TNF-α In Saliva Research Articles

Activity and levels of TNF-α, IL-6 and IL-8 in saliva of children and young adults with dental caries: a systematic review and meta-analysis

BackgroundCytokines play an important role in the immunopathogenesis of dental caries. A systematic review and meta-analysis was carried out with the following three objectives: 1)To deepen and discuss through a comprehensive analysis of the literature the effects of dental caries on the activity and levels of TNF-α, IL-6 and IL-8 in saliva of children and young adults, 2)To compare the levels of this cytokines in saliva of the exposure group (moderate-severe dental caries) with the control group (caries-free or mild dental caries), and 3)To determine whether the levels of these cytokines could be used as a complementary clinical diagnostic tool to assess the severity of dental caries.MethodsThe protocol followed PRISMA and Cochrane guidelines and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/MF74V. A digital search was performed in PubMed/MEDLINE, Cochrane, Scopus, and Google Schoolar databases from February 15th, 2012, to January 13th, 2024. The methodological validity of the selected studies was assessed using Joanna Briggs Institute (JBI) tool. A meta-analysis was performed using a random-effects model to evaluate the association between dental caries/health, and the concentration of TNF-α, IL-6 and IL-8.ResultsThe search strategy provided a total of 126 articles, of which 15 investigations met the inclusion criteria. The total number of patients studied was 1,148, of which 743 represented the case/exposure group, and 405 represented the control group. The age of the patients ranged from 3 to 25 years. IL-6 was the most prevalent cytokine in the saliva of children and young adults with active dental caries. The meta-analysis revealed that there are significant differences between the levels of IL-6 and TNF-α in saliva of children with active dental caries compared to their control groups.ConclusionsThe findings suggest that IL-6 and TNF-α levels may have potential as complementary biomarkers for assessing dental caries severity. However, further research is needed to validate these findings in larger and more diverse populations before clinical application.

Assessment of salivary tumor necrosis factor-alpha level in the initial stages of treatment with fixed appliances and clear aligners.

To assess and compare the tumor necrosis factor-alpha (TNF-α) levels in saliva samples during the initial stages of orthodontic treatment with fixed orthodontic appliances (FAs) and clear aligners (CAs). This longitudinal study comprised 40 patients (22 males, 18 females, mean age 22 ± 7 years) who were categorized into two equal-sized groups. Group A comprised 20 patients treated with FA, and Group B comprised 20 patients treated with CA. Unstimulated saliva was collected before the intiation of treatment and then collected again after the placement of the FA/CA at 24 hrs, 7th day, and on the 21st day in both groups. TNF-α levels were determined through ELISA. The data were subjected to statistical analysis. For intragroup comparison of TNF-α at different time points, the Wilcoxon matched-pairs signed-rank test was used, and for intergroup comparison of FAs and CAs at different time points, the Mann-Whitney U test was used. TNF-α levels in the saliva increased significantly at 24 hours, followed by a decline on the 7th day and 21st day in both groups. Changes in TNF-α levels were significantly higher in the FA group than those in the CA group at different time points. This study showed that the salivary TNF-α levels increased significantly during the initial stages of FA and CA treatment at different time points. The mean salivary TNF-α level in both FA and CA groups increased significantly at 24 hours, followed by a decline on the 7th day and then on the 21st day. There was a significant difference between the FA and CA treatment, where the CAs showed a significantly low level of TNF-α in saliva at different intervals of time when compared to the FAs.

Comparison of Oral Health and Salivary Biomarkers in Children with Juvenile Idiopathic Arthritis and Healthy Individuals.

