Submandibular Gland Duct Research Articles

Spatio-temporal expression of Sox2+ progenitor cells regulates the regeneration of rat submandibular gland

ObjectiveSox2 plays crucial roles in tissues homeostasis and regeneration. However, there are lack of a comprehensive examination of Sox2 expression and its functional role in submandibular gland regeneration. Therefore, we aimed to elucidate the impact of Sox2 on submandibular gland regeneration. Materials and MethodsA Sprague-Dawley rat submandibular gland duct ligation/de-ligation regeneration model was conducted in this study. Sox2-shRNA vectors were retro-ductally administered into the submandibular gland to establish a stable Sox2 knockdown model. Conventional histopathological and molecular biological methods were used to investigate phenotypic changes. ResultsThe submandibular gland normalized completely 28 days after ligature removal (following 7 days of duct ligation). AQP5 expression gradually increased after ligation removal until returning to normal levels. In submandibular gland regeneration, Sox2 re-expressed and co-expressed with AQP5+ acinar cells, and Sox2 expression peaked on day 14, recovered to normal on day 28, reproducing the developmental pattern. Sox2 knockdown hindered gland regeneration and induced irreversible fibrosis. The AQP5 expression was significantly lower than the contemporaneous solely ligated group, while the blue collagen deposition and the Vimentin expression increased prominently. The expression of CD68, IL-1β, TNF-α and IL-17A increased significantly, and epithelial cells in the Sox2 knockdown group expressed higher levels of IL-17A. ConclusionsThese findings highlight Sox2 as a crucial regulator of the acinar cell lineage. Sox2+ progenitor cells are pivotal for acinar cell maintenance, which is indispensable for submandibular gland regeneration. Collectively, our findings may help develop targeted interventions for enhancing tissue repair and preventing irreversible fibrosis in salivary gland disorders.

Expression of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in the rat submandibular gland is influenced by pre- and post-natal high-fat diet exposure.

Background: Incretins, i.e., glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) promote insulin secretion to reduce postprandial blood sugar. Previous studies found incretins in the salivary glands. However, the role of GLP-1 and GIP in the submandibular gland (SMG) is unclear. This study investigates the effects of a high-fat diet (HFD) on the expression of GLP-1 and GIP throughout the development of rat SMG. Methods: Pregnant 11-week-old Wistar rats were divided into two groups: those fed on a standard diet (n = 5) and those fed on a HFD (n = 5). From day 7 of pregnancy and throughout the lactation period, all the rats were fed on either a chow diet or HFD. The newborns were divided into four subgroups (n = 6): standard diet males (SM), HFD males (HM), standard diet females (SF), and HFD females (HF). The SMGs of 3- and 10-week-old rats from each subgroup were collected under general anesthesia. Moreover, body weight, food intake, and fasting blood sugar were measured. The mRNA expression of GLP-1 and GIP was quantified, and the localization was observed using immunohistochemistry (p < 0.05). Results: GLP-1 mRNA expression was statistically significantly more upregulated in HM than in HF at 3 weeks. Moreover, GLP-1 mRNA expression was significantly higher in HM than in both SM and HF at 10weeks. Although a decreasing trend was observed in GIP mRNA expression in both 3- and 10-week-old rats fed on a HFD, a significant difference between HM and SM only occurred at 3weeks. Furthermore, the GIP mRNA expression of HM was lower than that of HF at 10weeks. Immunohistochemical staining revealed GLP-1 and GIP expression mainly in the SMG duct system. Moreover, vacuolated cytoplasm in the duct was observed in rats fed on a HFD. Conclusion: Exposure to HFD during pre- and post-natal periods increased GLP-1 mRNA expression in the SMGs of male rats. However, GIP expression decreased following the HFD in male newborns. Furthermore, a decreasing trend of GIP mRNA expression was observed in male newborns after HFD feeding. Sex influenced incretin hormones secretion and obesity-related conditions. HFD during pre- and post-natal periods reprograms the epigenome, contributing to subsequent disease development.

A case of acute submandibular sialadenitis caused by a fish bone that strayed into the submandibular gland duct

AbstractBackgroundFish bones commonly stray into the tongue base, palatine tonsils, and pharyngeal mucosa but rarely into the submandibular gland duct.Case presentationA 74‐year‐old man developed acute sialadenitis after a fish bone strayed into the submandibular gland duct. Laboratory data revealed elevated S‐amylase level; computed tomography (CT) revealed linear opacification along the submandibular gland duct. Electron microscopic analysis confirmed the object to be a fish bone; the bone discharged spontaneously prior to a scheduled excision.ConclusionIdentification of foreign bodies is difficult with CT or other imaging modalities alone. Additional detailed examination, such as electron microscopy analysis, is required.

