The prognostic role of salivary miRNAs in oral squamous cell carcinoma: technical challenges and clinical perspectives.

In management of oral squamous cell carcinoma (OSCC), only a few biomarkers, ranging from clinical and histopathological features to molecular alterations, have been demonstrated to have clinical and prognostic utility. The intent of this narrative review is to present current findings on the use of salivary microRNAs (miRNAs) as prognostic oncologic biomarkers in patients with OSCC. The ability to predict survival or recurrence during follow-up by quantification of specific miRNAs in saliva has been shown in a number of studies, and serves as a possible feature to address in future well-designed clinical studies to confirm their prognostic value. The non-invasiveness of liquid biopsy techniques, the ease of saliva collection, and the abundance and stability of miRNAs in such a biologic fluid make it an attractive combination to improve management of OSCC. For salivary miRNAs to be used in routine practice, however, methodological and sampling standardisation are still needed to increase the power and accuracy of the results obtained.

Oral squamous cell carcinoma identification by FTIR spectroscopy of oral biofluids.

OBJECTIVES: This case study evaluated the efficacy of mid-infrared spectroscopy on the identification of oral squamous cell carcinoma, following the assessment of unstimulated whole saliva. STUDY DESIGN AND METHODS: The trial follows a matched case-control design. Saliva samples were characterized through mid-infrared spectroscopy, and chemometric tools were applied to distinguish between case and control participants, further identifying the spectral regions that played a pivotal role in the successful identification of oral squamous cell carcinoma. RESULTS: Mid-infrared spectroscopy was capable to discriminate between cancer patients and matched controls with 100% of correct predictions. Additionally, the spectral regions mostly contributing to the successful prediction were identified and found to be potentially associated with significant molecular changes crucial to the carcinogenic process. CONCLUSION: The application of mid-infrared spectroscopy in saliva analysis may be regarded as an innovative, noninvasive, low cost, and sensitive technique contributing to the identification of oral squamous cell carcionma.

Saliva-STAT: Sample-to-answer saliva test for COVID-19.

Highly accessible and highly accurate diagnostics are necessary to combat rapidly-spreading infectious diseases, such as the recent COVID-19 pandemic. While lateral flow antigen tests have become pervasive, they are insufficiently sensitive to detect early or asymptomatic disease. Nucleic acid amplification tests provide the needed sensitivity, but accessibility of these tests continues to be a challenge due to the need for precise sample processing steps. Here we report a sample-to-answer test for saliva samples (saliva-STAT) that utilizes a battery-powered handheld instrument and a low-cost easily-manufacturable sample cassette to perform a nucleic acid amplification test for viral pathogens. To enable a completely automated assay, we leverage thermally responsive alkane partitions (TRAPs) and paramagnetic beads for virus purification and concentration, as well as reagent addition and mixing. Notably, the saliva STAT easily accommodates directly-dispensed saliva samples (in contrast to microfluidic devices), which is necessary for self-testing. Using the saliva-STAT platform, we demonstrate detection of down to 0.2 copies/µL of SARS-CoV-2 virus in saliva samples. We envision that the saliva-STAT could be used in walk-in clinics, mobile clinics, public testing locations, and in the home. With minor adjustments to the assay, the saliva-STAT platform can easily be adapted for other respiratory viruses, such as Influenza.

Effects of chia seed (Salvia hispanica L.) supplementation on cardiometabolic health in overweight subjects: a systematic review and meta-analysis of RCTs.