This study examines the effects of juvenile idiopathic arthritis (JIA) on the oral health and detectability of inflammatory biomarkers IL-17, tumour necrosis factor-alpha (TNF-α) and total antioxidant status (TAS) in the saliva of children with JIA. This study included 117 participants (39 patients with JIA and 78 systemically healthy subjects aged 8-12 years). Demographic data, responses to an oral health-related questionnaire, saliva samples, periodontal parameters [plaque index (PI), gingival index (GI) and bleeding on probing (BOP)] and dental recordings [facial profile (FP) and dental occlusion relationship (DOR)] were obtained. Enzyme-linked immunosorbent assays were used to determine the levels of salivary IL-17, TNF-α and TAS. The Caries Assessment Spectrum and Treatment (CAST) index, FP and DOR distributions did not change between groups (P > 0.05). JIA patients had more temporomandibular joint (TMJ) discomfort than gingivitis patients and healthy subjects (P < 0.05). JIA patients had greater salivary IL-17 levels than healthy subjects (P < 0.05). The healthy group's TAS was higher than that of the JIA and gingivitis groups (P < 0.05). Saliva TNF-α levels were similar between groups (P > 0.05). PI, GI, BOP and TNF-α were positively associated with salivary IL-17 (P < 0.001). Elevated salivary IL-17 and TAS levels could be used as biological markers for discriminating the clinical health status of children with JIA and gingivitis.

Evaluation of salivary Tumor Necrosis Factor-Alpha in patients with hypothyroidism and periodontitis: A Case- Control Study

Introduction: The immune system has served as a bridge among periodontitis and the endocrine system, particularly in the case of thyroid disorders. After non-surgical periodontal therapy for hypothyroid patients, serum thyroid stimulating hormone levels fall within the normal limits, which reduces the inflammatory markers linked to both periodontal and hypothyroid diseases. The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α), released by macrophages, plays a significant role in bone loss caused by periodontitis. TNF-α will increase the production of collagenases, prostaglandin E2, chemokines and cytokines, cell adhesion molecules, and factors that are related to bone resorption. The aim of our study is to evaluate the salivary level of TNF-α in hypothyroidism patients with periodontitis in comparison to healthy controls.&#x0D; Material and subject: Saliva were collected from 90 subjects with age ranged between (22-65) years, 50 of them hypothyroid patients (25 patients with hypothyroidism and healthy periodontium, 25 patients with hypothyroidism and periodontitis) and 25 patients with periodontitis and systemically healthy compare with 15 subject as control (systemically healthy with healthy periodontium). Detection of TNF-α in saliva was done by using Enzyme Linked Immunosorbent Assay.&#x0D; &#x0D; Result: The current results revealed that salivary TNF-α levels are significantly high (p&lt;0.001) in diseases group (periodontitis group (132.8 ng/L), hypothyroid patients groups without periodontitis (128.4 ng/L) and with periodontitis (117.0 ng/L) as compared to control group (73.4 ng/L), while there are no significant difference between diseases group.&#x0D; Conclusion: Salivary TNF-α level increased significantly in all diseased groups (periodontitis group, hypothyroidism groups with and without periodontitis) in comparison to healthy subject.

Potential salivary and serum biomarkers for burning mouth syndrome and their relationship with anxiety/depression

Background/purposeThe pathophysiology of burning mouth syndrome (BMS), although considered a multifactorial etiology including psychological factors, is still not well understood. Hence, this study aimed to investigate the potential usage of salivary and serum biomarkers, including brain-derived neurotrophic factor (BDNF), interferon-gamma (IFN-γ), interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-α), in diagnosing BMS and their correlations with anxiety/depression. Materials and methods45 BMS patients and 14 healthy volunteers were enrolled. The patients were divided into BMS with anxiety/depression group and BMS without anxiety/depression group according to the scores of the Zung Self-rating Anxiety Scale (SAS) and Zung Self-rating Depression Scale (SDS). Additionally, concentrations of BDNF, IFN-γ, IL-1β, IL-6, IL-8, and TNF-α in saliva and those in serum among the patients and healthy volunteers were assessed by multiplex assay using Luminex 200TM system and Enzyme-linked immunosorbent assay (ELISA), respectively. ResultsAmong all the serum biomarkers, only BDNF showed a statistically significant decrease in the patients than the healthy volunteers (P < 0.05). Regarding saliva biomarkers, BDNF, IL-1β, and IL-8 all exhibited a statistically significant increase in all the BMS patients versus the healthy volunteers (P < 0.05) but only BDNF was significantly different between patients with anxiety/depression and healthy individuals when considering anxiety/depression. Among BMS patients with anxiety/depression, saliva TNF-α had positive associations with other biomarkers including BDNF, IFN-γ, IL-1β, IL-6, and IL-8 (P < 0.05). ConclusionThe increased concentration of saliva BDNF holds strong potential for diagnosing BMS and the elevated level of saliva TNF-α is crucial in identifying BMS patients with anxiety/depression.

