than those in the parotid gland and procedures in that gland were less successful (86.7% vs. 91.2%). Sialolithiasis treatment was most strongly associated with complications and failure then the other groups.

Sialoendoscopy has uncommon and limited complications. Procedures in the submandibular gland and for sialolithiasis treatment were more likely to result in complications and recurrences.

Dental fear and anxiety are frequently identified as major contributing factors to non-compliance, uncooperativeness, and difficulties during dental procedures in pediatric patients. These issues can lead to avoidance of dental treatment, resulting in long-term negative consequences for oral health and overall well-being. The assessment and quantification of psychological functioning (i.e., dental fear, anxiety, and self-perceived stress) has traditionally relied on self-reported questionnaires validated for the pediatric population. While this approach is cost-effective and non-invasive, it relies on subjective self-reported data, oftentimes influenced by parental or guardian interaction, especially in young children. Salivary diagnostics has recently emerged as an objective method for the procurement of biological molecules that serve as biomarkers for a variety of oral and systemic conditions. This literature review aims to comprehensively summarize the available literature on the correlation between psychological and salivary physiological measurements assessing dental fear, dental anxiety, and self-perceived stress in pediatric dental patients, highlighting the advantages and disadvantages of each method of assessment. Four databases (PubMed®, PsycInfo, Dentistry & Oral Sciences Source, and Web of Science) were searched for published articles, in the English language, assessing the correlation between psychological and physiological distress in children undergoing dental procedures. Studies on pediatric patients reveal positive correlations between salivary cortisol and dental fear, stress, and anxiety, especially in returning patients. Conversely, findings on salivary alpha-amylase and secretory immunoglobulin A were inconsistent, with some studies suggesting correlations with dental fear and prior dental experiences.

This systematic review examined the saliva composition of healthy children from birth to 18 years of age by assessing the salivary flow rate, pH, buffering capacity, and ion levels. This review followed the PRISMA guidelines. A systematic search was performed using PubMed, the Cochrane Library, and Scopus. Information regarding the salivary flow rate, pH, buffering capacity, and ion levels in whole saliva was systematically collected, and a qualitative synthesis was performed. The methodological quality of the studies was assessed using the JBI Critical Appraisal Tools.

Of the 3,268 retrieved studies, 41 were eligible for inclusion. Unstimulated salivary flow showed an age-related decrease, whereas stimulated salivary flow increased with age. The pH of the saliva remained consistent across different ages, whereas the buffering capacity showed an age-related increase. Salivary sodium, calcium, and potassium levels were lower in the younger children than in the older children. An investigation of salivary ion levels revealed lower average fluoride concentrations in Asian populations than in European populations. Most studies had a low or moderate risk of bias.

This systematic review highlights age-dependent differences in salivary flow and composition in healthy children from birth to 18 years of age. The flow rate of unstimulated saliva decreased with age, while the flow rate of stimulated saliva increased. The salivary pH remained stable, whereas the buffering capacity increased with age. Furthermore, salivary sodium, calcium, and potassium levels tend to increase with age. These findings underscore the dynamic nature of salivary composition from childhood to adolescence.

Background/Objectives: BuZhong Yiqi Formula (BZYQF) has significant ameliorative effects on type 2 diabetes mellitus (T2DM). However, its efficacy in alleviating the hyposalivation caused by T2DM needs to be confirmed, and its mechanism is unclear. Methods: Network pharmacology and molecular docking were combined to analyze the molecular mechanism by which BZYQF alleviates T2DM-caused hyposalivation. A T2DM rat model was induced to evaluate the efficacy of BZYQF. The total saliva before and after acid stimulation was collected to determine the salivary flow rate and salivary alpha-amylase (sAA) activity. The parotid (PG) and submandibular glands (SMG) of experimental rats were removed to perform histopathology observation, biochemical indicator determination, and expression detection of signaling molecules in the salivary secretion pathway. Results: The present study screened out 1014 potential targets of BZYQF regarding the treatment of T2DM. These targets were mainly involved in the formation of the receptor complex, exercising the neurotransmitter receptor activity and regulating secretion. They were significantly enriched in the salivary secretion pathway of β1-AR/PKA/AMY1 and CHRM3/IP3R/AQP5. Furthermore, in BZYQF, nine validated compounds were able to dock into the active site of β1-AR, and three validated compounds were able to dock into the active site of CHRM3. Animal experiments confirmed that BZYQF significantly reduces fasting blood glucose, total cholesterol and triglyceride levels; enhances insulin level and HOMA-IS (p < 0.05); and increases salivary flow rate (Basal: increase from 21.04 ± 14.31 to 42.65 ± 8.84 μL/min, effect size of Cohen's d = 6.80, p = 0.0078; Stimulated: increase from 36.88 ± 17.48 to 72.63 ± 17.67 μL/min, effect size of Cohen's d = 7.61, p = 0.0025) and sAA activity (Basal: increase from 0.68 ± 0.32 to 2.17 ± 0.77 U/mL, effect size of Cohen's d = 9.49, p = 0.0027; Stimulated: increase from 1.15 ± 0.77 to 4.80 ± 1.26 U/mL, effect size of Cohen's d = 13.10, p = 0.0001) in basal and stimulated saliva in T2DM rats. Further mechanistic studies revealed that BZYQF reduces glucose and lipid accumulation, enhances acetylcholine content, improves pathological lesions and inflammation, and significantly increases the expression of salivary secretion pathway signaling molecules, including PKA, IP3R, β1-AR, AQP5, CHRM3, and AMY1 in the PG and SMG of T2DM rats (p < 0.05). Conclusions: The present study demonstrated that BZYQF is able to alleviate T2DM-caused hyposalivation by improving glucose metabolism and activating the salivary secretion pathway in the PG and SMG of T2DM rats. This study might provide a novel rationale and treatment strategy for BZYQF in diabetes-induced hyposalivation in a clinical setting.

