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Objectives: The aim of this study was to estimate the prevalence of dental attrition in a young adult population and to explore associated factors. Method and materials: Dental students aged 18 to 40 years old with a minimum of 24 natural teeth were invited to take part in this cross-sectional study. Their demographic information, medical history, perceived stress, frequency of dietary acid intake, and frequency of oral habits were obtained through several questionnaires. Assessment of each type of tooth wear (erosion, attrition, and abrasion) was performed according to the tooth wear evaluation system (TWES 1.0). All participants underwent salivary tests. Statistical analysis was performed by chi-squared or Mann-Whitney tests and logistic regression models. Results: In total, 178 participants (88 women and 90 men) with a median age of 22 years were included and of those 74.7% (95% confidence interval [CI], 68% to 81%) had dental attrition. Univariate ana lysis revealed positive associations for male sex, age, body mass index, awake bruxism frequency, and erosive tooth wear with the presence of dental attrition. Multivariable logistic regression (Nagelkerke r2 = 0.31) indicated that dental attrition was associated with erosive tooth wear (adjusted odds ratio [aOR], 6.3; 95% CI, 2.8 to 14.2), body mass index (aOR, 1.3; 95% CI, 1.1-1.5), and age (aOR, 1.2; 95% CI 1.0 to 1.3). Conclusion: Dental attrition is present in most young adults of Catalonia. The associated factors were erosive tooth wear, body mass index, and age. Slight alterations of salivary parameters do not seem to predict dental attrition. [ABSTRACT FROM AUTHOR]

Objective: There are more than one million children and adolescents living with type 1 diabetes mellitus, and their number is steadily increasing. Diabetes affects oral health through numerous channels, including hyposalivation, immune suppression, and the inflammatory effect of glycation end-products. However, patients with type 1 diabetes must follow a strict sugar free diet that is proven to be carioprotective. Therefore, the aim of this systematic review and meta-analysis is to investigate whether children with type 1 diabetes have a difference in Decayed, Missing, Filled Teeth index (DMFT), salivary function, and periodontal status than children without diabetes, with an emphasis on glycemic control. Materials and Methods: PubMed, Embase and Cochrane libraries were screened for articles, using predefined search keys without any language or date restrictions. Two independent authors performed the selection procedure, extracted data from the eligible articles, carried out a manual search of the reference lists, and assessed the risk of bias using the Newcastle-Ottawa scale. Meta-analysis was performed in R using the random-effects model. Effect sizes were mean differences; subgroup analysis was performed on glycemic control. Results: 33 studies satisfied the eligibility criteria. 22 studies did not show a significant difference regarding the DMFT index between the diabetes and non-diabetes groups; six studies found that children living with diabetes had higher DMFT scores, compared to five studies that found significantly lower scores. Meta-analysis found no statistically significant differences in plaque, gingival, and calculus indexes, however it found significant differences in pooled DMFT indexes, and salivary flow rate. Subgroup analysis on glycemic control using DMFT values found significant differences in children with good and poor glycemic control with results of 0.26 (CI95%=-0.50; 1.03) and 1.46 (CI95%=0.57; 2.35), respectively. Conclusions: Children with poor glycemic control face higher risk of developing caries compared to good control and non-diabetes children. Regular dental check-ups and strict control of glycemic levels are highly advised for children living with type 1 diabetes, further emphasizing the importance of cooperation between dentists and diabetologists. [ABSTRACT FROM AUTHOR]

Objective: This study assessed the effect of cevimeline and different concentrations of gum arabic on the parotid gland of rats being given xerostomia-inducing methotrexate. Methods: One hundred twenty-five rats were divided into five equal groups of twenty-five each. The rats in Group I received basic diets, while those in Groups II, III, IV, and V received 20 mg/kg MTX as a single intraperitoneal dose on day one. Group III received 10 mg/kg CVM dissolved in saline orally and daily, and the other two groups received a 10% W/V aqueous suspension of GA. Therefore, Group IV received 2 ml/kg suspension orally and daily, while Group V received 3 ml/kg suspension orally and daily. After 9 days, the parotid glands were dissected carefully and prepared for hematoxylin and eosin (H&E) staining as a routine histological stain and caspase-3 and Ki67 immunohistochemical staining. Quantitative data from α-Caspase-3 staining and Ki67 staining were statistically analysed using one-way ANOVA followed by Tukey's multiple comparisons post hoc test. Results: Regarding caspase-3 and Ki67 immunohistochemical staining, one-way ANOVA revealed a significant difference among the five groups. For Caspase-3, the highest mean value was for group II (54.21 ± 6.90), and the lowest mean value was for group I (15.75 ± 3.67). The other three groups had mean values of 31.09 ± 5.90, 30.76 ± 5.82, and 20.65 ± 3.47 for groups III, IV, and V, respectively. For Ki67, the highest mean value was for group I (61.70 ± 6.58), and the lowest value was for group II (18.14a ± 5.16). The other three groups had mean values of 34.4 ± 9.27, 48.03 ± 8.40, and 50.63 ± 8.27 for groups III, IV, and V, respectively. Conclusion: GA, rather than the normally used drug CVM, had a desirable effect on the salivary glands of patients with xerostomia. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify peripheral and salivary gland (SG) biomarkers of response/resistance to B cell depletion based on the novel concise Composite of Relevant Endpoints for Sjögren Syndrome (cCRESS) and candidate Sjögren Tool for Assessing Response (STAR) composite endpoints. Methods: Longitudinal analysis of peripheral blood and SG biopsies was performed pre‐ and post‐treatment from the Trial of Anti–B Cell Therapy in Patients With Primary Sjögren Syndrome (TRACTISS) combining flow cytometry immunophenotyping, serum cytokines, and SG bulk RNA sequencing. Results: Rituximab treatment prevented the worsening of SG inflammation observed in the placebo arm, by inhibiting the accumulation of class‐switched memory B cells within the SG. Furthermore, rituximab significantly down‐regulated genes involved in immune‐cell recruitment, lymphoid organization alongside antigen presentation, and T cell co‐stimulatory pathways. In the peripheral compartment, rituximab down‐regulated immunoglobulins and auto‐antibodies together with pro‐inflammatory cytokines and chemokines. Interestingly, patients classified as responders according to STAR displayed significantly higher baseline levels of C‐X‐C motif chemokine ligand‐13 (CXCL13), interleukin (IL)‐22, IL‐17A, IL‐17F, and tumor necrosis factor‐α (TNF‐α), whereas a longitudinal analysis of serum T cell–related cytokines showed a selective reduction in both STAR and cCRESS responder patients. Conversely, cCRESS response was better associated with biomarkers of SG immunopathology, with cCRESS‐responders showing a significant decrease in SG B cell infiltration and reduced expression of transcriptional gene modules related to T cell costimulation, complement activation, and Fcγ‐receptor engagement. Finally, cCRESS and STAR response were associated with a significant improvement in SG exocrine function linked to transcriptional evidence of SG epithelial and metabolic restoration. Conclusion: Rituximab modulates both peripheral and SG inflammation, preventing the deterioration of exocrine function with functional and metabolic restoration of the glandular epithelium. Response assessed by newly developed cCRESS and STAR criteria was associated with differential modulation of peripheral and SG biomarkers, emerging as novel tools for patient stratification. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the diagnostic accuracy of the labial salivary gland biopsy based on multiple histopathological features in patients with suspected primary Sjögren syndrome (pSS). Methods: Patients from a diagnostic sicca cohort with clinically suspected pSS who underwent a labial gland biopsy were included. Patients were categorized as having pSS or non‐Sjögren syndrome sicca (non‐SS sicca) based on vignettes scored by an expert panel. Labial gland biopsies were analyzed for the presence of four histopathological features: focus score (FS) ≥1, prelymphoepithelial and lymphoepithelial lesions, immunoglobulin G plasma cell shift, and germinal centers. Sensitivity and specificity of histologic features were calculated, and the optimal cutoff value for the number of histopathological features needed to diagnose pSS was determined with receiver operating curve analysis. Results: A total of 38 patients were categorized as having pSS and 65 as having non‐SS sicca. In labial gland biopsies of patients with pSS, the prevalence of FS ≥1 was 82%, followed by 68% for pre‐lymphoepithelial and lymphoepithelial lesions, 63% for plasma cell shift, and 24% for germinal centers. Although FS ≥1 showed the highest sensitivity for patients with pSS (82%), specificity was higher for the other three features (98%–100%). The presence of two or more (of four) histopathological features had almost comparable sensitivity to FS alone, but specificity increased with 12% to 100%. For fulfillment of American College of Rheumatology/EULAR criteria, specificity increased from 84% to 95% when an abnormal biopsy was defined by the presence of two or more histopathological features instead of FS ≥1 only. Conclusion: The diagnostic accuracy of the labial gland biopsy increases when other histopathological features besides FS are taken into account, by reducing the number of false‐positive biopsies. [ABSTRACT FROM AUTHOR]