Potential noninvasive biomarkers for the malignant transformation of oral leukoplakia: A systematic review and meta-analysis.

The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.

THE CONCENTRATION OF INTERLEUKIN 6 AND TUMOR NECROSIS FACTOR ALPHA IN SALIVA AND BLOOD OF PATIENTS WITH INACTIVE MULTIPLE SCLEROSIS AND COEXISTING HASHIMOTO'S THYROIDITIS.

The concentration of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the blood is higher in patients with active multiple sclerosis (MS) compared to those with inactive disease. The concentration of IL-6 and TNF-α in the blood is higher in patients with Hashimoto's thyroiditis (HT) compared to those with a healthy thyroid. The aim of the study was to assess whether serum IL-6 and TNF-α levels correlated with saliva in patients with inactive MS and whether there was a difference in these groups of patients depending of thyroid status. We also examined the correlation of thyroid stimulating hormone (TSH) levels with thyroid status. The study included 54 patients in the inactive phase of MS. The level of cytokines in the blood was determined by chemiluminescence, and in saliva by ELISA. Blood and saliva IL-6 levels showed positive correlation, while blood and saliva TNF-α levels were not correlated. There was a significantly higher TSH level in patients with inactive MS with positive thyroid antibodies, without therapy, compared with those with negative antibodies.

Immunoregulatory Markers in Human Saliva – A Non-Invasive Approach in the Diagnosis of Oral Precancerous and Cancerous Lesions

Abstract Oral squamous cell carcinoma (OSCC) is the most common malignant tumor of the oral mucosa. Currently, the diagnosis of oral cancer is based on clinical examination and histopathological analysis. Numerous potential biomarkers have been suggested for oral cancer diagnosis, but the results are contradictory. A great achievement could be identification of biomarkers that indicate the early stage and progression of OSCC. Saliva is an easy to obtain biological fluid containing specific molecules for various pathologies. Some reliable saliva molecules described as oral biomarkers for OSCC are cytokines. A number of studies have shown that higher levels of the proinflammatory and proangiogenic cytokines, like IL-8, IL-6 and TNF-α in saliva could be used for early diagnosis of OSCC. Other studies have shown that the levels of some immunosuppressive cytokines (IL-4, IL-10, IL-13 and IL-1RA) are elevated in saliva in OSCC patients compared to controls. The importance of the immunoregulatory molecules as markers for OSCC is debated. Further studies are needed to identify clinically relevant biomarkers for screening and early detection of oral cancer.

Evaluation of TNF-α and IL-6 in saliva among diabetic retinopathy patients in East Coast Malaysia.

To compare tumour necrosis factor-alpha (TNF) and interleukin (IL)-6 levels in saliva between different stages of diabetic retinopathy (DR). This comparative cross-sectional study was conducted between January 2018 and November 2020. This study included diabetes mellitus (DM) patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). None of the patients with DM were included in the control group. Unstimulated saliva samples were then collected. TNF-α and IL-6 levels were measured. Altogether, 120 patients were included in the study (DM without DR, 33 patients; DM with NPDR, 30 patients; DM with PDR, 32 patients; non-DM, 25 patients). The mean IL-6 level in saliva was significantly higher in the DM group (0.033±0.005pg/ml) than in the non-DM group (0.027±0.001pg/ml) (p<0.001 after adjusting for covariates). There was no significant difference in the mean salivary TNF-α between patients with DM and those without DM after adjusting for covariates. The mean IL-6 in saliva was significantly higher in the NPDR (0.036±0.003pg/ml) and PDR (0.093±0.023pg/ml) groups than in the no DR group (0.027±0.001pg/ml) (p<0.001 and p<0.001, respectively). Mean TNF-α in saliva was significantly higher in the NPDR (0.086±0.022pg/ml) and PDR (0.093±0.023pg/ml) groups than in the no DR group (0.049±0.011pg/ml) (p=0.015 and p=0.003, respectively). There is an association between inflammatory biomarkers in saliva (IL-6 and TNF-α) and severity of DR among patients with DM, suggesting that these salivary biomarkers are potential biomarkers for screening, monitoring, and predicting the progression of DR.