This study pioneers the application of the ViPLUS module, utilizing plane-wave ultrasound to measure breast tissue viscosity and elasticity. The primary goal was to establish normal reference values for viscosity in healthy women. Secondary objectives included exploring correlations between breast tissue viscosity and breast density categories, hormonal influences, and menstrual cycle phases.

A prospective study was conducted on 245 asymptomatic women. Viscosity and elasticity measurements were obtained using the ViPLUS module, ensuring high reliability with stringent quality control measures. Data were statistically analyzed to evaluate correlations and group differences.

The median viscosity value for normal breast parenchyma was 1.7 Pa.s, with no significant variations based on breast density, menopausal status, or menstrual cycle phase. A strong correlation (rho = 0.866, p < 0.001) was observed between elasticity and viscosity values.

The findings suggest that breast viscosity is consistent across diverse physiological states, indicating its potential as an independent diagnostic marker. This parameter could be pivotal in future breast cancer screening strategies, especially for younger women and those with dense breasts.

To address the lack of nerve and blood supply after labial salivary gland transplantation (LSGT) resulting in glandular atrophy. We designed a modified LSGT, called insular infraorbital neurovascular pedicle LSGT, and evaluated the postoperative efficacy.

This is a prospective, single-centre, self-contained study.

The research was conducted at Beijing Tongren Hospital, Capital Medical University from July 2019 to March 2024.

Eight patients (nine eyes) with severe dry eye disease (DED) were enrolled in this study.

All patients underwent insular infraorbital neurovascular pedicle LSGT and were followed up for at least 6 months postoperatively.

Key evaluation indices were best-corrected visual acuity (BCVA), Ocular Surface Disease Index (OSDI) score, tear break-up time (TBUT), Corneal Fluorescence Staining (CFS) score, and Schirmer I test (SIT).

With a mean follow-up of 17.56±11.72 months, BCVA improved in four eyes and stabilized in five. OSDI score decreased from 59.33±14.37 to 26.27±10.14 (p<0.001). SIT improved from 0.00±0.00 mm to 5.44±2.01 mm (p<0.0001). TBUT increased from 0.23±0.48 s to 5.48±4.67 s (p=0.008). CFS scores decreased from 12.56±2.65 to 7.56±3.09 (p<0.001). All glands remained viable with good blood supply, and no serious complications were observed.

Insular infraorbital neurovascular pedicle LSGT for severe DED is a feasible and effective treatment, maintaining good secretory capacity and blood supply long-term.

ChiCTR2200056015.

This case report aimed to characterize primary pleomorphic adenoma cells obtained from a parotid gland tumor through tissue biopsy, primary cell culture, and immunohistochemical analysis.

A tissue biopsy sample from a 58-year-old patient with pleomorphic adenoma underwent histopathological examination and primary cell culture. The primary cells were characterized through immunohistochemical staining using antibodies against S-100, SMA, Vimentin, and cytokeratin AE1/AE3. Additionally, paraffin-embedded tissue sections were stained using cytokeratin AE1/AE3, Vimentin, Calponin, SMA, S100, and p63.

Primary cell culture revealed weak S-100 staining and positive SMA in myoepithelial cells, while Vimentin and AE1/AE3 were negative in all the cell population. In the paraffin-embedded tissue, cytokeratin exhibited strong cytoplasmic and membranous positivity in luminal cells. Vimentin showed cytoplasmic staining in myoepithelial cells. S-100 displayed weak nuclear and strong cytoplasmic immunoreactivity in myoepithelial cells. SMA presented weak membranous positivity in a few myoepithelial cells, and finally, p63 showed nuclear staining in abluminal cells. Calponin showed negative staining in neoplastic cells and stroma.

The results showed that primary component of pleomorphic adenoma comprises myoepithelial cells. The identification of cell cultured in vitro is pivotal in comprehending the cellular components of these neoplasms. This comprehensive characterization of primary pleomorphic adenoma cells provides insights into their morphology, immunophenotype, and histological features.

No permanent cure exists for salivary gland (SG) damage and consequent xerostomia (dry mouth) in patients undergoing radiotherapy for head and neck cancers. The lack of commercially available healthy human SG-derived cell lines has hindered in vitro studies of radiation-induced glandular injury. In this study, we successfully immortalized and characterized two novel human major SG-derived cell lines. Leveraging these cell lines and hyaluronic-acid hydrogels, we bioengineered distinct multicellular SG spheroids and microtissues expressing key acinar, ductal, myoepithelial, and mesenchymal cell markers in long-term cultures. Further, using this platform, we developed a proof-of-concept radiation injury model, demonstrating spheroid disruption characterized by actin depolymerization, DNA damage, apoptosis, and loss of SG-specific markers following radiation exposure. Notably, these detrimental effects were partially mitigated with a radioprotective agent. Our findings demonstrate that the bioengineered SG spheroids provide a scalable and versatile platform with significant potential for disease modeling and drug testing, thereby accelerating the development of targeted therapies for radiation-induced xerostomia.

Hyperlipidemia is a risky condition that can lead to atherosclerosis and other cardiovascular problems. Statins are used to treat hyperlipidemia. The most recommended medicine to treat hyperlipidemia is atorvastatin. On the contrary, clinical trials validated statins' negative effects. Omega-3 fatty acids have antioxidant properties and have been shown to improve a variety of disease processes in the general population, including inflammatory and immunological pathways, various cardiovascular diseases, and lipid regulation. The present research aimed to determine how atorvastatin affected the submandibular salivary gland (SMG) and whether omega-3 may have a protective impact.

Thirty adult male albino rats were divided into three equal groups and received drugs orally as a single daily dose for one week. Control group (I): received normal saline. Atorvastatin group (II): received a dose of 80 mg Kg-1 of Atorvastatin. Group III: received Omega-3 before Atorvastatin. All rats were sacrificed 2 h following the last dose, and blood samples were gathered for the biochemical study of fasting blood glucose level (FBGL). Specimens were obtained and processed for histological and histochemical studies.

Atorvastatin-treated rats showed degeneration of SMG acini. The acinar cells showed cytoplasmic vacuoles with dilated RER. Histochemical results revealed a marked decrease in total proteins. The biochemical study revealed an elevation in FBGL. The administration of Omega-3 with Atorvastatin minimizes these changes.

