The Effect of Umami Stimulation on Salivary Secretion Rate and Duration

Purpose: Umami reportedly promotes salivation. We aimed to investigate the effects of taste stimuli on slow and fast salivary secretion in humans using umami, sweet, and sour stimuli. Methods: Eight healthy women participated between 14:00 and 15:00, taking the circadian rhythm of salivary secretion into account. The types and concentrations of the taste solutions were glutamic acid (1.7 × 10−3 M), inosinic acid (9.8 × 10−3 M), and guanylic acid (9.8 × 10−3 M) for umami stimulation, citric acid (6.5 × 10−3 M) for acidity stimulation, and sucrose (1.6 × 10−2 M) for sweetness stimulation. First, the unstimulated salivary flow rate was measured. Then, 3 ml of a flavor solution was dropped under the tongue using a syringe. The saliva was expelled into an aluminum cup every minute and weighed. The first minute’s value minus 3 ml flavor solution was the stimulated salivary secretion rate produced by each flavor. The time-to-return to the initial unstimulated salivary flow rate was the duration of the stimulated saliva secretion rate. Results: The mean unstimulated salivary flow rate across participants was 0.64 ± 0.25 ml/min (range: 0.23 - 1.03 ml/min). The highest amount of saliva was induced by citric acid. There were significant differences between citric acid and the other flavor solutions (p < 0.05 for glutamic acid, inosinic acid, and sucrose;p < 0.01 for guanylic acid). There were no significant differences in duration of salivation between the flavor solutions. When the participants were divided into slow (0.45 ± 0.16 ml/min) and fast groups (0.83 ± 0.15 ml/min) based on their median resting salivary secretion rate, there were no significant differences between the two groups in the amount of saliva secreted at 1 minute after stimulation and the duration of the salivary secretion rate. Conclusion: Umami stimulation was effective in slowing salivary secretion and sustaining salivary secretion after stimulation.

A systematic review of salivary biomarkers in Parkinson's disease

The search fo r reliable and easily accessible biomarkers in Parkinson's disease is receiving a growing emphasis,to detect neurodegeneration from the prodromal phase and to enforce disease-modifying therapies.Despite the need for non-invasively accessible biomarke rs,the majo rity of the studies have pointed to cerebrospinal fluid or peripheral biopsies biomarkers,which require invasive collection procedures.Saliva represents an easily accessible biofluid and an incredibly wide source of molecular biomarkers.In the present study,after presenting the morphological and biological bases for looking at saliva in the search of biomarkers for Parkinson's disease,we systematically reviewed the results achieved so far in the saliva of different cohorts of Parkinson's disease patients.A comprehensive literature search on PubMed and SCOPUS led to the discovery of 289articles.After screening and exclusion,34 relevant articles were derived fo r systematic review.Alpha-synuclein,the histopathological hallmark of Parkinson's disease,has been the most investigated Parkinson's disease biomarker in saliva,with oligomeric alphasynuclein consistently found increased in Parkinson's disease patients in comparison to healthy controls,while conflicting results have been reported regarding the levels of total alpha-synuclein and phosphorylated alpha-synuclein,and few studies described an increased oligomeric alpha-synuclein/total alpha-synuclein ratio in Parkinson's disease.Beyond alpha-synuclein,other biomarkers to rgeting diffe rent molecular pathways have been explored in the saliva of Parkinson's disease patients:total tau,phosphorylated tau,amyloid-β1-42(pathological protein aggregation biomarkers);DJ-1,heme-oxygenase-l,metabolites(alte red energy homeostasis biomarkers);MAPLC-3beta(aberrant proteostasis biomarker);cortisol,tumor necrosis factor-alpha(inflammation biomarkers);DNA methylation,miRNA(DNA/RNA defects biomarkers);acetylcholinesterase activity(synaptic and neuronal network dysfunction biomarkers);Raman spectra,proteome,and caffeine.Despite a few studies investigating biomarkers to rgeting molecular pathways different from alpha-synuclein in Parkinson's disease,these results should be replicated and observed in studies on larger cohorts,considering the potential role of these biomarkers in determining the molecular variance among Parkinson's disease subtypes.Although the need fo r standardization in sample collection and processing,salivary-based biomarkers studies have reported encouraging results,calling for large-scale longitudinal studies and multicentric assessments,given the great molecular potentials and the non-invasive accessibility of saliva.