BACKGROUND: Obesity is a significant public health issue associated with various chronic diseases. Research has indicated that chia seeds have the potential to improve cardiometabolic health. However, due to the diversity of research and inconsistencies in study design, further investigation is needed to fully understand their clinical effects on overweight individuals. This review aims to comprehensively analyze the available evidence on the effects of chia seeds on cardiometabolic indices in overweight populations through a meta-analysis. METHODS: A comprehensive literature search was performed across PubMed, Web of Science, Scopus, and Embase databases from their inception until 01-03-2024 to identify randomized controlled trials (RCTs) evaluating the effect of chia on cardiometabolic indices in overweight subjects. The search strategy incorporated both Medical Subject Headings (MeSH). Following the screening, ten RCTs were finally included. The data, including subject characteristics, study design, and changes in serum biomarkers, were extracted and analyzed using Stata software version 18. RESULTS: The meta-analysis results reveal that chia supplementation no significant changes in lipid profile, including triglycerides (TG) (MD: - 5.80 mg/dL, p = 0.47), total cholesterol (TC) (MD: - 0.29 mg/dL, p = 0.95), high-density lipoprotein (HDL) (MD: 1.53 mg/dL, p = 0.33), and low-density lipoprotein (LDL) (MD: 0.63 mg/dL, p = 0.88). Similarity fasting blood glucose (FBG) (MD: - 0.03 mg/dL, p = 0.98), hemoglobin A1c (HbA1c) (MD: - 0.13%, p = 0.13), and insulin levels (MD: 0.45 µIU/mL, p = 0.78). However, chia seed supplementation was associated with a significant reduction in C-reactive protein (CRP) (MD: - 1.18 mg/L, p < 0.0001), but no significant changes were observed in interleukin-6 (IL-6) (MD: - 0.15, p = 0.70) or tumor necrosis factor-alpha (TNF-α) (MD: 0.03, p = 0.91). There was no significant effect on body mass index (BMI) (MD: 0.1 kg/m2, p = 0.91), but a significant reduction in waist circumference (WC) (MD: - 2.82 cm, p < 0.001) was noted. Additionally, chia seed supplementation resulted in a significant reduction in systolic blood pressure (BP) (MD: - 3.27 mmHg, p = 0.03), though diastolic BP changes were non-significant (MD: - 2.69 mmHg, p = 0.09). The studies showed low to moderate heterogeneity in outcome measures, with I2 < 50%. CONCLUSION: Chia seed supplementation does not significantly impact most lipid profile parameters and glycemic markers. However, it shows potential benefits in reducing WC, BP, and CRP. While chia seeds can be a valuable addition to cardiometabolic health management, they should be part of a broader health strategy that includes a balanced diet, exercise, and lifestyle modifications for optimal results.

Tick exposure biomarkers: A One Health approach to new tick surveillance tools.

The spread of tick-borne disease (TBD) is escalating globally, driven by climate change and socio-economic shifts, underlining the urgency to improve surveillance, diagnostics, and control strategies. Ticks can transmit a range of pathogens increasing the risk of transmission of human and veterinary diseases such as Lyme disease, tick-borne encephalitis, theileriosis, anaplasmosis, or Crimean-Congo hemorrhagic fever. Surveillance methods play a crucial role in monitoring the spread of tick-borne pathogens (TBP). However, there are shortcomings in the current surveillance methods regarding risks related to ticks. Human-tick encounters offer a novel metric for disease risk assessment, integrating human behavior into traditional surveillance models. However, to more reliably measure tick exposure, a molecular marker is needed. The identification of antibodies against arthropod salivary proteins as biomarkers for vector exposure represents a promising avenue for enhancing existing diagnostic and surveillance metrics. Here we explore how the use of tick saliva biomarkers targeting recombinant proteins and synthetic peptides could significantly improve the assessment of TBD transmission risk and the effectiveness of vector control measures. With focused efforts on creating a biomarker against tick exposure suitable for humans and domestic animals alike, tick surveillance, diagnosis and control would be more achievable and aid in reducing the mounting threat of TBP through a One Health lens.

Salivary and Serum Analytes and Their Associations with Self-rated Health Among Healthy Young Adults.

BACKGROUND: Understanding the biological processes underlying poor self-rated health (SRH) can inform prevention efforts. The COVID-19 pandemic highlighted the importance of using self-reported measures and self-collected biospecimens, such as saliva, to understand physiological functioning and assist with health surveillance and promotion. However, the associations between salivary analytes and SRH remain understudied. The current study addresses this gap. METHODS: In a laboratory-based study, 99 healthy adults (Mage = 23.8 years, SD = 4.5, 55% men, 43% non-Hispanic White) reported their SRH and provided saliva and blood samples that were assayed for adiponectin, C-reactive protein (CRP), uric acid (UA), and cytokines (IL-1ß, IL-6, IL-8, TNF-α). Principal component analyses assessed the component loadings and generated factor scores for saliva and serum analytes. Binary logistic regressions examined the associations between these components and poor SRH. RESULTS: Salivary analytes loaded onto two components (component 1: adiponectin and cytokines; component 2: CRP and UA) explaining 58% of the variance. Serum analytes grouped onto three components (component 1: IL-8 and TNF-α; component 2: CRP, IL-1ß, and IL-6; component 3: adiponectin and UA) explaining 76% of the variance. Higher salivary component 1 scores predicted higher odds of reporting poor SRH (OR 1.53, 95%CI [1.10, 2.11]). Higher serum component 2 scores predicted higher odds of reporting poor SRH (OR 2.37, 95%CI [1.20, 4.67]). When examined in the same model, salivary component 1 (OR 1.79, 95%CI [1.17, 2.75]) and serum component 2 were associated with poorer SRH (OR 7.74, 95%CI [2.18, 27.40]). CONCLUSIONS: In our sample, whether measured in saliva or serum, indices of inflammatory processes were associated with SRH.