Atorvastatin has been proven to induce histological changes in SMG, and these changes can be attenuated by Omega-3. However, Omega-3 has no effect on FBGL.

Primary Sjögren's syndrome (pSS) is a chronic autoimmune disease primarily affecting exocrine glands such as the salivary glands, leading to impaired secretion and sicca symptoms. As the mainstay of salivation, salivary gland epithelial cells (SGECs) have an important role in the pathology of pSS. Emerging evidence suggests that the interplay between immunological factors and SGECs may not be the initial trigger or the sole mechanism responsible for xerostomia in pSS, challenging conventional perceptions. To deepen our understanding, current research regarding SGECs in pSS was reviewed. Among the extensive aberrations in cellular architecture and function, this review highlighted certain alterations of SGECs that were identified to occur independently of or in absence of lymphocytic infiltration. In particular, some of these alterations may serve as upstream factors of immuno-inflammatory responses. These findings underscore the significance of introspecting the pathogenesis of pSS and developing interventions targeting SGECs in the early stages of the disease.

In several cases, a person can have an abnormal mass in the outer mandible or under the tongue and is usually accompanied with the decrease of saliva. Early and accurate examination is needed to diagnose this case. In this case report, we present two cases of salivary glands defect. The aim of this article is to submit two cases to review the etiology, risk factors, clinical manifestation, and examination methods of sialadenitis using a modified contrast injector to the duct of salivary gland. CASE 1: A 17-year-old man came with a complaint of a lump under the right jaw. Sialography examination using a modified syringe with abbocath 24G showed an occlusion of the right and left Warton duct stoma. Right and left Bartholin's duct stoma occlusion post excision and marsupialization of the ranula. The complaint felt shrink after sialography. Three months follow-up, the patient said the lump was no longer felt and there were no complaints. CASE 2: A 19-year-old man came with a complaint of clear fluid coming out when eating on the surgical scar under the right side of the jaw. From the plain photo, it appears that there is a missing amputatum of the right mandibular symphysis, body, angle, ramus processus condylaris et coronoideus of the left mandible. Sialography examination using a modified syringe with abbocath 24G showed suggest a sialocutaneous fistula (cut of the right mandibular ramus region to Stensen's duct and submandibular). Then the patient underwent fistula excision. A month follow-up after the excision patient had no feeling of lump but sometimes 3-4 drops still came out.

Salivary tract injury is a quite rare case. Most frequent etiologies are iatrogenic. Sialography is a simple but effective method to identify obstruction of the salivary tract, including salivary tract injury. According to several studies, sialography identifies sialolithiasis with high sensitivity and specificity.

Sialography is a simple but effective method that is beneficial for the treatment and examination with high specificity and sensitivity to assess the possibility of obstruction of the salivary ducts.

The cat represents an important model in order to investigate basic physiological knowledge of salivary secretion as well as pharmacokinetics of active substances.

The aim of the study was to review in which diagnostic application areas saliva testing is routinely used and in which areas it could be further explored in the future.

Literature relevant to the research question was collected in March 2022 using the Pubmed database.

The diagnosis of infectious diseases in cat saliva is one of the most important fields of application. Saliva diagnostics may also indicate dental diseases, allergies or kidney and other metabolic diseases. Sexual and stress hormones can also be measured in cat saliva. A number of clinically relevant allergens in cat saliva that may cause allergies in humans has been investigated and described, in addition to infectious agents that can be transmitted from cats to humans.

Saliva testing in cats can be useful in many areas, including the detection of infectious diseases, allergies and dental disease. However, it is far from being used to its full potential within veterinary medicine.

The exocrine salivary gland secretes saliva, a fundamental body component to maintain oral homeostasis. Saliva is composed of water, ions, and proteins such as amylase, mucins, and immunoglobulins that play essential roles in the digestion of food, lubrication, and prevention of dental caries and periodontitis. An increasing number of people experience saliva hyposecretion due to aging, medications, Sjögren's syndrome, and radiation therapy for head and neck cancer. However, current treatments are mostly limited to temporary symptomatic relief. This review explores the molecular mechanisms underlying saliva secretion and hyposecretion to provide insight into putative therapeutic targets for treatment. Proteins implicated in saliva secretion pathways, including Ca2+ -signaling proteins, aquaporins, soluble N-ethylmaleimide-sensitive factor attachment protein receptors, and tight junctions, are aberrantly expressed and localized in patients with saliva hyposecretion, such as Sjögren's syndrome. Analysis of studies on the mechanisms of saliva secretion and hyposecretion suggests that crosstalk between fluid and protein secretory pathways via Ca2+ /protein kinase C and cAMP/protein kinase A regulates saliva secretion. Impaired crosstalk between the two secretory pathways may contribute to saliva hyposecretion. Future research into the detailed regulatory mechanisms of saliva secretion and hyposecretion may provide information to define novel targets and generate therapeutic strategies for saliva hyposecretion.

Salivary gland hypofunction (SGH) caused by systemic disease, drugs, aging, and radiotherapy for head and neck cancer can cause dry mouth, which increases the risk of disorders such as periodontitis, taste disorders, pain and burning sensations in the mouth, dental caries, and dramatically reduces the quality of life of patients. To date, the treatment of SGH is still aimed at relieving patients' clinical symptoms and improving their quality of life, and is not able to repair and regenerate the damaged salivary glands. Pluripotent stem cells (PSCs), including embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and extended pluripotent stem cells (EPSCs), are an emerging source of cellular therapies that are capable of unlimited proliferation and differentiation into cells of all three germ layers. In recent years, the immunomodulatory and tissue regenerative effects of PSCs, their derived cells, and paracrine products of these cells have received increasing attention and have demonstrated promising therapeutic effects in some preclinical studies targeting SGH. This review outlined the etiologies and available treatments for SGH. The existing efficacy and potential role of PSCs, their derived cells and paracrine products of these cells for SGH are summarized, with a focus on PSC-derived salivary gland stem/progenitor cells (SGS/PCs) and PSC-derived mesenchymal stem cells (MSCs). In this Review, we provide a conceptual outline of our current understanding of PSCs-based therapy and its importance in SGH treatment, which may inform and serve the design of future studies.

