Submandibular Gland Research Articles

Single-Cell RNA-Seq and Histological Analysis Reveals Dynamic Lrig1 Expression During Salivary Gland Development.

The development of the salivary gland (SG) is a complex process regulated by multiple signaling pathways in a spatiotemporal manner. Various stem/progenitor cell populations and respective cell lineages are involved in SG morphogenesis and postnatal maturation. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) has been identified as critical regulator of stem cells by virtue of its ability to restrain stem cell proliferation, indicating its potential role in the development of several maxillofacial tissues and in the regulation of the quiescence in adult tissues. This study aimed to investigate the expression pattern and functions of Lrig1 in the developing and mature murine submandibular gland (SMG). To accomplish this objective, we collected the murine SMGs at different developmental stages and examined the expression pattern and levels of Lrig1 with qRT-PCR, immunofluorescent (IF) and RNAscope staining. We observed that Lrig1 was widely distributed in both epithelial and mesenchymal cells throughout embryonic and neonatal stages, with specific localization in the more mature epithelium. Furthermore, through single-cell RNA sequencing (scRNA-Seq) and IF techniques, we confirmed that LRIG1 is highly concentrated along with SMG progenitor markers in acinar and basal cells. Additionally, transcription factors (TFs) that could regulate LRIG1 expression were predicted from JASPAR databases and their motifs were identified by the UCSC browser's BLAT tool. Gene Ontology (GO) enrichment analyses on postnatal day 5 (PN5) scRNA-Seq data also provided insights into Lrig1's functions in SG development. Finally, we also conducted in vitro experiments on a human salivary gland (HSG) cell line to assess LRIG1's impact on HSG proliferation and migration, as well as its potential upstream regulatory TFs. Taken together, our study reveals that LRIG1 plays a vital role in SG development.

Assessment of the Prospective Protection of Quercetin on Irradiated Submandibular Salivary Gland in Mice

Assessment of the Prospective Protection of Quercetin on Irradiated Submandibular Salivary Gland in Mice

Management of a Huge Arteriovenous Malformation of the Tongue with the Submandibular Gland Flap: A Case Report

Management of a Huge Arteriovenous Malformation of the Tongue with the Submandibular Gland Flap: A Case Report

Androgens suppress the sialyltransferases ST3GAL1 and ST3GAL4 and modulate mucin 10 glycosylation in the submandibular gland, related to sex differences in commensal microbiota composition in mice.

Sex differences exist in the commensal microbiota that impact on multiple physiological processes in the host. Here, we examined the mechanism by which the sex differences are formed. In addition to the epithelial ductal cell, the acinar cell mass in the submandibular gland was associated with androgen-androgen receptor (AR) signaling. There was a sex difference in the formation of submandibular mucin 10 (MUC10) in SDS-PAGE. Neuraminidase treatment, which hydrolyzes terminal sialic acid, influenced the mobility shift of MUC10. Androgen-AR signaling negatively regulated St3 β-galactoside α-2,3-sialyltransferase 1 (St3gal1) and St3gal4 in the submandibular gland. There was a trend and significant sex differences in α-diversity (Shannon, p=0.09) and β-diversity (unweighted UniFrac) in oral microbiota composition, respectively. Some female-preferring bacteria including Akkermansia muciniphila can assimilate mucin by degrading terminal sialic acids. Our results indicate that androgen-AR signaling suppresses ST3GAL1 and ST3GAL4, which can influence sex differences in commensal microbiota composition.

