Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully e...Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.展开更多
AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially wi...AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.展开更多
Autologous submandibular gland（SMG） transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and the...Autologous submandibular gland（SMG） transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously.This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients＇ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.展开更多
To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to th...To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 cases.RESULTSThe sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid administration.CONCLUSIONSG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.展开更多
BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases ha...BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases have occurred in the parotid gland.The exact nature of SPA is unclear,but its tumor nature has recently been proposed.Although SPA has a good prognosis after adequate surgery,atypical lesions might occur,ranging from mild dysplasia to carcinoma in situ in some cases.To the best of our knowledge,only five cases of SPA in the submandibular gland have been reported to date.Here,we present two new cases of SPA involving the submandibular gland.CASE SUMMARY A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan,China,with complaints of moderate pain,recurrent swelling,and a mass in the submandibular area.After admission,the two cases of the submandibular mass were examined physically.The boundary of the submandibular tumor was clear,and the range of motion was good.After preoperative examinations,surgery was performed on a selective basis.Postoperative histopathological examination revealed a well-defined mass with acinar structures,ducts,or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma.There were flat and cuboidal cells,and eosinophils in the duct epithelium.There was also a eosinophilic substance in the lumen of dilated cysts.No atypical epithelial hyperplasia,invasive growth,or carcinoma in situ was found.Based on the above findings,the mass was diagnosed as SPA.Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up,respectively.CONCLUSIONSPA is a rare disease of the salivary gland. Even though it has a good prognosisafter adequate surgery, atypical lesions may occur from mild dysplasia tocarcinoma in situ. However, no recurrence, distant metastasis, or mortality hasbeen reported for submandibular gland SPA. Clinicians and pathologists shouldbe familiar with the characteristics of SPA in the submandibular gland to avoidmisdiagnosis and overtreatment.展开更多
BACKGROUND Salivary duct carcinoma(SDC)is a rare,extremely aggressive malignancy that arises in the submandibular gland.It can metastasize locally early and therefore is an important differential diagnosis of metastat...BACKGROUND Salivary duct carcinoma(SDC)is a rare,extremely aggressive malignancy that arises in the submandibular gland.It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis.CASE SUMMARY We report a case of SDC in the submandibular gland that presented diagnostic difficulty.The lesion was coincidentally discovered through examination of the radiolucent area of the maxilla.Imaging failed to confirm the possibility of specific inflammation,leading us to execute an open biopsy to verify the diagnosis.The surgical specimen showed that the submandibular gland was primarily replaced with a calcified body.Following histological analysis and confirmation,we performed surgical resection,radiotherapy,and various chemotherapies.CONCLUSION Radiographic imaging characteristics of lymph node metastases of salivary gland cancer,especially of SDC,may resemble other cervical lymphadenitis;calcification at the submandibular gland is the landmark of SDC occurring at the submandibular gland.展开更多
BACKGROUND Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness.However,recent studies have found that endoscopic removal failure(ERF)is not unusual,and s...BACKGROUND Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness.However,recent studies have found that endoscopic removal failure(ERF)is not unusual,and stones in such cases still need to be removed with other surgical methods.If the risk of ERF can be predicted preoperatively,it could be helpful for surgeons when choosing the appropriate therapy.AIM To develop a predictive nomogram for the risk of ERF when treating submandibular stones based on their preoperative clinical features.METHODS A total of 180 patients with 211 submandibular stones treated from January 2012 to December 2020 were included in the current study.Based on the preoperative clinical features of the stones,independent risk factors for ERF were identified by logistic regression analysis.The stones were then randomly divided into training and testing sets.A nomogram was constructed to predict the risk of ERF using the training set and then validated using both sets.The predictive performance of the nomogram was assessed by calibration curves and the concordance index(Cindex).RESULTS Three independent predictors,location(P=0.040),transverse diameter(P<0.001)and longitudinal diameter(P<0.001)measured on the cone beam computed tomography(CBCT)images of the submandibular stones,were identified and included in the predictive nomogram.Calibration curves of the nomogram showed good agreement between the predicted and observed probabilities in both sets.The C-index in the training set was 0.917(95%CI,0.875-0.959)and that in the testing set was 0.925(95%CI,0.862-0.989).CONCLUSION A nomogram based on the location,transverse and longitudinal diameters on CBCT images of submandibular stones showed satisfactory efficacy in predicting the risk of ERF preoperatively when treating submandibular stones.展开更多
Intravascular papillary endothelial hyperplasia is an unusual benign vascular lesion of the skin and subcutaneous tissue consisting of papillary formations lined with proliferative endothelial cells. The clinical char...Intravascular papillary endothelial hyperplasia is an unusual benign vascular lesion of the skin and subcutaneous tissue consisting of papillary formations lined with proliferative endothelial cells. The clinical characteristic is not specific and the diagnosis is based on histological examination. The lesion is often mistaken for angiosarcoma and a group of other benign and malignant vascular lesions. IPEH has been relatively rarely described in the head and neck region. An uncommon case located in the submandibular and sublingual region is presented which was misinterpreted as venous malformations and malignant tumors of vascular origin initially. A surgical excision was performed and no recurrences have been found after 5 years of follow-up.展开更多