Monitoring SARS-CoV-2 IgA, IgM and IgG antibodies in dried blood and saliva samples using antibody proximity extension assays (AbPEA).

Using a modified proximity extension assay, total and immunoglobulin (Ig) class-specific anti-SARS-CoV-2 antibodies were sensitively and conveniently detected directly from ø1.2 mm discs cut from dried blood and saliva spots (DBS and DSS) without the need for elution. For total Ig detection, antigen probes were prepared by conjugating recombinant spike protein subunit 1 (S1-RBD) to a pair of oligonucleotides. To detect isotype-specific antibody reactivity, one antigen probe was replaced with oligonucleotide-conjugated antibodies specific for antibody isotypes. Binding of pairs of oligonucleotide-conjugated probes to antibodies in patient samples brings oligonucleotides in proximity. An added DNA polymerase uses a transient hybridization between the oligonucleotides to prime synthesis of a DNA strand, which serves as a DNA amplicon that is quantified by real-time PCR. The S1-RBD-specific IgG, IgM, and IgA antibodies in DBS samples collected over the course of a first and second vaccination exhibited kinetics consistent with previous reports. Both DBS and DSS collected from 42 individuals in the autumn of 2023 showed significant level of total S1-RBD antibodies with a correlation of R = 0.70. However, levels in DSS were generally 10 to 100-fold lower than in DBS. Anti-S1-RBD IgG and IgA in DSS demonstrated a correlation of R = 0.6.

Association between salivary inflammatory mediators and oral mucositis in patients with cancer undergoing chemotherapy.

PURPOSE: Oral mucositis is a severe adverse event in patients undergoing chemotherapy and radiotherapy that may lead to the termination of cancer treatment. This study aimed to elucidate the relationship between salivary inflammatory mediators and oral mucositis in patients undergoing chemotherapy. METHODS: This prospective cohort study included 167 patients who underwent chemotherapy at our institution between June 2020 and November 2023. We evaluated the association between chemotherapy-induced oral mucositis and salivary inflammatory mediators using multiple comparison tests and logistic regression analyses. RESULTS: Of the 167 patients, 67 (40.1%) had oral mucositis. Dunn's multiple comparison test revealed that interleukin-6 was significantly higher in oral mucositis of grades 2 and ≥ 3 (P < 0.01) and tumor necrosis factor (TNF)-α was significantly higher in oral mucositis of grades 3-4 (P < 0.01). Logistic regression analysis showed that the risk of oral mucositis was significantly higher for tumor necrosis factor (TNF)-α > 4.4 pg/mL than for TNF-α ≤ 4.4 pg/mL (adjusted odds ratio, 2.4; 95% confidence interval, 1.1-5.3; P = 0.03). CONCLUSION: Saliva is useful in evaluating inflammation in patients with chemotherapy-induced oral mucositis. Furthermore, TNF-α may be a predictive marker for the severity of oral mucositis in patients undergoing chemotherapy.

Salivary Molecular Spectroscopy with Machine Learning Algorithms for a Diagnostic Triage for Amelogenesis Imperfecta.