Evaluation of the Anti-inflammatory Effect of Nanocinnamon Gel on Oral Health

Aims: The study aimed to evaluate the anti-inflammatory effects of nanocinnamon gel on salivary concentrations of cytokines: interleukine-6( IL-6) and tumor necrosis factor-alpha ( TNF-α) in chronic gingivitis.Material and Methods: prepared nanocinnamon gel 2% concentration from nanocinnamon powder. The study was carried out on the randomized clinical trial of chronic gingivitis comprises of 45 patients of age between (18-50)years old .They were divided into three groups, fifteen for each group , treatment involved mechanical therapy by scaling and polishing at dental clinic and drug treatment in which the first group applied to the mechanical treatment alone, , second group received chlorhexidine gel topically and third group received nanocinnamon gel topically , the treated groups used the gel twice daily at least ten minute for three weeks. Unstimulated saliva was collected for each individuals and at least two hours after any food intake to disregard the food stimulatory effect on salivary secretions. ELISA kits (Enzyme Linked Immunosorbent Assay) used to measure IL-6 and TNF-α in saliva . Data were analyzed using kruscal-wallias H test and Friedmans̓ test analysis range test. Results: the results of present study showed that there were no significant differences in salivary IL-6 among groups after treatment however , there were significantly decreasing in salivary TNF-α of nanocinnamon group after 21 days of interval therapy in comparison to control group. Conclusion :The use of nanocinnamon gel have anti-inflammatory effect against gingivitis and the changes in the salivary concentrations of IL-6 and TNF-α can help in the diagnosis of periodontal disease

Evaluate the Anti-inflammatory Effects of Nanocinnamon Gel on Salivary Cytokines: Tumor Necrosis factor-alpha (TNF-α) and Interleukine-6 (IL-6) in Chronic Gingivitis

Aims: The study aimed to evaluate the anti-inflammatory effects of nanocinnamon gel on salivary concentrations of cytokines: interleukine-6( IL-6) and tumor necrosis factor-alpha ( TNF-α) in chronic gingivitis.Material and Methods: prepared nanocinnamon gel 2% concentration from nanocinnamon powder. The study was carried out on the randomized clinical trial of chronic gingivitis comprises of 45 patients of age between (18-50)years old .They were divided into three groups, fifteen for each group , treatment involved mechanical therapy by scaling and polishing at dental clinic and drug treatment in which the first group applied to the mechanical treatment alone, , second group received chlorhexidine gel topically and third group received nanocinnamon gel topically , the treated groups used the gel twice daily at least ten minute for three weeks. Unstimulated saliva was collected for each individuals and at least two hours after any food intake to disregard the food stimulatory effect on salivary secretions. ELISA kits (Enzyme Linked Immunosorbent Assay) used to measure IL-6 and TNF-α in saliva . Data were analyzed using kruscal-wallias H test and Friedmans̓ test analysis range test. Results: the results of present study showed that there were no significant differences in salivary IL-6 among groups after treatment however , there were significantly decreasing in salivary TNF-α of nanocinnamon group after 21 days of interval therapy in comparison to control group. Conclusion :The use of nanocinnamon gel have anti-inflammatory effect against gingivitis and the changes in the salivary concentrations of IL-6 and TNF-α can help in the diagnosis of periodontal disease

Inflammatory mediators in saliva and gingival fluid of children with congenital heart defect.

