Salivary assessment of the immune/inflammatory responses and oxidative stress in older adults vaccinated with CoronaVac or ChadOx-1.

BACKGROUND: Although important information concerning COVID-19 vaccination is available, the effects of the CoronaVac and ChadOx-1 vaccines on immunity and the redox balance in the upper airway mucosa of the aged population are not fully understood. Therefore, the aim of this study was to investigate the impacts of two doses of the CoronaVac or ChadOx-1 vaccine on immune/inflammatory responses and oxidative stress in the airway mucosa of older adults. METHODS: Seventy-six older adults of both sexes, with a mean age of 75.1 ± 6.4 years, were separated according to vaccination status into the CoronaVac (n = 52) and ChadOx-1 (n = 24) groups. Saliva samples were collected before (pre) and 30 days after (post) the administration of the second dose of the CoronaVac or ChadOx-1 vaccine to assess the levels of antibodies (sIgA and IgG), antimicrobial peptides, cytokines, and oxidant/antioxidant agents. RESULTS: The immunogenicity in the ChadOx-1 group was 37.5% for sIgA and 25% for IgG, while that in the CoronaVac group was 18.9% for sIgA and 13.2% for IgG. Intergroup analysis revealed that (1) lower levels of IFN-α, IFN-γ, and IL-10 and a greater IFN-γ/IL-10 ratio, in addition to a greater IL-6/IL-10 ratio, were found in both the pre- and postvaccination periods, and (2) lower levels of total sIgA, IL-12p70, IL-17A, TNF-α, and the IL-12p70/IL-10 ratio, in addition to higher levels of specific sIgA for SARS-CoV-2 antigens and lysozyme, were observed only in the postvaccination period in the ChadOx-1 group than in the CoronaVac group. Intragroup analysis revealed (1) a significant increase in the salivary levels of total peroxides in the postvaccination period compared to those in the prevaccination period in both volunteer groups; (2) a decrease in the levels of lysozyme and the ratio between total antioxidant capacity (TAC) and total peroxides in the postvaccination period in the CoronaVac group compared with those in the prevaccination period; and (3) decreases in the TNF-α, IL-6, and IL-12p70 levels, and the IL-12p70/IL-10 ratio in the ChadoX-1 group, as well as a higher lactoferrin concentration in the postvaccination period than in the prevaccination period. Several positive and negative correlations between the parameters assessed here were found. CONCLUSIONS: In general, the ChadOx-1 group exhibited improvements in both immune/inflammatory responses and redox balance and greater immunogenicity than did the CoronaVac group.

Point-of-care testing for COVID-19: a simple two-step molecular diagnostic development and validation during the SARS-CoV-2 pandemic.

BACKGROUND: During the coronavirus disease 19 (COVID-19) pandemic, diagnostic testing of the general population proved challenging due to limitations of the gold-standard diagnostic procedure using reverse transcription real-time polymerase chain reaction (RT-qPCR) for large-scale testing on the centralised model, especially in low-resource areas. OBJECTIVES: To address this, a point-of-care (PoC) diagnostic protocol for COVID-19 was developed, providing fast, reliable, and affordable testing, particularly for low-mid develop areas. METHODS: The PoC diagnostic process combines a simple paper-based RNA extraction method housed within a 3D-printed plastic device with a colorimetric reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay. Nasopharyngeal/oropharyngeal swabs (NOS) and saliva samples were tested between 2020 and 2021, with the assistance of Santa Catarina's State Health Secretary, Brazil. FINDINGS: The developed diagnostic protocol showed a limit of detection of 9,900 copies and an overall diagnostic specificity of 98% for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from 1,348 clinical analysed samples. The diagnostic sensitivity was 95% for NOS samples, 85% for early morning saliva, and 69% for indiscriminate saliva. MAIN CONCLUSIONS: In conclusion, the developed device successfully extracted SARS-CoV-2 viral RNA from swabs and saliva clinical samples. When combined with colorimetric RT-LAMP, it provides results within 45 min using minimal resources, thus delivering a diagnostic kit protocol that is applicable in large-scale sampling.