Idiopathic dilatation of the submandibular gland duct

Lithiasis and stenosis may cause salivary duct dilatation due to the increased pressure in the duct upstream of the obstruction. Idiopathic dilatations, also called megaducts, with no associated increase in pressure, have only been described in the parotid gland. The aim of this study was to describe the characteristics of submandibular duct dilatation unrelated to lithiasis, stenosis, or an imperforate duct, to report the existence of submandibular megaducts. This retrospective single-centre study included patients treated at La Conception University Hospital, Marseille, France, between 2007 and 2019. Patients with submandibular duct dilatation of ≥4 mm confirmed by magnetic resonance imaging sialography (sialo-MRI), who also underwent sialendoscopy to identify any associated stenosis, were included. Patients with lithiasis, stenosis, an imperforate ostium, or a history of trauma or surgery to the floor of the mouth were excluded. Five patients (three female, two male) aged 30–76 years with idiopathic duct dilatations in nine submandibular glands were included. The most commonly reported symptoms were submandibular swelling, pruritus, and discomfort, mostly outside mealtimes. Recurrence of symptoms after treatment was frequent. This study is novel in describing submandibular megaducts as opposed to dilatation caused by high pressure associated with stenosis, with confirmation by sialo-MRI and sialendoscopy.

An immunohistochemical study of the vasculature and stem cells and carbonic anhydrase IV in the ducts of irradiated and normal human submandibular salivary glands

ABSTRACT Therapeutic irradiation for cancers of the head and neck causes serious and irreversible damage to the salivary glands; the resulting adverse effects on salivary quality and quantity produce detrimental effects on teeth and oral mucosa. The salivary effects have been related mostly to loss of serous acini; damage to the ducts is relatively minor. Other radiation effects include fibrosis, adiposis and vascular damage. Stem cells in the salivary gland ducts have the potential to generate acinar cells in vitro and in vivo. I investigated the ducts and vasculature in irradiated and normal human submandibular glands using immunohistochemical localization of biomarkers of stem cells, duct function and blood vessels. Stem cell markers CK5 and Sca-1 labeled the cytoplasm of the basal and intercalated duct cells and all duct cells, respectively, in both normal and irradiated glands. CA IV, which participates in regulating salivary electrolytes and acid-base balance, labeled the cytoplasm of all ducts. CD34 labeling demonstrated more extensive vasculature in the irradiated glands than in the normal glands. My findings suggest that duct stem cells and at least one duct function persisted, and the vasculature was greater, despite moderate fibrosis, in the irradiated gland.

Carbon quantum dots as immune modulatory therapy in a Sjögren's syndrome mouse model.

The objective of the study was to evaluate the therapeutic effects of carbon quantum dots (CQDs) in immunomodulation on non-obese diabetic (NOD) mice, as the model for Sjögren's syndrome (SS). Carbon quantum dots were generated from Setaria viridis via a hydrothermal process. Their toxic effects were tested by cell viability and blood chemistry analysis, meanwhile therapeutic effects were investigated in NOD mice in the aspects of saliva flow, histology, and immune cell distribution. Carbon quantum dots, with rich surface chemistry and unique optical properties, showed non-cytotoxicity in vitro or no damage in vivo. Intravenously applied CQDs alleviated inflammation in the submandibular glands in NOD mice after 6-week treatments. The inflammatory area index and focus score were significantly decreased in CQD-treated mice. Besides, the levels of anti-SSA and anti-SSB were decreased in the presence of CQDs. The stimulated saliva flow rates and weight of submandibular glands were significantly increased in CQD-treated mice by reducing the apoptosis of cells. The CD3+ and CD4+ T cells distributed around the ducts of submandibular glands were significantly decreased, while the percentage of Foxp3+ cells was higher in CQD-treated mice than that in the control group. Our findings suggest that CQDs may ameliorate the dysregulated immune processes in NOD mice.

The histologic comparison of submandibular gland between yak and yellow cattle.