(a) To compare levels of pro- and anti-inflammatory mediators in saliva and gingival crevicular fluid (GCF) in children with and without congenital heart defects (CHDcases and controls) and to test whether a systemic component exists in CHD cases by controlling for gingivitis and plaque scores. (b) To correlate the levels of pro- and anti-inflammatory mediators in GCF and saliva with plaque bacterial composition among CHD cases and controls. Whole un-stimulated saliva and GCF samples were collected (60 CHD cases, 60 controls [Sudan]) and were analysed for levels of prostaglandin E2 (PGE2), interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α), interleukin-1ra (IL-1ra) and interleukin-10 (IL-10) levels. These levels were correlated with the previously reported levels of four red complex bacteria. Significantly elevated levels of PGE2 and IL-1β in GCF and IL-1β and TNF-α in saliva were detected among CHD cases compared with controls. General linear model (GLM) analyses revealed that PGE2 and IL-1β levels remained significantly higher in GCF and saliva samples, respectively, among CHD cases after controlling for gingivitis and plaque score, whereas TNF-α and IL-10 levels were significantly lower in their GCF samples. Additionally, IL-1β level was significantly positively correlated to the counts of the four red complex species in their GCF. In addition to higher levels of some pro-inflammatory mediators in saliva and GCF corresponding to more gingivitis in CHD cases, also a systemic inflammatory component exists and is reflected in these two oral fluids.

Association between obesity and adipokines levels in saliva and gingival crevicular fluid: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to compare adipokines' levels in gingival crevicular fluid (GCF) and saliva between individuals with obesity and individuals without obesity. Computerized searches were conducted in four electronic databases (PubMed, Medline via Ovid, Web of Science, and Scopus). Manual searches and a Google Scholar search, limiting the search to the first 100 hits, were also conducted. Two calibrated authors performed the study selection, data extraction, and quality assessment of included articles. The quality of the included articles was evaluated using the University of Adelaide Tool. The electronic searches retrieved 929 titles/abstracts. Following the removal of duplicated references, 613 titles/abstracts were assessed. Thirty-four articles were included. Meta-analysis demonstrated that tumor necrosis factor-α (TNF-α) concentration in saliva was statistically increased in individuals with obesity compared with individuals without obesity (P<0.05). By contrast, the meta-analysis showed no difference in the concentrations of resistin, adiponectin, leptin, ghrelin, and interleukin 6 in saliva and of resistin, adiponectin, leptin, interleukin 6, interleukin 8, tumor necrosis factor α, and plasminogen activator inhibitor 1 in GCF between individuals with and without obesity (P>0.05). Individuals with obesity presented higher levels of TNF-α in saliva than individuals without obesity. TNF-α in saliva sampling may be a helpful marker for obesity. For the other adipokines, no difference was observed, but the limited availability and heterogeneity of data do not allow us to assertively state whether changes of adipokines in GCF and saliva are associated with obesity.

Study on the effect of in vitro cultured calculus bovis in perioperative period after H-UPPP operation

Objective:TThe aim of this study is to investigate the effect of in vitro cultured Calculus Bovis on the inflammation of oropharynx and body in patients with OSA during the perioperative period of H-UPPP.Method:Eighty patients with OSA and H-UPPP indications were enrolled. The patients were divided into experimental group and control group by random number table, 40 cases in each group. The experimental group was given in vitro cultured Calculus Bovis, while the control group was not given bovine bezoar in vitro. The postoperative oropharyngeal pain, time to resume normal diet, local edema, concentration of IL-1β, IL-8 and TNF-α in saliva, and concentration of IL-1β, IL-8 and TNF-α in blood were compared between the two groups. Result:The pain of oropharynx in the experimental group was lighter than that in the control group on the 3rd, 5th and 7th day after operation (P<0.05), but there was no significant difference in the pain of oropharynx between the two groups on the 1st day after operation(P>0.05); the time of restoring normal diet in the experimental group was shorter than that in the control group (P<0.05); the edema of oropharynx in the experimental group was lighter than that in the control group on the 5th and 7th day after operation (P<0.05).The levels of IL-1β, IL-8 and TNF-α in saliva were lower than those in control group on the 3rd, 5th and 7th day after operation (P<0.05), and the levels of IL-1β, IL-8 and TNF-α in blood on the 5th and 7th day after operation were lower than those in control group (P<0.05).Conclusion:In vitro perioperative period of H-UPPP can improve the postoperative sore throat and local edema of oropharynx, shorten the time of normal diet and reduce the expression of related inflammatory factors in oropharynx and blood.