Saliva metabolomics: concepts and applications in oral disorders.

OBJECTIVES: The purpose of this review was to present the basic concepts of metabolomics methodology and the use of saliva for diagnostic, prognostic, and predictive strategies. MATERIAL AND METHODS: This review followed the focus in: "saliva metabolomics" and "oral diseases". The authors searched studies on PubMed database. The inclusion criteria were original studies and reviews that assessed metabolomics techniques. A descriptive analysis was performed considering the study design, approach system, clinical steps, and tools for the determination of profile or biomarkers metabolites, and the advantages and disadvantages. RESULTS: Metabolomic analyses use a combination of analytical instrumentation and informatic tools to provide information on metabolite characteristics. In this review we described different technologies applied and the advantages and limitations of each technique. Furthermore, in the literature search, we retrieved 25 studies that investigated saliva metabolites in oral diseases: 8 studies used targeted analysis and 17 untargeted metabolomics approaches. Most studies included patients with periodontal diseases, oral squamous cell carcinoma, and Sjögren Syndrome. The most frequently reported metabolites were glycine, leucine, phenylalanine, dipeptides, linoleic acid, arachidonic acid, tyrosine, choline, taurine, lactate, valine, and proline. CONCLUSIONS: Metabolomics analysis has emerged as a powerful tool for tumor diagnosis and to enhance tumor classification, including salivary gland tumors (SGTs). It also holds promise for developing personalized treatment plans and defining more precise prognostic categories. CLINICAL RELEVANCE: Metabolomics is the most functional and comprehensive technique for monitoring and understanding gene functions and identifying the biochemical state of an organism in response to genetic and environmental changes.

Oral mucositis management with photobiomodulation, Bidens pilosa L. (Asteraceae) and Curcuma longa L. (Zingiberaceae), the FITOPROT herbal medicine, and its influence on inflammatory cytokine levels: a randomized clinical trial.

PURPOSE: This randomized clinical trial aimed to compare the effects of a mucoadhesive formula, containing curcuminoids from Curcuma longa L. and glycerinated extract of Bidens pilosa L. (FITOPROT), associated with photobiomodulation (PBM), and of PBM exclusively, on the incidence of oral mucositis (OM)-induced by radiotherapy (RT) in the head and neck region, and the salivary expression of inflammatory cytokines, in patients with head neck cancer. METHODS: Patients were randomly assigned into two intervention groups-FITOPROT + PBM (n = 25) or PBM (n = 27). PBM protocol comprised a wavelength of 660 nm, 25 mW, 0.25 J/point, and daily irradiation from the first until the last day of RT. FITOPROT was gargled twice a day. All patients underwent a preventive oral care program throughout the study. OM degree, salivary concentration of nitrite, and inflammatory (IL-1, TNFα, IL-6, IL-8, and IL-12p70), and anti-inflammatory (IL-10) cytokines were assessed at baseline, and at the 7th, 14th, 21st, and 30th RT sessions. RESULTS: There were no differences in the OM degree between groups, but the RT dose significantly affected the OM. The RT significantly affected the salivary nitrite, TNFα, IL-1ß, and IL-10 concentrations. CONCLUSION: FITOPROT associated with PBM showed limited effects on preventing the incidence of severe OM compared to PBM alone. However, FITOPROT + PBM may be associated with nitrite and cytokine balance, which may contribute to the occurrence of fewer cases of severe OM. TRIAL REGISTRATION: Brazilian Clinical Trials database (ReBEC; RBR-9vddmr), registered UTN code: U1111-1193-2066, registered in August 8th, 2017.

Herpesviruses and human papillomaviruses in saliva and biopsies of patients with orofacial tumors.

