Dry eye syndrome is a relatively common disease of the tears and ocular surfaces that results in discomfort, visual disturbance, and tear film instability with possible damage to the ocular surfaces. Microvascular submandibular gland (SMG) transfer offers a surgical alternative for a permanent autologous substitution of tears using the basal secretion of a transplanted SMG. Long-term follow-up reveals that this technique is a lasting and effective solution for patients with severe dry eye syndrome. The uncomfortable symptoms were relieved, and the frequency of use of pharmaceutical tear substitutes was reduced. Objective examination showed significant improvement in tear film and some features of ocular surface such as breakup time of tear film and corneal staining. Patients may suffer from obstruction of Wharton's duct or epiphora after surgery. Activation of secretion-related receptors could improve the early hypofunction of the denervated SMG and prevent the duct obstruction. Reduction surgery, partial SMG transplantation, uses of atropine gel or Botulinum toxin A could be the choices of treatment for epiphora.
Obstructive sialadenitis; Keratoconjunctivitis sicca; Submandibular gland transplantation
miR-34a is an important tumor suppressor gene in various cancer types. But little is known about the dysregulation of miR-34a in tongue squamous cell carcinoma (TSCC). In this study, we investigate the expression and potential role of miR-34a in TSCC.
We evaluated miR-34a expression and its relationship with clinicopathological characters in 75 pairs of TSCC samples, and confirmed the role of miR-34a for predicting lymph node metastases from a further 15 pairs of paraffin-embedded TSCC specimens with stringent clinicopathological recruitment criteria using quantitative reverse transcription polymerase chain reaction (qRT-PCR). The effects of miR-34a on cell proliferation, migration and invasion were examined in TSCC cell lines using Cell Counting Kit-8 assay, wound healing assay and transwell assay, respectively. The effects of miR-34a on the expression of matrix metalloproteinase (MMP) 9 and 14 were detected by luciferase reporter assays and Western blot analysis. The expression of miR-34a, MMP9 and MMP14 were also confirmed in TSCC samples by in situ hybridization and immunohistochemistry.
miR-34a expression in tumor tissues from TSCC patients with positive lymph node metastases was significantly lower than that with negative lymph node metastases. Overexpression of miR-34a significantly suppressed migration and invasion in TSCC cells and simultaneously inhibited the expression of MMP9 and MMP14 through targeting the coding region and the 3′untranslated region, respectively. Moreover, miR-34a expression in TSCC was inversely correlated with protein expression of MMP9 and MMP14 in the TSCC samples.
miR-34a plays an important role in lymph node metastases of TSCC through targeting MMP9 and MMP14 and may have potential applications in prognosis prediction and gene therapy for lymph node metastases of TSCC patients.
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 glands.
aquaporin-5; apoptosis; botulinum toxin A; M3-muscarinic acetylcholine receptor; submandibular gland
Adiponectin and adiponectin receptors (AdipoR1/2) are expressed in various tissues and are involved in the regulation of multiple functions such as energy metabolism and inflammatory responses. However, the effect of adiponectin and AdipoRs in submandibular glands has not been fully evaluated. In the present study, we found that mRNA and protein of both adiponectin and AdipoR1/2 were expressed in rat submandibular glands and in the SMG-C6 cell line, as evidenced by RT-PCR and Western blot analysis. Immunofluorescence staining showed that adiponectin was diffused in the cytoplasm, while AdipoR1/2 was concentrated in the membrane of acinar cells. Saliva flow was significantly increased by full length adiponectin (fAd) or globular adiponectin (gAd) perfusion in isolated rat submandibular glands. 5-Aminoimidazole-4-carboxamide-1-4-ribofuranoside (AICAR), an adenosine monophosphate activated protein kinase (AMPK) activator, also increased saliva secretion. fAd, gAd, and AICAR all increased the average width of apical tight junctions in perfused submandibular glands, and decreased transepithelial electrical resistance (TER) in SMG-C6 cells, suggesting that adiponectin promoted secretion by modulating paracellular permeability. fAd and gAd increased p-AMPK levels, while AraA, an AMPK antagonist, abolished fAd- and gAd-induced changes in secretion, tight junction ultrastructure, and TER. Moreover, both AdipoR1 and AdipoR2 were required for fAd- or gAd-induced p-AMPK and TER responses, suggesting from their inhibition following AdipoR1 or AdipoR2 knockdown, and co-knockdown of AdipoRs by RNA interference. Our results suggest that adiponectin functions as a promoter of salivary secretion in rat submandibular glands via activation of AdipoRs, AMPK, and paracellular permeability.
miR-195 is aberrantly expressed in multiple types of disease. But little is known about the dysregulation of miR-195 in tongue squamous cell carcinoma (TSCC). In this study, we investigated the roles of miR-195 in the development and progression of TSCC.