The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva pr...The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva production at 37°C was 5.5-fold that at 25°C with pilocarpine stimulation and 9.8-fold that at 25°C with cevimeline stimulation. Both of these muscarinic agonists are used clinically. With the experimental agonist carbachol (CCh), saliva secretion was increased with an increase in temperature, but the CCh concentration producing the peak flow was the same in both dose-response curves, suggesting that the muscarinic receptor itself is not responsible for the temperature dependence. Purinergic agonists also induced temperature-dependent saliva production ex vivo. The calcium ionophore A23187 failed to have a significant effect on saliva production. The CCh-induced increase in intracellular Ca2+ also upregulated the initial increase and sustained the plateau phase of saliva flow. Thus, muscarinic receptor stimulation of saliva production is temperature sensitive due to an increase in intracellular Ca2+.展开更多
The possible role of submandiblular glands (SMG) in the development of obesity was studied in two types of genetically obese mice, ob/ob and yellow Ay: Obesity is caused by hyperplasia followed by hypertrophy in ob/ob...The possible role of submandiblular glands (SMG) in the development of obesity was studied in two types of genetically obese mice, ob/ob and yellow Ay: Obesity is caused by hyperplasia followed by hypertrophy in ob/ob mice and mainly by hypertrophy in Ay mice.The histological features of SMGs exhibited clear sexual dimorphism in both mice similarto lean controls. The SMGs of ob/ob mice was smaller in size and had smaller granular convoluted tubular portions than lean controls, while the SMGs of Ay mice did not differ from lean controls. Sialoadenectomy before and after development of obesity gCnerally reduced the gain of body weights in both sexes of Ay mice but not in ob/ob mice. The content of epidermal growth factor (EGF) in the SMGs was higher in Ay mice and lower in ob/ob mice than their controls. The possible role of EGF in the SMGs in the development of obesity is discussed展开更多
BACKGROUND Occult thyroid papillary carcinoma(OTPC)is typically characterized by initial presentation with cervical lymph node metastasis and can be detected through ultrasound.However,the initial and sole manifestati...BACKGROUND Occult thyroid papillary carcinoma(OTPC)is typically characterized by initial presentation with cervical lymph node metastasis and can be detected through ultrasound.However,the initial and sole manifestation was a submandibular solid-cystic mass.High-frequency ultrasound,enhanced multislice computed tomography(CT)scan,and thyroid function tests revealed no abnormalities,which is relatively uncommon.CASE SUMMARY A 24-year-old Chinese female,who studied at a university in Shandong Province,presented to the clinic in June 2019 with a right submandibular mass that she had noticed 2 mo earlier.Clinical examination revealed a 2-cm,nontender,movable solid-cystic mass in the submandibular region,with no palpable thyroid mass observed.Ultrasonography revealed a 2.0 cm×1.1 cm solid-cystic mass in the right submandibular region,and the thyroid gland showed no abnormalities.CT scan and 131I whole body follow-up scan showed that there were no abnormalities in the thyroid.However,cytology and pathology showed papillary tumor cell clusters,consistent with papillary thyroid carcinoma.Thus,we performed total thyroidectomy and right neck lymph node dissection.The pathology revealed the thyroid was detected as classical thyroid micropapillary carcinoma,and lymph nodes of levels VI central and levels II,III,IV,V on the right side showed no tumor metastasis.The patient was followed up for 2 years without significant recurrence.CONCLUSION The presentation of a submandibular solid-cystic mass as the primary and solitary indication of OTPC is relatively uncommon.Fine needle aspiration is advised for evaluating neck masses.展开更多
Epidermal cysts are very common skin lesions and 1.6% are seen in oral cavity. But epidermal cyst in submandibular region is extremely rare with only 3 such reported cases in last 25 years. Here we present a rare case...Epidermal cysts are very common skin lesions and 1.6% are seen in oral cavity. But epidermal cyst in submandibular region is extremely rare with only 3 such reported cases in last 25 years. Here we present a rare case of epidermal cyst in left submandibular space in a 53-year-old female.展开更多
BACKGROUND： Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotec...BACKGROUND： Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE： To observe the effect of 17 beta-estradiol on the content of norepinephrine （NE） and level of tumor necrosis factor （TNF） in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN： A randomized control animal study SETTINGS： Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS： Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group： sham-operated group, ovariectomy＋6-OHDA＋saline group, ovariectomy＋6-OHDA＋17β-estradiol 50, 200 and 500 μg/kg groups. METHODS： The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy＋6-OHDA＋176-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA （8 mg/kg）, and then immediately given 176-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy＋6-OHDA＋saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector （HPLC-ECD）, and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay. MAIN OUTCOME MEASURES： The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS： All the 50 rats were involved in the analysis of results. （1） The NE content was obviously lower in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（1 035±196）, （1 823±314） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（1 004±253）, （1 035±196） ng/g, P 〉 0.05], but obviously higher in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（1 487±268）, （1 939±274）, （1 035±196） ng/g, P 〈 0.05]. （2） The TNF level was obviously higher in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（3.498±0.792）, （1.893±0.533） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋ 6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（3.328 ±0.712）, （3.498±0,792） ng/g, P 〉 0.05], but obviously lower in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（2.639±0.438）, （2.016±0.619）, （3.498＋0.792） ng/g, P 〈 0.05]. CONCLUSION： Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.展开更多