OBJECTIVES: To determine the prevalence and association of HPV and Herpesviruses in saliva and tissue samples of patients with orofacial tumors. METHODS: Biopsies of tumors were done, and saliva samples were collected from patients with orofacial tumors for the determination of viruses using nested multiplex PCR. Independent variables were sex, age, comorbidities, tumor stage, and length of stay. Outcome variables were the presence or absence of herpesviruses and HPV. Descriptive summaries and inferential statistics were done. RESULTS: A hundred patients were included in the study. Prevalence of herpesviruses and HPV were 17.6 % and 57.0 % in tumors, and 48.3 % and 60.0 % in the saliva of patients respectively. Herpesviruses detected included EBV (21.3 %), HHV-7 (11.2 %), CMV (6.7 %), HSV-1 (5.1 %), HSV-2 (1.1 %), VZV (1.1 %), and Kaposi sarcoma virus (0.6 %). The most prevalent HPV genotypes were HPV-42 (29 %), HPV-43 (22.7 %), HPV-52 (22.2 %), HPV-39 (18.8 %), and HPV-18 (9.1 %). The odds of EBV being detected in malignant orofacial tumors were 2 times that of benign orofacial tumors. HPV DNA in the saliva of patients with orofacial tumors was 69.7 %, compared to 18.2 % of the control sample (p < 0.001). The median length of stay for all participants was 6.5 days, those associated with viruses stayed longer. CONCLUSION: There was a high prevalence of Herpesviruses and HPV in saliva and tumor samples of patients with orofacial tumors, signalling some potential for more work to be done in this area.

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.

Salivary detection of Chikungunya virus infection using a portable and sustainable biophotonic platform coupled with artificial intelligence algorithms.

The current detection method for Chikungunya Virus (CHIKV) involves an invasive and costly molecular biology procedure as the gold standard diagnostic method. Consequently, the search for a non-invasive, more cost-effective, reagent-free, and sustainable method for the detection of CHIKV infection is imperative for public health. The portable Fourier-transform infrared coupled with Attenuated Total Reflection (ATR-FTIR) platform was applied to discriminate systemic diseases using saliva, however, the salivary diagnostic application in viral diseases is less explored. The study aimed to identify unique vibrational modes of salivary infrared profiles to detect CHIKV infection using chemometrics and artificial intelligence algorithms. Thus, we intradermally challenged interferon-gamma gene knockout C57/BL6 mice with CHIKV (20 µl, 1 X 105 PFU/ml, n = 6) or vehicle (20 µl, n = 7). Saliva and serum samples were collected on day 3 (due to the peak of viremia). CHIKV infection was confirmed by Real-time PCR in the serum of CHIKV-infected mice. The best pattern classification showed a sensitivity of 83%, specificity of 86%, and accuracy of 85% using support vector machine (SVM) algorithms. Our results suggest that the salivary ATR-FTIR platform can discriminate CHIKV infection with the potential to be applied as a non-invasive, sustainable, and cost-effective detection tool for this emerging disease.

Salivary biomarkers in non-invasive oral cancer diagnostics: a comprehensive review.

OBJECTIVE: This review aims to provide a comprehensive analysis of the effectiveness of saliva as a non-invasive diagnostic marker for oral cancer. Despite progress in oral cancer diagnosis and prognosis, the 5-year survival rate remains low due to the resistance to treatment and delayed diagnosis, which can be attributed to various factors including tobacco and alcohol consumption, genetic damage, and human papillomavirus (HPV). The potential use of saliva as an easily accessible non-invasive screening and diagnostic method arises from its direct contact with the lesion site. METHODOLOGY: Data for this study were gathered via a comprehensive literature evaluation using search engines such as the PubMed, Web of Science, Google Scholar, and SciFinder. RESULTS: Identifying salivary biomarkers shows potential to transform oral cancer diagnostics by offering a reliable alternative to the traditional invasive methods. Saliva is an abundant reservoir for both cell-bound and cell-free organic and inorganic constituents. Thus, saliva is an appropriate field for research in proteomics, genomics, metagenomics, and metabolomics. CONCLUSION: This review provides a comprehensive elucidation of salivary biomarkers and their function in non-invasive oral cancer diagnosis, demonstrating their potential to enhance patient outcomes and reduce the impact of this devastating disease.