Background: This study aimed to investigate the homogeneity of the major salivary glands in multiple sclerosis (MS) patients using ultrasonography (USG), assess DMFT indices, measure resting salivary flow rates, and compare these values with healthy individuals. Methods: In this study, 20 individuals diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) (mean age 36.15 ± 8.51) and 20 systemically healthy individuals (mean age 35.7 ± 9.22) were included. Oral and radiologic examinations were performed in all individuals. The parotid and submandibular salivary glands were examined using USG, and their homogeneity was assessed based on the scoring system recommended by the Outcome Measures in Rheumatology Clinical Trials (OMERACT) study group. Resting salivary flow rates and DMFT indices were measured, and the obtained data were subjected to statistical analysis. Results: The parotid glands exhibited more heterogeneity on USG within the MS patient group than the control group, with a statistically significant difference between the two groups (p = 0.015). A statistically significant correlation was observed in total homogeneity values between the patient and control groups (p = 0.021). Furthermore, the MS patient group exhibited higher DMFT indices and lower salivary flow rates than the control group. The difference between the DMFT indices and salivary flow rate between the patient groups was statistically significant (p = 0.004 and p = 0.002 respectively). Conclusions: The parenchyma of the major salivary glands in MS patients exhibited decreased homogeneity than the healthy controls. Additionally, the MS group showed a decrease in salivary flow rate and an increase in the DMFT index. Autonomic dysfunction and medications used for MS are thought to cause salivary gland hypofunction and dry mouth. It can be interpreted that hyposalivation and motor skill losses in MS patients lead to an increase in DMFT index. [ABSTRACT FROM AUTHOR]

Introduction: Endotracheal intubation and mechanical ventilation are the most frequently used life-sustaining interventions in critical care. Prolonged intubation can lead to post-extubation dysphagia, affecting the individual's nutritional level and communication ability. Thereupon, this study aims to assess the effectiveness of swallowing and oral care interventions in resuming oral intake and increasing salivary flow in post-extubation patients. Methods: A randomized controlled trial was conducted in critical care units of a tertiary care setting, where 92 post-extubation patients who had undergone intubation for=48 hours were enrolled. The intervention group received swallowing and oral interventions, including safe swallowing education (SSE), toothbrushing, salivary gland massage, oral cavity, and swallowing exercises. In contrast, the control group received standard oral care every 8th hour. Oral intake was assessed daily with the Functional Oral Intake Scale, and the salivary flow measurement was assessed with oral Schirmer's test on the 1st, 3rd, and 7th day after extubation. Results: The baseline demographic and clinical characteristics showed that the groups were homogenous. The intervention group achieved total oral intake two days earlier than the control group. Findings also showed that the participants in the intervention group had a significant increase in salivary flow than in the control group on the 3rd and 7th days of the intervention. Conclusion: Swallowing and oral care interventions help post-extubation patients resume early oral intake and increase salivary flow after prolonged intubation. Hence, it improves the patient's outcome toward a healthy life. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of a salivary gland massage program to improve salivary flow, swallowing, and oral hygiene in older type 2 diabetes patients. Methods: This randomized control trial consisted of 73 older diabetes patients with a low salivary flow; 39 and 34 in intervention and control groups, respectively. The intervention group received a salivary gland massage from a trained dental nurse, whereas the control group received a dental education. The salivary flow rates were collected using spit methods at baseline, 1‐month and 3‐month follow up. All participants were examined for the objective and subjective symptoms of xerostomia, the Simplified Debris Index and the Repetitive Saliva Swallowing Test. Results: After 3 months, the resting (0.32 vs 0.14 mL/min, P < 0.001) and stimulating salivary flow (3.66 vs 2.83 mL/min, P = 0.025) in the intervention group was significantly higher than the control group. The objective symptoms in the intervention group were significantly lower than the control group after 3 months (1.41 vs 2.26, P = 0.001). The participants who were able to swallow least three times in the Repetitive Saliva Swallowing Test in the intervention group increased by 35.89% after 3 months, whereas the control group increased by 8.82%. Oral hygiene was improved in both groups, but the changes in the intervention were significantly greater than in the control group. Conclusions: The 3‐month salivary glands massage program increases the salivary flow rate, and affects swallowing, objective dry mouth symptoms and oral hygiene in older patients with type 2 diabetes. Geriatr Gerontol Int 2023; 23: 549–557. [ABSTRACT FROM AUTHOR]

The article emphasizes the need for increased focus on the salivary glands in the context of Sjögren's syndrome, particularly in relation to COVID-19. Topics discussed include the impact of COVID-19 on salivary gland function in patients with Sjögren's syndrome, the potential exacerbation of symptoms due to the virus, and the implications for patient management and treatment strategies.