Salivary metabolites are promising noninvasive biomarkers of druginduced liver injury

BACKGROUND Drug-induced liver injury(DILI)is one of the most common adverse events of medication use,and its incidence is increasing.However,early detection of DILI is a crucial challenge due to a lack of biomarkers and noninvasive tests.AIM To identify salivary metabolic biomarkers of DILI for the future development of noninvasive diagnostic tools.METHODS Saliva samples from 31 DILI patients and 35 healthy controls(HCs)were subjected to untargeted metabolomics using ultrahigh-pressure liquid chromatography coupled with tandem mass spectrometry.Subsequent analyses,including partial least squares-discriminant analysis modeling,t tests and weighted metabolite coexpression network analysis(WMCNA),were conducted to identify key differentially expressed metabolites(DEMs)and metabolite sets.Furthermore we utilized least absolute shrinkage and selection operato and random fores analyses for biomarker prediction.The use of each metabolite and metabolite set to detect DILI was evaluated with area under the receiver operating characteristic curves.RESULTS We found 247 differentially expressed salivary metabolites between the DILI group and the HC group.Using WMCNA,we identified a set of 8 DEMs closely related to liver injury for further prediction testing.Interestingly,the distinct separation of DILI patients and HCs was achieved with five metabolites,namely,12-hydroxydodecanoic acid,3-hydroxydecanoic acid,tetradecanedioic acid,hypoxanthine,and inosine(area under the curve:0.733-1).CONCLUSION Salivary metabolomics revealed previously unreported metabolic alterations and diagnostic biomarkers in the saliva of DILI patients.Our study may provide a potentially feasible and noninvasive diagnostic method for DILI,but further validation is needed.

Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

A Study on the Correlation between Salivary Cortisol Content and Anxiety and Depression in Pregnant and Postpartum Women

Objective: To analyze the correlation between salivary cortisol content and anxiety and depression in pregnant and postpartum women. Method: 300 pregnant and postpartum women who were admitted from January 2021 to December 2021 were selected as the research subjects. They were all tested with the Hamilton Anxiety Scale (HAMA) and the Edinburgh Postnatal Depression Scale (EPDS). 40 pregnant women with anxiety and depression were selected as the observation group, and 50 normal pregnant women were selected as the control group, adopting logistic regression analysis to investigate the correlation between salivary cortisol and postpartum anxiety and depression during pregnancy. Result: The salivary cortisol levels in the observation group were significantly higher than those in the control group before bedtime, after waking up the next day, 15 minutes after waking up, 30 minutes after waking up, 60 minutes after waking up, and 1 hour before lunch (p < 0.05). Maternal depression and anxiety were not related to age, weight, gestational age, negative events, or history of adverse pregnancy and childbirth (p > 0.05). Maternal depression and anxiety are closely related to salivary cortisol levels and educational background (p Conclusion: There is a close correlation between anxiety and depression and an increase in cortisol levels, suggesting that the salivary cortisol awakening response during pregnancy has a predictive effect on the occurrence of postpartum depression.

Autologous mesenchymal stem cells offer a new paradigm for salivary gland regeneration

Salivary gland(SG)dysfunction,due to radiotherapy,disease,or aging,is a clinical manifestation that has the potential to cause severe oral and/or systemic diseases and compromise quality of life.Currently,the standard-of-care for this condition remains palliative.A variety of approaches have been employed to restore saliva production,but they have largely failed due to damage to both secretory cells and the extracellular matrix(niche).