Cortisol and cortisone determination by disposable pipette extraction (DPX) and ultra-efficient liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) in urine and saliva samples from patients with Parkinson's disease.

Higher serum cortisol levels appear to be associated with stress that can overlap or manifest anxiety, fatigue, depression, and sleep dysfunction. These are common and intrusive non-motor symptoms of Parkinson's disease (PD). Thus, stress has been proposed to mediate Parkinson's disease development, and cortisol has been suggested as a biomarker for the generation of stress-related symptoms in Parkinson's disease. This study describes sensitive and robust disposable pipette extraction (DPX) and ultra-efficient liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method to determine cortisol and cortisone (as potential endocrine biomarkers for Parkinson's disease) in 24-h urine and saliva samples obtained from Parkinson's disease patients. Important parameters on DPX extraction were optimized to achieve the best extraction recovery and cleanup efficiency. The proposed method was linear from 0.5 (lower limit of quantification) to 500 ng mL-1 for cortisol and from 3.0 (lower limit of quantification) to 500 ng mL-1 for cortisone. To determine whether urinary cortisol and urinary cortisone are adequate as biomarkers to evaluate the level of anxiety in patients suffering from Parkinson's disease, twenty-nine Parkinson's disease patients (18 with anxiety and 11 without anxiety) were selected for urine analysis. Based on the obtained results, 24-h urine samples obtained from Parkinson's disease patients with anxiety had higher cortisone levels than samples obtained from healthy controls. Receiving operating curves (ROC) analysis, which presented the area under the ROC curve (AUC = 0.733), showed that urinary cortisone levels (µg/24-h urine) were sensitive (56.3%) and specific (93.3%) for distinguishing Parkinson's disease patients with anxiety from healthy controls. In terms of salivary results, PD patients' samples taken 30 min after waking up had higher cortisol and cortisone levels than healthy controls, while their samples taken at night had lower cortisol and cortisone levels.

The effect of dexmedetomidine-ketamine combination versus dexmedetomidine on behavior of uncooperative pediatric dental patients: a randomized controlled clinical trial.

OBJECTIVE: Uncooperative behavior in pediatric dentistry is one of the most common manifestations of dental anxiety. Managing anxious patients can be attained by moderate sedation. This study aimed to compare the effect of sedation by dexmedetomidine-ketamine combination (DEX-KET) versus dexmedetomidine (DEX) on behavior of uncooperative pediatric dental patients. METHODOLOGY: In total, 56 uncooperative healthy children (3-5 years old) requiring dental treatment were divided randomly into two groups: Group I (study group), which received buccal dexmedetomidine (2 µg/kg) and ketamine (2 mg/kg), and Group II (control group), which received only buccal dexmedetomidine (4 µg/kg). Drugs effects were assessed in terms of hemodynamic parameters, patient's drug acceptance, child behavior, postoperative effect of sedation, amnesic effect, incidence of adverse events, as well as procedural induced stress measured by salivary secretory immunoglobulin A (s-IgA). RESULTS: Hemodynamic results did not reveal a statistically significant difference between the two study groups (P>0.05). There was a significant difference in patient's acceptance to sedative drug between both groups, favoring DEX (p=0.005). Children who received DEX-KET showed significantly better behavior than those who received DEX for local anesthesia (p=0.017) and during operative procedure (p=0.037). Adverse events, post-operative and amnesic effects of drugs were comparable in both groups (p>0.05). Moreover, the mean difference in the salivary s-IgA levels between initial and final value was not statistically significant between both groups (p=0.556). CONCLUSION: Both DEX-KET combination and DEX alone are effective in providing hemodynamic stability. DEX-KET combination significantly improved the behavior of sedated children compared to DEX alone but the drug acceptance was decreased in the DEX-KET group. Both regimens did not have a negative effect on postoperative behavior of children and had comparable amnesic effect with no significant adverse events. Salivary s-IgA is not considered a potential stress biomarker in sedated children.