Radiation therapy is a critical strategy for the treatment of malignant tumors. X‐ray external radiation has been successfully used to treat head and neck cancer. On the other hand, 131I internal radiation has been effective in managing differentiated thyroid cancer. However, these therapies cause radiation damage to salivary glands. Radiation sialadenitis is the most common complication associated with radiotherapy applied to the head and neck and it severely affects patients' quality of life. Since DNA is the main intracellular target of radiation, and the integrity of the DNA structure is critical to genomic stability and the cellular survival of salivary glands, regulating radiation‐induced DNA damage offers great promise in preventing and managing radiation sialadenitis. In this review, we summarize recent progress in DNA damage and repair in irradiated salivary glands. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the performance of diffusion-weighted magnetic resonance imaging (DW-MRI) as a noninvasive tool for assessing parotid gland function in type 2 diabetes mellitus (T2DM) patients. Methods: T2DM patients (n = 40, male, age 40–60 years) and healthy controls (n = 40) were examined. Salivary function was assessed using 1.5D echo-planar diffusion-weighted imaging. The examinations were performed before and every 3 min until 10 times after acid stimulation with a 500-mg vitamin C pill. The maximum apparent diffusion coefficient (ADC) in the parotid glands (pADCmax) and time to peak ADC in the parotid glands (pTmax) during stimulation were obtained. ADC values at every time point and the peak value of ADC were compared between the two groups and statistically analyzed. Results: The ADC values in the parotid gland in the resting state in the patient group were slightly lower than those in the healthy controls ((1.02 ± 0.08) × 10−3 mm2/s vs. (1.11 ± 0.09) × 10−3 mm2/s, p > 0.05). The ADCs in the healthy controls increased after stimulation until they gradually reached their peak. The ADCs in the patient group first decreased after stimulation and then gradually increased until they peaked. The pADCmax in the patient group was significantly lower than that in the healthy controls ((1.45 ± 0.08) × 10−3 mm2/s vs. (1.7 ± 0.06) × 10−3 mm2/s, p < 0.05). The peak ADCs in the parotid gland and relative signal intensity after acid stimulation were significantly correlated (r = 0.666, p < 0.05). Conclusion: DW-MRI before and after acid stimulation is potentially useful for noninvasive prediction of diabetes-induced xerostomia severity. ADC value is a sensitive indicator of parotid gland dysfunction and may indirectly reflect the degree of this dysfunction caused by fat deposition. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present work we investigated the clinical utility of Al[18F]F-NOTA-Octreotide (Al[18F]F-OC) in comparison to [68Ga]Ga-DOTA-TATE in patients diagnosed with neuroendocrine tumours. Our aim was to verify the recently published, promising results for Al[18F]F-NOTA-Octreotide in the Latin-American population. Al[18F]F-NOTA-Octreotide provided excellent image quality, detected NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. PET imaging of neuroendocrine tumours (NET) is well established for staging and therapy follow-up. The short half-life, increasing costs, and regulatory issues significantly limit the availability of approved imaging agents, such as [68Ga]Ga-DOTA-TATE. Al[18F]F-NOTA-Octreotide provides a similar biodistribution and tumour uptake, can be produced on a large scale and may improve access to precision imaging. Here we prospectively compared the clinical utility of [68Ga]Ga-DOTA-TATE and Al[18F]F-NOTA-Octreotide in the Latin-American population. Our results showed that in patients with stage IV NETs [68Ga]Ga-DOTA-TATE presents higher physiological uptake than Al[18F]F-NOTA-Octreotide in the liver, hypophysis, salivary glands, adrenal glands (all p < 0.001), pancreatic uncinated process, kidneys, and small intestine (all p < 0.05). Nevertheless, despite the lower background uptake of Al[18F]F-NOTA-Octreotide, comparative analysis of tumour-to-liver (TLR) and tumour-to-spleen (TSR) showed no statistically significant difference for lesions in the liver, bone, lymph nodes, and other tissues. Only three discordant lesions in highly-metastases livers were detected by [68Ga]Ga-DOTA-TATE but not by Al[18F]F-NOTA-Octreotide and only one discordant lesion was detected by Al[18F]F-NOTA-Octreotide but not by [68Ga]Ga-DOTA-TATE. Non-inferiority analysis showed that Al[18F]F-NOTA-Octreotide is comparable to [68Ga]Ga-DOTA-TATE. Hence, our results demonstrate that Al[18F]F-NOTA-Octreotide provided excellent image quality, visualized NET lesions with high sensitivity and represents a highly promising, clinical alternative to [68Ga]Ga-DOTA-TATE. [ABSTRACT FROM AUTHOR]

Objective: Deep lobe parotid tumour is commonly removed with the covering superficial lobe of parotid gland. Total or subtotal parotidectomy leads to an increase in surgical morbidity. This study evaluated recurrence and function after selective deep lobe parotidectomy via retroauricular hairline (Roh's) incision for pleomorphic adenoma. Materials and methods: Twenty‐eight patients with deep lobe parotid pleomorphic adenomas underwent selective deep lobe parotidectomy with preservation of the superficial lobe and the facial lobe via Roh's incision. Each patient was evaluated with any complications, cosmetic and salivary functions and local recurrence. Results: Superficial lobe‐preserving surgery via Roh's incision was successfully applied to all patients without injury to the facial nerve and the Stensen's duct for a median operation time of 65 min. Facial nerve paralysis was found only temporarily in 9 (32%) patients, and other complications were minimal. None of the patients had postoperative Frey's syndrome. Salivary secretory function in the operated side was well preserved. No recurrence was found in the patients for a median follow‐up of 94 months. Conclusions: Selective deep lobe parotidectomy via Roh's incision is a reliable option of treatment for deep lobe parotid pleomorphic adenoma. [ABSTRACT FROM AUTHOR]

Objectives: To assess the long‐term outcome of sialendoscopy‐assisted combined approach for parotid sialolithotomy with gland preservation. Patients and Methods: A retrospective study of patients treated with a combined sialendoscopic and open approach was conducted between 2011 and 2020. Demographic data of patients such as operative technique, stone size, stone location, complications, and symptom relief were collected. Patients were followed up via clinical examination and questionnaires. Results: Seventy‐four patients were included and underwent endoscopy‐assisted combined operations for the removal of 98 parotid stones. Of the 98 stones, 92(94%) stones were completely removed and 6(6%) were partially removed. At a mean follow‐up of 47.1 ± 35 months, 65 of 74 patients (88%) achieved long‐term success. Patients with stone incomplete removal were significantly more often to develop the recurrence of obstructive symptoms (p = 0.000) There were no cases of facial nerve injury or fistula formation. Gland function was preserved in 73 of 74 patients (99%). Conclusions: The combined approach for parotid stones is a safe and gland‐preserving alternative to parotidectomy. The techniques described here show high success rates and good long‐term results, and they avoided the need for gland resection in >95% of cases. [ABSTRACT FROM AUTHOR]

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Mucin in saliva plays a critical role in the hydration and lubrication of the oral mucosa by retaining water molecules, and its impaired function may be associated with hyposalivation-independent xerostomia. Age-dependent effects on salivary gland function and rheological properties of secreted saliva are not fully understood as aging is a complex and multifactorial process. We aimed to evaluate age-related changes in the rheological properties of saliva and elucidate the underlying mechanism. We performed ex vivo submandibular gland (SMG) and sublingual gland (SLG) perfusion experiments to collect saliva from isolated glands of young (12 wk old) and aged (27 mo old) female C57BL/6J mice and investigate the rheological properties by determining the spinnbarkeit (viscoelasticity). While fluid secretion was comparable in SMG and SLG of both mice, spinnbarkeit showed a significant decrease in SLG saliva of aged mice than that of young mice. There were no significant differences in GalNAc concentration between young and aged SLG saliva. Liquid chromatography/tandem mass spectrometry analysis of SLG saliva revealed that (Hex)1 (HexNAc)1 (NeuAc)1 at m/z 793.31 was the most abundant O-glycan structure in SLG saliva commonly detected in both mice. Lectin staining of salivary gland tissue showed that SLG stained strongly with Maackia amurensis lectin II (MAL II) while Sambucus nigra agglutinin (SNA) stained little, if any, SLG. The messenger RNA expression of St3gal 1 that encodes an α-2,3 sialic acid sialyltransferase SIAT4-A showed a decrease in SLG of aged mice, confirmed by a Western blot analysis. Lectin blot analysis in SLG saliva revealed that the relative signal intensity detected by MAL II was significantly lower in aged SLG. Our results suggest that spinnbarkeit decreases in SLG of aging mice due to downregulation of sialic acid linked to α-2,3 sialic acid sialyltransferase expression. [ABSTRACT FROM AUTHOR]