Lymphatic malformation (ML), formerly called cystic lymphangioma is a benign hamartomatous tumor of lymphatic vessels. The onset of lymphangiomas is either at birth (60% to 70%) or up to two years of age (90%) and rar...Lymphatic malformation (ML), formerly called cystic lymphangioma is a benign hamartomatous tumor of lymphatic vessels. The onset of lymphangiomas is either at birth (60% to 70%) or up to two years of age (90%) and rare in adults. These malformations can occur in any region of the body, Lymphangiomas have marked predilection for the head and neck region (50% - 70%). The most common location in the mouth is the dorsum of tongue. If the positive diagnosis is generally easy, the therapeutic management remains controversial. We report the clinical case of a 23-year-old adult patient with cystic lymphangioma on the floor of the oral cavity extending gradually to the right submandibular region. The clinically suspected tumor was thoroughly explored using tomodensitometry. The treatment consisted of complete resection by a cervicotomy with histological examination confirming the macroscopic diagnosis of cystic lymphangioma. Follow-up at 3 years showed no recurrence.展开更多
Dermoid cyst of the oral floor is rare benign tumour, who having three histological aspects: dermoid, teratoid and epidermoid. This one is characterized by the presence of a squamous stratified epithelium with cutaneo...Dermoid cyst of the oral floor is rare benign tumour, who having three histological aspects: dermoid, teratoid and epidermoid. This one is characterized by the presence of a squamous stratified epithelium with cutaneous remnants. It may occur in any part of the body, however their frequency in the ENT sphere is relatively scarce. Seven per cent (7%) only of epidermoid cysts occur in the cervico-facial area, 1.6% of which locate at the floor level. When they are located submandibular, they can pose diagnostic difficulties and look like a tumour of the submaxillary gland. We report two cases of epidermoid cyst of the floor. Both patients suffered from swelling of the submandibular gland. Magnetic Resonance Imaging was not requested due to lack of resources. However, surgery allowed in both cases the excision of a cyst next to a normal submandibular gland. Patients did well post operatively.展开更多
Objective To evaluate the clinical results of sub-mandibular retropharyngeal cervical vertebrahook-plate (RCHP)reconsruction for the treatment of of C2 vertebral body tumors.Methods Nine patents with C2 vertebral body...Objective To evaluate the clinical results of sub-mandibular retropharyngeal cervical vertebrahook-plate (RCHP)reconsruction for the treatment of of C2 vertebral body tumors.Methods Nine patents with C2 vertebral body tumors展开更多
Background Transplanting a vascularized autologous submandibular gland （SMG） is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in ...Background Transplanting a vascularized autologous submandibular gland （SMG） is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in the blood vessels of SMG. The present study aimed to investigate the submandibular glands at the microanatomy level. Methods The microanatomy of blood vessels including arteries and veins of submandibular gland was investigated using 30 adult corpses and 60 submandibular glands were anatomized under a surgical microscope. The lengths and diameters of the arterial and venous glandular branches were measured using sliding caliper. Results The submandibular gland was mainly supplied by the facial artery and submental artery, partly by the lingual artery and external jugular artery. The venous drainage of the submandibualr gland occurred through the anterior facial vein, the venae comitantes of facial artery, the vein close to the Whaston＇s duct （the hilum vein）, and seldom drained to external jugular vein and other veins. Conclusions The anatomy of SMG is a complicated structure. Determining the main blood vessels of the submandibular gland is very important to achieve a successful vascularized autologous SMG transplant.展开更多
Autophagy is a catabolic process which is involved in the development of many diseases including diabetes mellitus and its complications. Hyposalivation is a common complication of diabetes mellitus, whereas its mecha...Autophagy is a catabolic process which is involved in the development of many diseases including diabetes mellitus and its complications. Hyposalivation is a common complication of diabetes mellitus, whereas its mechanism remains unclear. Here, we observed that the stimulated salivary flow rate of SMG was significantly decreased in db/db mice, a diabetic mice model. The expressions of aquaporin 5(AQP5), a water channel protein, were decreased, whereas the m RNA level of AQP5 was increased in SMGs of both diabetic patients and mice. Under transmission electron microcope, more autophagosomes were detected in diabetic SMGs. Expressions of autophagy related proteins LC3 II, Beclin-1 and ATG5 were increased, meanwhile autophagy substrate p62 was decreased in SMGs of diabetic patients and mice, indicating that autophagy was activated in diabetic SMG.Double immunofluorescence staining showed that the colocalization of AQP5 and LC3 was increased in SMGs of diabetic mice.In cultured SMG-C6 cells, high glucose(HG), but not high osmotic pressure, reduced AQP5 protein expression and induced autophagy. Moreover, inhibition of autophagy by 3-methyladenin, an autophagy inhibitor, or by autophagy-related gene 5 siRNA, decreased HG-induced AQP5 reduction in SMG-C6 cells. Additionally, the expression of p-p85, p-Akt and p-mTOR were decreased in HG-treated SMG-C6 cells. Pretreatment with 740 Y-P, a PI3 K agonist, significantly suppressed HG-induced autophagy and AQP5 degradation. Taken together, these results indicate that autophagy plays a crucial role in AQP5 degradation in diabetic SMG via PI3 K/Akt/mTOR signaling pathway, which contributes to the dysfunction of diabetic SMG. Our study provides a novel mechanism of diabetic hyposalivation.展开更多