Green Tea Kombucha Impacts Inflammation and Salivary Microbiota in Individuals with Excess Body Weight: A Randomized Controlled Trial.

BACKGROUND: Green tea kombucha (GTK) is a fermented beverage with promising health benefits, but few studies proved its impact on human health. Thus, we aimed to investigate the impact of GTK on weight loss, inflammation, and salivary microbiota in individuals with excess body weight. METHODS: This is a randomized controlled clinical trial that lasted 10 weeks with two groups of individuals with excess body weight: control (CG; n = 29; caloric restriction) and kombucha (KG; n = 30; caloric restriction + 200 mL GTK). Body composition, anthropometry, saliva, and blood collection were performed in the beginning and end of the intervention. Plasma interleukins were determined by flow cytometry. Salivary microbiota was analyzed by 16S rRNA sequencing. RESULTS: Both groups decreased weight, BMI, and body fat (p < 0.001) after the intervention, but there were no differences between groups. The KG reduced lipid accumulation product (LAP) (p = 0.029). Both groups decreased IL-1ß and IL-8, but IL-6 increased in the CG (p = 0.023) compared to the kombucha group. Alpha and beta diversity of salivary microbiota increased in the KG. Moreover, the KG presented lower Bacillota/Bacteroidota ratio (p = 0.028), and BMI was positively associated with the Bacillota phylum. CONCLUSIONS: GTK did not enhance weight loss, but it decreased the LAP. GTK helped in the inflammatory profile and induced positive changes in oral microbiota composition.

Effect of combining aminomethacrylate and fluoride against erosive and abrasive challenges on enamel and dentin.

This study evaluated the effect of solutions containing aminomethacrylate copolymer (AA) and sodium fluoride (F; 225 ppm F-) or fluoride plus stannous chloride (FSn; 225 ppm F-, 800 ppm Sn2+) against enamel and dentin erosion/abrasion. Solutions F, FSn, AA, F+AA, FSn+AA, and deionized water as negative control were tested. Bovine enamel and dentin specimens (n = 13/solution/substrate) underwent a set of erosion-abrasion cycles (0.3% citric acid [5 min, 4×/day], human saliva [1 h, 4×/day], brushing [15 s, 2×/day], and treatments [2 min, 2×/day]) for each of five days. Initial enamel erosion was evaluated using Knoop microhardness after the first and second acid challenge on day 1, and surface loss with profilometry after day 5. KOH-soluble fluoride was assessed. Data were analyzed with ANOVA/Tukey tests. The combination of fluoride and AA resulted in higher protection against enamel erosion, whereas this was not the case for the combination of AA and FSn. All treatments protected against enamel and dentin loss. The lowest surface loss values were observed with F+AA and FSn+AA. The polymer did not significantly influence the KOH-soluble fluoride formation on enamel/dentin specimens. The aminomethacrylate copolymer effectively enhanced the efficacy of sodium fluoride against initial erosion and improved the control of enamel and dentin wear of F and FSn solutions.

Non-invasive diagnostic test for lung cancer using biospectroscopy and variable selection techniques in saliva samples.

Lung cancer is one of the most commonly occurring malignant tumours worldwide. Although some reference methods such as X-ray, computed tomography or bronchoscope are widely used for clinical diagnosis of lung cancer, there is still a need to develop new methods for early detection of lung cancer. Especially needed are approaches that might be non-invasive and fast with high analytical precision and statistically reliable. Herein, we developed a swab "dip" test in saliva whereby swabs were analysed using attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy harnessed to principal component analysis-quadratic discriminant analysis (QDA) and variable selection techniques employing successive projections algorithm (SPA) and genetic algorithm (GA) for feature selection/extraction combined with QDA. A total of 1944 saliva samples (56 designated as lung-cancer positive and 1888 designed as controls) were obtained in a lung cancer-screening programme being undertaken in North-West England. GA-QDA models achieved, for the test set, sensitivity and specificity values of 100.0% and 99.1%, respectively. Three wavenumbers (1422 cm-1, 1546 cm-1 and 1578 cm-1) were identified using the GA-QDA model to distinguish between lung cancer and controls, including ring C-C stretching, CN adenine, Amide II [δ(NH), ν(CN)] and νs(COO-) (polysaccharides, pectin). These findings highlight the potential of using biospectroscopy associated with multivariate classification algorithms to discriminate between benign saliva samples and those with underlying lung cancer.