Background: Xerostomia and changes in saliva characteristics are common side-effects in patients with head and neck cancer (HNC) undergoing radiotherapy, which negatively impact their oral health. However, there are no consensus standards for intervention to manage these problems. The aim of this study was to determine the effect of an integrated supportive program on xerostomia and saliva characteristics at a 1-year follow-up of patients with HNC radiated with a low dose to the major salivary glands. Methods: The CONSORT guidelines for a randomized controlled trial were used. Participants with a low overall dose to major salivary glands were randomly allocated to an intervention group (n = 47) or a control group (n = 45). The intervention group received usual care and an integrated supportive program, which included three steps: face-to-face education; face-to-face coaching at 1 month post-radiotherapy; and four telephone coaching sessions at 2, 3, 6, and 9 months post-radiotherapy. The face-to-face education consisted of oral hygiene instruction, oral self-care strategies, facial and tongue muscle exercises, and salivary gland massage. Adherence to the intervention was evaluated using a questionnaire completed during the 9 months follow-up. The control group received usual care. The unstimulated saliva flow rate and xerostomia were assessed in both groups. Results: A total of 79 participants (40 in the intervention group and 39 in the control group) completed the 12 months follow-up. The intervention group achieved significantly greater relief from xerostomia than the control group after 3 months (intervention group: 35.1 ± 5.9 versus control group: 38.0 ± 5.9, P = 0.027) and 12 months follow-up (intervention group: 18.5 ± 4.1 versus control group: 22.8 ± 4.3, P < 0.001). A higher unstimulated saliva flow rate was observed in the intervention group than the control group at 12 months follow-up (intervention group: 0.16 ± 0.08 versus control group: 0.12 ± 0.07, P = 0.035). Adherence to the intervention was generally good. Conclusion: This integrated supportive program with good adherence relieved xerostomia and had a positive effect on unstimulated saliva flow rate among patients with HNC radiated with a low dose to the major salivary glands during the 12 months of follow-up. Trial registration: Chinese Clinical Trial Registry ChiCTR2100051876 (08/10/2021), retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Although topical steroids are an effective treatment for oral lichen planus, they can have suppressive effects on oral immunity and predispose the patients to Candida overgrowth. Lactoferrin is a crucial local immunity protein in the oral cavity with important antimicrobial activity. The aim of this study was to prospectively investigate salivary lactoferrin secretion levels and Candida colonization in oral lichen planus patients treated with fluocinolone acetonide 0.1% in orabase. Methods: Saliva samples were collected from 15 oral lichen planus subjects who had never received topical steroid treatment prior to this study and 15 healthy volunteers to determine their salivary lactoferrin levels using an enzyme-linked immunosorbent assay and to investigate the presence of oral Candida species at baseline and 3 months after treatment with fluocinolone acetonide 0.1% in orabase. Statistical analysis was performed to compare lactoferrin secretion and Candida colonization levels between the groups using the Mann–Whitney U test for independent data or the Wilcoxon Signed-Rank test for paired data. Results: The salivary lactoferrin secretion level was not significantly different between the control group and oral lichen planus patients or between before and after treatment with fluocinolone acetonide 0.1% in orabase (P > 0.05). Candida was detected in 11 (73.33%) healthy volunteers, 8 (53.33%) oral lichen planus patients before treatment, and 9 (60%) oral lichen planus patients after treatment with fluocinolone acetonide 0.1% in orabase. There was no significant difference in Candida counts between the groups (P > 0.05). Conclusion: Our study indicates that using fluocinolone acetonide 0.1% in orabase to treat oral lichen planus for 3 months did not affect salivary lactoferrin protein secretion or Candida carriage. Trial registration The trial was registered at the Thai Clinical Trials Registry (TCTR identifier: TCTR20200723002). [ABSTRACT FROM AUTHOR]

Introduction: Various methods of analysis for the assay of chemotherapeutic agent 5-Fluorouracil (5-FU) in human and animal biological fluids have previously been reported. However, there is no standardization for detecting 5-FU in the hamsters' saliva that received the chemotherapeutic agent. Objective: Considering that the administration of 5-FU in some way changes the morphology and function of the salivary glands, and that the presence of the chemotherapeutic agents in the oral mucosa may lead to some oral complications, the aim of this study was to determine the presence of 5-FU in the hamsters' saliva that received the chemotherapeutic agent, by means of the High Performance Liquid Chromatography technique (HPCL) since this animal model is used in studies of 5-FU induced oral mucositis and glandular hypofunction. Methods: Twelve animals were divided into 4 groups: CP and CPI, in which the animals received pilocarpine (CP) or pilocarpine + isoproterenol (CPI) and the chemotherapy vehicle intraperitoneally; and Groups QP and QPI, in which the animals received the same secretagogues listed above, and the chemotherapeutic agent 5-FU, respectively. After the secretagogue administration, saliva was collected from all the animals for a period of 60 mins. Subsequently, the saliva was frozen at -80 °C for later determination of the chemotherapeutic agent by HPLC. After the the chromatograms analysis, and based on the results obtained, it was possible to identify the presence of 5-FU in the saliva samples from hamsters that received the chemotherapeutic agent intraperitonally, by the HPLC technique. [ABSTRACT FROM AUTHOR]

Although the physiological control of salivary secretion has been well studied, the impact of disease on salivary gland function and how this changes the composition and function of saliva is less well understood and is considered in this review. Secretion of saliva is dependent upon nerve-mediated stimuli, which activate glandular fluid and protein secretory mechanisms. The volume of saliva secreted by salivary glands depends upon the frequency and intensity of nerve-mediated stimuli, which increase dramatically with food intake and are subject to facilitatory or inhibitory influences within the central nervous system. Longer-term changes in saliva secretion have been found to occur in response to dietary change and aging, and these physiological influences can alter the composition and function of saliva in the mouth. Salivary gland dysfunction is associated with different diseases, including Sjögren syndrome, sialadenitis, and iatrogenic disease, due to radiotherapy and medications and is usually reported as a loss of secretory volume, which can range in severity. Defining salivary gland dysfunction by measuring salivary flow rates can be difficult since these vary widely in the healthy population. However, saliva can be sampled noninvasively and repeatedly, which facilitates longitudinal studies of subjects, providing a clearer picture of altered function. The application of omics technologies has revealed changes in saliva composition in many systemic diseases, offering disease biomarkers, but these compositional changes may not be related to salivary gland dysfunction. In Sjögren syndrome, there appears to be a change in the rheology of saliva due to altered mucin glycosylation. Analysis of glandular saliva in diseases or therapeutic interventions causing salivary gland inflammation frequently shows increased electrolyte concentrations and increased presence of innate immune proteins, most notably lactoferrin. Altering nerve-mediated signaling of salivary gland secretion contributes to medication-induced dysfunction and may also contribute to altered saliva composition in neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Objective Early diagnosis is critical to reduce long-term disability in patients with JIA by ensuring prompt treatment. The aim of this cross-sectional study was to evaluate the salivary gland function in JIA, addressing specifically oligoarticular (JIA1) and polyarticular (JIA2) subtypes, compared with healthy controls. This may contribute to the identification of salivary risk indicators of the disease that may help diagnosis at an early stage or even before the onset of other clinical evidence. Methods Twenty-eight patients with JIA1, 28 patients with JIA2, according to the ILAR criteria, and 28 healthy controls (C) were included in the study. Exclusion criteria were any concurrent medical condition. Data on medication, dietary and oral hygiene habits were collected using a questionnaire. All patients underwent oral examination and saliva measurement. Results While stimulated salivary flow rate (SFR) was significantly lower in JIA1 compared with JIA2 and C (P < 0.001), both salivary buffer capacity and pH were similar in the two JIA groups but statistically different from C (P = 0.002 and P = 0.010, respectively). Children with very low SFR (<3.5 ml) exhibited a 16-fold higher likelihood of being affected by JIA1 rather than JIA2 (P = 0.003), while no association was observed between low flow rate and JIA subtype (P = 0.744). Conclusion These preliminary data suggest impairment of salivary gland function as a risk indicator for JIA1 with no association with dietary habits and drug intake. [ABSTRACT FROM AUTHOR]

