Human Salivary Micro-RNA in Patients with Parotid Salivary Gland Neoplasms

Background

Currently, clinical examination, ultrasound scanning (with or without fine needle aspiration cytology), preoperative CT-scan and MRI are available for the differential diagnosis of parotid gland swelling. A preliminary non-invasive salivary diagnostic tool may be helpful in the clinical decision making process. Altered salivary micro-RNA (miRNA) expression levels have been observed in saliva from patients with various cancers. Therefore, we investigated miRNA expression levels in saliva samples from patients with a parotid gland neoplasm using Human miRNA cards in comparison to controls.

Results

In the discovery phase, eight miRNAs were identified having different expression levels in patients compared to controls. In the validation phase, the differences in miRNA expression levels between patients and controls were confirmed for seven out of eight discovered miRNAs (p < 0.001). A combination of two miRNAs yielded a receiver-operator-characteristics curve with an AUC of 0.94 (95% CI: 0.87–1.00; sensitivity 91%; specificity 86%). Validation of discovered miRNAs in segregated collected parotid saliva revealed that expression of these miRNAs differ between whole saliva and parotid saliva.

Conclusions

A two miRNA combination can predict the presence of a parotid gland neoplasm. Furthermore, this study suggested that the identified, patient-specific, salivary miRNAs were not derived from the parotid gland itself.     

Replication of Oral BK Virus in Human Salivary Gland Cells

BK polyomavirus (BKPyV) is the most common viral pathogen among allograft patients. Increasing evidence links BKPyV to the human oral compartment and to HIV-associated salivary gland disease (HIVSGD). To date, few studies have analyzed orally derived BKPyV. This study aimed to characterize BKPyV isolated from throat wash (TW) samples from HIVSGD patients. The replication potential of HIVSGD-derived clinical isolates HIVSGD-1 and HIVSGD-2, both containing the noncoding control region (NCCR) architecture OPQPQQS, were assessed and compared to urine-derived virus. The BKPyV isolates displayed significant variation in replication potential. Whole-genome alignment of the two isolates revealed three nucleotide differences that were analyzed for a potential effect on the viral life cycle. Analysis revealed a negligible difference in NCCR promoter activity despite sequence variation and emphasized the importance of functional T antigen (Tag) for efficient replication. HIVSGD-1 encoded full-length Tag, underwent productive infection in both human salivary gland cells and kidney cells, and expressed viral DNA and Tag protein. Additionally, HIVSGD-1 generated DNase-resistant particles and by far surpassed the replication potential of the kidney-derived isolate in HSG cells. HIVSGD-2 encoded a truncated form of Tag and replicated much less efficiently. Quantitation of infectious virus, via the fluorescent forming unit assay, suggested that HIVSGD BKPyV had preferential tropism for salivary gland cells over kidney cells. Similarly, the results suggested that kidney-derived virus had preferential tropism for kidney cells over salivary gland cells. Evidence of HIVSGD-derived BKPyV oral tropism and adept viral replication in human salivary gland cells corroborated the potential link between HIVSGD pathogenesis and BKPyV.     

Sodium Tungstate on Some Biochemical Parameters of the Parotid Salivary Gland of Streptozotocin-Induced Diabetic Rats: A Short-Term Study

Several studies have shown the antidiabetic properties of sodium tungstate. In this study, we evaluated some biochemical parameters of the parotid salivary gland of streptozotocin-induced diabetic rats treated with sodium tungstate solution (2 mg/ml). The studied groups were: untreated control (UC), treated control (TC), untreated diabetic (UD), and treated diabetic (TD). After 2 and 6 weeks of treatment, parotid gland was removed and total protein and sialic acid (free and total) concentration and amylase and peroxidase activities were determined. Data were compared by variance analysis and Tukey test (p < 0.05). The sodium tungstate treatment modestly decreased the glycemia of streptozotocin-induced diabetic rats. At week 2 of the study, parotid gland of diabetic rats presented a reduction of total protein concentration (55%) and an increase of amylase (120%) and peroxidase (160%) activities, free (150%) and total (170%) sialic acid concentration. No alteration in the evaluated parameters at week 6 of the study was observed. Sodium tungstate presented no significant effect in parotid gland. Our results suggest that diabetes causes initial modification in biochemical composition of parotid. However, this gland showed a recovery capacity after 6 week of the experimental time. Sodium tungstate has no effect in peripheral tissues, such as salivary glands.     