Scanning Electron Microscopy of the Oropharyngeal Floor of Northern Bobwhite (Colinus virginianus, Linnaeus, 1758) Focusing on the Numerical and Regional Distribution of the Taste Buds

ABSTRACTThe architecture of the avian oropharynx corresponds to the feeding pattern. The present study aims to provide data on morphology, morphometry, and spatial distribution of taste buds in the oropharyngeal floor of the northern bobwhite (Colinus virginianus) using gross anatomy, morphometric, and scanning electron microscopy. The lower beak tip and tomia revealed the presence of variably‐sized dermal papillae. The prefrenular part of the oral floor had an interrupted median groove. Numerous taste buds and rostral submandibular salivary gland openings were detected alongside this groove. The tongue partially filled the oral floor. Its rostral end formed a median pointed process, the lingual nail. The dorsolateral aspects of the lingual apex and body showed hair‐like and rosette‐shaped filiform papillae of variable densities and sizes. However, these parts were devoid of taste buds. On the other hand, the surface mucosa of the lingual root presented numerous scale‐like cellular elevations and a large number of taste buds. Examination of cross sections in the lingual root suggested the presence of two groups of caudal lingual salivary glands, central and lateral. The laryngeal mound contained taste buds that protruded from the surface epithelium into the lumen. The mucosa of the pharyngeal floor contained many taste buds that appeared similar to those detected on the laryngeal mound, except for the large taste pores, excessive cellular porosity, and denser microvilli. The total proportions of the taste buds in the oral and pharyngeal floors were 34.1% and 65.81%, respectively. The proportions of taste buds were 34.1%, 57.26%, 4.27%, and 4.27% in the sublingual floor, lingual root, laryngeal mound, and pharyngeal wall, respectively. In conclusion, this study provides comprehensive data on the oropharynx of northern bobwhite and will help to understand mechanisms governing food gustation in the studied bird and other related birds.

Bilateral Sialadenitis as an Uncommon Initial Manifestation of Infectious Mononucleosis: A Case Report.

Sialadenitis has rarely been reported in patients with infectious mononucleosis (IM). Our patient was a 22-year-old man who presented with bilateral swelling of the parotid and submandibular glands, a fever, malaise, and splenomegaly. Laboratory tests revealed an increased percentage of atypical lymphocytes in the leukocyte fraction. Serological testing for antibodies against Epstein-Barr virus (EBV) revealed an acute infection pattern. The patient was diagnosed with sialadenitis associated with IM caused by EBV infection. With symptomatic treatment, the salivary gland swelling completely resolved within a week. This case suggests that EBV-induced IM should be included in the differential diagnosis of diffuse sialadenitis with elevated atypical lymphocyte counts.

Submandibular Sialolithiasis Associated with Sialadenitis –A Case Report

Sialadenitis, an inflammation of major salivary glands is commonly associated with the obstruction of the salivary duct due to sialolith. The submandibular gland is particularly susceptible to sialolithiasis. This case report discusses a 33 year old female patient who reported with a swelling below the tongue/floor of the mouth associated with pain for a week A comprehensive investigation has indicated the presence of multiple sialoliths. The treatment involved surgical removal of the sialoliths, accompanied by antibiotic therapy. Therefore, this case report emphasizes the presence of multiple sialoliths in a female patient.

Developmental studies of the sublingual and mandibular salivary glands in Japanese quails (Coturinx coturinx japonica)

BackgroundThe Japanese quail (Coturinx coturnix japonica) has a crucial role in the lives of humanity since the 12th century and continues to play main roles in our industry and scientific research. The advantages that the Japanese quail has, such as heavy egg production and high-quality meat with low cholesterol and fat contents, Moreover, the Japanese quail is easily managed, with high feeding conversion, low cost of investment, and high rate of returns. Salivary glands are a part of the lingual apparatus that secretes serios and mucous saliva. Whereas, the saliva secretions have different roles in the food variation, apprehension, and moisture of food bolus. The morphological and cytochemical analysis are done on 20 healthy Japanese quail embryos of 6th, 10th, 11th, and 13th days of incubation and 25 healthy quail chicks at hatching day old, 7th, 14th, 30th, and 60th days old. These samples are investigated histologically, histochemically, and scanned by electron microscopy serially. Our purpose of the study is to highlight the area of the oropharyngeal salivary glands and their role in food variation, as few studies spoke about that in Japanese quail.ResultsThe primordia of the sublingual and mandibular salivary glands were noticed at the 6th and 10th days of the prehatching respectively as an epithelial bud. After hatching, both primordia were elongated and differentiated into secretory units. These glands were mucous polystomatic tubulo-alveolar paired glands, which were situated in the submucosa of the oropharyngeal floor (sublingual floor and paralingual grooves). The sublingual glands consisted of 3–5 lobes extended from the two Os ceratobranchial by their wide ends caudally, to beyond the median sulcus of the prefrenular part of the sublingual space rostrally. The taste buds were variable in size and position. The mandibular glands lay on the paralingual groove, which arose at the 10-day old embryo. The mandibular glands were located dorsomedial to the sublingual glands and extended longitudinally from the rostral border of the frenulum linguae to the caudal tips of the sublingual glands. The taste buds decreased in volume and number with advancing age.ConclusionOverall, salivary glands increase in their alcianophilic activity of the secretions with advancing age, which indicates low PH within the secretory end pieces.