Untargeted stimulated and unstimulated salivary metabolomics and saliva flow rate in children.

OBJECTIVE: The present study aimed to determine the salivary flow and metabolomic profile of stimulated and unstimulated saliva in children. MATERIALS AND METHODS: Children who attended the Pediatric Dentistry Clinic of the State University of Rio de Janeiro -UERJ between 3 and 12 years of age were selected. Unstimulated and stimulated whole saliva, using mechanical stimulus, were collected. The samples were centrifuged at 12,000 g, 4oC for 1 h. The 1H- NMR spectra were acquired in 500 MHz equipment. The data were extracted into 0.03 ppm buckets in AMIX, and multivariate analysis (PLS-DA and O-PLS-DA) was performed in Metaboanalyst 2.0. For other analyses, such as salivary flow, the data was tabulated in the SPSS 20.0 statistical package, analyzed descriptively, and after applying the Wilcoxon test. The interval of confidence was set at 95%. RESULTS: The mean age was 7.5 (± 1.94), and 47.0% (n = 31) were female, 63.6% (n = 42). The median flow rate for stimulated saliva was 0.74 (IC 0.10-2.40) and was statistically higher (p < 0.001; Wilcoxon test) than unstimulated was 0.39 (IC 0.00-1.80). Children older than seven years old also presented a higher difference between unstimulated and stimulated saliva (p = 0.003; Mann-Whitney test). The PLS-DA and O-PLS-DA demonstrated a different profile in stimulated and unstimulated saliva. Acetate, glucose, propionate, and lysine were higher in the unstimulated whole saliva than in stimulated saliva. Isoleucine, N-acetyl sugar, hydroxybutyrate, glutamate, leucine, propionate, butyrate, valine, isoleucine, succinate, saturated fatty acid, and histidine were found in greater amounts in the saliva of patients with stimulated saliva. CONCLUSION: The stimulated saliva presented a higher flow rate, and older children exhibited a higher flow rate resulting from it's the stimulus. The mechanical stimulus increased the levels of the major metabolites.

Glucocorticoid Sensitivity Among Young Survivors of Childhood Acute Lymphoblastic Leukemia: What Does It Matter?

The aim of the study was to assess glucocorticoid sensitivity in survivors of childhood acute lymphoblastic leukemia using in vivo and in vitro tests. Thirty leukemia survivors of both sexes aged ≥18 years participated in the study and at least two years after therapy withdrawal. In vivo tests comprised: a) a very low dose intravenous dexamethasone suppression test for measurement of serum cortisol before, after, and % suppression, compared with 32 age-matched controls; and b) 0.25 mg overnight oral dexamethasone suppression test for assessment of salivary cortisol before, after, and % suppression. In vitro methods comprised: c) glucocorticoid receptor polymorphisms: BcI1-NR3C1 and A3669G; and d) splicing variant of glucocorticoid receptor GR-α mRNA by real-time quantitative polymerase chain reaction, compared with 32 controls. There was a reduction in salivary cortisol, and 73.3% of leukemia survivors showed high sensitivity according to % suppression after oral dexamethasone (p<0.05). Serum cortisol at baseline, after the test, % suppression after intravenous dexamethasone, and the percentage of high sensitivity were reduced in the leukemia group (%F=36.7; p<0.05). The BcI1-NR3C1 and A3669G polymorphisms were present in 11/30 (36.7%) and 5/30 (16.7%) patients, respectively. GR-α mRNA levels were lower in the leukemia group than in the controls (p<0.05). Survivors of acute lymphoblastic leukemia presented with reduced glucocorticoid sensitivity. Glucocorticoid sensitivity allows individualized treatment to avoid adverse effects and may be involved in cardiovascular disease risk among this particular group of cancer survivors.