Salivary Tumor Necrosis Factor-Alpha and Dental Caries in Children and Adolescents

Background: Dental caries is one of the most common diseases during childhood. Saliva can modulate the process of decay, as a rich source of host factors. It has been shown that tumor necrosis factor-alpha (TNF-α) is secreted more in the saliva of individuals with active caries. No study has addressed the relationship between TNF-α levels and age or compared children’s immune response at different age groups and during adolescence. Objectives: The present study aimed at evaluating the pro-inflammatory cytokine level of TNF-α in saliva and its association with caries in different age groups of children and adolescents. Methods: In this case-control study, 128 children and adolescents were divided to four age groups of 32. In each group, half of the individuals had no decay (control group) and the other half had > 4 decayed teeth (case group). Overall, 5 mL of non-stimulated saliva was spitted in sterile tubes for 15 minutes. Furthermore, 1 mL of each sample was centrifuged for five minutes at 12000 rpm. Salivary level of TNF-α was measured using the Enzyme Linked Immunosorbent Assay (ELISA) standard kit. Results: A total of 79 children were studied. The mean TNF-α levels in the case group was 35.20 ± 16.23 Pg/mL and in the control group, this was 26.20 ± 6.25 Pg/mL (P value = 0.001). The mean TNF-α level was significantly higher in the age group of six to 12 years than the age group of 13 to 18 years (P value = 0.01). Conclusions: The results of this study indicated that decay plays an important role in increasing cytokine TNF-α in non-stimulatory saliva, there is no confirming evidence of the direct effect of age on immune function yet.

Cytokine Levels and Human Herpesviruses in Saliva from Clinical Periodontal Healthy Subjects with Peri-Implantitis: A Case-Control Study.

This study evaluated the presence of cytokines (IL-1β, IL-2, IL-4, IL-6, MCP-1, MIP-1α, MIP-1β, and TNF-α) and human herpesvirus (HSV1, HSV2, EBV, CMV, VZV, HHV6, HHV7, and HHV8) in saliva samples taken from subjects with and without peri-implantitis. Forty-two periodontally healthy subjects were divided according to peri-implant condition: healthy and peri-implantitis groups. The clinical parameters as probing depth, clinical attachment level, plaque index, gingival bleeding, bleeding on probing, and suppuration were evaluated. For cytokine detection, multiplex analysis was performed, and PCR assay was used to identify herpesviruses. No significant differences were found in cytokine levels between groups (p > 0.05). The presence of herpesvirus was 1.97-fold higher in patients with peri-implantitis (odds ratio, CI 0.52–7.49). The association of the presence or absence of herpesvirus with the salivary markers was statistically significant for MIP-1β (p = 0.0087) and TNF-α (p = 0.0437) only in the peri-implantitis group. The presence of herpesviruses in patients with peri-implantitis suggests the development of a proinflammatory environment, which is characterized by increased expression of MIP-1β and TNF-α in saliva.

Oral inflammation promotes oral squamous cell carcinoma invasion.

Oral squamous cell carcinoma (OSCC) represents 95% of oral malignancies and invasion, and metastasis underlies disease morbidity and mortality. We recently established a direct link between oral inflammation and cancer invasion by showing that neutrophils increase OSCC invasion through a tumor necrosis factor (TNFα)-dependent mechanism. The objective of this study was to characterize OSCC-associated inflammation and to determine the molecular mechanisms underlying inflammation-mediated OSCC invasion. Our results showed a significant increase in neutrophil infiltration, the neutrophil-to-lymphocyte ratio in the OSCC microenvironment and increased inflammatory markers, particularly TNFα in saliva. We performed next-generation sequencing of the TNFα-treated OSCC cells and showed marked overexpression of over 180 genes distributed among clusters related to neutrophil recruitment, invasion, and invadopodia. At the molecular level, TNFα treatment increased phosphoinositide 3-kinase (PI3K)-mediated invadopodia formation and matrix metalloproteinase (MMP)-dependent invasion. We show here that TNFα promotes a pro-inflammatory and pro-invasion phenotype leading to the recruitment and activation of inflammatory cells in a paracrine mechanism. Increased TNFα in the tumor microenvironment tips the balance towards invasion leading to decreased overall survival and disease-free survival. This represents a significant advancement of oral cancer research and will support new treatment approaches to control OSCC invasion and metastasis.