Background Miniature pig （minipig） is increasingly used as a large animal model for a variety of biomedical studies. Little information is available in the literature on anatomy, histology and sialogragh of the subm...Background Miniature pig （minipig） is increasingly used as a large animal model for a variety of biomedical studies. Little information is available in the literature on anatomy, histology and sialogragh of the submandibular gland of the minipig. The purpose of this study was to characterize the morphology of a miniature pig＇s （minipig） submandibular gland as a large animal model for further biomedical studies. Methods Five minipigs were subjected to sialographic, anatomic, histologic, histochemical and uhrastructural evaluations for submandibular glands. Results Sialograms showed a long, horizontal main excretory duct and a pear-shaped gland located inferoposterior to the angle of the mandible. The submandibular glands lied superficial to the suprahyoid, and infrahyoid muscle groups, and were covered by the inferior portion of the parotid gland. The submandibular glands were characterized by a mixed parenchyma of mucous and serous secretory aeini. Alcian blue （AB） staining and periodic acid-Schiff （PAS） reactions demon-strated that minipig submandibular glands synthesized and secreted acid mucous substances by serous cells and polysaccharide, and neutral mucous substances, by mucous cells. Conclusion The submandibular gland of the minipig is considered a useful large salivary gland animal model for biomedical studies.展开更多
Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceU...Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceUular permeability in submandibular glands. However, the molecular mechanisms underlying AMPK-modulated paraceUular permeability are unknown. In this study, we found that AICAR, an AMPK agonist, increased saliva secretion in the isolated rat submandibular glands, decreased transepithelial electrical resistance （TER）, and increased 4 kDa FITC-dextran flux in cultured SMG-C6 cells. AICAR also induced redistribution of tight junction protein claudin-4, but not claudin-1, claudin-3, occtudin, or ZO-1, from the cytoplasm to the membrane. Moreover, knockdown of claudin-4 by shRNA suppressed while claudin-4 re-expression restored the TER and 4 kDa FITC-dextran flux responses to AICAR. Additionally, AICAR increased ERK1/2 phosphorylation, and inhibition of ERK1/2 by U0126, an ERK1/2 kinase inhibitor, or by siRNA decreased AICAR-induced TER responses. AICAR induced the serine S199 phosphorylation of claudin-4 and enhanced the inter- action of claudin-4 and occludin. Furthermore, pretreatment with U0126 significantly suppressed AMPK-modulated phosphorytation, redistribution, and interaction with occludin of claudin-4. Taken together, these results indicated that claudin-4 played a crucial role in AMPK-rnodutated paraceUular permeability and ERK1/2 was required in AMPK-modulated tight junction barrier function in subman- dibular gland.展开更多
基金grants from the National Natural Science Foundation of China （Nos. 30973336 and 81100762）.
文摘Botulinum toxin A （BTXA） has been used in several clinical trials to treat excessive glandular secretion; however, the precise mechanism of its action on the secretory function of salivary gland has not been fully elucidated. In this study, we aimed to investigate the effect of BTXA on secretion of submandibular gland in rabbits and to identify its mechanism of action on the secretory function of salivary gland. At 12 weeks after injection with 5 units of BTXA, we found a significant decrease in the saliva flow from submandibular glands, while the salivary amylase concentration increased. Morphological analysis revealed reduction in the size of acinar cells with intracellular accumulation of secretory granules that coalesced to form a large ovoid structure. Expression of M3-muscarinic acetylcholine receptor （M3 receptor） and aquaporin-5 （AQP5） mRNA decreased after BTXA treatment, and distribution of AQP5 in the apical membrane was reduced at 1, 2 and 4 weeks after BTXA injection. Furthermore, BTXA injection was found to induce apoptosis of acini. These results indicate that BTXA decreases the fluid secretion of submandibular glands and increases the concentration of amylase in saliva. Decreased expression of M3 receptor and AQP5, inhibition of AQP5 translocation, and cell apoptosis might involve in BTXA-reduced fluid secretion of submandibular lands.
基金Supported by Cooperation survey and research project of the Nippon Foundation of the Japan-China Medical Association (2006-12)the International cooperation project (BZ2006058) of Bureau of Science and Technology of Jiangsu Province,China
文摘AIM： TO determine whether Chinese herbs （CHs） relieve xerostomia （dry mouth） by increasing salivary secretion. METHODS： The submandibular glands of Wistar rats were surgically isolated and perfused arterially with buffered salt solution. After control perfusion, recording started 5 min prior to the start of stimulation. After fluid secretion was induced by 0.2 μmol/L carbamylcholine （CCh） in the perfusate for 10 min, Chinese herb （CH） was added in the perfusion for 5 min. CCh was then overloaded at 0.2 μmol/L in the perfusion for 20 min. The volume of salivary fluid secretion was recorded by a computer-controlled balance system. RESULTS： Saliva secretion formed an initial ephemeral peak at 30 s followed by a gradual increase to a sustained level. CH alone induced no or little saliva in all types of CH selected. During perfusion with CH,overloading of CCh promoted fluid secretion in 1S of 20 CHs. This promotion was classified into four patterns, which were eventually related to the categories of CH： Overall sustained phase was continuously raised （Yin-nourishing, fluid production-promoting and heatclearing agents）; The sustained secretion rose to reach a maximum then decreased （Qi-enhancing agent）; Sustained secretion rose to reach the highest maximum and was then sustained with a slight decline （swelling-reducing, phlegm-resolving and pus-expelling agents）; Stimulation of salivary secretion without any added stimulants. Addition of CCh raised the fluid secretion to reach the highest maximum then sharply decreased to a lower sustained level （blood activating agent）. CONCLUSION： The present findings lead to the conclusion that various CHs have different promotional effects directly on the salivary gland.