Amelogenesis imperfecta (AI) is a genetic disease characterized by poor formation of tooth enamel. AI occurs due to mutations, especially in AMEL, ENAM, KLK4, MMP20, and FAM83H, associated with changes in matrix proteins, matrix proteases, cell-matrix adhesion proteins, and transport proteins of enamel. Due to the wide variety of phenotypes, the diagnosis of AI is complex, requiring a genetic test to characterize it better. Thus, there is a demand for developing low-cost, noninvasive, and accurate platforms for AI diagnostics. This case-control pilot study aimed to test salivary vibrational modes obtained in attenuated total reflection fourier-transformed infrared (ATR-FTIR) together with machine learning algorithms: linear discriminant analysis (LDA), random forest, and support vector machine (SVM) could be used to discriminate AI from control subjects due to changes in salivary components. The best-performing SVM algorithm discriminates AI better than matched-control subjects with a sensitivity of 100%, specificity of 79%, and accuracy of 88%. The five main vibrational modes with higher feature importance in the Shapley Additive Explanations (SHAP) were 1010 cm-1, 1013 cm-1, 1002 cm-1, 1004 cm-1, and 1011 cm-1 in these best-performing SVM algorithms, suggesting these vibrational modes as a pre-validated salivary infrared spectral area as a potential biomarker for AI screening. In summary, ATR-FTIR spectroscopy and machine learning algorithms can be used on saliva samples to discriminate AI and are further explored as a screening tool.

Optimization of saliva sampling methods for analysis of bile acids by UHPLC-MS.

This study investigated methods for sampling bile acids in saliva, a potential non-invasive diagnostic biofluid. Bile acids have been implicated in causing damage and permanent changes to the esophageal mucosa and increasing the risk of developing Barrett's esophagus, a condition that can potentially progress to esophageal cancer. Three saliva collection methods were compared: spitting, Salivette® swabs, and Salivette Cortisol® swabs. Spitting emerged as the superior method with the highest recoveries and the least interference, likely due to Salivette swabs retaining bile acids or introducing unknown interferences. All saliva samples were analyzed by UHPLC-MS/MS using the Zorbax RRHD Eclipse Plus C18 column (3 × 50 mm, 1.8 µm) in gradient elution of 0.1 % formic acid in water and methanol. Saliva sample stability was assessed over 14 days, reflecting typical storage times. The levels of detected bile acids were stable for the measured period (RSD ≤ 22 %) and no degradation was observed. Bile acid levels in saliva fluctuated throughout the day, with the greatest changes observed for glycine-conjugated bile acids after meals. To minimize sampling variability, saliva collection by spitting after overnight fasting is recommended for future studies. Our findings are applicable for standardized bile acid sampling and are currently applied in a large clinical study evaluating bile acids as potential susceptibility markers for Barrett's esophagus diagnostics.

Volatile sulfur compounds, biofilm, and salivary parameters in patients with periodontal disease: a cross-sectional study.

This cross-sectional study aimed to evaluate the interplay between volatile sulfur compounds (VSC), biofilm, salivary parameters, and periodontal status in patients with and without periodontal disease. Sixty-four subjects diagnosed with periodontitis and 60 periodontally healthy individuals were included. Probing depth, clinical attachment level, bleeding on probing, tongue coating index, plaque index, number of teeth, spinnability of unstimulated whole saliva, and salivary flow rate were evaluated. The concentrations of VSC were quantified using a portable gas chromatograph. The mean differences in hydrogen sulfide, methyl mercaptan, salivary flow, spinnability, and plaque index did not exhibit statistically significant variances between the two groups. However, a pronounced tongue coating index and a diminished tooth count showed statistical significance in the periodontitis group (p = 0.039; p < 0.001). Unstimulated salivary flow rate less than 0.25 mL/min was statistically significant in the periodontitis group (p = 0.032). After controlling for confounding factors, bleeding on probing remained significant. A positive correlation between periodontal parameters and VSC concentration was found. An inverse correlation was also noted between the spinnability of saliva and tongue coating index (-0.34; p < 0.001). Salivary parameters may contribute to the formation of tongue coating and are correlated with periodontal status. Bleeding on probing, clinical attachment level, and probing depth were identified as potential contributors to VSC formation.

Intra- and inter-day variations in oral metabolites from mouth-rinsed water determined using capillary electrophoresis-mass spectrometry metabolomics.