Tight junctions (TJs) are cell-cell interactions that localize at the most apical portion of epithelial/endothelial cells. One of the predominant functions of TJs is to regulate material transport through paracellular pathway, which serves as a selective barrier. In recent years, the expression and function of TJs in salivary glands has attracted great interest. The characteristics of multiple salivary gland TJ proteins have been identified. During salivation, the activation of muscarinic acetylcholine receptor and transient receptor potential vanilloid subtype 1, as well as other stimuli, promote the opening of acinar TJs by inducing internalization of TJs, thereby contributing to increased paracellular permeability. Besides, endothelial TJs are also redistributed with leakage of blood vessels in cholinergic-stimulated submandibular glands. Furthermore, under pathological conditions, such as Sjögren's syndrome, diabetes mellitus, immunoglobulin G4-related sialadenitis, and autotransplantation, the integrity and barrier function of TJ complex are impaired and may contribute to hyposalivation. Moreover, in submandibular glands of Sjögren's syndrome mouse model and patients, the endothelial barrier is disrupted and involved in hyposecretion and lymphocytic infiltration. These findings enrich our understanding of the secretory mechanisms that link the importance of epithelial and endothelial TJ functions to salivation under both physiological and pathophysiological conditions.

Salivary gland dysfunction affects millions globally, and tissue engineering may provide a promising therapeutic avenue. This review delves into the current state of salivary gland tissue engineering research, starting with a study of normal salivary gland development and function. It discusses the impact of fibrosis and cellular senescence on salivary gland pathologies. A diverse range of cells suitable for tissue engineering including cell lines, primary salivary gland cells, and stem cells are examined. Moreover, the paper explores various supportive biomaterials and scaffold fabrication methodologies that enhance salivary gland cell survival, differentiation, and engraftment. Innovative engineering strategies for the improvement of vascularization, innervation, and engraftment of engineered salivary gland tissue, including bioprinting, microfluidic hydrogels, mesh electronics, and nanoparticles, are also evaluated. This review underscores the promising potential of this research field for the treatment of salivary gland dysfunction and suggests directions for future exploration.

Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

The submandibular gland (SMG) and sublingual gland (SLG) are two of three major salivary glands in mammals and comprise serous and mucous acinar cells. The two glands share some functional properties, which are largely dependent on the types of acinar cells. In recent years, while ScRNA-seq (single-cell sequencing) with a 10 × platform has been used to explore molecular markers in salivary glands, few studies have examined the acinar heterogeneity and unique molecular markers between SMG and SLG. This study aimed to identify the molecular markers of acinar cells in the SLG and SMG. We performed ScRNA-seq analyses in 4-week-old mice and verified the screened molecular markers using reverse transcription-quantitative real-time PCR, immunohistochemistry, and immunofluorescence. Our results showed prominently heterogeneous acinar cells, although there was great similarity in the cluster composition between the two glands at 4 weeks. Furthermore, we demonstrated that Agt is a specific marker of SMG serous acinar cells, whereas Gal is a specific marker of SLG mucous acinar cells. Trajectory inference revealed that Agt and Gal represent two types of differential acinar cell clusters during late development in adults. Thus, we reveal previously unknown specific markers for salivary acinar cell diversity, which has extensive implications for their further functional research.

The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF-a disease that affects salivary gland (SG) function-is caused by mutations of the CFTR gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.

Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 μm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 μm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 106 cells/mL). Our work demonstrates hydrogel feature control across multiple length scales, and a new paradigm for addressing SG restoration by creating microscale tissue engineered components.

Saliva modulates the environment of the oral biofilm through pH buffer, microbial attachment to host surfaces, and nutritional source. The ecology of stress occurs when a physical factor adversely impacts an ecosystem or its biotic components. Therefore, reduced salivary flow can affect oral-host balance. The leading causes of hyposalivation include disease-associated Sjögren's syndrome (SS) and menopausal women as aging-associated. However, little is known about the oral microbiome integrated with sex hormones in hyposalivation. This study aimed to characterize the hyposalivation microbiome caused by aging or disease affecting the salivary glands in women.

We included 50 women older than 40 years of age in any menopausal phase. We collected stimulated saliva from 25 women diagnosed with SS (SS) and 25 without SS (non-SS). The bacterial profile of the patients was obtained by 16S rRNA sequencing. Bioinformatics analysis used machine learning to analyze the cohort's signs, symptoms, and bacterial profile. Salivary estradiol as a sex hormone variation level was determined.

We obtained that 79% of the SS group, and 52% of the non-SS group had hyposalivation. We found a negatively correlated Prevotella-age and Rothia-estradiol in the SS group. Highlight, we found that the cause of the hyposalivation in the study did not explain differences in microbial diversity comparing non-SS and SS groups. Therefore, microbial communities found in hyposalivation but not related to systemic conditions suggest that changes in the oral environment might underpin host-microbial balance.

The salivary microbiome was similar in women with and without SS. However, hyposalivation showed two distinctive clusters associated with the bacterial population profiles. Our study suggests that local ecological disturbances could drive the change in the microbiome.

Xerostomia is a salivary gland dysfunction that negatively impacts the life quality of patients; however, there is no effective treatment for xerostomia. Bioengineered organs, generated using stem cells obtained from newborn salivary glands and ligated injury models, are a new organ transplantation strategy that could be feasible for xerostomia treatment. Reconstruction of salivary gland organoids by seed cells obtained from human minor salivary glands will offer theoretical fundaments and technology support for clinical application and organ regeneration research. Herein, we aimed to propose a new method for culturing and enriching adult human minor salivary gland stem cells in vitro in a three-dimensional (3D) environment via Wnt signaling activation.