Saliva levels of caspase-1, TNF-α, and IFN-γ in primary Sjögren’s syndrome: oral mucosal abnormalities revisited

Background/aim: Abnormalities in oral mucosal immunity contribute to complex pathogenesis of primary Sjögren's syndrome (pSjS). We aimed to measure saliva and serum levels of caspase-1, tumor necrosis factor-alpha (TNF-α) and interferon gamma (IFN-γ) in patients with pSjS. Materials and methods: We studied 43 pSjS patients fulfilling the AECG criteria and 30 age/sex-matched healthy controls, as well as 39 rheumatoid arthritis (RA) patients as a disease control group. ESSDAI scores were less than seven in all patients with pSjS, indicating low disease activity. Quantitative analyses were made in serum and whole saliva samples. The statistical analysis was performed using SPSS 19.0. Results: While no significant difference was found in serum measurements, saliva levels of TNF-α and caspase-1 were significantly higher in pSjS patients versus healthy controls when using the Mann-Whitney U test. On the other hand, in the pSjS group, saliva levels of TNF-α and caspase-1 were also significantly higher compared to the RA group using Student's t-test. In the pSjS group, those parameters did not show any correlation with disease duration, seropositivity, and smoking. Conclusion: Despite low disease activity, saliva TNF-α and caspase-1 levels were found to be significantly higher in the pSjS group, which may suggest a possible advantage of local anticytokine treatments in selected cases.

Effect of cetylpyridinium chloride Buccal Tablets on perioperative application of OSAHS patients

Objective:To investigate the effect of Cetylpyridinium Chloride Buccal Tablets on perioperative application of OSAHS patients.Method:Sixty patients of OSAHS were randomly divided into treatment group and control group according to the ratio of 1:1, using randomized single-blind controlled trial. The treatment group was treated with Cetylpyridinium Chloride Buccal Tablets in perioperative period and the control group was not. All patients accepted UPPP. Pharyngeal pain, pharyngeal edema, levels of IL-1, IL-8 and TNF-α in saliva were analyzed on the first day, third day and fifth day after surgery.Result:Compared with control group, the pharyngeal pain of treatment group was slighter on the third day and fifth day (P< 0.05). The levels of IL-1β, IL-8 and TNF-α in saliva were lower on the third day and fifth day (P< 0.05).Conclusion:Applying Cetylpyridinium Chloride Buccal Tablets during perioperative period can effectively relieve postoperative pharyngeal pain and inflammatory response in patients with OSAHS.

Salivary and serum levels of tumor necrosis factor-alpha in oral lichen planus: a systematic review and meta-analysis study

Tumor necrosis factor-α (TNF-α) has a role in the progression of the oral lichen planus (OLP). The aim of this meta-analysis study was to evaluate the salivary and serum TNF-α levels in patients with OLP. We searched in the databases of PubMed/Medline, Science direct, Scopus, Web of Science, and Cochrane Library for studies reported from 1983 to 2016. All studies were checked for evaluation of salivary and serum levels of TNF-α in patients with OLP compared with healthy controls. Twelve studies were included in the meta-analysis. The mean difference of 7 studies reporting salivary TNF-α levels in patients with OLP versus healthy controls was 25.90 pg/mL (95% confidence interval [CI] 15.31-36.49; P<.00001) and 7 studies reporting serum TNF-α levels was 1.65 pg/mL (95% CI-0.82 to 4.11; P=.19). In patients with OLP, the higher levels of TNF-α in saliva compared with serum suggest that measurement of this marker in saliva may be more useful than in serum for determining diagnostic and therapeutic aims.