Developmental Interactions in the Dipteran Salivary Gland

The dipteran salivary gland is considered from several pointsof view. Its development in relation to chromosomal puffingsuggests that this tissue, perhaps more than any other, representsmajor evidence for differential activation and inactivationof genes during development. From studies of this tissue wehave gained further insight into concepts of tissue and stagespecificity. Factors regulating puffing during development includethe natural hormone, ecdysone, as well as a host of other substancesand environmental factors which affect cellular metabolism. Breakdown of the salivary gland seems ultimately to be controlledby chromsomal puffing. In this case one of the first detectablebiochemical alterations in the gland is the accumulation ofthe enzyme DNase. This enzyme may play a role in digesting thechromosomes themselves, thus accomplishing regulated self-destructionof the cell's synthetic machinery.     

Solitary Plasmacytoma of the Parotid Gland with Crystalline Inclusions: A Case Report

Background  

Solitary extramedullary plasmacytoma of the parotid gland is a rare condition. Intracytoplasmic Crystalline inclusions in the tumor are even rarer and have been reported only once in the parotid gland.     

Oral Defenses and Disease: Salivary Gland Function 1

Recent studies on parotid gland flow rate and composition in healthy subjects do not support the conventional wisdom that there is a gradual deterioration in salivary gland function with aging. With gustatory stimulation a diminution in flow rate was observed only in post-menopausal women taking medications. Studies of whole saliva and preliminary studies of submandibular saliva flow rate, however, suggest that these glands may exhibit functional changes not seen in the parotid. This would be consistent with histological findings. Reports to date on age effects on composition suggest modest selective changes in electrolytes (e.g. sodium) and only subtle changes in proteins (e.g. amylase isoenzymes). Clinical concerns (rampant caries, stomatitis, periodontal disease) arise largely because of the high number of elderly on medications or therapeutic interventions that affect salivary flow and the increase in incidence of diseases of the salivary gland (e.g. sialadeneitis, Sjogren's, sarcoidosis). Reduction in flow rate and alterations in composition diminish salivary protective mechanisms, i.e. antibacterial activity, lubrication and protection of soft tissues, and maintenance of hard tissue integrity. Recent research on structure of mucins, the nature of the salivary lipids and interactions among salivary proteins should stimulate a second generation of studies on both the effects of aging per se and aberrations resulting from disease. Stimulation of compromised function and development of more effective salivary substitutes are also important areas of research.     

Investigation of Susceptibility Genes Triggering Lachrymal/Salivary Gland Lesion Complications in Japanese Patients with Type 1 Autoimmune Pancreatitis

Autoimmune pancreatitis (AIP) is a unique form of chronic pancreatitis characterized by high serum IgG4 concentration and a variety of complicating extra-pancreatic lesions. In particular, lachrymal/salivary gland lesions tend to manifest in a highly active AIP disease state, and several genes are speculated to be associated with the onset of this complication. We therefore searched for candidate susceptibility genes related to lachrymal/salivary gland lesions in a genome-wide association study (GWAS) with the GeneChip Human Mapping 500k Array Set (Affymetrix, CA) that was followed by fine mapping of additional single nucleotide polymorphisms (SNPs) in strongly significant genes with TaqMan assays. Venous blood samples were obtained from 50 type 1 AIP patients with lachrymal/salivary gland lesions (A group) and 53 type 1 AIP patients without (B group). The mean values of IgG and IG4 were both significantly different (P<0.05) between the groups. SNPs that showed a significant association with the A group at the genome-wide level (P<0.0001) were identified and subsequently used in fine SNP mapping of candidate genes. In total, five SNPs had a positive association with complicated AIP (most notably rs2284932 [P=0.0000021]) and five SNPs possessed a negative association (particularly rs9371942 [P=0.00000039]). Among them, KLF7, FRMD4B, LOC101928923, and MPPED2 were further examined for complication susceptibility using additional SNPs that were not included in the GWAS. Individual genotyping of KLF7 rs2284932 revealed that the frequency of the minor C allele was significantly increased (P=0.00062, Pc=0.0018, OR=2.98, 95%CI=1.58-5.65) in group A. The minor T allele of rs4473559 in FRMD4 demonstrated a significant association in the A group (P=0.00015, OR=3.38, 95%CI=1.77-7.65). In the LOC101928923 gene, the frequency of the minor C allele of rs4379306 was significantly decreased in group A in both TaqMan and GWAS analyses. Lastly, the minor C allele of MPPED2 rs514644 carried a significantly increased risk of complications. These four genes may be linked with the onset of lachrymal/salivary gland lesions in type 1 AIP patients and require further study.     