Obtained and characterized human minor salivary gland stem cells (hMSGSCs) with self-organization ability were 3D-cultured to generate organoids. We examined hMSGSCs proliferation and colony formation using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assays. Telomerase reverse transcriptase staining, flow cytometry, immunofluorescence assay, RNA isolation, RT-PCR, and qPCR were performed to assess hMSGSCs structure and the function of reconstructive organoids in vitro.

hMSGSCs showed typical epithelial-like characteristics, such as positive for CD49f and cell KRT expression. hMSGSCs served as adult stem cells in salivary glands and could differentiate into acinar and duct cells. Upon the addition of Noggin, CHIR99021, and Wnt3A to the 3D culture system, hMSGSCs showed higher LGR5 expression and decreased AMY1B and MUC5B expression. Therefore, the Wnt and bone morphogenetic protein (BMP) pathways are important in regulating hMSGSCs self-organization and differentiation.

We showed that the stem cell properties of hMSGSCs in a 3D culture system can be maintained by activating the Wnt signaling pathway and inhibiting the BMP signaling pathway. Our findings contribute new insights on salivary gland organoid generation in vitro.

Orofacial soft tissue wounds caused by surgery for congenital defects, trauma, or disease frequently occur leading to complications affecting patients' quality of life. Scarring and fibrosis prevent proper skin, mucosa and muscle regeneration during wound repair. This may hamper maxillofacial growth and speech development. To promote the regeneration of injured orofacial soft tissue and attenuate scarring and fibrosis, intraoral and extraoral stem cells have been studied for their properties of facilitating maintenance and repair processes. In addition, the administration of stem cell-derived extracellular vesicles (EVs) may prevent fibrosis and promote the regeneration of orofacial soft tissues. Applying stem cells and EVs to treat orofacial defects forms a challenging but promising strategy to optimize treatment. This review provides an overview of the putative pitfalls, promises and the future of stem cells and EV therapy, focused on orofacial soft tissue regeneration.

This study aimed to assess if Nigella sativa oil (NSO), a health supplement containing thymoquinone as a major component, can act as a protective agent in salivary gland stem cells following radiotherapy (RT) damage.

Forty, 10-week-old, male C3H/HeJ mice were randomized to four experimental groups: sham RT + H2O gavage (control) (N = 4); 15 Gy RT + H2O gavage (N = 12); sham RT + NSO gavage (N = 12); and 15 Gy RT + NSO gavage (N = 12). Weight changes, saliva production, and salivary gland histopathologic staining were recorded for each group over the course of the experiment.

All mice in the sham RT + H2O gavage and sham RT + NSO gavage groups demonstrated 100% 60-day survival. RT + H2O compared to RT + NSO gavaged mice were significantly underweight by an average of 6.4 g (p < .001). Salivary output showed significant decline in RT + H2O gavaged mice at days 3 and 16, whereas salivary output in RT + NSO during these same time periods was comparable to the control. At day 60, all mice that survived recovered salivary function regardless of their treatment arm. Salivary specimens from the RT + NSO gavage group demonstrated early signs of recovery of Kr 5+ salivary gland stem cells in both submandibular and sublingual glands at day 16 with complete recovery by day 60, marked by strong histopathologic staining, whereas the RT + H2O gavage group did not recover as effectively.

NSO may help preserve salivary function in mice treated with RT and may mitigate xerostomia by accelerating the recovery of salivary gland stem cells.

Not applicable.

Salivary gland (SG) dysfunction, due to radiotherapy, disease, or aging, is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life. Currently, the standard-of-care for this condition remains palliative. A variety of approaches have been employed to restore saliva production, but they have largely failed due to damage to both secretory cells and the extracellular matrix (niche). Transplantation of allogeneic cells from healthy donors has been suggested as a potential solution, but no definitive population of SG stem cells, capable of regenerating the gland, has been identified. Alternatively, mesenchymal stem cells (MSCs) are abundant, well characterized, and during SG development/homeostasis engage in signaling crosstalk with the SG epithelium. Further, the trans-differentiation potential of these cells and their ability to regenerate SG tissues have been demonstrated. However, recent findings suggest that the "immuno-privileged" status of allogeneic adult MSCs may not reflect their status post-transplantation. In contrast, autologous MSCs can be recovered from healthy tissues and do not present a challenge to the recipient's immune system. With recent advances in our ability to expand MSCs in vitro on tissue-specific matrices, autologous MSCs may offer a new therapeutic paradigm for restoration of SG function.

Heavy episodic ethanol (EtOH) consumption is a typical pattern, especially among younger people. The therapeutic effect of exercise on EtOH damage has not yet been fully elucidated. Therefore, this study aims to investigate whether moderate exercise can reduce the damage generated by ethanol consumption in salivary glands and saliva. Thus, 32 male Wistar rats were divided into four groups: control (sedentary animals treated with water); training (trained animals treated with EtOH); EtOH (sedentary animals treated with EtOH); and EtOH + training (trained animals treated with ethanol). EtOH was administered to the animals at a dose of 3 g/kg/day at a concentration of 20% w/v for three consecutive days per week via intragastric gavage. The training was performed on a treadmill for five successive days. At the end of the 4-week experimental protocol, the animals were euthanized, and salivary glands and saliva were collected for oxidative biochemistry analysis. Our results showed that EtOH consumption generated changes in the oxidative biochemistry of the salivary glands and saliva. Thus, it was possible to conclude that moderate physical exercise can significantly recover antioxidant activity, reducing the damage generated by EtOH.

The auditory tube (AT), an osteocartilaginous channel, connects the nasopharynx to the middle ear cavity. At the nasopharyngeal opening of the AT, there are dense collections of submucosal glands. In a recent article, Valstar et al. proposed these nasopharyngeal tubal glands conglomerate as salivary glands, which starkly contrasts with their previously known anatomy for being a component of the respiratory tract. This study examines the contesting views regarding the taxonomical categorization of the nasopharyngeal tubal glands.