The purpose of this study was to compare between the histochemical characteristics and the expression of epidermal growth factor (EGF) and it's receptor (EGFR) in the submandibular gland (SMG) of adult yaks and yellow cattle. The SMG tissues of yaks and yellow cattles were collected for histochemical, immunohistochemical (IHC), immunofluorescence (F-IHC)，real-time quantitative polymerasechain reaction (RT-qPCR) and Western blotting methods. The results showed that the striated ducts of SMG were highly developed and connected to the intercalated ducts, which were shorter and directly connected to the acini. Compared with yellow cattle, yak SMG contains more mucous acini. Immunofluorescence showed significant expression of EGF and its receptor in both striated and intercalated ducts of these two species of cattle. Statistical analysis divulged that the distribution density of EGF and EGFR in the SMG of the yak was both significantly higher than that in yellow cattle (p < 0.05). Furthermore, the mRNA expression of EGF and EGFR in yak SMG was also higher than that in yellow cattle. The above results indicated that the intercalated ducts and striated ducts are the main expression sites of EGF and EGFR, the acidic mucin and EGF secreted from SMG of yak were more than that from yellow cattle. The results of this study provide powerful data for the study of physiological functions of submaxillary gland in ruminants and also provide important clues for the study of adaptive physiological mechanisms in plateau organisms.

Expression with early postnatal peak and female-dominant sexual dimorphism of phospholipase D (PLD) 2 in submandibular gland ducts in situ of mice.

In the present study, expression and localization of PLD2 were examined in mouse submandibular glands in situ in comparison with those of PLD1 previously reported by the present authors. In immunoblots, PLD2-expression was high at postnatal 0week (P0W) and P2W, and at P4W decreased considerably with the decrease of the male gland more marked, and at P8W it was undetectable in the male gland, but remained faint in the female. In the male gland at P8W after castration at P6W, PLD2-expression reappeared faintly. In the female glands with daily injections of testosterone started at P6W, at P8W the expression was undetectable. In immunohistochemistry, PLD2 was localized throughout immature duct epithelia without distinct regional differences in its intensity at P0W and P2W. PLD2-localization was weak and diffuse in granular convoluted tubules at P4W and negligible there at P8W in the female gland, while it was at negligible levels in the tubules at P4W and at undetectable levels there at P8W in the male gland. The expression changes detected in immunoblots after castration or testosterone injection were duplicated in granular convoluted tubules in immunohistochemistry. The present findings suggest that PLD2 is dominantly involved in proliferation/differentiation/apoptosis of most immature ductal cells at early postnatal and at least perinatal stages, different from PLD1. This also indicates that the female-dominant sexual dimorphism of PLD2-expression occurs in synchrony of differentiation of granular convoluted tubules at puberty and at young adulthood, similar to PLD1 though at much lower levels.

EXTRAORAL APPROACH FOR THE TREATMENT OF A LARGE PROPORTIONS SIALOLITHIASIS AFFECTING THE SUBMANDIBULAR GLAND

Sialolithiasis is defined as the development of stones within the parenchyma or ducts of the salivary glands, and it frequently affects the submandibular gland duct of male adults. We report a case of sialolithiasis occurring in the submandibular gland parenchyma and its surgical treatment. A 44-year-old male patient was referred for evaluation of a painful swelling in the submandibular region with 1-week evolution. The extraoral examination revealed a volume growth in the right submandibular region. Intraorally, there were no alterations. The panoramic radiography revealed a well-defined radiopaque lesion measuring approximately 2.5 cm. The clinical and radiographic findings established the sialolithiasis diagnosis. The treatment consisted of the excision of both sialolith and the right submandibular gland due to its location in the parenchyma, under general anesthesia, using an extraoral submandibular approach. The specimen was subsequently sent to the laboratory for histologic confirmation. The patient's recovery was uneventful.