Chronic sclerosing sialadenitis of the parotid gland mimicking a neoplasm

Chronic sclerosing sialadenitis or Küttner tumor is a benign chronic inflammatory disease of the salivary gland, most commonly involving the submandibular salivary gland in middle aged adults. We describe the magnetic resonance imaging features of a rare case of Küttner tumor with isolated parotid gland involvement in a child, to emphasize on the need for increased awareness among radiologists regarding the possibility and imaging features of this condition, and to enable its timely diagnosis and appropriate management.

Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study

Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements.

Ultrasonic Image Characteristics of Palatine Tonsils in Healthy Children and Analysis of Factors Influencing Image Quality.

To explore the ultrasonic image characteristics of palatine tonsils in healthy children and the factors affecting image quality. A total of 750 images of palatine tonsils were collected from 375 healthy children. According to ultrasonic image quality, the images were divided into three groups. Both systemic and local factors were analyzed among the different groups. The palatine tonsils showed quasi-circular or flat oval, low echo or light and dark band arrangement, a striped medium echo, and a clear boundary. Age, height, weight, body mass index, body surface area, distance from the skin to the posterior margin of the tonsils, thickness of the anterior soft tissue of the tonsils, and thickness of the anterior submandibular gland of the tonsils were significantly different among the different image quality groups (p < 0.05). Multivariate logistic regression analyses revealed that height, weight, thickness of the anterior soft tissue of the tonsils, and thickness of the anterior submandibular gland of the tonsils were independent factors affecting the quality of the ultrasonic images of the palatine tonsils. There are characteristic ultrasonic image manifestations of the palatine tonsils. Tonsil ultrasound image quality is affected by individual and local factors.

Cannabinoid regulation of sex-dependent murine odorant-stimulated salivation

Salivation is easily taken for granted, but without normal salivation, simple essential tasks such as chewing and swallowing become difficult, with consequences for quality of life, nutrition and oral health. Many important drug classes cause dry mouth as a side effect, contributing substantially to patient non-compliance. Available treatments are mostly palliative. Cannabis user complaints of dry mouth prompted a study that showed that basal salivation is likely regulated by cannabinoid CB1 receptors on neurons that innervate the submandibular gland. But what about stimulated salivation? The adjoining parotid gland releases saliva in response to olfactory or other cues and contributes a large portion of the net salivation in humans. We investigated cannabinoid regulation of stimulated salivation using functional and protein-expression studies in mice. In developing a model of stimulated salivary responses to food-related odorants in mice, we noted sex-dependent responses to food-related cues. Only male mice learned to salivate in response to the odor of peanut butter while only female mice responded to a chocolate hazelnut spread. Both males and females responded to sugar or marmite. Testing peanut butter, we found that the cannabinoid receptor agonist CP55940 (0.5 mg/kg, IP) lowered baseline salivation, as shown previously, but also prevented the odorant-induced increase in salivation. CB1 receptors are expressed in axons innervating the parotid gland, paralleling our findings in the submandibular gland. Notably, we also found that CB1 deletion impaired some responses (those to peanut butter and chocolate hazelnut spread) but not others (sugar or marmite). In mice, the CB1 antagonist SR141716 (4 mg/kg, IP) prevented a previously learned salivary response to peanut butter. We find that CB1 receptors are expressed in a subset of glomeruli in coronal sections of olfactory bulb that may serve as a site of action for scent-specific effects of CB1 receptors. We additionally observe CB1 expression in accessory olfactory bulb. In summary, we find a novel sex-dependence in responses to a subset of food-related odorant cues and that cannabinoid receptors regulate some of these responses. We propose that CB1 receptors act at the parotid gland to inhibit stimulated salivation but also in the olfactory system, where functional CB1 receptors are required for salivary responses to specific appetitive odors.