Diagnostic efficacy of diffusion-weighted imaging and semiquantitative and quantitative dynamic contrast-enhanced magnetic resonance imaging in salivary gland tumors

BACKGROUND Increased use of functional magnetic resonance imaging(MRI)methods such as diffusion-weighted imaging(DWI)and dynamic contrast-enhanced(DCE)MRI consisting of sequential contrast series,allows us to obtain more information on the microstructure,cellularity,interstitial distance,and vascularity of tumors,which has increased the discrimination power for benign and malignant salivary gland tumors(SGTs).In the last few years,quantitative DCE MRI data containing T1 perfusion parameters(K_(trans),K_(ep)and V_(e)),were reported to contribute to the differentiation of benign or malignant subtypes in SGTs.AIM To evaluate the diagnostic efficacy of DWI and semiquantitative and quantitative perfusion MRI parameters in SGTs.METHODS Diffusion MRI[apparent diffusion coefficient(ADC)value]with a 1.5 T MR machine,semiquantitative perfusion MRI[time intensity curve(TIC)pattern],and quantitative perfusion MRI examinations(K_(trans),K_(ep)and V_(e))of 73 tumors in 67 patients with histopathological diagnosis performed from 2017 to 2021 were retrospectively evaluated.In the ADC value and semiquantitative perfusion MRI measurements,cystic components of the tumors were not considered,and the region of interest(ROI)was manually placed through the widest axial section of the tumor.TIC patterns were divided into four groups:Type A=T_(peak)>120 s;type B=T_(peak)≤120 s,washout ratio(WR)≥30%;type C=T_(peak)≤120 s,WR<30%;and type D=flat TIC.For the quantitative perfusion MRI analysis,a 3D ROI was placed in the largest solid component of the tumor,and the K_(trans),K_(ep)and V_(e)values were automatically generated.RESULTS The majority of SGTs were located in the parotid glands(86.3%).Of all the SGTs,68.5%were benign and 31.5%were malignant.Significant differences were found for ADC values among pleomorphic adenomas(PMAs),Warthin's tumors(WTs),and malignant tumors(MTs)(P<0.001).PMAs had type A and WTs had type B TIC pattern while the vast majority of MTs and other benign tumors(OBTs)(54.5%and 45.5%,respectively)displayed type C TIC pattern.PMAs showed no washout,while the highest mean WR was observed in WTs(59%±11%).K_(trans)values of PMAs,WTs,OBTs,and MTs were not significantly different.K_(ep)values of PMAs and WTs were significantly different from those of OBTs and MTs.Mean V_(e)value of WTs was significantly different from those of PMAs,OBTs,and MTs(P<0.001).CONCLUSION The use of quantitative DCE parameters along with diffusion MRI and semiquantitative contrastenhanced MRI in SGTs could improve the diagnostic accuracy.

Relation of tea ingestion to salivary redox and flow rate in healthy subjects

The biochemistry of human saliva can be altered by food intake.The benefits of tea drinking were extensively studied but the influence of tea ingestion on human saliva has not been revealed.The work aimed to investigate the immediate and delayed effect of vine tea,oolong tea and black tea intake on certain salivary biochemistry and flow rate.The saliva samples of healthy subjects were collected before,after and 30 min after tea ingestion.The chemical compositions and antioxidant capacity of tea samples were analyzed to correlate with salivary parameters.Principal component analysis indicated that the effects of vine tea consumption were dominated by increasing salivary flow rate(SFR),production rate of total protein(TPC),thiol(SH),malondialdehyde,catalase activity and antioxidant capacity(FRAP)in saliva.The antioxidant profile of studied tea samples(FRAP,polyphenols,flavonoids)was positively correlated with salivary SFR,TPC,SH and FRAP but negatively correlated with salivary uric acid concentration in saliva.