基金supported by grants from the National Natural Science Foundation of China(No.81671005 and 81470756)
文摘Autologous submandibular gland（SMG） transplantation has been proved to ameliorate the discomforts in patients with severe keratoconjunctivitis sicca. The transplanted glands underwent a hypofunctional period and then restored secretion spontaneously.This study aims to investigate whether autonomic nerves reinnervate the grafts and contribute to the functional recovery, and further determine the origin of these nerves. Parts of the transplanted SMGs were collected from the epiphora patients, and a rabbit SMG transplantation model was established to fulfill the serial observation on the transplanted glands with time. The results showed that autonomic nerves distributed in the transplanted SMGs and parasympathetic ganglionic cells were observed in the stroma of the glands. Low-dense and unevenly distributed cholinergic axons, severe acinar atrophy and fibrosis were visible in the patients＇ glands 4–6 months post-transplantation, whereas the cholinergic axon density and acinar area were increased with time. The acinar area or the secretory flow rate of the transplanted glands was statistically correlated with the cholinergic axon density in the rabbit model, respectively. Meanwhile, large cholinergic nerve trunks were found to locate in the temporal fascia lower to the gland, and sympathetic plexus concomitant with the arteries was observed both in the adjacent fascia and in the stroma of the glands. In summary, the transplanted SMGs are reinnervated by autonomic nerves and the cholinergic nerves play a role in the morphological and functional restoration of the glands. Moreover, these autonomic nerves might originate from the auriculotemporal nerve and the sympathetic plexus around the supplying arteries.
文摘To assess the role of ultrasonography of submandibular glands (SGs) in the diagnosis of type 1 autoimmune pancreatitis (AIP).METHODSThirty-seven patients who were definitively diagnosed with type 1 AIP according to the international consensus diagnostic criteria (ICDC) for AIP at our institution between December 1990 and April 2016 were retrospectively reviewed. Findings by physical examination, ultrasonography, and scintigraphy of SGs were analyzed to reach a diagnosis based on the ICDC for AIP. The efficacy of corticosteroid treatment in the resolution of hypoechoic lesions in SGs was also evaluated by assessment with ultrasonography before and after treatment in 18 cases.RESULTSThe sensitivity of multiple hypoechoic lesions in SGs by ultrasonography for the diagnosis of sialadenitis in type 1 AIP (84%) was higher than that of physical examination (46%), scintigraphy (28%), and SGs thickness (49%). Ultrasonographic evidence of hypoechoic lesions in SGs improved the definitive diagnosis of sialadenitis and type 1 AIP by the ICDC criteria in 11 (30%) and 2 (5.4%) cases, respectively. Multiple hypoechoic lesions in SGs were resolved or disappear by corticosteroid administration in 14 of 16 cases with hypoechoic lesions in SGs, whereas the ultrasonographic findings in the remaining 2 cases with hypoechoic lesions in SGs and the 2 cases with homogenous SG parenchyma remained unchanged after corticosteroid administration.CONCLUSIONSG ultrasonography to detect multiple hypoechoic lesions might be useful for type 1 AIP diagnosis by improving diagnostic accuracy together with the ICDC sialadenitis criteria.
基金National Natural Science Foundation of China,No.82002893.
文摘BACKGROUND Sclerosing polycystic adenosis(SPA)is a rare disease of salivary glands,similar to fibrocystic disease of the breast.It occurs over a wide age range and exhibits a slight female preference.Most SPA cases have occurred in the parotid gland.The exact nature of SPA is unclear,but its tumor nature has recently been proposed.Although SPA has a good prognosis after adequate surgery,atypical lesions might occur,ranging from mild dysplasia to carcinoma in situ in some cases.To the best of our knowledge,only five cases of SPA in the submandibular gland have been reported to date.Here,we present two new cases of SPA involving the submandibular gland.CASE SUMMARY A 50-year-old woman and a 52-year-old woman were referred to Tongji Hospital in Wuhan,China,with complaints of moderate pain,recurrent swelling,and a mass in the submandibular area.After admission,the two cases of the submandibular mass were examined physically.The boundary of the submandibular tumor was clear,and the range of motion was good.After preoperative examinations,surgery was performed on a selective basis.Postoperative histopathological examination revealed a well-defined mass with acinar structures,ducts,or cystic dilated glands of various sizes scattered in a large number of proliferative sclerosing stroma.There were flat and cuboidal cells,and eosinophils in the duct epithelium.There was also a eosinophilic substance in the lumen of dilated cysts.No atypical epithelial hyperplasia,invasive growth,or carcinoma in situ was found.Based on the above findings,the mass was diagnosed as SPA.Both patients have remained asymptomatic and no recurrence or distant metastasis had occurred by the 7-mo and 5-year follow-up,respectively.CONCLUSIONSPA is a rare disease of the salivary gland. Even though it has a good prognosisafter adequate surgery, atypical lesions may occur from mild dysplasia tocarcinoma in situ. However, no recurrence, distant metastasis, or mortality hasbeen reported for submandibular gland SPA. Clinicians and pathologists shouldbe familiar with the characteristics of SPA in the submandibular gland to avoidmisdiagnosis and overtreatment.
文摘BACKGROUND Salivary duct carcinoma(SDC)is a rare,extremely aggressive malignancy that arises in the submandibular gland.It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis.CASE SUMMARY We report a case of SDC in the submandibular gland that presented diagnostic difficulty.The lesion was coincidentally discovered through examination of the radiolucent area of the maxilla.Imaging failed to confirm the possibility of specific inflammation,leading us to execute an open biopsy to verify the diagnosis.The surgical specimen showed that the submandibular gland was primarily replaced with a calcified body.Following histological analysis and confirmation,we performed surgical resection,radiotherapy,and various chemotherapies.CONCLUSION Radiographic imaging characteristics of lymph node metastases of salivary gland cancer,especially of SDC,may resemble other cervical lymphadenitis;calcification at the submandibular gland is the landmark of SDC occurring at the submandibular gland.