Oncocytic lipoadenoma of the parotid gland: a case report and a review of the literature.

Oncocytic lipoadenomas are a rare sub-category of fat-containing tumors of the salivary glands. These tumors are characterized by their oncocyte-predominant epithelial component admixed with mature adipocytes. This condition has been rarely reported to affect the parotid and the submandibular glands. We report a case of a 69-year-old male who presented to our otolaryngology outpatient department with a complaint of a gradually growing right-sided infra-auricular neck mass. A surgical full mass excision was performed, and a histopathological evaluation yielded a tumor with oncocytes organized in tubular structures. This paper presents the fourth unusual case of a giant oncocytic lipoadenoma of the parotid gland measuring 11.5 × 10.5 × 11.5cm in anteroposterior, transverse, and cranial planes, respectively.

Risk factors of level Ib lymph node metastasis and clinical outcome of its selectively prophylactic irradiation in nasopharyngeal carcinoma: A real-world study

PurposeTo evaluate the risk factor of level Ib lymph node metastasis (LNM) and the clinical outcome of its selectively prophylactic irradiation (pRT) in nasopharyngeal carcinoma (NPC) patients treated with IMRT. Methods518 NPC patients receiving radical IMRT were collected. The structures of primary tumor invasions and neck LNM levels were analyzed bilaterally to estimate the risk factors of level Ib LNM. Patients with level Ib LNM and submandibular gland (SMG) invasion received level Ib pRT. The level Ib recurrence-free survival (RFSIb), regional recurrence-free survival (RRFS), and the incidence of ≥ grade 2 xerostomia at 1-year post-IMRT were compared in negative level Ib LNM patients who omitted, received unilateral, or bilateral level Ib pRT. ResultsThirteen (2.5 %) patients with 18 sides had level Ib LNM. Ipsilateral SMG invasion was an independent risk factor for level Ib LNM. With a median follow-up time of 98.0 months, the 5-year RFSIb, 5-year RRFS and the incidence of xerostomia ≥ grade 2 at 1-year post-IMRT in negative level Ib LNM patients who omitted pRT, received unilateral, bilateral pRT to the level Ib were 99.7 % vs.100 % vs. 97.5 % (P = 0.110), 98.0 % vs. 92.1 % vs. 95.1 % (P = 0.120) and 28.0 % vs. 38.3 % vs. 90.0 % (P < 0.001), respectively. ConclusionsOur study revealed that ipsilateral SMG invasion was the independent risk factor for the level Ib LNM. Omitting pRT in patients without ipsilateral level Ib LNM and SMG invasion did not increase the RFSIB and RRFS, and reduced the incidence of xerostomia. Further multi-center prospective randomized clinical trial is warranted.

Tubarial salivary glands show a low relative contribution to functional salivary gland tissue mass.