BACKGROUND AND AIMS: Collecting clinical samples without inconveniencing participants is desirable. The profile of metabolites in mouth-rinsed water is similar to that in saliva. However, the intra- and inter-day variations in unstimulated or stimulated saliva metabolites from mouth-rinsed water have yet to be clarified. Thus, we aimed to fill this research gap using capillary electrophoresis-mass spectrometry metabolomics. MATERIALS AND METHODS: We collected mouth-rinsed water from 15 healthy participants at 9:00, 11:30, 14:00, and 16:30 daily for 3 days. In total, 509 metabolite concentrations from 180 samples were obtained using capillary electrophoresis time-of-flight mass spectrometry. Variations in each metabolite were evaluated using the Wilcoxon signed-rank test to determine at which time/day significant differences occurred after removing metabolites without significant changes using the Friedman test. RESULTS: Of 167 frequently detected metabolites, 100 exhibited intra-day variations, and none exhibited inter-day variations. Intra-day variations were classified into four patterns, and the intra-day variation in each metabolite was assessed. The variations may reflect elapsed time after meals, oral cleaning, or circadian rhythms. CONCLUSION: This study could serve as a reference for improving the design of future clinical trials and the accuracy of metabolome analysis of mouth-rinsed water samples collected at different dates and times.

The diagnostic value of CYFRA 21-1 in oral squamous cell carcinoma: a meta-analysis.

BACKGROUND: Previous studies have revealed the importance of CYFRA 21-1 in the diagnosis of oral squamous cell cancer (OSCC). However, the results are inconsistent. This meta-analysis is to evaluate CYFRA 21-1's efficacy in distinguishing OSCC. METHODS: Systematic searches of Web of Science, PubMed, and CNKI (1996-2024) were conducted following the Preferred Reporting ltems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Analysis of 693 patients and 548 controls yielded combined sensitivity (SEN) of 0.71 (95% CI: 0.68, 0.75), specificity (SPE) of 0.88 (95% CI: 0.85, 0.90), and area under the curve (AUC) of 0.927. Subgroup analysis showed higher SEN (0.88), SPE (0.93), and AUC (0.962) in saliva versus serum. Enzyme-linked immunosorbent assay (ELISA) demonstrated superior performance over enzyme-linked immunosorbent assay (ECLIA) (AUC: 0.968 vs. 0.868). CONCLUSION: CYFRA 21-1 is effective in OSCC diagnosis, with ELISA showing better sensitivity. Saliva emerges as a promising diagnostic medium compared to serum. REGISTRATION: PROSPERO CRD42024566835.

Dysbiosis of pro-inflammatory and anti-inflammatory salivary cytokines during psoriasis providing a therapeutic window and a valuable diagnostic aid in future.

The objective of this article is to evaluate the salivary levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukin-2 (IL-2), and IL-10 in patients with active psoriasis and compare them with those in healthy control subjects. This study included 60 subjects who were clinically diagnosed cases with active psoriasis (categorized further into 33 mild to moderate and 27 severe cases based on the Psoriasis Area Severity Index score) and 60 age- and gender-matched healthy control subjects. Levels of TNF-α, IFN-γ, IL-2, and IL-10 in the unstimulated saliva of subjects were determined via enzyme-linked immunosorbent assay (BT Lab). The salivary levels of TNF-α, IFN-γ, and IL-2 were significantly higher, whereas IL-10 concentration was significantly reduced in psoriatic patients in comparison to controls, and the difference increased with the progressing severity of the disease. Assessment of cytokine profiles in psoriasis patients is significant for diagnostic validation and monitoring the disease severity. Saliva offers an alternate, noninvasive, and readily available biological sample for evaluating cytokine levels. Extensive research in this field has been recommended for better scientifically proven conclusions.

Relationship between Plasma and Saliva Urea Nitrogen Concentrations in New Zealand Red Deer Calves (Cervus elaphus).

Red deer (Cervus elaphus), like other ruminants, excrete approximately 70% of the nitrogen they ingest. Developing ways in which to reduce the rate of loss, such as manipulating the diet or selecting for efficiency of growth, requires close monitoring of the plasma urea N (PUN) concentration which, in turn, requires a simple, safe, and reliable method for collecting samples. Saliva is easier to collect than blood, but the relationship between the salivary urea N (SUN) and the PUN is not known for red deer. This was therefore evaluated in two strains of mixed-sex red deer calves (Cervus elaphus): a phenotype with a high seasonality of growth (H, n = 10) and a phenotype with a low seasonality of growth (L, n = 13). Both phenotypes were divided into two groups, which were each offered one of two forage-based diets ad libitum: a medium-quality diverse treatment and a low-quality perennial ryegrass-white clover treatment. Blood and saliva samples for the determination of the PUN and SUN were collected at dawn every four weeks for five months (April to September 2022). There was a strong linear relationship between the PUN and SUN in the pooled sample (R2 = 0.65, p < 0.001). The estimations of the PUN were significantly improved by adding diet and the date of sampling into the model (p < 0.001), but not phenotype (p > 0.75). SUN represents a reliable index of the PUN, and collecting saliva therefore represents a simple and inexpensive alternative to collecting blood samples in studies of nitrogen metabolism in red deer.