基金Supported by Guangdong Basic and Applied Basic Research FoundationNo. 2019A1515012139
文摘BACKGROUND Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness.However,recent studies have found that endoscopic removal failure(ERF)is not unusual,and stones in such cases still need to be removed with other surgical methods.If the risk of ERF can be predicted preoperatively,it could be helpful for surgeons when choosing the appropriate therapy.AIM To develop a predictive nomogram for the risk of ERF when treating submandibular stones based on their preoperative clinical features.METHODS A total of 180 patients with 211 submandibular stones treated from January 2012 to December 2020 were included in the current study.Based on the preoperative clinical features of the stones,independent risk factors for ERF were identified by logistic regression analysis.The stones were then randomly divided into training and testing sets.A nomogram was constructed to predict the risk of ERF using the training set and then validated using both sets.The predictive performance of the nomogram was assessed by calibration curves and the concordance index(Cindex).RESULTS Three independent predictors,location(P=0.040),transverse diameter(P<0.001)and longitudinal diameter(P<0.001)measured on the cone beam computed tomography(CBCT)images of the submandibular stones,were identified and included in the predictive nomogram.Calibration curves of the nomogram showed good agreement between the predicted and observed probabilities in both sets.The C-index in the training set was 0.917(95%CI,0.875-0.959)and that in the testing set was 0.925(95%CI,0.862-0.989).CONCLUSION A nomogram based on the location,transverse and longitudinal diameters on CBCT images of submandibular stones showed satisfactory efficacy in predicting the risk of ERF preoperatively when treating submandibular stones.
文摘Intravascular papillary endothelial hyperplasia is an unusual benign vascular lesion of the skin and subcutaneous tissue consisting of papillary formations lined with proliferative endothelial cells. The clinical characteristic is not specific and the diagnosis is based on histological examination. The lesion is often mistaken for angiosarcoma and a group of other benign and malignant vascular lesions. IPEH has been relatively rarely described in the head and neck region. An uncommon case located in the submandibular and sublingual region is presented which was misinterpreted as venous malformations and malignant tumors of vascular origin initially. A surgical excision was performed and no recurrences have been found after 5 years of follow-up.
文摘The physiological and pharmacological responses of an ex vivo mouse submandibular gland were used to study fluid secretion and cell signaling in response to muscarinic stimulation at increasing temperatures. Saliva production at 37°C was 5.5-fold that at 25°C with pilocarpine stimulation and 9.8-fold that at 25°C with cevimeline stimulation. Both of these muscarinic agonists are used clinically. With the experimental agonist carbachol (CCh), saliva secretion was increased with an increase in temperature, but the CCh concentration producing the peak flow was the same in both dose-response curves, suggesting that the muscarinic receptor itself is not responsible for the temperature dependence. Purinergic agonists also induced temperature-dependent saliva production ex vivo. The calcium ionophore A23187 failed to have a significant effect on saliva production. The CCh-induced increase in intracellular Ca2+ also upregulated the initial increase and sustained the plateau phase of saliva flow. Thus, muscarinic receptor stimulation of saliva production is temperature sensitive due to an increase in intracellular Ca2+.
文摘The possible role of submandiblular glands (SMG) in the development of obesity was studied in two types of genetically obese mice, ob/ob and yellow Ay: Obesity is caused by hyperplasia followed by hypertrophy in ob/ob mice and mainly by hypertrophy in Ay mice.The histological features of SMGs exhibited clear sexual dimorphism in both mice similarto lean controls. The SMGs of ob/ob mice was smaller in size and had smaller granular convoluted tubular portions than lean controls, while the SMGs of Ay mice did not differ from lean controls. Sialoadenectomy before and after development of obesity gCnerally reduced the gain of body weights in both sexes of Ay mice but not in ob/ob mice. The content of epidermal growth factor (EGF) in the SMGs was higher in Ay mice and lower in ob/ob mice than their controls. The possible role of EGF in the SMGs in the development of obesity is discussed
文摘BACKGROUND Occult thyroid papillary carcinoma(OTPC)is typically characterized by initial presentation with cervical lymph node metastasis and can be detected through ultrasound.However,the initial and sole manifestation was a submandibular solid-cystic mass.High-frequency ultrasound,enhanced multislice computed tomography(CT)scan,and thyroid function tests revealed no abnormalities,which is relatively uncommon.CASE SUMMARY A 24-year-old Chinese female,who studied at a university in Shandong Province,presented to the clinic in June 2019 with a right submandibular mass that she had noticed 2 mo earlier.Clinical examination revealed a 2-cm,nontender,movable solid-cystic mass in the submandibular region,with no palpable thyroid mass observed.Ultrasonography revealed a 2.0 cm×1.1 cm solid-cystic mass in the right submandibular region,and the thyroid gland showed no abnormalities.CT scan and 131I whole body follow-up scan showed that there were no abnormalities in the thyroid.However,cytology and pathology showed papillary tumor cell clusters,consistent with papillary thyroid carcinoma.Thus,we performed total thyroidectomy and right neck lymph node dissection.The pathology revealed the thyroid was detected as classical thyroid micropapillary carcinoma,and lymph nodes of levels VI central and levels II,III,IV,V on the right side showed no tumor metastasis.The patient was followed up for 2 years without significant recurrence.CONCLUSION The presentation of a submandibular solid-cystic mass as the primary and solitary indication of OTPC is relatively uncommon.Fine needle aspiration is advised for evaluating neck masses.