In 2021, the tubarial salivary glands (TSGs) were newly identified on prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) as macroscopic glands in the nasopharyngeal wall. However, the relative contribution of the TSGs to the total salivary gland function, and consequently on the development of xerostomia after external beam radiotherapy (EBRT) or PSMA-targeted radionuclide therapy (RNT) is not known. Therefore, we aimed to determine the presence of the TSGs and to quantify uptake in the TSGs on PSMA PET. Qualitative and quantitative analyses were performed on 68Ga-PSMA-11 PET/CT scans of 100 patients with prostate cancer. The mean and maximum standardized uptake value (SUVmean and SUVmax) in the TSGs were measured and compared to the parotid, submandibular and sublingual salivary glands (PSGs, SMSGs and SLSGs, respectively). Furthermore, proportional function of the TSGs was compared to the PSGs, SMSGs and SLSGs based on the total organ PSMA (TO-PSMA). The TSGs were visible on 95% of the 68Ga-PSMA-11 PET/CT scans. The normalized median SUVmean and SUVmax was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001) compared to the TSGs, but not for the SLSGs (p = 0.242 and p = 0.300, respectively). The normalized median TO-PSMA was significantly higher for the PSGs (p < 0.001) and SMSGs (p < 0.001), and significant lower for the SLSGs (p < 0.001) compared the TSGs. The SUVmean, SUVmax and TO-PSMA of the TSGs were most comparable to the SLSGs. However, the measured PSMA uptake may be disproportional towards the saliva production. Therefore, future studies should focus on the relation between PSMA uptake and salivary function before and after PSMA therapy.

A Stratification Approach Based on Salivary Gland Ultrasonography for Assessing Secretory Function in Sjögren's Disease.

Our aim was to develop an ultrasonographic scoring model for staging hypofunction of salivary gland (SG) in patients suffering from Sjögren's disease (SjD). The assessment of SG secretory hypofunction was conducted by measuring whole salivary flows. B-mode ultrasonography was performed bilaterally on the parotid and submandibular glands to evaluate the Gland score and OMERACT score quantitatively. The correlation between these scores and SG secretory function in SjD patients was analyzed, leading to the development of an ultrasonographic scoring model for staging SG hypofunction. A one-center derivation cohort comprising 164 SjD patients and a double-center validation cohort consisting of 107 SjD patients were included. Both ultrasonographic scores demonstrated excellent discriminatory ability between SjD patients with hypofunction and those with normal function (both AUC>0.8, p<0.001). A novel ultrasonographic scoring model revealed that low total OMERACT scores (<5) indicated initial-stage SG hypofunction, while high scores (>9) suggested end-stage hypofunction. Conversely, patients with moderate-level total OMERACT scores (5~9) require further stratification using total Gland scores. The incidence of SG hypofunction among all 271 SjD patients was found to be 18% in the initial stage, 58% in the progressive stage, and 100% in the end stage (p<0.001). Furthermore, the incidence of lacrimal gland involvement and hyperglobulinemia (IgG>16 IU/mL) was significantly lower in the initial-stage patients compared to those at other stages (all p<0.001). The novel ultrasonographic scoring model incorporates precise definitions for each stage, providing a robust and clinically significant approach to stratify salivary gland secretory hypofunction in SjD.

Radioanatomy of Salivary Glands

Salivary glands are the first organs of digestion secreting their digestive juices into the oral cavity. Parotid, submandibular, and sublingual glands are the major paired salivary glands in the decreasing order of their size. In addition, multiple small minor salivary glands are noted randomly distributed in the upper aerodigestive tract, including paranasal sinuses and parapharyngeal spaces. The imaging is directed to the major salivary glands. Commonly used imaging methods include plain radiography and conventional sialography. Recently, high-resolution ultrasonography (HRUS) is being increasingly used for targeted salivary gland imaging. However, the advent of cross-sectional imaging techniques such as computed tomography (CT) and magnetic resonance imaging (MRI) have revolutionized the imaging of salivary glands. This article illustrates the role of imaging in evaluating the variegated disease pattern of the major salivary glands.