Pattern and Trends in the Presentation of Salivary Gland Tumours in a Tertiary Centre in Gombe, Northeast Nigeria

Background: Salivary gland tumours (SGTs) are rare, but recent reports suggest an increasing incidence. Although there are previous Nigerian studies on the patterns of SGTs, patterns and trends of disease may change over time. The aim of this study was to describe the pattern of presentation of SGTs, and to determine the trends in occurrence of SGTs at Federal Teaching Hospital (FTH), Gombe over a period of 15 years. Method: This descriptive study included cases of histologically diagnosed SGTs from January 2008 to December 2022. Relevant information (age, gender, site, year of diagnosis, and histopathologic diagnosis) was extracted from the cancer registers and histopathologic records. The lesions were then categorized into benign and malignant SGTs and grouped into three groups spanning 5 years each based on the year of diagnosis. Data analysis was done using IBM SPSS version 23, and p ≤ 0.05 was considered statistically significant. Results: There were 93 (61.2%) benign and 59 (38.8%) malignant SGTs. Benign SGTs had a mean age of 36.4 ± 13.6 years, and were more common in females (57.0%), and in the parotid (41.9%). Pleomorphic adenoma (94.6%) was the most common benign SGT. Malignant SGTs had a mean age of 44.5 ± 18.4 years, with male predilection (54.2%) and occurrence mostly in the palate (27.6%) and parotid (22.4%). Mucoepidermoid carcinoma (39.0%) and adenoid cystic carcinoma (32.2%) were the most frequent malignant SGTs. The mean age of occurrence of malignant SGTs was significantly higher than that of benign SGTs (p = 0.005). The trend analysis showed that there has been a steady rise in the proportion of males presenting with malignant SGTs. Similarly, there has been a steady increase in the frequency of benign SGTs in the parotid. The palate was the predominant site for the malignant SGTs between 2008 and 2012, but in the last five years (2018 to 2022), the parotid has become the predominant site. Over the duration of the study, the ratio of benign to malignant SGTs has remained relatively constant. Conclusion: While the overall pattern of presentation of SGTs in Gombe is similar to reports in the literature, this study has identified some changes in trends over the years.

Salivary proteins and microbiota as biomarkers for early childhood caries risk assessment

Early childhood caries （ECC） is a term used to describe dental caries in children aged 6 years or younger. Oral streptococci, such as Streptococcus mutans and Streptococcus sorbrinus, are considered to be the main etiological agents of tooth decay in children. Other bacteria, such as Prevotella spp. and Lactobacillus spp., and fungus, that is, Candida albicans, are related to the development and progression of ECC. Biomolecules in saliva, mainly proteins, affect the survival of oral microorganisms by multiple innate defensive mechanisms, thus modulating the oral microflora. Therefore, the protein composition of saliva can be a sensitive indicator for dental health. Resistance or susceptibility to caries may be significantly correlated with alterations in salivary protein components. Some oral microorganisms and saliva proteins may serve as useful biomarkers in predicting the risk and prognosis of caries. Current research has generated abundant information that contributes to a better understanding of the roles of microorganisms and salivary proteins in ECC occurrence and prevention. This review summarizes the microorganisms that cause caries and tooth-protective salivary proteins with their potential as functional biomarkers for ECC risk assessment. The identification of biomarkers for children at high risk of ECC is not only critical for early diagnosis but also important for preventing and treating the disease.

Salivary duct carcinoma of the submandibular gland presenting a diagnostic challenge: A case report

BACKGROUND Salivary duct carcinoma(SDC)is a rare,extremely aggressive malignancy that arises in the submandibular gland.It can metastasize locally early and therefore is an important differential diagnosis of metastatic disease in cervical lymph nodes or specific lymphadenitis such as tuberculous cervical lymphadenitis.CASE SUMMARY We report a case of SDC in the submandibular gland that presented diagnostic difficulty.The lesion was coincidentally discovered through examination of the radiolucent area of the maxilla.Imaging failed to confirm the possibility of specific inflammation,leading us to execute an open biopsy to verify the diagnosis.The surgical specimen showed that the submandibular gland was primarily replaced with a calcified body.Following histological analysis and confirmation,we performed surgical resection,radiotherapy,and various chemotherapies.CONCLUSION Radiographic imaging characteristics of lymph node metastases of salivary gland cancer,especially of SDC,may resemble other cervical lymphadenitis;calcification at the submandibular gland is the landmark of SDC occurring at the submandibular gland.