Age-Related Changes in Rat Sublingual Salivary Gland Morphology1

Sublingual salivary glands were removed from 3.5-, 12-, 18- and 24-month-old Fisher 344 male rats and examined for age-related changes in morphology. Morphometric analysis revealed stability in the proportional volume of acinar tissue, connective tissue and vascular tissue across age groups. The proportion of gland volume occupied by ducts increased with age due to an increase in proportional volume of striated ducts. A number of qualitative age-related changes were noted including an increase in squamous metaplasia of duct epithelium, periductal lymphocytic foci and diffuse periductal lymphocytic infiltration. Consolidated deposits were identified in the lumen of intralobular ducts and appeared most frequent in young animals and declined in frequency with age. These morphologic changes while apparently age-related were evident by 12 months of age indicating that developmental and maturational factors rather than senescence may account for these findings.     

四川短尾唾液腺的组织学观察

利用生物显微技术观察和研究了四川短尾鼩(Anourosorex squamipes)唾液腺的组织结构。结果表明,腮腺属纯浆液腺,有闰管和分泌管,无颗粒曲管;颌下腺属混合腺,以混合性腺泡为主,有少量浆液性腺泡和黏液性腺泡,有闰管、颗粒曲管和分泌管;舌下腺属纯黏液腺,有闰管和分泌管,无颗粒曲管,但在分泌管上存在有颗粒曲管细胞。     

The Journey of Malaria Sporozoites in the Mosquito Salivary Gland

The life cycle of malaria parasites in the mosquito vector is completed when the sporozoites infect the salivary gland and are ready to be injected into the vertebrate host. This paper describes the fine structure of the invasive process of mosquito salivary glands by malaria parasites. Plasmodium gallinaceum sporozoites start the invasion process by attaching to and crossing the basal lamina and then penetrating the host plasma membrane of the salivary cells. The penetration process appears to involve the formation of membrane junctions. Once inside the host cells, the sporozoites are seen within vacuoles attached by their anterior end to the vacuolar membrane. Mitochondria surround, and are closely associated with, the invading sporozoites. After the disruption of the membrane vacuole, the parasites traverse the cytoplasm, attach to, and invade the secretory cavity through the apical plasma membrane of the cells. Inside the secretory cavity, sporozoites are seen again inside vacuoles. Upon escaping from these vacuoles, sporozoites are positioned in parallel arrays forming large bundles attached by multilammelar membrane junctions. Several sporozoites are seen around and inside the secretory duct. Except for the penetration of the chitinous salivary duct, our observations have morphologically characterized the entire process of sporozoite passage through the salivary gland.     

Systemic Transplantation of Human Adipose Tissue-Derived Mesenchymal Stem Cells for the Regeneration of Irradiation-Induced Salivary Gland Damage

Objectives

Cell-based therapy has been reported to repair or restore damaged salivary gland (SG) tissue after irradiation. This study was aimed at determining whether systemic administration of human adipose-derived mesenchymal stem cells (hAdMSCs) can ameliorate radiation-induced SG damage.

Methods

hAdMSCs (1×10⁶) were administered through a tail vein of C3H mice immediately after local irradiation, and then this infusion was repeated once a week for 3 consecutive weeks. At 12 weeks after irradiation, functional evaluations were conducted by measuring salivary flow rates (SFRs) and salivation lag times, and histopathologic and immunofluorescence histochemistry studies were performed to assay microstructural changes, apoptosis, and proliferation indices. The engraftment and in vivo differentiation of infused hAdMSCs were also investigated, and the transdifferentiation of hAdMSCs into amylase-producing SG epithelial cells (SGCs) was observed in vitro using a co-culture system.

Results

The systemic administration of hAdMSCs exhibited improved SFRs at 12 weeks after irradiation. hAdMSC-transplanted SGs showed fewer damaged and atrophied acinar cells and higher mucin and amylase production levels than untreated irradiated SGs. Immunofluorescence TUNEL assays revealed fewer apoptotic cells in the hAdMSC group than in the untreated group. Infused hAdMSCs were detected in transplanted SGs at 4 weeks after irradiation and some cells were found to have differentiated into SGCs. In vitro, a low number of co-cultured hAdMSCs (13%–18%) were observed to transdifferentiate into SGCs.

Conclusion

The findings of this study indicate that hAdMSCs have the potential to protect against irradiation-induced cell loss and to transdifferentiate into SGCs, and suggest that hAdMSC administration should be viewed as a candidate therapy for the treatment of radiation-induced SG damage.