A rare case of a pleomorphic adenoma of the submandibular gland

We report the case of a 27-year-old female with a painless slowly growing mass that had developed over 2 years in the right submandibular region. Physical examination revealed a firm painless submandibular mass. Fine-needle aspiration and computed tomography (CT) scan concluded a pleomorphic adenoma of the submandibular gland. The patient underwent a right total submandibular sialoadenectomy. Histopathological examination confirmed the diagnosis of pleomorphic adenoma arising from the submandibular gland. Transient palsy of the marginal mandibular division of the facial nerve was noted post-operatively, which recovered with supportive management. Pleomorphic adenoma of the submandibular gland represents a diagnostic and therapeutic dilemma in young adults. Preoperative evaluation, including MRI/CT scan and fine-needle aspiration, is recommended in all cases. Total submandibular sialoadenectomy is the standard recommended treatment to minimise recurrences and avoid malignant transformation.

Salivary Gland Volume Predicts Malnutrition in Irradiated Head and Neck Cancer Patients: A Prospective Analysis.

Xerostomia following (chemo-) radiotherapy (CRT) is common in head and neck (HNC) patients. This prospective study focused on investigating the link between salivary gland function and the onset of malnutrition in HNC patients. Between 2018 and 2020, 61 HNC patients scheduled for curative CRT were prospectively recruited. Nutritional status was assessed by bioelectrical impedance analysis (BIA) and xerostomia was evaluated based on the Common Terminology Criteria for Adverse Events, (CTCAE). Patient-reported outcomes for xerostomia-related symptoms, such as "dry mouth" and "sticky saliva", were also collected. Data were assessed at the beginning of therapy, during treatment, at the end of treatment, and during follow-up. Organs at risk were contoured including the submandibular and parotid glands. Dose-volume parameters were extracted for the mean Dose (Dmean), V15 Gy, V30Gy and V45Gy. No correlation was found between the dosimetric parameters [Dmean, V15Gy (%), V30Gy (%) and V45Gy (%)] and the occurrence of malnutrition [defined by a fat-free mass index (FFMI) <15 kg/m2 (♀) and <17 kg/m2 (♂) kg/m2 and/or body-mass index (BMI) <18.5 kg/m2] at any of the three time points tested. However, the volume of the parotid glands prior to therapy appeared to be related to the development of malnutrition. This effect was not observed with the submandibular glands. A cumulative parotid gland volume of 55.3 cm3 was identified as the threshold for malnutrition at the second follow-up examination. Although none of the dosimetric factors were associated with the development of malnutrition, the baseline parotid gland volume emerged as an independent predictor of malnutrition in head and neck cancer patients with xerostomia.

Challenges in the diagnosis and management of soft tissue tumors of the oral cavity.

Soft tissue lesions are among the most prevalent forms of tumors or tumor-like alterations within the oral cavity. They exhibit a wide spectrum of characteristics, ranging from benign, noninvasive lesions to malignant tumors, which collectively present a diagnostic challenge. A 67-year-old patient presented with an incidental finding of induration on the right cheek during dental hygiene. The intraoral examination revealed a soft, non-tender swelling measuring 20 mm in diameter. The sensitivity and percussion tests for the teeth in the fourth quadrant yielded unremarkable results. Panoramic radiography (OPG) revealed tip-ping of the premolars and an unclear apical finding in region 44. Cone-beam computed tomography (CBCT) revealed a sharply defined, lobulated hypodense lesion in the right buccal area. To clarify the diagnosis and optimize perioperative management, a 3 Tesla dental magnetic resonance imaging (MRI) scan was performed. This identified a 23×6×23 mm lipoma along the right mandibular ramus, causing detachment of the buccinator and de-pressor anguli oris muscles. A cinematic rendering reconstruction derived from the MRI data facilitated enhanced visualization for preoperative planning. The surgical excision was performed under local anesthesia, resulting in the successful removal of the neoplasm while preserving the mental nerve and submandibular gland. Histo-pathology confirmed the presence of a lobulated mature cell lipoma. The patient exhibited no complications during the removal of the sutures, with complete wound healing and no recurrence observed. This article highlights the efficacy of advanced MRI diagnostics and post-processing techniques in the management of ambiguous soft tissue neoplasms.