Overall and cause-specific survival for mucoepidermoid carcinoma of the major salivary glands:Analysis of 2210 patients

BACKGROUND Mucoepidermoid carcinoma(MEC)is a rare malignancy of the head and neck;however,it accounts for a majority of the tumors of the salivary glands.This study used a national population-based registry to describe the pre-treatment and treatment-related prognostic factors that influence survival in patients with MEC of the major salivary glands.To our knowledge,this is the largest populationbased study examining predictors of both overall and cause-specific survival of MEC of the major salivary glands.AIM To identify prognostic factors influencing overall survival(OS)and cause-specific survival(CSS)of patients with MEC of the major salivary glands.METHODS We used the Surveillance,Epidemiology and End-Results Database of the National Cancer Institute to investigate a variety of factors that could influence survival of patients diagnosed with mucoepidermoid carcinoma of the major salivary glands.A total of 2210 patients diagnosed with MEC of the major salivary glands during the years of 1975-2016 were studied.The primary endpoints were OS and CSS.Cox regression analysis was used to perform univariate and multivariate analyses of clinical variables such as age at diagnosis,diagnosis year,sex,race,tumor size,stage,grade,treatment with or without surgical excision,and adjuvant radiotherapy treatment.RESULTS A total of 2210 patients diagnosed with MEC of the major salivary glands met inclusion criteria.In this study,95%of patients underwent surgical excision and 41%received adjuvant radiation therapy.Median OS time for Grade I,II,and III/IV was 401 mo(±48.25,95%CI),340 mo(±33.68,95%CI)and 55 mo(±11.05,95%CI),respectively.Univariate analysis revealed that lack of surgical excision was associated with decreased OS[hazard ratio(HR)4.26,P<0.0001]and that patients with localized disease had improved OS compared to both regional and distant disease(HR 3.07 and 6.96,respectively,P<0.0001).Additionally,univariate analysis demonstrated that male sex,age over 50 at diagnosis,Grade III tumors,and increasing tumor size were associated with worsened OS(P<0.0006).Univariate analysis of CSS similarly revealed that lack of surgical excision and Grade III carcinoma conferred decreased CSS(HR 4.37 and 5.44,respectively,P<0.0001).Multivariate analysis confirmed that increasing age,in 10-year age bands,advanced tumor stage,increasing tumor size,Grade III carcinoma,male sex,and lack of surgical excision were associated with a statistically significant decrease in OS and CSS(P<0.04).Of note,multivariate analysis revealed that the use of adjuvant radiation therapy was not associated with improved OS or CSS.CONCLUSION Multivariate analysis demonstrated increasing age,advanced tumor stage,increasing tumor size,Grade III carcinoma,male sex,and lack of surgical excision were associated with decreased OS and CSS(P<0.04).

Conservative and functional surgery in the treatment of salivary gland tumours

The principle of modern oncological surgery is to conserve the functional organs or tissues as much as possible based on eradication of the tumour.For salivary gland tumours,conservative and functional salivary surgery,including partial sialoadenectomy as well as anatomical and functional preservation of the facial nerve,great auricular nerve,superficial musculoaponeurotic system (SMAS),and Stensen’s duct,has become increasingly popular.In the present review,we discuss the following aspects of conservative and functional surgery in the treatment of salivary gland tumours:(i) partial superficial parotidectomy (PP) to treat benign parotid gland tumours,(ii) modification of surgical incisions to improve cosmetic results,(iii) modification of the surgical approach to decrease complications,(iv) extracardial dissection to treat benign superficial parotid tumours,(v) partial sialoadenectomy to treat benign submandibular gland tumours,and (vi) 125I brachytherapy to preserve facial nerves.The majority of the operated parotid or submandibular glands are preserved,and surgical complications are also decreased.Conservative and functional surgery plays a significant role in maintaining normal salivary gland function and in improving patients’ quality of life during the treatment of salivary gland tumours and thus should be further promoted.