The AT glands in context were examined in human cadavers grossly, and microscopically using routine and special (Hematoxylin and Eosin [H&E] and Periodic acid-Schiff [PAS] respectively), as well as immunohistochemical (for alpha-SMA and salivary amylase) staining methods and compared with the major and minor salivary glands and the submucosal glands in the trachea. Further, a biochemical analysis was performed to detect the presence of salivary amylase in the oral and nasopharyngeal secretions of the four living human subjects, representing major salivary glands and tubal glands, respectively.

The submucosal seromucous glands with a surface lining of respiratory epithelium were observed at the nasopharyngeal end of AT. The cells in the tubal glands showed cytoplasmic positivity for alpha-SMA, which indicated the presence of the myoepithelial cells; however, this expression was significantly lower than in the seromucous submucosal glands within the trachea. Salivary alpha-amylase was undetectable in the cadaveric tissue samples. Moreover, the amylase level in the nasopharyngeal swabs was negligible compared to the oral swabs.

The anatomical location along the respiratory tract, the presence of respiratory epithelium in the overlying mucosa, their morpho-functional resemblance to the seromucous glands in the trachea, and the absence of salivary amylase strongly indicate that the tubal glands are taxonomically different from the salivary glands. Given the available evidence, their existing recognition as a part of the respiratory tract and an integral component of the AT seems more appropriate.

Saliva-secreting and transporting cells are part of the complex cellular milieu of the human salivary gland, where they play important roles in normal glandular physiology and diseased states. However, comprehensive molecular characterization, particularly at single-cell resolution, is still incomplete, in part due to difficulty in procuring normal human tissues. Here, we perform an in-depth analysis of male and female adult human submandibular gland (SMG) samples by bulk RNA sequencing (RNA-seq) and examine the molecular underpinnings of the heterogeneous cell populations by single-cell (sc) RNA-seq. Our results from scRNA-seq highlight the remarkable diversity of clusters of epithelial and nonepithelial cells that reside in the SMG that is also faithfully recapitulated by deconvolution of the bulk-RNA data sets. Our analyses reveal complex transcriptomic heterogeneity within both the ductal and acinar subpopulations and identify atypical SMG cell types, such as mucoacinar cells that are unique to humans and ionocytes that have been recently described in the mouse. We use CellChat to explore ligand-receptor interactome predictions that likely mediate crucial cell-cell communications between the various cell clusters. Finally, we apply a trajectory inference method to investigate specific cellular branching points and topology that offers insights into the dynamic and complex differentiation process of the adult SMG. The data sets and the analyses herein comprise an extensive wealth of high-resolution information and a valuable resource for a deeper mechanistic understanding of human SMG biology and pathophysiology.

Agenesis of the salivary glands is an extremely uncommon finding, and in the majority of cases, it is associated with facial syndromes or malformations. Reports in the literature have, however, indicated that agenesis of the major salivary glands can occur in isolation, and this anomaly is believed to occur due to a failure in the developmental process. Herein, we present two cases of isolated unilateral agenesis of major salivary glands.

We describe two clinical cases of occasional radiographic findings on orthopantomography (OPG) that were performed routinely, for which the definitive diagnosis may be uncertain. After an accurate remote and recent anamnesis, for reasons of exclusion, we hypothesize a rare case of the retention of a contrast medium in the parenchyma of the major salivary glands (parotid, submandibular, and sublingual) and their excretory ducts as a consequence of sialography examination. In the first case we analyzed, we found it difficult to classify the radiographic signs on the sublingual glands, left parotid, and submandibular, while in the second case, only the right parotid was involved. Using CBCT, the spherical findings were highlighted, with multiple having different dimensions, as well as radiopaque in their peripheral portion and more radiolucent inside them. We could immediately exclude salivary calculi, which usually have a more elongated/ovoid shape and appear homogeneously radiopaque without radiolucency areas. These two cases (of hypothetic medium contrast retention with unusual and atypical clinical-radiographic presentation) have very rarely been comprehensively and correctly documented in the literature. No papers have a follow-up longer than 5 years. We conducted a review of the literature on the PubMed database, finding only six articles reporting similar cases. Most of them were old articles, demonstrating the low frequency of this phenomenon. The research was performed using the following keywords: "sialography", "contrast medium", "retention" (six papers) and "sialography", and "retention" (13 papers). Some articles were present in both searches, and the really significant ones (defined after a careful reading of the entire article and not only of the abstract) resulted only in six occurrences in a time span from 1976 to 2022.

In this study, we investigated the salivary film thickness and the MUC5B levels at various intra-oral locations in healthy volunteers, with a focus on the palate. Besides, measurements of the palatal surface area were included to explore the possible relationships between the palatal surface area and the palatal salivary film and MUC5B levels.

The salivary film thickness was determined using filter strips, which were pressed to the mucosal surfaces of five different intra-oral locations; conductance was then analysed using a Periotron. After elution of the strips, the MUC5B levels at various intra-oral locations were determined using ELISA. The palatal surface area was measured using an intra-oral scanner. The surface area was subsequently calculated using the software.

The anterior tongue had the thickest salivary film and also the highest levels of MUC5B, while the anterior palate had the thinnest salivary film and lowest MUC5B levels. There was no association between the palatal surface area and the salivary film thickness of the palate.

The salivary film and MUC5B levels are unequally distributed over the intra-oral regions of the soft tissues. The lack of association between the palatal surface area and the salivary film thickness indicates that a larger surface area is not associated with a relative thinner palatal salivary film.

The results of the current study increase our understanding of saliva distribution in the oral cavity and could be used as reference values for future studies.

Primary submandibular gland tumors are relatively rare. Due to its low incidence and broad spectrum phenotypic, biological and clinical heterogeneity types, a wide range of options have been developed to treat this tumor. To date, however, efficacious standard treatment regimens are lacking. Here, the authors present a case of a patient with an advanced submandibular gland tumor. Histological and imaging results diagnosed the case as stage IV submandibular gland adenocarcinoma with multiple metastases. The patient was subjected to systemic platinum-based chemotherapy combined with sintilimab. A primary lesion complete response was observed after six cycles of treatment. This case affirms the efficacy of the PD-1 inhibitor sintilimab combined with platinum-based chemotherapy as a first-line treatment for advanced submandibular gland tumors.