Establishing correlations between normal pancreatic and submandibular gland ducts

BackgroundThe objectives of this study were to evaluate the relationship between ductal morphometry and ramification patterns in the submandibular gland and pancreas in order to validate their common fractal dimension.MethodsX-ray ductography with software-aided morphometry were obtained by injecting barium sulphate in the ducts of post-mortem submandibular gland and pancreas specimens harvested from 42 adult individuals.ResultsThree cases were excluded from the study because of underlying pathology. There was a significant correlation between the length of the main pancreatic duct (MPD) and the intraglandular portion of the right submandibular duct (SMD) (r = 0.3616; p = 0.028), and left SMD (r = 0.595; p < 0.01), respectively, but their maximal diameters did not correlate (r = 0.139—0.311; p > 0.05). Both dimensions of the SMD showed a significant right-left correlation (p < 0.05). The number of MPD side branches (mean = 37) correlated with the number of side branches of left SMD, but not with the right one (mean = 9). Tortuosity was observed in 54% of the MPD, 32% of the right SMD, and 24% of the left SMD, with mutual association only between the two salivary glands.ConclusionsAlthough the length of intraglandular SMD and MPD correlate, other morphometric ductal features do not, thus suggesting a more complex relationship between the two digestive glands.

Congenital atresia of the submandibular gland duct: report of two clinical cases with spontaneous regression and literature review

Background: Congenital atresia of the submandibular gland duct is a rare condition, originated during the embryogenic process, characterized by swelling in the region of the oral floor. A few cases of congenital atresia of the submandibular gland duct have appeared in the literature and only one reports no surgical intervention to date.&#x0D; Case series: In the present study reports two cases of babies with clinical findings demonstrating swelling well-defined in the region of the oral floor, slightly translucent bluish color, painless to palpation, without finding stones or salivary drainage and apparently with no perforation of the submandibular gland duct. Both patients were kept under observation, later presenting spontaneous regression.&#x0D; Conclusion: This study highlights the importance of conducting a thorough clinical examination in addition to showing that the use of complementary exams may not be essential.

Sialin mediates submandibular gland regeneration ability by affecting polysialic acid synthesis.

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.

Systemic immune response development in Albino rats after retrograde instillation of COVID-19 vaccine to submandibular salivary gland: An experimental study

ObjectiveThis study aimed to investigate whether using the submandibular gland duct (SMD) as an alternative mucosal route for vaccine administration induced anti-COVID-19 specific immunity. Material and methodsForty rats were randomized equally into four groups; Group I: Rats did not receive any intervention. Group II: Rats were subjected to intramuscular (IM) injection of COVID-19 vaccine. Group III: Rats were subjected to ductal cannulation by retrograde instillation of sterile saline into right SMD. Group IV: Rats in this group who had 0.5 ml of COVID-19 vaccine retrogradely injected into the right SMD. Subsequently, rats were examined for anti-COVID-19 specific antibodies (IgG). Also, light microscopic observation of glandular changes and immunohistochemical staining for CD20 was performed. ResultsThe obtained results demonstrated a significant increase in anti-COVID-19 IgG levels in all rats vaccinated via intraductal immunization (group IV) compared to group II. Histologically, ectopic follicles were found within the glandular lobules of the inoculated submandibular gland (SMG) in group IV. In addition, the nearby lymph node in group IV demonstrated reactive follicle characteristics in the form of activated secondary follicles with germinal centers (GCs). Immunohistochemically, CD20 was localized in group IV in GCs of the ectopic lymphoid tissue and the nearby lymph nodes while group I, group II, and III demonstrated negative immunoreactivity. ConclusionThe immune response demonstrated by intraductal SG immunization is generally more significant than that elicited by IM inoculation of the same vaccine.

CTRP3 promotes TNF-α-induced apoptosis and barrier dysfunction in salivary epithelial cells

BackgroundC1q/tumour necrosis factor-related protein 3 (CTRP3) plays important roles in metabolism and inflammatory responses in various cells and tissues. However, the expression and function of CTRP3 in salivary glands have not been explored. MethodsThe expression and distribution of CTRP3 were detected by western blot, polymerase chain reaction, immunohistochemical and immunofluorescence staining. The effects of CTRP3 on tumour necrosis factor (TNF)-α-induced apoptosis and barrier dysfunction were detected by flow cytometry, western blot, co-immunoprecipitation, and measurement of transepithelial resistance and paracellular tracer flux. ResultsCTRP3 was distributed in both acinar and ductal cells of human submandibular gland (SMG) and was primarily located in the ducts of rat and mouse SMGs. TNF-α increased the apoptotic rate, elevated expression of cleaved caspase 3 and cytochrome C, and reduced B cell lymphoma-2 (Bcl-2) levels in cultured human SMG tissue and SMG-C6 cells, and CTRP3 further enhanced TNF-α-induced apoptosis response. Additionally, CTRP3 aggravated TNF-α-increased paracellular permeability. Mechanistically, CTRP3 promoted TNF-α-enhanced TNF type I receptor (TNFR1) expression, inhibited the expression of cellular Fas-associated death domain (FADD)-like interleukin-1β converting enzyme inhibitory protein (c-FLIP), and increased the recruitment of FADD with receptor-interacting protein kinase 1 and caspase 8. Moreover, CTRP3 was significantly increased in the labial gland of Sjögren's syndrome patients and in the serum and SMG of nonobese diabetic mice. ConclusionsThese findings suggest that the salivary glands are a novel source of CTRP3 synthesis and secretion. CTRP3 might promote TNF-α-induced cell apoptosis through the TNFR1-mediated complex II pathway.