Background: Nicotine addiction is associated with nicotine absorption from the buccal mucosa, and it is stated that the main factor that determines nicotine absorption is saliva pH. In the literature, the effects of changes in saliva pH values after eating and drinking on smoking desire in smokers were not questioned. Aim: To show the effect of saliva pH changes on smoking desire. The secondary aim was to show the impact of coffee and water drinking on saliva pH and smoking on oral-dental health (oral hygiene and gingival bleeding). Study Design: Case--control study. Methods: A questionnaire was administered that included "Sociodemographic Data Form" and smoking history and Fagerstroö m Test for Nicotine Dependence (FTND). Oral and dental examinations were performed with mirror sonds and using oral hygiene standard Silness and Leoö e plaque index and DMFT Index (Index of Decayed Missing or Filled Teeth). Untreated saliva samples were taken, and baseline saliva flow rate and pH values were measured. To assess pH changes, saliva pH was remeasured after sugar-free instant coffee and water consumption. Smoking desire was evaluated with the Visual Analog Scale (VAS). Results: In this study, 24 (55.8%) females and 19 (44.2%) males were among the 43 smoking and 39 nonsmoking cases. Smoking was signifi- cantly associated with poor oral hygiene (in smokers 4.71 (±1.40), in non-smokers 2.30 (±1.59); P < .01). DMFT index was higher in smokers than in non-smokers (in smokers 6.45 (±3.69), in non-smokers 3.87 (±2.67); P < .01). Gingival bleeding was more prevalent in smokers (0.68 (±0.76)) than non-smokers (1.20 (±0.90); P = .009). Salivary flow rates were lower in smokers (in smokers 2.56 (±1.34), in non-smokers 3.00 (±1.22), P = .06). In both groups, pH values increased after coffee consumption and decreased after water; in smokers basal: 6.67 (±0.41), pH coffee: 6.93 (±0.36), pH water: 6.85 (±0.33); in non-smokers pH basal: 6.84 (±0.37), pH coffee: 7.02 (±0.37), pH water: 6.97 (±0.31), P < .01. The VAS values of smokers at basal 4.73 (±3.21); P < 0.01, after coffee consumption 4.91 (±3.08); P < .01, and after water 3.15 (±2.72); P < .01. Conclusion: The saliva pH increased after coffee consumption and decreased after drinking water. Besides, VAS values decreased significantly after drinking water. The results suggest that a simple behavior such as drinking water may be used in conjunction with behavioral and cognitive therapies to pursue smoking cessation. [ABSTRACT FROM AUTHOR]

Background: Nodal metastasis in salivary gland malignancies has important clinical implications; a good understanding of their complex anatomy is paramount to the head and neck surgeon. Methods: A contemporary and comprehensive literature review was conducted of the lymphatic drainage of the salivary glands, with special emphasis on its surgical applications. Results: The parotid gland has extraglandular and intraglandular nodes acting as a single functional drainage unit. Intraglandular parotid notes are unique to the parotid gland, and consist of a larger superficial group and a smaller deep group. The presence of intraglandular submandibular nodes, as described by early anatomists, is much debated nowadays. The sublingual glands drain to the lingual lymph nodes, which are divided into median, intermediate and lateral groups. Conclusion: This review highlights the complex arrangements of lymph nodes draining the salivary glands. It may provide a valid anatomical explanation for the nodal metastasis patterns commonly seen in salivary gland malignancy. [ABSTRACT FROM AUTHOR]

Radioiodine (131I, RAI) has traditionally been used in thyroid cancer treatment but its benefit should be balanced against possible risks. Among them, salivary gland dysfunction has often been discussed, although the reported data have been inconsistent. The aim of our prospective study was to evaluate salivary gland function in 31 thyroidectomised patients (6 men, 25 women; median age 52 yr) before and 4–6 months after RAI remnant ablation (RRA), using activity of 3.7 GBq 131I‐NaI. Salivary gland uptake and excretion fractions were quantitatively assessed with 99mTc – pertechnetate salivary gland scintigraphy. Pre‐ and post‐treatment values were compared using Wilcoxon signed rank test. No statistically significant difference in the pre‐ and post‐treatment values was observed in parotid or submandibular glands uptake, or in the parotid or submandibular excretion fractions. The calculated power for minimum relevant difference of 25% with the sample size of 31 ranged between 86% and 96% for the individual variables, making our negative results reasonably reliable. The results suggest that RRA with the most commonly used activity of 3.7 GBq has no important impact on salivary gland function. Therefore, the concerns about putative salivary gland functional deterioration following RRA are probably unjustified. [ABSTRACT FROM AUTHOR]

Our previous studies indicated that YIGSR-A99 peptides chemically conjugated to fibrin hydrogel (FH) and applied to wounded submandibular gland (SMG) in vivo, formed new organized salivary tissue, whereas wounded SMG treated with FH alone or in the absence of a scaffold showed disorganized collagen formation and poor tissue healing. While these studies indicated that damaged SMG grow and differentiate when treated with FH containing L1 peptide, they were performed only in female mice. However, there is a well-established sexual dimorphism present in mouse SMG (e.g., males develop well-differentiated granular convoluted tubules, but these structures are poorly developed in females) and little is known about how these sex differences influence wound healing events. Therefore, the goal of this study was to conduct comparative analyses of regeneration patterns in male and female mice using L1p-FH in a wounded SMG mouse model. Particularly, we focused on sex-dependent wound healing events such as macrophage polarization, vascularization, tissue organization, and collagen deposition, and how these events affect salivary gland functioning: [ABSTRACT FROM AUTHOR]

The article presents the taste and smell disorders in patients because of COVID-19 have been reported along with various other clinical problems and the potential role of salivary gland. Topics include the novel coronavirus disease has caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) constitutes a public health emergency of international concern.

The article discusses research which investigated effectiveness of aspirin-triggered resolvin D1 (AT-RvD1) in treating Sjögren syndrome (SS) in a mouse model. Topics explored include symptoms which characterize SS such as salivary gland inflammation, the prevention of chronic inflammation following AT-RvD1 administration in addition to saliva secretion restoration, and the observed reduction of pro-inflammatory cytokine gene associated with SS.

Salivary gland dysfunction occurs in several autoimmune and immune-related conditions, including Sjögren syndrome (SS); immune checkpoint inhibitor-induced sicca (ICIS) that develops in some cancer patients and is characterized by severe, sudden-onset dry mouth; and autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Although subjects with these conditions present with oral dryness and often exhibit inflammatory infiltration of the salivary gland, little is known about the B-cell humoral responses directed against salivary gland protein targets. In this study, autoantibodies were evaluated against Ro52, Ro60, and La, as well as against a panel of 22 proteins derived from the salivary proteome. The tested cohort included healthy volunteers and subjects with SS, ICIS, and APECED without and with sicca. As expected, a high percentage of autoantibody seropositivity was detected against Ro52, Ro60, and La in SS, but only a few ICIS patients were seropositive for these autoantigens. A few APECED subjects also harbored autoantibodies to Ro52 and La, but only Ro60 autoantibodies were weakly associated with a small subset of APECED patients with sicca. Additional testing of the salivary panel failed to detect seropositive autoantibodies against any of the salivary-enriched proteins in the SS and ICIS subjects. However, APECED subjects selectively demonstrated seropositivity against BPI fold containing family A member 1 (BPIFA1), BPI fold containing family A member 2 (BPIFA2)/parotid salivary protein (PSP), and lactoperoxidase, 3 salivary-enriched proteins. Moreover, high levels of serum autoantibodies against BPIFA1 and BPIFA2/PSP occurred in 30% and 67% of the APECED patients with sicca symptoms, respectively, and were associated with an earlier age onset of oral dryness (P = 0.001). These findings highlight the complexity of humoral responses in different sicca diseases and provide new insights and biomarkers for APECED-associated sicca (ClinicalTrials.gov: NCT00001196; NCT00001390; NCT01425892; NCT01386437). [ABSTRACT FROM AUTHOR]

Background: Metabolomics is the study of metabolome which describes the full repertoire of small molecules, and the analysis of salivary metabolomics may help in identifying tumor-specific biomarkers for early diagnosis and prediction of tumor progression. The aim of the study was to evaluate the clinical utility of salivary metabolites in oral leukoplakia and oral squamous cell carcinoma.Methods: Salivary metabolomic profile of patients diagnosed with oral leukoplakia (n = 21) and oral squamous cell carcinoma (n = 22) was compared with apparently normal controls (n = 18) using Q-TOF-liquid chromatography-mass spectrometry. MassHunter profile software and Metlin database were used for metabolite identification. ANOVA to identify the regulation of metabolites between the three groups, t test (P < 0.05) to signify the changes between two groups, and chi-square test (P < 0.05) to indicate the presence or absence of metabolites in the study participants of the three groups were performed.Results: Significant upregulation of 1-methylhistidine, inositol 1,3,4-triphosphate, d-glycerate-2-phosphate, 4-nitroquinoline-1-oxide, 2-oxoarginine, norcocaine nitroxide, sphinganine-1-phosphate, and pseudouridine in oral leukoplakia and OSCC was noted. Downregulated compounds in the diseased groups included l-homocysteic acid, ubiquinone, neuraminic acid, and estradiol valerate.Conclusion: A range of salivary metabolites were significantly altered in oral leukoplakia and oral squamous cell carcinoma. Further, it is necessary to evaluate the clinical utility of the individual metabolites in preventing malignant transformation of oral leukoplakia and to improve prognosis of oral squamous cell carcinoma. [ABSTRACT FROM AUTHOR]