Mechanism involved in Danshen-induced fluid secretion in salivary glands

AIM:Danshen's capability to induce salivary fluid secretion and its mechanisms were studied to determine if it could improve xerostomia.METHODS:Submandibular glands were isolated from male Wistar rats under systemic anesthesia with pentobarbital sodium.The artery was cannulated and vascularly perfused at a constant rate.The excretory duct was also cannulated and the secreted saliva was weighed in a cup on an electronic balance.The weight of the accumulated saliva was measured every 3 s and the salivary flow rate was calculated.In addition,the arterio-venous difference in the partial oxygen pressure was measured as an indicator of oxygen consumption.In order to assess the mechanism involved in Dansheninduced fluid secretion,either ouabain(an inhibitor of Na+/K+ ATPase) or bumetanide(an inhibitor of NKCC1) was additionally applied during the Danshen stimulation.In order to examine the involvement of the main membrane receptors,atropine was added to block the M3 muscarinic receptors,or phentolamine was added to block the α1 adrenergic receptors.In order to examine the requirement for extracellular Ca2+,Danshen was applied during the perfusion with nominal Ca2+ free solution.RESULTS:Although Danshen induced salivary fluid secretion,88.7 ± 12.8 μL/g-min,n = 9,(the highest value around 20 min from start of DS perfusion was significantly high vs 32.5 ± 5.3 μL/g-min by carbamylcholine,P = 0.00093 by t-test) in the submandibular glands,the time course of that secretion differed from that induced by carbamylcholine.There was a latency associated with the fluid secretion induced by Danshen,followed by a gradual increasein the secretion to its highest value,which was in turn followed by a slow decline to a near zero level.The application of either ouabain or bumetanide inhibited the fluid secretion by 85% or 93%,and suppressed the oxygen consumption by 49% or 66%,respectively.These results indicated that Danshen activates Na+/K+ ATPase and NKCC1 to maintain Cl- release and K+ release for fluid secretion.Neither atropine or phentolamine inhibited the fluid secretion induced by Danshen(263% ± 63% vs 309% ± 45%,227% ± 63% vs 309% ± 45%,P = 0.899,0.626 > 0.05 respectively,by ANOVA).Accordingly,Danshen does not bind with M3 or α1 receptors.These characteristics suggested that the mechanism involved in DS-induced salivary fluid secretion could be different from that induced by carbamylcholine.Carbamylcholine activates the M3 receptor to release inositol trisphosphate(IP3) and quickly releases Ca2+ from the calcium stores.The elevation of [Ca2+]i induces chloride release and quick osmosis,resulting in an onset of fluid secretion.An increase in [Ca2+]i is essential for the activation of the luminal Cl- and basolateral K+ channels.The nominal removal of extracellular Ca2+ totally abolished the fluid secretion induced by Danshen(1.8 ± 0.8 μL/g-min vs 101.9 ± 17.2 μL/g-min,P = 0.00023 < 0.01,by t-test),suggesting the involvement of Ca2+ in the activation of these channels.Therefore,IP3-store Ca2+ release signalling may not be involved in the secretion induced by Danshen,but rather,there may be a distinct signalling process.CONCLUSION:The present findings suggest that Danshen can be used in the treatment of xerostomia,to avoid the systemic side effects associated with muscarinic drugs.