The production and secretion of saliva is an essential function of the salivary glands. Saliva is a complicated liquid with different functions, including moistening, digestion, mineralization, lubrication, and mucosal protection. This review focuses on the mechanism and neural regulation of salivary secretion, and saliva is secreted in response to various stimuli, including odor, taste, vision, and mastication. The chemical and physical properties of saliva change dynamically during physiological and pathophysiological processes. Moreover, the central nervous system modulates salivary secretion and function via various neurotransmitters and neuroreceptors. Smell, vision, and taste have been investigated for the connection between salivation and brain function. The immune and endocrine functions of the salivary glands have been explored recently. Salivary glands play an essential role in innate and adaptive immunity and protection. Various immune cells such as B cells, T cells, macrophages, and dendritic cells, as well as immunoglobins like IgA and IgG have been found in salivary glands. Evidence supports the synthesis of corticosterone, testosterone, and melatonin in salivary glands. Saliva contains many potential biomarkers derived from epithelial cells, gingival crevicular fluid, and serum. High level of matrix metalloproteinases and cytokines are potential markers for oral carcinoma, infectious disease in the oral cavity, and systemic disease. Further research is required to monitor and predict potential salivary biomarkers for health and disease in clinical practice and precision medicine.

The submandibular ganglion is a small fusiform-shaped cluster of cell bodies of the parasympathetic nervous system. Parasympathetic innervation of the submandibular gland is not only responsible for the secretion of saliva, but it also plays a main role in the development and regeneration of the gland. The parasympathetic root of the submandibular ganglion or the posterior branch of the lingual nerve to the submandibular ganglion is one of three roots of the submandibular ganglion. Using standard search engines (PubMed, Google), papers in English discussing the anatomy, embryology, variations, and clinical significance of the parasympathetic root of the submandibular ganglion were reviewed.

High rates of recurrence and distant metastasis are a foremost challenge in the management of adenoid cystic carcinoma (ACC), occurring in approximately 40% of all ACC patients. Despite the morbidity and mortality resulting from recurrent/metastatic (R/M) disease, there are no FDA-approved systemic agents for these patients. In this review, we summarize pertinent ACC pathophysiology and its implications for different systemic treatment regimens in R/M ACC. We review the evidence for the most widely used systemic agents - cytotoxic chemotherapy and tyrosine kinase inhibitors (TKIs) targeting VEGFR - in addition to immune checkpoint inhibitors and non-TKI biologic agents. Exciting emerging targets for R/M ACC, including inhibitors of Notch signaling, stemness, PRMT5, and Axl, are also discussed. Lastly, we review local therapies for small-volume lung disease in patients with oligometastatic ACC, specifically pulmonary metastasectomy and stereotactic body radiation therapy (SBRT). Future development of targeted molecular agents which exploit the underlying biology of this disease may yield novel therapeutic options to improve clinical outcomes in patients with R/M ACC.

Mimicking the complex architecture of salivary glands (SGs) outside their native niche is challenging due their multicellular and highly branched organization. However, significant progress has been made to recapitulate the gland structure and function using several in vitro and ex vivo models. Hydrogels are polymers with the potential to retain a large volume of water inside their three-dimensional structure, thus simulating extracellular matrix properties that are essential for the cell and tissue integrity. Hydrogel-based culture of SG cells has seen a tremendous success in terms of developing platforms for cell expansion, building an artificial gland, and for use in transplantation to rescue loss of SG function. Both natural and synthetic hydrogels have been used widely in SG tissue engineering applications owing to their properties that support the proliferation, reorganization, and polarization of SG epithelial cells. While recent improvements in hydrogel properties are essential to establish more sophisticated models, the emphasis should still be made towards supporting factors such as mechanotransduction and associated signaling cues. In this concise review, we discuss considerations of an ideal hydrogel-based biomaterial for SG engineering and their associated signaling pathways. We also discuss the current advances made in natural and synthetic hydrogels for SG tissue engineering applications.

Multiple pathologies and non-pathological factors can disrupt the function of the non-regenerative human salivary gland including cancer and cancer therapeutics, autoimmune diseases, infections, pharmaceutical side effects, and traumatic injury. Despite the wide range of pathologies, no therapeutic or regenerative approaches exist to address salivary gland loss, likely due to significant gaps in our understanding of salivary gland development. Moreover, identifying the tissue of origin when diagnosing salivary carcinomas requires an understanding of human fetal development. Using computational tools, we identify developmental branchpoints, a novel stem cell-like population, and key signaling pathways in the human developing salivary glands by analyzing our human fetal single-cell sequencing data. Trajectory and transcriptional analysis suggest that the earliest progenitors yield excretory duct and myoepithelial cells and a transitional population that will yield later ductal cell types. Importantly, this single-cell analysis revealed a previously undescribed population of stem cell-like cells that are derived from SD and expresses high levels of genes associated with stem cell-like function. We have observed these rare cells, not in a single niche location but dispersed within the developing duct at later developmental stages. Our studies introduce new human-specific developmental paradigms for the salivary gland and lay the groundwork for the development of translational human therapeutics.

The salivary glands produce saliva and are important in maintaining oral health. Saliva keeps the mouth moist, cleanses the oral cavity, aids digestion, and has antibacterial properties. Saliva also helps in swallowing and speech. Investigating the development of the salivary glands is thus relevant in the context of both health and disease. Various cell culture methods have been used to study salivary gland development, including culturing cells in two dimensions (2D). Under physiological conditions, cells constantly interact with other cells and the extracellular matrix, which controls complex biological functions such as cell migration and apoptosis, and can modulate gene expression. Since many of these functions are not accurately represented or reproduced in 2D culture, the results of in vitro experiments using such culture methods are often not reflected in vivo. The use of 3D cultures, such as organ cultures, has helped address this issue and has emerged as a model that better reflects the in vivo physiological environment. Here, we describe a protocol for establishing submandibular salivary gland organ culture that is more concise and simpler than previous methods and includes the separation and dissection of the salivary glands. We also describe the use of environmental stress (hypoxic stimulation) and inhibitors (U0126, LY294002, and rapamycin) to elucidate signaling pathways involved in salivary gland development. This protocol can provide researchers with a simpler and more robust method of salivary gland organ culture, enabling analysis of organ-based signaling pathways to advance developmental biology research. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Submandibular salivary gland organ culture Basic Protocol 2: Analysis of salivary gland development in the presence of hypoxia and signaling pathway inhibitors Basic Protocol 3: Western blotting using submandibular salivary gland organ culture.