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes. [ABSTRACT FROM AUTHOR]

Background: The Milan System for Reporting Salivary Gland Cytopathology (Milan System) has previously shown its diagnostic utility by categorizing the seven cytology findings in salivary gland lesions. However, there has been lack of study about the risk of high-grade malignancy in the cytology diagnosis based on the Milan System. Thus, we tried to identify the diagnostic ability of the Milan System for high-grade malignancy and to suggest an improved diagnostic approach for preoperative estimation of high-grade malignancy using the Milan System.Methods: A total of 413 patients with parotid gland tumors, who had undergone surgical resection from 2011 to 2015 were included in the present study retrospectively. Cytopathology was reclassified according to the Milan System by two independent reviewers. The outcomes were risk of malignancy and risk of high-grade malignancy. The diagnostic performance of the Milan System category [Malignant] for detecting high-grade malignancy was calculated.Results: The risk of malignancy was 83.3% and 100% in the Milan System categories [Suspicious for Malignancy] and [Malignant], respectively. Meanwhile, the risk of high-grade malignancy was 16.7% and 55.9% in these two categories. Disease-free survival of patients with high-grade malignancy was significantly worse than those with low- and intermediate-grade malignancy. Union combining the Milan System category [Malignant] with the presence of nodal metastasis suggested high-grade malignancy with an acceptable diagnostic sensitivity (0.889-0.963) and negative predictive value (0.900-0.966).Conclusions: The Milan System category [Malignant] with the presence of nodal metastasis suggested parotid gland tumors as high-grade malignancy in a pretreatment setting. [ABSTRACT FROM AUTHOR]

Abstract Background Salivary secretion is an important parameter reflecting the health status of an individual and has been used clinically for the diagnosis of various oral diseases, such as xerostomia. Salivary metabolomic profiling is considered an emerging potential tool for the detection of various systemic diseases. To our knowledge, this is the first study to investigate the quantitative relationship between salivary secretion volume and salivary metabolomic profile. Methods To evaluate inter- and intra-day variations in salivary secretion, 234 saliva samples were collected three times per day for three days from 13 subjects and analyzed. Capillary electrophoresis-mass spectrometry was used for non-targeted quantification of water-soluble metabolites. Results No significant inter- or intra-day variations were observed in salivary secretion volume. No significant inter-day variations were observed in metabolomic patterns. In contrast, significant intra-day variations were observed in salivary metabolomic profiles. The difference was more obvious for stimulated saliva than for unstimulated saliva. These profile changes were independent of salivary secretion volume. Conclusions Our results indicated that diurnal change had a greater effect on salivary metabolomic profiles than the other factors. Hence, sampling time should be tightly controlled to minimize unexpected bias in the clinical use of salivary metabolomics. Highlights • Salivary metabolomic profiles showed significant inter-day variation. • Intra-day difference was not observed in metabolomic profiles. • The inter-day variation of metabolites was smaller for stimulated saliva. • The sampling time affected metabolite concentrations in the collected saliva. [ABSTRACT FROM AUTHOR]

Tousled and its homologs are evolutionarily conserved serine/threonine kinases present in plants and animals. Human Tousled‐like kinases, TLK1 and TLK2, are implicated in chromatin assembly during DNA replication, chromosome segregation during mitosis, as well as in DNA damage response and repair. They share a high degree of sequence similarity, but have few non‐redundant functions. Our laboratory has studied TLK1 and found that it increases the resistance of cells to ionizing radiation (IR) damage through expedited double‐strand break (DSB) repair. DSBs are life‐threatening lesions which when repaired restore DNA integrity and promote cell survival. A major focus in our laboratory is to dissect TLK1′s role in DSB response and repair and study its usefulness in averting salivary gland hypofunction, a condition that invariably afflicts patients undergoing regional radiotherapy. The identification of anti‐silencing factor 1 (ASF1), histone H3, and Rad9 as substrates of TLK1 links the protein to chromatin organization and DNA damage response and repair. However, recent findings of new interacting partners that include NEK1 suggest that TLK1 may play a broader role in DSB repair. This review provides a brief overview of the DNA damage response and DSB repair, and it highlights our current understanding of TLK1 in the process. [ABSTRACT FROM AUTHOR]

Hirudo nipponia (known as Shui Zhi in Chinese) is a well-known Chinese medicine with numerous active ingredients in its body, especially in its saliva. This native Chinese blood-sucking leech has been used for therapeutic purposes since before 100 AD. Modern Chinese physicians use it for a wide range of diseases. Genomic data and molecular information about the pharmacologically active substances produced by this medicinal leech are presently unavailable despite this organism’s medicinal importance. In this study, we performed transcriptome profiling of the salivary glands of medicinal leech H. nipponia using the Illumina platform. In total, 84,657,362 clean reads were assembled into 50,535 unigenes. The obtained unigenes were compared to public databases. Furthermore, a unigene sequence similarity search and comparisons with the whole transcriptome of medical leech were performed to identify potential proteins. Finally, more than 21 genes were predicted to be involved in anticoagulatory, antithrombotic, antibacterial, anti-inflammatory and antitumor processes, which might play important roles in the treatment of various diseases. This study is the first analysis of a sialotranscriptome in H. nipponia. The transcriptome profile will shed light on its genetic background and provide a useful tool to deepen our understanding of the medical value of H. nipponia. [ABSTRACT FROM AUTHOR]

Development and maturation of submandibular salivary glands are influenced by intrauterine diabetic environment. Several studies investigated the effects of diabetes on the salivary glands. However, the effects of maternal diabetes on the submandibular glands of the offspring was not properly examined. Therefore, the present study was designed to describe the changes in the development of the submandibular glands of the offspring of diabetic mothers. The submandibular glands of the offspring of Streptozotocin (STZ)-induced diabetic female rats were examined at two and four weeks after birth. Detection of mRNA demonstrated that maternal diabetes affects the level of different indicators. The reduction of expression of epidermal growth factor (EGF); a protein mitogen, cytokeratin 5 (CK5); an epithelial cell progenitor, CK7 and aquaporin 5 (AQP5); differentiation markers and B cell lymphoma 2 (Bcl2); an antiapoptotic marker were found. Increase in Bcl2-associated X protein (Bax); an apoptotic marker was detected. These changes indicate their effects on saliva secretion, glands tumorigenesis, growth of normal oral flora and oral microbes, with decreased protein synthesis and production of xerostomia and dental caries. Loss of normal glandular architecture, significant increase in fibrosis, by the detection of collagen fibers, and stagnation of secretory granules were found with atrophic changes in the acinar cells. Marked defect of polysaccharides in the acinar cells, denoting functional changes, was manifested by significant reduction of the intensity of periodic acid-Schiff (PAS) reaction. The positive immunoreactivity of caspase-3, denoting cellular apoptosis, and minimal reaction of alpha-smooth muscle actin (α SMA) and proliferating cell nuclear antigen (PCNA) were evident in the offspring of diabetic mothers. We conclude that maternal diabetes produces degenerative effects in the structure and function of the submandibular salivary glands of the offspring, reflecting possible influences on their secretory activity affecting oral and digestive health. [ABSTRACT FROM AUTHOR]