Nerve Growth Factor and Vascular Endothelial Growth Factor: Retrospective Analysis of 63 Patients with Salivary Adenoid Cystic Carcinoma

Aim To detect the expression of nerve growth factor （NGF） and vascular endothelial growth factor （VEGF） in salivary adenoid cystic carcinoma （SACC） tissues, as well as to determine the correlation between growth factor expression and prognosis in SACC. Methodology Medical records of 63 patients surgically treated for SACC between January 1988 and October 2005 were reviewed. Immunohistochemistry was performed to examine the expression of NGF and VEGF in tumor tissues. Kaplan-Meier analysis and Cox＇s proportional hazard regression model were applied to assess predictors of survival. Results NGF and VEGF were overexpressed in SACC tissues, compared with those in normal salivary tissues （P〈0.05）, and the staining intensity of these two factors was stronger in groups of solid subtype, advanced TNM stage, perineural invasion and recurrence. Patients with high- expression of NGF and VEGF, solid subtype, advanced stage, perineural invasion, recurrence and extended resection alone had worse survival rates （P〈0.05）. Conclusion NGF and VEGF are expressed increasingly in the tissues of SACC cases with invasion and metastasis. NGF expression and VEGF expression are independent prognosis factors for survival.

Cloning and RNA interference analysis of the salivary protein C002 gene in Schizaphis graminum

The full-length c DNA of functionally-unknown salivary protein C002 in Schizaphis graminum was cloned using rapid amplification of c DNA ends（RACE） and designated as Sg C002（Gen Bank accession no. KC977563）. It is 767 bp long and encodes a protein of 190 amino acid residues with a predicted mass of 21.5 k Da and a predicted cleavage site of N-terminal signal peptide between the 24 th and the 25 th residues. Sg C002 is specifically expressed in salivary gland with the highest level at the 2nd instar. Introducing Sg C002-specific 476-si RNA, but not 546-si RNA to aphids through artificial diet significantly suppressed Sg C002 expression. Silencing Sg C002 gene led to lethality of the aphid on wheat plants, but not on pure artificial diet. Our study demonstrated that artificial diet-mediated RNAi can be a useful tool for research on the roles of genes in aphid salivary gland, and also provided new insights into the characteristics of C002 in wheat aphids.

Localization and potential function of androgen receptor in rat salivary gland

Aim： To investigate the localization and quantity of androgen receptor （AR） in the salivary glands of rats with further analysis on the effect of castration. Methods： Sixty male Wistar rats, aged 30-60 days, were randomly divided into three groups （castrated, sham-operated and normal controls） with 20 rats in each group. The rats in the castrated group were castrated and the submaxillary glands were removed after 1 week. The salivary glands of the rats in the sham-operated and the normal control groups were also removed. Parts of the salivary glands were fixed for immuohistochemistry and in situ hybridization assays. Other parts were used for Western blot. Results： AR immunoreactivity in the three groups was localized in the glandular epithelial cells of the serous acinus and the glandular duct of the salivary gland, mainly in the nuclei. AR mRNA hybridization signals in the salivary glands of the castrated group were mainly distributed in the epithelial cells of the convoluted and secretary ducts; AR mRNA in the sham-operated and the normal control groups were found in the epithelial cells of the convoluted, the secretary and the excretory ducts. The quantity of AR in the salivary glands was decreased significantly in the castrated rats compared with the sham-operated and the normal controls. Moreover, epidermal growth factor （EGF） secreted by the salivary glands was also decreased in the castrated rats. Conclusion： Castration appears to affect the production of AR in the salivary gland and the distribution of the AR mRNA and could further affect the function of the salivary gland. The changes of AR and the distribution of AR mRNA may play an important role in the interactions between the testes and the salivary gland. （Asian J Androl 2005 Sep; 7： 295-301）

Ghrelin-induced cSrc activation through constitutive nitric oxide synthase-dependent S-nitrosylation in modulation of salivary gland acinar cell inflammatory responses to <i>Porphyromonas gingivalis</i>