Sexual hormones changes in burning mouth syndrome: A systematic review.

BACKGROUND: Burning mouth syndrome (BMS) is a chronic pain condition affecting the oral cavity. This condition mostly affects peri- or postmenopausal women; for this reason, sexual hormonal changes have been implicated in BMS pathogenesis. METHODS: A systematic review was performed in MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library and EMBASE without restriction for language or year. Eligibility criteria were controlled studies addressing the PICO question: (P) patients with BMS; (I) detection of the sex hormones; (C) patients without BMS; (O) changes on sexual hormones as a risk factor for BMS severity. Risk of bias was performed with Newcastle-Ottawa Quality Assessment Scale. RESULTS: Four studies were included. Salivary levels were evaluated in three studies and serum blood was used in one. Three studies analysed oestradiol and/or dehydroepiandrosterone (DHEA), two assessed progesterone and one evaluated follicle-stimulating hormone (FSH). Oestradiol results were contradictory, with two studies reporting lower levels in BMS patients compared to controls and one finding the opposite. DHEA was statistically lower in the BMS group in one study. Progesterone showed opposite results in two studies, although none with statistical significance. FSH was statistically higher in the BMS group compared to controls. Correlation of hormones with quality of life was performed in three studies and there was no significant correlation with self-perceived symptoms severity. CONCLUSION: Sexual hormones can be altered in BMS, especially oestradiol. Despite these changes, we did not find correlation between hormone fluctuation and BMS symptoms intensity affecting quality of life. These findings suggested the need for further investigation on hormonal alterations, which may be a promising target on BMS management.

Expression of IL-33 in subjects with periodontitis: a systematic review and meta-analysis.

BACKGROUND: Activation of the IL-33/ST2 axis leads to the production of proinflammatory cytokines and thus to the triggering of osteoclastogenesis, which is why it plays an important role in the immunopathogenesis of periodontitis. The aim of this study was to compare IL-33 levels in serum, plasma, saliva and gingival crevicular fluid (GCF) of subjects with chronic periodontitis (CP) in comparison with the control group (CG). METHODS: This systematic review and meta-analysis followed the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered in the Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/YHUWA . Six electronic databases were used for study identification; PubMed, Google Scholar, ScienceDirect, Web of Science, Scopus and Dentistry & Oral Sciences Source from March 10, 2012 to April 30, 2024. The Joanna Briggs Institute (JBI) tool was used to assess the quality of the included cross-sectional articles and clinical trials. RESULTS: Of the 949 articles identified, 14 were included according to the inclusion and exclusion criteria. The total number of individuals studied in the included investigations was 814 of whom 445 had CP and 369 were healthy. The reported age range was from 20 to 50 years, with a mean age ± standard deviation of 40.29 ± 7.83 years. Four hundred and twenty-six (52%) patients were men and 388 (48%) were women. Meta-analysis revealed that there is an increase in IL-33 levels in plasma, saliva and GCF of subjects with CP compared to CG (p = * < 0.05). CONCLUSIONS: This study found a significant increase in IL-33 levels in different biological samples (plasma, saliva and GCF) of individuals with CP compared to CG, thus IL-33 has potential to be a biomarker in the diagnosis of periodontitis.

Targeted saliva metabolomics in Sjögren's syndrome.

OBJECTIVE: Sjögren's Syndrome (SS) is a chronic inflammatory autoimmune exocrinopathy, and although, the role of metabolism in the autoimmune responses has been discussed in diseases such as lupus erythematosus, rheumatoid arthritis, psoriasis and scleroderma. There is a lack of information regarding the metabolic implications of SS. Considering that the disease affects primarily salivary glands; the aim of this study is to evaluate the metabolic changes in the salivary glands' microenvironment using a targeted metabolomics approach. METHODS: The saliva from 10 patients diagnosed with SS by the American-European consensus and 10 healthy volunteers was analyzed in an Ultra-high Performance Liquid Chromatograph Coupled Mass Spectrometry (UPLC-MS). RESULTS: The results showed an increased concentration in SS of metabolites involved in oxidative stress such as lactate, alanine and malate, and amino acids involved in the growth and proliferation of T-cells, such as arginine, leucine valine and isoleucine. CONCLUSIONS: These results revealed that is possible to differentiate the metabolic profile of SS and healthy individuals using a small amount of saliva, which in its turn may reflect the cellular changes observed in the microenvironments of damaged salivary glands from these patients.