文摘Epidermal cysts are very common skin lesions and 1.6% are seen in oral cavity. But epidermal cyst in submandibular region is extremely rare with only 3 such reported cases in last 25 years. Here we present a rare case of epidermal cyst in left submandibular space in a 53-year-old female.
文摘BACKGROUND： Recent researches have indicated that estrogen has extensive neuroprotective effects. So some studies designed ovariectomized animal models and administrated with estrogen, so as to verify its neuroprotective effects. OBJECTIVE： To observe the effect of 17 beta-estradiol on the content of norepinephrine （NE） and level of tumor necrosis factor （TNF） in submandibular glands of rats with sympathetic nerve injury, and analyze the dose-dependence and pathway of action. DESIGN： A randomized control animal study SETTINGS： Department of Hand Surgery, the 252 Hospital of Chinese PLA; Department of Hand Surgery Union Hospital affiliated to Tongji Medical College, Huazhong University of Science and Technology. MATERIALS： Fifty healthy female Wistar rats were randomly divided into 5 groups with 10 rats in each group： sham-operated group, ovariectomy＋6-OHDA＋saline group, ovariectomy＋6-OHDA＋17β-estradiol 50, 200 and 500 μg/kg groups. METHODS： The experiments were carried out in Tongji Medical College, Huazhong University of Science and Technology between October 2005 and March 2006. Bilateral ovaries were only exposed but not resected for the rats in the sham-operated group, but bilateral ovaries were resected in all the other groups. In the ovariectomy＋6-OHDA＋176-estradiol 50, 200 and 500 μg/kg groups, the rats were administrated with intraperitoneal injection of 6-OHDA （8 mg/kg）, and then immediately given 176-estradiol of corresponding dosages respectively, once a day for 10 days continuously. Rats in the sham-operated group and ovariectomy＋6-OHDA＋saline group were administrated with saline of the same volume. After administration, 5 rats in each group were killed to determine the NE contents in bilateral submandibular glands with high performance liquid chromatography-electrochemical detector （HPLC-ECD）, and the other 5 rats were used to determine the TNF levels in submandibular glands with enzyme-linked immunosorbant assay. MAIN OUTCOME MEASURES： The NE contents and TNF levels in submandibular glands of rats in each group were observed. RESULTS： All the 50 rats were involved in the analysis of results. （1） The NE content was obviously lower in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（1 035±196）, （1 823±314） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（1 004±253）, （1 035±196） ng/g, P 〉 0.05], but obviously higher in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（1 487±268）, （1 939±274）, （1 035±196） ng/g, P 〈 0.05]. （2） The TNF level was obviously higher in the ovariectomy＋6-OHDA＋saline group than in the sham-operated group [（3.498±0.792）, （1.893±0.533） ng/g, P 〈 0.05], there were no significant differences between the ovariectomy＋ 6-OHDA＋17β-estradiol 50 μg/kg group and ovariectomy＋6-OHDA＋saline group [（3.328 ±0.712）, （3.498±0,792） ng/g, P 〉 0.05], but obviously lower in the ovariectomy＋6-OHDA＋17β-estradiol 200 and 500 μg/kg groups than in the ovariectomy＋6-OHDA＋saline group [（2.639±0.438）, （2.016±0.619）, （3.498＋0.792） ng/g, P 〈 0.05]. CONCLUSION： Estrogen has obvious protective effect dose-dependently on 6-OHDA induced chemical sympathetic nerve terminal injury in rats, and it may play its protective role by reducing TNF level and ameliorating inflammatory reaction.
文摘Lymphatic malformation (ML), formerly called cystic lymphangioma is a benign hamartomatous tumor of lymphatic vessels. The onset of lymphangiomas is either at birth (60% to 70%) or up to two years of age (90%) and rare in adults. These malformations can occur in any region of the body, Lymphangiomas have marked predilection for the head and neck region (50% - 70%). The most common location in the mouth is the dorsum of tongue. If the positive diagnosis is generally easy, the therapeutic management remains controversial. We report the clinical case of a 23-year-old adult patient with cystic lymphangioma on the floor of the oral cavity extending gradually to the right submandibular region. The clinically suspected tumor was thoroughly explored using tomodensitometry. The treatment consisted of complete resection by a cervicotomy with histological examination confirming the macroscopic diagnosis of cystic lymphangioma. Follow-up at 3 years showed no recurrence.
文摘Dermoid cyst of the oral floor is rare benign tumour, who having three histological aspects: dermoid, teratoid and epidermoid. This one is characterized by the presence of a squamous stratified epithelium with cutaneous remnants. It may occur in any part of the body, however their frequency in the ENT sphere is relatively scarce. Seven per cent (7%) only of epidermoid cysts occur in the cervico-facial area, 1.6% of which locate at the floor level. When they are located submandibular, they can pose diagnostic difficulties and look like a tumour of the submaxillary gland. We report two cases of epidermoid cyst of the floor. Both patients suffered from swelling of the submandibular gland. Magnetic Resonance Imaging was not requested due to lack of resources. However, surgery allowed in both cases the excision of a cyst next to a normal submandibular gland. Patients did well post operatively.