Summary: Immune cell‐mediated destruction of salivary glands is a hallmark feature of Sjögren syndrome. Similar to the female predominance in humans, female non‐obese diabetic (NOD) mice develop spontaneous salivary gland autoimmunity. However, in both humans and mice it is unclear what factors contribute to the initial immune infiltration of the salivary glands. Here, we used an adoptive transfer model of Sjögren syndrome to determine if female mice harbor a sex‐specific defect in salivary‐gland‐protective regulatory T (Treg) cells. Transfer of cervical lymph node (LN) cells from female NOD mice into sex‐matched NOD‐severe combined immunodeficient (SCID) recipients resulted in sialadenitis, regardless of the presence or absence of Treg cells. In contrast, transfer of cervical LN cells from male NOD mice into sex‐matched NOD‐SCID recipients only resulted in sialadenitis when Treg cells were depleted before transfer, suggesting that male NOD mice have functional salivary‐gland‐protective Treg cells. Notably, the host environment affected the ability of Treg cells to prevent sialadenitis with testosterone promoting salivary gland protection. Treg cells from male mice did not protect against sialadenitis in female recipients. Testosterone treatment of female recipients of bulk cervical LN cells decreased sialadenitis, and Treg cells from female mice were capable of protecting against development of sialadenitis in male recipients. Hence, our data demonstrate that female NOD mice develop sialadenitis through a defect in salivary‐gland‐protective Treg cells that can be reversed in the presence of testosterone. [ABSTRACT FROM AUTHOR]

The authors convey their thoughts about cellular plasticity in salivary gland regeneration. Topics mentioned include two types of ductal progenitor cells that respond to radiation differently, lineage tracing for a longer period of 90 days after irradiation, and the impact of differentiated duct cells on cell fate upon ectopic expression of the Sox10 transcription factor.

Abstract Development of the salivary gland is characterized by extensive branching morphogenesis and lumen formation, the latter of which is closely associated with differentiation into acinar and ductal cells. Although various molecules, including signaling and cell adhesion molecules, have been implicated in salivary gland development, transcription factors (TFs) regulating the expression of those molecules and morphological development of the gland are largely unknown. Here we show that knockdown of the epithelial TF, Grainyhead-like 2 (Grhl2), with siRNA in developing mouse submandibular salivary gland (SMG) cultured ex vivo resulted in retardation of epithelial development. This retardation was concomitant with suppression of gene expression for the cell adhesion molecules, such as E-cadherin and the extracellular protease inhibitor SPINT1, and with the disorganized deposition of the basal lamina protein laminin. ChIP-PCR demonstrated the binding of Grhl2 protein to the Spint1 gene in the SMG. Notably, addition of recombinant SPINT1 protein in cultured SMG overcame the suppressive effects of Grhl2 siRNA on epithelial development and laminin deposition. These findings show that Grhl2 regulation of SPINT1 expression controls salivary gland development. [ABSTRACT FROM AUTHOR]

In the recent past, we demonstrated that a great deal is going on in the salivary glands of Drosophila in the interval after they release their glycoprotein‐rich secretory glue during pupariation. The early‐to‐mid prepupal salivary glands undergo extensive endocytosis with widespread vacuolation of the cytoplasm followed by massive apocrine secretion. Here, we describe additional novel properties of these endosomes. The use of vital pH‐sensitive probes provided confirmatory evidence that these endosomes have acidic contents and that there are two types of endocytosis seen in the prepupal glands. The salivary glands simultaneously generate mildly acidic, small, basally‐derived endosomes and strongly acidic, large and apical endosomes. Staining of the large vacuoles with vital acidic probes is possible only after there is ambipolar fusion of both basal and apical endosomes, since only basally‐derived endosomes can bring fluorescent probes into the vesicular system. We obtained multiple lines of evidence that the small basally‐derived endosomes are chiefly involved in the uptake of dietary Fe3+ iron. The fusion of basal endosomes with the larger and strongly acidic apical endosomes appears to facilitate optimal conditions for ferrireductase activity inside the vacuoles to release metabolic Fe2+ iron. While iron was not detectable directly due to limited staining sensitivity, we found increasing fluorescence of the glutathione‐sensitive probe CellTracker Blue CMAC in large vacuoles, which appeared to depend on the amount of iron released by ferrireductase. Moreover, heterologous fluorescently‐labeled mammalian iron‐bound transferrin is actively taken up, providing direct evidence for active iron uptake by basal endocytosis. In addition, we serendipitously found that small (basal) endosomes were uniquely recognized by PNA lectin, whereas large (apical) vacuoles bound DBA lectin. [ABSTRACT FROM AUTHOR]

Tissues from Australian brushtail possums ( Trichosurus vulpecula ) that had been experimentally infected with wobbly possum disease (WPD) virus (WPDV) were examined to elucidate pathogenesis of WPDV infection. Mononuclear inflammatory cell infiltrates were present in livers, kidneys, salivary glands and brains of WPD-affected possums. Specific staining was detected by immunohistochemistry within macrophages in the livers and kidneys, and undefined cell types in the brains. The highest viral RNA load was found in macrophage-rich tissues. The detection of viral RNA in the salivary gland, serum, kidney, bladder and urine is compatible with transmission via close physical contact during encounters such as fighting or grooming, or by contact with an environment that has been contaminated with saliva or urine. Levels of viral RNA remained high in all tissues tested throughout the study, suggesting that on-going virus replication and evasion of the immune responses may be important in the pathogenesis of disease. [ABSTRACT FROM AUTHOR]

Summary: Saliva is a complex fluid produced by 3 pairs of major salivary glands and by hundreds of minor salivary glands. It comprises a large variety of constituents and physicochemical properties, which are important for the maintenance of oral health. Saliva not only protects the teeth and the oropharyngeal mucosa, it also facilitates articulation of speech, and is imperative for mastication and swallowing. Furthermore, saliva plays an important role in maintaining a balanced microbiota. Thus, the multiple functions provided by saliva are essential for proper protection and functioning of the body as a whole and for the general health. A large number of diseases and medications can affect salivary secretion through different mechanisms, leading to salivary gland dysfunction and associated oral problems, including xerostomia, dental caries and fungal infections. The first part of this review article provides an updated insight into our understanding of salivary gland structure, the neural regulation of salivary gland secretion, the mechanisms underlying the formation of saliva, the various functions of saliva and factors that influence salivary secretion under normal physiological conditions. The second part focuses on how various diseases and medical treatment including commonly prescribed medications and cancer therapies can affect salivary gland structure and function. We also provide a brief insight into how to diagnose salivary gland dysfunction. [ABSTRACT FROM AUTHOR]

Background: CD44 is a transmembranous proteoglycan, with a main role of cell adhesion to other cells and to extracellular matrix involved in the preservation of three-dimensional structure of organs. Pleomorphic adenoma (PA) is a common benign salivary gland tumor, composed of myoepithelial and ductal components. Carcinoma ex-PA (CXPA) is malignant transformation of the epithelial elements in PA. The aim of this study was to evaluate CD44 expression by immunohistochemistry in these two tumors and normal salivary gland near these tumors. Materials and Methods: In this cross-sectional immunohistochemical study, 40 paraffin blocks (formalin fixed, paraffin embedded) with thirty belonging to PA and ten blocks of CXPA and 18 paraffinized blocks of normal salivary glands' tissue adjacent to tumoral tissue (13 in the vicinity of PA and 5 in the vicinity of CXPA) were selected. Immunohistochemical expression of CD44 was observed and compared with each other. For data analysis, we used Chi-square, Kruskal–Wallis, and Mann–Whitney tests and the quantity of P values was considered 0.05. Results: There was a significant difference in CD44 expression frequency between PA, CXPA, and normal salivary glands with higher expression noted in CXPA. Furthermore, expression frequency of CD44 in adjacent normal salivary gland of CXPA was significantly higher than PA. There was no significant difference in the expression of CD44 with respect to lymph node metastasis. Conclusion: Higher expression of CD44 in CXPA might illustrate CD44's role in malignant transformation of PA. [ABSTRACT FROM AUTHOR]