Salivary Interleukin-13 and Transforming Growth Factor Beta as Potential Biomarkers of Cancer Cachexia.

Cancer cachexia is a syndrome characterized by weight and muscle loss and functional impairment, strongly influencing survival in cancer patients. In this study, we aimed to establish the role of saliva cytokine measurement in cancer cachexia investigation and define two potential independent salivary biomarkers of the condition. METHODS: serum and saliva specimens were obtained from 78 patients. Forty-six patients were non-cachectic, and 32 patients were cachectic (per SCRINIO group criteria), all with metastatic solid tumors. Commercial ELISA kits were used to determine the salivary and serum concentrations of interleukin 13 (IL-13) and transforming growth factor beta (TGF-ß) in two patient groups and healthy controls. Laboratory values were obtained from the hospital information system, and weight and height were measured at the time of sampling. RESULTS: A statistically significant difference was observed between the groups in saliva IL-13 concentrations but no difference in serum concentrations. Statistically significant differences were also observed between the groups in saliva and serum concentrations of TGF-ß. Logistic regression analysis has identified salivary IL-13 and TGF-ß as independent factors for cancer cachexia. CONCLUSIONS: We demonstrated saliva as a valuable specimen for cachexia investigation and established IL-13 and TGF-ß as potential cancer cachexia biomarkers. Further research is needed to evaluate these findings.

Effect of blood and artificial saliva contamination on marginal adaptation and sealing ability of different retrograde filling materials: A comparative analysis.

Objective: The objective of this study was to evaluate the effect of blood and artificial salivary contamination of different root-end filling materials on microleakage using a confocal laser scanning microscope and on marginal adaptation using a scanning electron microscope. Materials and Methods: Eighty noncarious single-rooted teeth with mature apices were taken. After retro-cavity preparation, they were randomly assigned into two major groups (n = 40). They were contaminated with blood and artificial saliva, respectively. Each major group was divided randomly into four subgroups (n = 10) and filled as follows: Subgroup A, Biodentine; Subgroup B, bioactive bone cement; Subgroup C, Cention N; and Subgroup D, Bio-C Repair. The samples were sectioned transversely at 1 and 2 mm from the root apex and checked under a confocal laser scanning microscope for microleakage and under an scanning electron microscope for marginal adaptation. The average mean values were calculated. Independent samples t-tests, paired t-tests, and one-way analysis of variance with Tukey's post hoc tests were done to analyze the data. Results: All the tested materials showed marginal gaps and dye leakage. The Bio-C Repair group showed the least mean marginal gap and dye leakage values, followed by bioactive bone cement, Biodentine, and Cention N, respectively, in both blood and artificial saliva contamination. However, the mean marginal gaps and dye leakage between the major groups were statistically insignificant. Conclusion: In an overall comparison, Bio-C Repair was found to be superior in terms of marginal adaptation and sealing ability under the test conditions.

The use of saliva and blood progesterone to profile the menstrual cycles of youth professional football players.

Background: Understanding individual ovarian hormone cycles and their relationship with health, performance and injuries is highly important to practitioners supporting female athletes. Venous blood sampling is the current gold standard for measuring the ovarian hormones, but the invasive nature of this method presents a major barrier in sport environments. Saliva analysis may offer an alternative method as it is non-invasive, allowing the sample to be collected "in situ", with relative ease, necessary in applied sport environments. Objective: The aims of this study were: (i) To compare the concentration of progesterone between capillary blood and saliva, (ii) To assess the efficacy of weekly measurements of progesterone for determining if ovulation has occurred in elite eumenorrheic football players, and (iii) To establish a saliva criteria cut-off for establishing ovulation and assessing the sensitivity, specificity and accuracy values of the method. Methodology: Twenty-one professional and semi-professional, Spanish league female football players (18.6 ± 1.5 years, 58.1 ± 6.0 kg, 164.0 ± 4.8 cm) with natural menstrual cycles, completed the study. Capillary blood and saliva samples were collected from each participant on twelve occasions each separated by at least 7 days. All samples were collected in the morning, following an overnight fast. Results: According to luteal phase serum progesterone concentrations, 11 out of 21 (52%) players presented with menstrual irregularities (oligomenorrheic n = 6, anovulatory n = 4, amenorrhoeic n = 1). A significant correlation was observed between plasma and saliva progesterone in the estimated eumenorrheic group (r = 0.80, p = <0.001, 95% CI 0.72-0.86). The association between serum and saliva progesterone was weaker in the oligomenorrheic group (r = 0.47, p = <0.001, 95% CI 0.27-0.64) and was not present in the anovulatory or amenorrhoeic groups. Conclusions: Salivary measurements of progesterone are well correlated with capillary blood when taken during eumenorrheic menstrual cycles and presents a viable, non-invasive method of establishing characteristic progesterone fluctuations in applied sport settings. The strength of the association appears to be concentration dependent. A luteal phase saliva progesterone (P4) >50 pg/ml and >1.5× follicular baseline has good sensitivity, specificity, and accuracy to indicate ovulation compared to established criteria for serum progesterone.