文摘Objective To evaluate the clinical results of sub-mandibular retropharyngeal cervical vertebrahook-plate (RCHP)reconsruction for the treatment of of C2 vertebral body tumors.Methods Nine patents with C2 vertebral body tumors
文摘Background Transplanting a vascularized autologous submandibular gland （SMG） is considered an effective method to treat severe keratoconjunctivitis sicca. But the operation may fail due to the anatomic variances in the blood vessels of SMG. The present study aimed to investigate the submandibular glands at the microanatomy level. Methods The microanatomy of blood vessels including arteries and veins of submandibular gland was investigated using 30 adult corpses and 60 submandibular glands were anatomized under a surgical microscope. The lengths and diameters of the arterial and venous glandular branches were measured using sliding caliper. Results The submandibular gland was mainly supplied by the facial artery and submental artery, partly by the lingual artery and external jugular artery. The venous drainage of the submandibualr gland occurred through the anterior facial vein, the venae comitantes of facial artery, the vein close to the Whaston＇s duct （the hilum vein）, and seldom drained to external jugular vein and other veins. Conclusions The anatomy of SMG is a complicated structure. Determining the main blood vessels of the submandibular gland is very important to achieve a successful vascularized autologous SMG transplant.
基金supported by National Natural Science Foundation of China (81570993, 81671005)Beijing Natural Science Foundation of China (7162100)
文摘Autophagy is a catabolic process which is involved in the development of many diseases including diabetes mellitus and its complications. Hyposalivation is a common complication of diabetes mellitus, whereas its mechanism remains unclear. Here, we observed that the stimulated salivary flow rate of SMG was significantly decreased in db/db mice, a diabetic mice model. The expressions of aquaporin 5(AQP5), a water channel protein, were decreased, whereas the m RNA level of AQP5 was increased in SMGs of both diabetic patients and mice. Under transmission electron microcope, more autophagosomes were detected in diabetic SMGs. Expressions of autophagy related proteins LC3 II, Beclin-1 and ATG5 were increased, meanwhile autophagy substrate p62 was decreased in SMGs of diabetic patients and mice, indicating that autophagy was activated in diabetic SMG.Double immunofluorescence staining showed that the colocalization of AQP5 and LC3 was increased in SMGs of diabetic mice.In cultured SMG-C6 cells, high glucose(HG), but not high osmotic pressure, reduced AQP5 protein expression and induced autophagy. Moreover, inhibition of autophagy by 3-methyladenin, an autophagy inhibitor, or by autophagy-related gene 5 siRNA, decreased HG-induced AQP5 reduction in SMG-C6 cells. Additionally, the expression of p-p85, p-Akt and p-mTOR were decreased in HG-treated SMG-C6 cells. Pretreatment with 740 Y-P, a PI3 K agonist, significantly suppressed HG-induced autophagy and AQP5 degradation. Taken together, these results indicate that autophagy plays a crucial role in AQP5 degradation in diabetic SMG via PI3 K/Akt/mTOR signaling pathway, which contributes to the dysfunction of diabetic SMG. Our study provides a novel mechanism of diabetic hyposalivation.
文摘Background Miniature pig （minipig） is increasingly used as a large animal model for a variety of biomedical studies. Little information is available in the literature on anatomy, histology and sialogragh of the submandibular gland of the minipig. The purpose of this study was to characterize the morphology of a miniature pig＇s （minipig） submandibular gland as a large animal model for further biomedical studies. Methods Five minipigs were subjected to sialographic, anatomic, histologic, histochemical and uhrastructural evaluations for submandibular glands. Results Sialograms showed a long, horizontal main excretory duct and a pear-shaped gland located inferoposterior to the angle of the mandible. The submandibular glands lied superficial to the suprahyoid, and infrahyoid muscle groups, and were covered by the inferior portion of the parotid gland. The submandibular glands were characterized by a mixed parenchyma of mucous and serous secretory aeini. Alcian blue （AB） staining and periodic acid-Schiff （PAS） reactions demon-strated that minipig submandibular glands synthesized and secreted acid mucous substances by serous cells and polysaccharide, and neutral mucous substances, by mucous cells. Conclusion The submandibular gland of the minipig is considered a useful large salivary gland animal model for biomedical studies.
文摘Tight junction plays an important rote in mediating paraceUular permeability in epithelia. We previously found that activation of AMP- activated protein kinase （AMPK） increased saliva secretion by modulating paraceUular permeability in submandibular glands. However, the molecular mechanisms underlying AMPK-modulated paraceUular permeability are unknown. In this study, we found that AICAR, an AMPK agonist, increased saliva secretion in the isolated rat submandibular glands, decreased transepithelial electrical resistance （TER）, and increased 4 kDa FITC-dextran flux in cultured SMG-C6 cells. AICAR also induced redistribution of tight junction protein claudin-4, but not claudin-1, claudin-3, occtudin, or ZO-1, from the cytoplasm to the membrane. Moreover, knockdown of claudin-4 by shRNA suppressed while claudin-4 re-expression restored the TER and 4 kDa FITC-dextran flux responses to AICAR. Additionally, AICAR increased ERK1/2 phosphorylation, and inhibition of ERK1/2 by U0126, an ERK1/2 kinase inhibitor, or by siRNA decreased AICAR-induced TER responses. AICAR induced the serine S199 phosphorylation of claudin-4 and enhanced the inter- action of claudin-4 and occludin. Furthermore, pretreatment with U0126 significantly suppressed AMPK-modulated phosphorytation, redistribution, and interaction with occludin of claudin-4. Taken together, these results indicated that claudin-4 played a crucial role in AMPK-rnodutated paraceUular permeability and ERK1/2 was required in AMPK-modulated tight junction barrier function in subman- dibular gland.