Salivary glands produce various neurotrophins that are thought to regulate salivary function during normal and pathological conditions. Prosaposin (PSAP) is a potent neurotrophin found in several tissues and various biological fluids and may play roles in the regulation of salivary function. However, little is known about PSAP in salivary glands. As the functions of salivary glands are diverse based on age and sex, this study examines whether PSAP and its receptors, G protein-coupled receptor 37 (GPR37) and GPR37L1, are expressed in the salivary glands of rats and whether sex and aging affect their expression. Immunohistochemical analysis revealed that PSAP and its receptors were expressed in the major salivary glands of rats, although their expression varied considerably based on the type of gland, acinar cells, age and sex. In fact, PSAP, GPR37 and GPR37L1 were predominantly expressed in granular convoluted tubule cells of the submandibular gland and the intensity of their immunoreactivity was higher in young adult female rats than age-matched male rats, which was more prominent at older ages (mature adult to menopause). On the other hand, weak PSAP, GPR37 and GPR37L1 immunoreactivity was observed mainly in the basal layer of mucous cells of the sublingual gland. Triple label immunofluorescence analysis revealed that PSAP, GPR37 and GPR37L1 were co-localized in the basal layer of acinar and ductal cells in the major salivary glands. The present findings indicate that PSAP and its receptors, GPR37 and GPR37L1, are expressed in the major salivary glands of rats and their immunoreactivities differ considerably with age and sex. [ABSTRACT FROM AUTHOR]

The overall goal is to study the effect of low-level laser therapy (LLLT) on membrane distribution of major water channel protein aquaporin 5 (AQP5) in salivary gland during hyperglycemia. Par C10 cells treated with high glucose (50 mM) showed a reduced membrane distribution of AQP5. The functional expression of AQP5 was downregulated due to intracellular Ca 2+ overload and ER stress. This reduction in AQP5 expression impairs water permeability and therefore results in hypo-salivation. A reduced salivary flow was also observed in streptozotocin (STZ)-induced diabetic mice model and the expression of AQP5 and phospho-AQP5 was downregulated. Low-level laser treatment with 850 nm (30 mW, 10 min = 18 J/cm 2 ) reduced ER stress and recovered AQP5 membrane distribution via serine phosphorylation in the cells. In the STZ-induced diabetic mouse, LLLT with 850 nm (60 J/cm 2 ) increased salivary flow and upregulated of AQP5 and p-AQP5. ER stress was also reduced via downregulation of caspase 12 and CHOP. In silico analysis confirmed that the serine 156 is one of the most favorable phosphorylation sites of AQP5 and may contribute to the stability of the protein. Therefore, this study suggests high glucose inhibits phosphorylation-dependent AQP5 membrane distribution. High glucose induces intracellular Ca 2+ overload and ER stress that disrupt AQP5 functional expression. Low-level laser therapy with 850 nm improves salivary function by increasing AQP5 membrane distribution in hyperglycemia-induced hyposalivation. [ABSTRACT FROM AUTHOR]

Human gaze is an important indicator of dominant and submissive behaviours related to positioning in a social hierarchy. This study investigated face gazing after a chance-determined contest and its linkage to salivary testosterone (sal-T) reactivity in athletic women. Twenty-six women athletes completed a coin-toss game on days 7 (D7), 14 (D14) and 21 (D21) of a single menstrual cycle. The game was played against an unknown opponent of similar age with the winner congratulated and rewarded with all coins. Gazing towards an opponent's head or face was timed after each contest (over 2 min) from video footage. Salivary T (sal-T) was assessed before and 15 min after these contests. The sal-T residuals increased after winning and decreased after losing on D7, D14 and D21 (p < 0.05). Gaze times were longer after a loss (M = 7.8 s) than a win (M = 3.1 s) across all days. Regression analyses revealed that the sal-T residuals and contest outcome interacted to predict gaze time. Upon deconstruction we found that, when losing a contest, a larger sal-T response (i.e., smaller decline) predicted a longer gaze (β = 1.71, p = 0.004), but no association was evident when winning (β = −0.06, p = 0.821), and these slope patterns differed (p = 0.011). In conclusion, winning a contest by chance increased sal-T responsivity and decreased opponent gaze across the menstrual cycle. A positive relationship between individual sal-T reactivity and gaze duration was observed, but only when losing. These preliminary results support suggestions that women's T may help modulate post-competition behaviours (e.g., face gazing) possibly to achieve social cohesion and cooperation. [ABSTRACT FROM AUTHOR]

Leeches (Annelida: Hirudinea) possess powerful salivary anticoagulants and, accordingly, are frequently employed in modern, authoritative medicine. Members of the almost exclusively marine family Piscicolidae account for 20% of leech species diversity, and they feed on host groups (e.g., sharks) not encountered by their freshwater and terrestrial counterparts. Moreover, some species of Ozobranchidae feed on endangered marine turtles and have been implicated as potential vectors for the tumor-associated turtle herpesvirus. In spite of their ecological importance and unique host associations, there is a distinct paucity of data regarding the salivary transcriptomes of either of these families. Using next-generation sequencing, we profiled transcribed, putative anticoagulants and other salivary bioactive compounds that have previously been linked to blood feeding from 7 piscicolid species (3 elasmobranch feeders; 4 non-cartilaginous fish feeders) and 1 ozobranchid species (2 samples). In total, 149 putative anticoagulants and bioactive loci were discovered in varying constellations throughout the different samples. The putative anticoagulants showed a broad spectrum of described antagonistic pathways, such as inhibition of factor Xa and platelet aggregation, which likely have similar bioactive roles in marine fish and turtles. A transcript with homology to ohanin, originally isolated from king cobras, was found in Cystobranchus vividus but is otherwise unknown from leeches. Estimation of selection pressures for the putative anticoagulants recovered evidence for both positive and purifying selection along several isolated branches in the gene trees, and positive selection was also estimated for a few select codons in a variety of marine species. Similarly, phylogenetic analyses of the amino acid sequences for several anticoagulants indicated divergent evolution. [ABSTRACT FROM AUTHOR]

Dynamic alterations in oral microbiota are closely related to the development of dental caries;however, changes in salivary microbiota during this process have not been extensively studied. In addition, increasing evidence suggests that oral microbiome profiles differ according to dentition stages, but it is unclear whether they change with age during the same dentition, such as deciduous dentition. These two aspects were investigated in a 2-year follow-up study, and caries-free preschool children with complete deciduous dentition were enrolled. Saliva was collected and oral examination was conducted at the beginning of this trial, and then every subsequent 6 months for a total of five time points (T0, T1, T2, T3, and T4). Based on the clinical examination of teeth at the end of the trial, subjects were divided into health-to-health (H-H, N = 11) and health-to-caries (H-C, N = 12) groups at every time point. A total of 115 saliva samples from 23 subjects was detected by sequencing 16S rDNA V3-V4 hypervariable regions with the Illumina MiSeq platform to obtain microbiome profiles, and 100 samples finally passed quality control for further analyses. A total of 4,328,852 high-quality sequencing reads passed quality-control testing, representing 14 phyla, 27 classes, 43 orders, 67 families, and 127 genera. An a diversity analysis showed that salivary microbial diversity was similar in all groups, and a b diversity analysis showed that salivary microbial community structure changed with dental caries. Linear discriminant analysis effect size (LEfSe) analysis revealed that the abundance of the genera Atopobium, Megasphaera, and Veillonella increased significantly, while that of the genera Shuttleworthia and Rothia decreased significantly with the development of dental caries. Megasphaera and Veillonella were enriched at the early stage of deciduous dentition whereas Peptococcus, Rothia, and Treponema were enriched at the later stage. The core microbiome in the H-H and H-C groups comprised 26 and 29 genera, respectively, with statistical differences observed in 11 shared core genera. These results provide new insights into variations in the salivary microbiome related to dental caries and age in the deciduous dentition period. [ABSTRACT FROM AUTHOR]