Rekürren aftöz stomatitli hastalarda serum ve tükürükte dermcidin düzeylerinin araştırılması ve tükürük bezinde dermcidin analizi

Objective Recurrent aphthous stomatitis (RAS) is a common self-limiting oral mucosa disease. In this study, it was aimed to determine the dermcidin level in the serum and saliva of patients with RAS, the presence of dermcidin in the salivary gland and its role in the pathogenesis of RAS. Methods Thirty-one patients presenting with RAS and 30 control subjects participated in this study. Dermcidin levels in serum and saliva of patients and control group were studied in accordance with the working procedures specified in the catalogs of the human dermcidin ELISA kit. The presence of dermcidin in salivary glands was assessed by immunohistochemical analysis. Results A statistically significant difference was found when the mean salivary dermcidin levels (105.80 ± 80.14 ng/mL) of the RAS patients were compared with the mean salivary dermcidin levels (456.13 ± 354.59 ng/mL) of the control group (P=0.000). There was no statistically significant difference between the mean serum dermcidin levels (316.41 ± 784.55 ng/mL) of the RAS patient and those of (130.65 ± 179.75 ng/mL) the control group. Dermcidin immunoreactivity was observed in the parotid gland, submandibular gland and interlobular striated ducts. Conclusion The findings in this study showed that striated cells in salivary gland synthesized dermcidin. Low levels of dermcidin with antimicrobial properties in saliva were considered as a predisposing factor for RAS.

Management of an unusual giant submandibular gland sialolith with a sialo-cutaneous fistula; A case report

Objective: Sialolithiasis is the most common disease of the salivary glands that can promote sialadenitis and mostly are found in the submandibular gland.1,3 Usually characterized by swelling, pain, infection, and dilation of the salivary duct reduced salivary flow and purulent discharge.2,3 The size may vary from less than 1 mm to a few cm in largest diameter, with most sialoliths being <10 mm in size.2,4We reported a giant submandibular sialolith related to sialo-cutaneous fistula that is likely less commonly reported in the literature. Methods: A 48 old years old male presented with swelling and pain on the left submandibular region since 2 months before the admission, purulent discharges from the fistula near the bulge on the left submandibular area, also from the left floor of the mouth. There was a history of trauma on the swelling are approximately 10 years ago. Computed Tomography (CT) Scan showed the presence of a cylindrical and elongated sialolith located within the Wharton's duct of the left submandibular gland, Panoramic radiograph showed a radiopaque structure superimposed on the left submandibular area. diagno submandibular area. Diagnosis of left submandibular gland sialolithiasis was established. Surgical removal of the sialolith via submandibular approach incision followed by necrotomy of the infected cutaneous fistula was performed under general anesthesia. Results: The extracted sialolith was hard in consistency, brown colored, rounded, and elongated with a dimension of 33 mm long. Administration of antibiotics, analgetic, and corticosteroid injections during hospitalization for three days after surgery than followed up on day seventh. The patient showed no significant postoperative complications the salivary flow was seen to be normal, and no signs of nerve injuries. Conclusion: Sialolithiasis considered to be the most common salivary gland disease, cutaneous fistula related to a giant submandibular gland sialolith is still less commonly reported in the literature. Conservative treatments are distinctive to small-sized sialoliths. Surgical removal is the treatment of choice for both trans-oral or submandibular approaches in our present case.