Streamlined integrated protein isoelectric focusing using microfluidic paper-based device.

An innovative integrated paper-based microdevice was developed for protein separation by isoelectric focusing (IEF), allowing for robust design thanks to a 3D-printed holder integrating separation channel, reservoirs, and electrodes. To reach robustness and precision, the optimization focused on the holder geometry, the paper nature, the reservoir design, the IEF medium, and various focusing parameters. A well-established and stable pH gradient was obtained on a glass-fiber paper substrate with simple sponge reservoirs, and the integration of the electrodes in the holder led to a straightforward system. The separation medium composed of water/glycerol (85/15, v/v) allowed for reducing medium evaporation while being an efficient medium for most hydrophobic and hydrophilic proteins, compatible with mass spectrometry detection for further proteomics developments. To our knowledge, this is the first report of the use of glycerol solutions as a separation medium in a paper-based microdevice. Analytical performances regarding pH gradient generation, pI determination, separation efficiency, and resolution were estimated while varying the IEF experimental parameters. The overall process led to an efficient separation within 25 min. Then, this methodology was applied to a sample composed of saliva doped with proteins. A minimal matrix effect was evidenced, underscoring the practical viability of our platform. This low-cost, versatile and robust paper-based IEF microdevice opens the way to various applications, ranging from sample pre-treatment to integration in an overall proteomic-on-a-chip device.

Engineering a dysbiotic biofilm model for testing root caries interventions through microbial modulation.

BACKGROUND: This study aimed to engineer and optimise a dysbiotic biofilm model to develop in vitro root caries for investigating microbial modulation strategies. The model involved growing complex biofilms from a saliva inoculum collected from four volunteers using two strategies. In the first strategy ("pre-treatment strategy"), bovine root slabs were used, and two natural compounds were incorporated at time 0 of the 10-day biofilm experiment, which included sucrose cycles mimicking the cariogenic environment. In the second strategy ("post-treatment strategy"), mature biofilms were grown in a modified Calgary biofilm device coated with collagen and hydroxyapatite for 7 days and then were exposed to the same natural compounds. The metatranscriptome of each biofilm was then determined and analysed. Collagenase activity was examined, and the biofilms and dentine were imaged using confocal and scanning electron microscopy (SEM). Mineral loss and lesion formation were confirmed through micro-computed tomography (µ-CT). RESULTS: The pH confirmed the cariogenic condition. In the metatranscriptome, we achieved a biofilm compositional complexity, showing a great diversity of the metabolically active microbiome in both pre- and post-treatment strategies, including reads mapped to microorganisms other than bacteria, such as archaea and viruses. Carbohydrate esterases had increased expression in the post-treated biofilms and in samples without sugar cycles, while glucosyltransferases were highly expressed in the presence of sucrose cycles. Enrichment for functions related to nitrogen compound metabolism and organic cyclic component metabolism in groups without sucrose compared to the sucrose-treated group. Pre-treatment of the roots with cranberry reduced microbial viability and gelatinase (but not collagenase) activity (p < 0.05). SEM images showed the complexity of biofilms was maintained, with a thick extracellular polysaccharides layer. CONCLUSIONS: This root caries model was optimized to produce complex cariogenic biofilms and root caries-like lesions, and could be used to test microbial modulation in vitro. Pre-treatments before biofilm development and cariogenic challenges were more effective than post-treatments. The clinical significance lies in the potential to apply the findings to develop varnish products for post-professional tooth prophylaxis, aiming at implementing a strategy for dysbiosis reversal in translational research. Video Abstract.