A peptide hormone, ghrelin, recognized for its role in the regulation of nitric oxide production has emerged as an important modulator of oral mucosal inflammatory responses to periodontopathic bacterium, P. gingivalis. As cSrc kinase plays a major role in controlling the activity of nitric oxide synthase (NOS) system, in this study we investigated the influence of P. gingivalis LPS on the processes of Src activation in rat sublingual gland acinar cells. The LPS-induced enhancement in the activity of inducible (i) iNOS and the impairment in constitutive (c) cNOS were reflected in the suppression in cSrc activity and the extent of its phosphorylation at Tyr416. Further, we show that the countering effect of ghrelin on the LPS-induced changes in cSrc activity and the extent of its phosphorylation was accompanied by a marked reduction in iNOS and the increase in cNOS activation through phosphorylation at Ser1179. Moreover, the effect of ghrelin on cSrc activation was associated with the kinase S-nitrosylation that was susceptible to the blockage by cNOS inhibition. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to disturbances in cNOS phosphorylation that exerts the detrimental effect on the processes of cSrc activation through cNOS mediated S-nitrosylation. We also show that the effect of ghrelin on P. gingivalis-induced inflammatory changes are manifested in the enhancement in cSrc activation through S-nitrosylation and the increase in its phosphorylation at Tyr416.

Role of ghrelin in modulation of s-nitrosylation-Dependent akt inactivation induced in salivary gland acinar cells by porphyromonas gingivalis

Ghrelin, a peptide hormone, newly identified in oral mucosal tissue, has emerged re-cently as a principal modulator of the in-flammatory responses to bacterial infection through the regulation of nitric oxide syn-thase system. In this study, using rat sub-lingual salivary gland acinar cells, we report that lipopolysaccharide (LPS) of periodon-topathic bacterium, P. gingivalis- induced enhancement in the activity of inducible ni-tric oxide synthase (iNOS) was associated with the suppression in Akt kinase activity and the impairment in constitutive (c) cNOS phosphorylation. Further, we show that the detrimental effect of the LPS on Akt activa-tion, manifested in the kinase protein S-nitrosylation and a decrease in its phos-phorylation at Ser473, was susceptible to suppression by iNOS inhibitor, 1400W. Moreover, we demonstrate that a peptide hormone, ghrelin, countered the LPS- induced changes in Akt activity and NOS system. This effect of ghrelin was reflected in the decreased in Akt S-nitrosylation and the increase in its phosphorylation at Ser473, as well as cNOS activation through phos-phorylation. Our findings suggest that P. gingivalis-induced up-regulation in iNOS leads to Akt kinase inactivation through S-nitrosylation that impacts cNOS activation through phosphorylation. We also show that the countering effect of ghrelin on P. gingivalis-induced disturbances in Akt ac-tivation are manifested in a decrease in the kinase S-nitrosylation and the increase in its phosphorylation.

Periodontitis may induce gut microbiota dysbiosis via salivary microbiota

The aim of this study was to identify whether periodontitis induces gut microbiota dysbiosis via invasion by salivary microbes.First,faecal and salivary samples were collected from periodontally healthy participants(PH group,n=16)and patients with severe periodontitis(SP group,n=21)and analysed by 16S ribosomal RNA sequencing.Significant differences were observed in both the faecal and salivary microbiota between the PH and SP groups.Notably,more saliva-sourced microbes were observed in the faecal samples of the SP group.Then,the remaining salivary microbes were transplanted into C57BL6/J mice(the C-PH group and the C-SP group),and it was found that the composition of the gut microbiota of the C-SP group was significantly different from that of the C-PH group,with Porphyromonadaceae and Fusobacterium being significantly enriched in the C-SP group.In the colon,the C-SP group showed significantly reduced crypt depth and zonula occludens-1 expression.The m RNA expression levels of pro-inflammatory cytokines,chemokines and tight junction proteins were significantly higher in the C-SP group.To further investigate whether salivary bacteria could persist in the intestine,the salivary microbiota was stained with carboxyfluorescein diacetate succinimidyl ester and transplanted into mice.We found that salivary microbes from both the PH group and the SP group could persist in the gut for at least 24 h.Thus,our data demonstrate that periodontitis may induce gut microbiota dysbiosis through the influx of salivary microbes.