A Giant Sialolith Consisted of Tooth-like Tissue in the Duct of Submandibular Gland

A Giant Sialolith Consisted of Tooth-like Tissue in the Duct of Submandibular Gland

Nerve growth factor protects salivary glands from irradiation-induced damage

AimsRadiotherapy has become a basic treatment modality for head and neck cancer. However, radiotherapy results in inevitable side effects, particularly radiation sialadenitis, that significantly impairs quality of life. A previous study indicated that nerve growth factor (NGF) has a radio-protective effect, but the mechanism was not determined in salivary glands. In this study, we explored the functional role and mechanism regarding how NGF protects salivary glands against IR-induced damage. Main methodsHuman salivary gland (HSG) cells and C57BL/6 mice were selected to establish an IR-induced salivary gland damage model in vitro and in vivo. Recombinant NGF protein and NGF siRNA and over-expression plasmids were applied to manipulate NGF expression in vitro. AAV-NGF was retrogradely perfused into the submandibular gland (SMG) through the SMG duct to manipulate NGF expression in vitro. Small-molecule inhibitors and siRNAs were applied to inhibit AKT and JNK. Western blotting, quantitative PCR, flow cytometry and histology assays were performed to analyse the functional role and mechanism of NGF. Key findingsOur study demonstrated that NGF expression was upregulated following radiotherapy both in human HSG cells and mouse SMG tissues. NGF could reduce IR-induced HSG cell apoptosis, and AAV-mediated gene therapy could restore the salivary flow rate and protect the salivary gland against IR-induced apoptosis in vivo. Mechanistically, NGF protects salivary glands from IR-induced apoptosis by de-phosphorylating JNK kinase rather than promoting AKT phosphorylation. SignificanceThe current study findings indicated that the modulation of the NGF pathway might prevent IR-induced salivary hypo-function.

GIANT SIALOLITH IN SUBMANDIBULAR DUCT WITH 10 YEARS OF EVOLUTION: A CASE REPORT

The aim of this study is to report a rare case of giant sialolith located in the submandibular gland and to discuss the types of treatment with their benefits. A 42-year-old female patient presented a nodular, fibrous, sessile, painful, and mucosa-like lesion located in the right-side submandibular gland duct, which had 2.5 cm in dimensions and 10 years of evolution. Radiographic examination was requested to confirm the diagnostic hypothesis of sialolith. Surgical treatment was performed by intraoral access in the obliterated duct region, and afterward the affected gland kept in operation without relapses or postoperative complications. Numerous forms of treatment are used in the calculi removal from ductal system, and treatment may range according to size, shape, and location of the calculus. Early diagnosis is essential because of painful symptoms and discomfort. The aim of this study is to report a rare case of giant sialolith located in the submandibular gland and to discuss the types of treatment with their benefits. A 42-year-old female patient presented a nodular, fibrous, sessile, painful, and mucosa-like lesion located in the right-side submandibular gland duct, which had 2.5 cm in dimensions and 10 years of evolution. Radiographic examination was requested to confirm the diagnostic hypothesis of sialolith. Surgical treatment was performed by intraoral access in the obliterated duct region, and afterward the affected gland kept in operation without relapses or postoperative complications. Numerous forms of treatment are used in the calculi removal from ductal system, and treatment may range according to size, shape, and location of the calculus. Early diagnosis is essential because of painful symptoms and discomfort.

Disruption of tight junctions contributes to hyposalivation of salivary glands in a mouse model of type 2 diabetes.

Tight junction (TJ) plays an important role in regulating paracellular fluid transport in salivary glands; however, little is known about the involvement of TJs in diabetes salivary glands. This study aimed to investigate the alterations of TJs and their possible contribution in diabetes-induced hyposalivation. Here, we observed that the morphologies of submandibular glands (SMGs) were impaired, characterized by enlarged acini accumulation with giant secretory granules, which were significantly reduced in atrophic ducts in SMGs of db/db mice, a spontaneous model of type-2 diabetes. However, the secretory granules were increased and scattered in the acini of diabetes parotid glands (PGs). Other ultrastructural damages including swollen mitochondria, expansive endoplasmic reticulum, and autophagosomes were observed in the diabetes group. The levels of TJ proteins including claudin-1 (Cldn1) and claudin-3 (Cldn3) were increased, whereas those of claudin-4 (Cldn4), occludin (Ocln), and zonula occludens-1 (ZO-1) were decreased in SMGs of db/db mice. Higher Cldn1 and Cldn3 and lower claudin-10 (Cldn10) and Ocln levels were observed in PGs of diabetes mice. Taken together, the structures of SMGs and PGs were impaired in diabetes mice, and the disruption of TJ integrity in both SMGs and PGs may contribute to diabetes-induced hyposalivation.