Salivary glands produce and secrete saliva, which is essential for maintaining oral health and overall health. Understanding both the unique structure and physiological function of salivary glands, as well as how they are affected by disease and injury, will direct the development of therapy to repair and regenerate them. Significant recent advances, particularly in the OMICS field, increase our understanding of how salivary glands develop at the cellular, molecular, and genetic levels: the signaling pathways involved, the dynamics of progenitor cell lineages in development, homeostasis, and regeneration, and the role of the extracellular matrix microenvironment. These provide a template for cell and gene therapies as well as bioengineering approaches to repair or regenerate salivary function.

The submandibular gland (SMG) and the sublingual gland (SLG) are two of the three major salivary glands in mammals. In mice, they are adjacent to each other and open into the oral cavity, producing saliva to lubricate the mouth and aid in food digestion. Though salivary gland dysfunction accompanied with fibrosis and metabolic disturbance is common in clinic, in-depth mechanistic research is lacking. Currently, research on how to rescue salivary function is challenging, as it must resort to using terminally differentiated acinar cells or precursor acinar cells with unknown differentiation. In this study, we established reversely immortalized mouse primary SMG cells (iSMGCs) and SLG cells (iSLGCs) on the first postnatal day (P0). The iSMGCs and iSLGCs grew well, exhibited many salivary gland characteristics, and retained the metabolism-related genes derived from the original tissue as demonstrated using transcriptome sequencing (RNA-seq) analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of these two cell lines, which overlapped with those of the SMG and SLG, were enriched in cysteine and methionine metabolism. Furthermore, we investigated the role of bone morphogenetic protein 9 (BMP9), also known as growth differentiation factor 2(Gdf2), on metabolic and fibrotic functions in the SMG and SLG. We demonstrated that iSMGCs and iSLGCs presented promising adipogenic and fibrotic responses upon BMP9/Gdf2 stimulation. Thus, our findings indicate that iSMGCs and iSLGCs faithfully reproduce characteristics of SMG and SLG cells and present a promising prospect for use in future study of salivary gland metabolism and fibrosis upon BMP9/Gdf2 stimulation.

Sialin is a multifunctional molecule with a well-described role in physiological equilibrium regulation. The aim of this study was to elucidate the role of sialin in salivary glands regeneration.

Submandibular gland duct ligation/deligation of rat was performed to develop a rat model of submandibular gland regeneration. Phenotype changes were investigated using western blotting and quantitative real-time polymerase chain reaction, as well as immunohistochemical staining. LV-slc17a5-RNAi vectors were injected into the submandibular glands via retroductal instillation to establish a stable sialin knockdown model.

Submandibular gland tissue structure could completely restore 28 days after duct deligation, when the duct had been ligated for 7 days. The expression of sialin, polysialic acid, and polysialyltransferase IV was significantly increased on day 0 after duct deligation, and it returned to the level of the control group at day 28. Moreover, sialin knockdown could weakened gland regeneration by reducing polysialic acid synthesis. Supplementing drinking water with polysialic acid precursors (ManNAc) in drinking water could partially rescue submandibular gland regeneration in sialin knockdown rats.

These data indicated that sialin was vital for submandibular gland regeneration which mediated the process of gland regeneration by affecting the polysialic acid synthesis.

The aim of this study was to identify the efficacy of diffusion kurtosis imaging (DKI) in tracking and monitoring the dynamic change of parotid glands (PGs), submandibular glands (SMGs), sublingual glands (SLGs), and acute xerostomia in nasopharyngeal carcinoma (NPC) patients treated with induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT).

The prospective study recruited 42 participants treated with IC+CCRT. All patients underwent DKI scanning six times: before IC, before RT, in the middle of the RT course, immediately after RT, and 1 and 3 months post-RT. Mean diffusion coefficient (MD) and mean kurtosis (MK) of PG, SMG, SLG, saliva flow rate measured under resting (uSFR) and stimulated condition (sSFR), and xerostomia questionnaire (XQ) scores were recorded.

At each time point, sSFR was significantly higher than uSFR (p < 0.05 for all). MD of the salivary glands and XQ scores increased over time while MK, uSFR, and sSFR decreased. After IC, the significant differences were detected in MD and MK of bilateral SMG and MK of the left SLG (p < 0.05 for all), but not in MD and MK of PG, uSFR, sSFR, and XQ scores. After RT, sSFR at 1m-RT decreased significantly (p = 0.03) while no significant differences were detected in uSFR and XQ scores. Moderate-strong correlations were detected in ΔMD-PG-R%, ΔMK-PG-R%, ΔMD-PG-L%, ΔMK-PG-L%, ΔMD-SMG-R%, ΔMK-SMG-R%, ΔMD-SMG-L%, ΔMK-SMG-L%, and ΔMD-SLG-R%, with correlation coefficients (p < 0.05 for all) ranging from 0.401 to 0.714. ΔuSFR% was correlated with ΔMD-SMG% (p = 0.01, r = -0.39), ΔMD-SLG% (p < 0.001, r = -0.532), and ΔMK-SMG% (p < 0.001, r = -0.493). ΔsSFR% correlated with ΔMD-PG% (p = 0.001, r = -0.509), ΔMD-SMG% (p = 0.015, r = -0.221), and ΔMK-PG% (p < 0.001, r = 0.524). ΔXQ% was only correlated with ΔMK-PG% (p = 0.004, r = 0.433).

DKI is a promising tool for tracking and monitoring the acute damage of PG, SMG, and SLG induced by IC+CCRT in NPC patients.