Using quantitative reverse transcription-polymerase chain reaction (qRT-PCR), we evaluated miR-195 expression in TSCC samples from 81 patients. Overall survival of these patients was examined using Kaplan–Meier curves with log-rank tests and the Cox proportional hazards model. The expression of two known miR-195 target genes, Cyclin D1 and Bcl-2, was also examined in the TSCC samples by immunohistochemistry. The effects of miR-195 overexpression on cell cycle progression and apoptosis and its effects on the expression of Cyclin D1 and Bcl-2 were examined in transfected TSCC cell lines (SCC-15 and Cal27) using fluorescence-activated cell sorting assays, luciferase reporter assays, and Western blots.
Reduced miR-195 expression was associated with tumor size and the clinical stage of TSCC tumors. Kaplan–Meier survival analysis indicated that the TSCC patients with reduced expression of miR-195 had poor overall survival and in multivariable analyses low levels of miR-195 emerged as an independent prognostic factor for this clinical outcome. Levels of miR-195 expression were inversely correlated with the expression of Cyclin D1 and Bcl-2. Overexpression of miR-195 inhibited cell cycle progression, promoted apoptosis, and reduced Cyclin D1 and Bcl-2 expression in two TSCC cell lines.
miR-195 may have potential applications as a prognostic factor for TSCC patients.
To enhance the accuracy of radioactive seed implants in the head and neck, a digital model individual template, containing information simultaneously on needle pathway and facial features, was designed to guide implantation with CT imaging. Thirty-one patients with recurrent and local advanced malignant tumors of head and neck after prior surgery and radiotherapy were involved in this study. Before 125I implants, patients received CT scans based on 0.75mm thickness. And the brachytherapy treatment planning system (BTPS) software was used to make the implantation plan based on the CT images. Mimics software and Geomagic software were used to read the data containing CT images and implantation plan, and to design the individual template. Then the individual template containing the information of needle pathway and face features simultaneously was made through rapid prototyping (RP) technique. All patients received 125I seeds interstitial implantation under the guide of the individual template and CT. The individual templates were positioned easily and accurately, and were stable. After implants, treatment quality evaluation was made by CT and TPS. The seeds and dosages distribution (D90,V100,V150) were well meet the treatment requirement. Clinical practice confirms that this approach can facilitate easier and more accurate implantation.
Digital model; individual template; radioactive seeds; head and neck
In the title compound, C18H22N4OS2, the six-membered rings are almost coplanar, showing a dihedral angle between the mean planes of 9.0 (4)°, while the triazol ring is nearly perpendicular to the thiochromen-4-one unit, making an angle of 89.8 (4)°. In the crystal, C—H⋯N hydrogen bonds link the molecules in a stacked arrangement along the c axis.
In the title compound, C10H8F2N4O, the dihedral angle between the rings is 65.4 (1)°. In the crystal, intermolecular O—H⋯N and C—H⋯F hydrogen bonds link the molecules in a stacked arrangement along the a and c axes, respectively.
In the title compound, C11H9FN2O, the dihedral angle between the rings is 87.50 (4)°. In the crystal, intermolecular C—H⋯N hydrogen bonds link the molecules in a stacked arrangement along the c axis.
The asymmetric unit of the title compound, C14H10FN3OS2, contains two independent molecules which differ in the relative orientations of the triazole and allylsulfanyl groups with respect to the planar thiochromen-4-one frameworks. The N—N—C—C torsion angles are 128.2 (5) and −120.9 (5)°, while the C—S—C—S torsion angles are −17.4 (4) and 16.4 (4)°. In the crystal, intermolecular C—H⋯O and C—H⋯N hydrogen bonds link the molecules in a stacked arrangement along the a axis.
The asymmetric unit of the title compound, C13H10FN3OS2, contains two independent molecules, which differ slightly in the relative orientations of the triazole and ethylsulfanyl groups with respect to the planar thiochromen-4-one frameworks. The dihedral angles between the mean planes of the triazole groups and the corresponding six-membered C5OS rings are 56.8 (1) and 52.9 (1)°, while the S—C—S—C dihedral angles are −11.7 (2) and −16.3 (2)°. In the crystal structure, intermolecular C—H⋯O and C—H⋯N hydrogen bonds link the molecules in a stacked arrangement along the a axis. A weak intramolecular C—H⋯·O interaction results in the formation of a non-planar five-membered ring.
In the title compound, C15H12FN3O3S2, the two six-membered rings are essentially coplanar, their mean plnes making a dihedral angle of 1.1 (2)°. The carbonyl C, the two attached non-fused C atoms and the S atom deviate from the plane of the benzene ring by −0.046 (5), −0.017 (5), 0.000 (6), 0.026 (4) Å, respectively. The angle between the mean planes of the triazole ring and the sulfur heterocycle is 53.3 (1)°. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules in a stacked arrangement along the a axis.
In the title compound, C13H10ClFO3S2, the two-ring system is essentially planar, the mean plane of the benzene ring being inclined at 6.0 (2)° to the plane of the remaining four atoms. The ethylsulfanyl group is almost coplanar with the two rings [dihedral angle = 6.4 (2)°], while the carboxylate group is almost perpendicular to it [dihedral angle = 72.4 (2)°]. In the crystal structure, intermolecular C—H⋯O and C—H⋯F hydrogen bonds link the molecules in a stacked arrangement along the a axis.