The relationship between salivary cytokines and oral cancer and their diagnostic capability for oral cancer: a systematic review and network meta-analysis.

BACKGROUND: Oral cancer (OC) is a common malignancy in clinical practice. Saliva testing is a convenient and noninvasive early diagnostic technique for OC. Several salivary cytokines have been identified as potential biomarkers for OC, including IL-8, IL-6, TNF-α, IL-1ß, and IL-10. Nonetheless, the optimal cytokine for OC diagnosis remains inconclusive and highly contentious. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were comprehensively retrieved to collect all case-control studies on OC. A meta-analysis was performed to compare the levels of salivary IL-8, IL-6, IL-10, TNF-α, and IL-1ß in OC patients and healthy controls. Network meta-analysis (NMA) was carried out to probe into the accuracy of these salivary cytokines in diagnosing OC. RESULTS: This analysis included 40 studies, encompassing 1280 individuals with OC and 1254 healthy controls. Significantly higher levels of salivary IL-8, IL-6, TNF-α, IL-1ß, and IL-10 were observed in patients with OC in comparison to healthy controls. The results of NMA showed that TNF-α had the highest diagnostic accuracy for OC, with a sensitivity of 79% and a specificity of 92%, followed by IL-6 (sensitivity: 75%, specificity: 86%) and IL-8 (sensitivity: 80%, specificity: 80%). CONCLUSION: This study suggests that IL-8, IL-6, IL-10, TNF-α, and IL-1ß may be potential diagnostic biomarkers for OC. Among them, TNF-α, IL-6, and IL-8 are highly accurate in the diagnosis of OC. Nevertheless, further studies that eliminate other confounding factors are warranted, and more standardized procedures and large-scale studies are needed to support the clinical use of saliva testing.

The relationship between oxidative stress markers and temporomandibular disorders: A systematic review and meta-analysis.

Background: Oxidative stress has a role in many pathologic conditions, including oral diseases and temporomandibular joint disorders (TMDs) pathophysiology. This study compared the selected oxidative biomarkers' levels in TMD patients and healthy controls in a systematic review and meta-analysis. Materials and Methods: Medline/PubMed, Scopus, Web of Science, Google Scholar, and Embase were systematically searched for English articles up to October 2022 using MeSH and free keywords. Joanna Briggs Institute checklist was used to assess the risk of bias. Differences between biomarker levels in TMD patients were compared to the control group. Results: Ten case-control studies were included based on inclusion and exclusion criteria with a total of 659 patients: 314 with TMD and 345 healthy controls. The studies investigated 15 markers, including total oxidant status (TOS), total antioxidant status, and malondialdehyde (MDA). There was a significant difference in the salivary MDA of patients with TMD in comparison with healthy people; standard mean difference = 3.22 (95% confidence interval [CI]: 0.28-6.16); I 2 = 96.0%). The Antioxidant status in serum was significantly lower in patients with TMD in comparison with healthy people; weighted mean difference = -0.52 (95% CI: -0.90 to -0.14; I 2 = 97.0%). The result of TOS was inconclusive. Conclusion: Salivary MDA and serum total antioxidative status measurements may be used as a biomarker for diagnosing TMD. Due to the lack of sufficient evidence, it is not possible to express a definite relation between the amount and type of marker and TMD diagnosis, which suggests that more case-control studies with larger sample sizes are required.