Polymorphism of salivary proteins and risk of periodontal diseases: A systematic review and meta-analysis of clinical studies.

OBJECTIVES: The present systematic review and meta-analysis aimed to assess the association between salivary protein polymorphisms and the risk of periodontal diseases (PD). DATA: The review incorporated cross-sectional, case-control, retrospective/prospective cohort, and randomized controlled trials assessing the influence of salivary protein polymorphisms on the risk of PD development were included in this review. SOURCES: A thorough literature search was conducted across electronic databases, namely PubMed, Scopus, Embase, and Web of Science, without any restrictions on publication language and year. STUDY SELECTION: A total of 168 studies were identified, of which 19 were eligible for inclusion. The risk of bias (RoB) assessment of the included studies was conducted at the methodological level. RESULTS: A total of 16 studies were included. Polymorphism in the gene encoding TNF-α was found to be protective against gingivitis, while those encoding IL-1α and IL-1ß were associated with developing gingivitis. Of the 42 proteins investigated, various gene polymorphisms were identified as protective or risk factors for periodontitis. Protective genes include CFH, DNMT1, OPRM1, and TLR9. Conversely, certain salivary protein genes (e.g., CRP, ERN1, FAM5C, IDH2, LTA, TET2, MPA, NLRP3, TLR4) were associated with periodontitis risk. Notably, IL6, MMP9, and MUC7 genes showed no association with PD, while MMP13 was linked to early implant loss. Overall, the meta-analysis found a statistically significant association between salivary proteins' polymorphisms and risk of PD. CONCLUSIONS: Salivary protein polymorphisms significantly influence PD, revealing protective and risk-associated genotypes. Despite limitations, findings suggest therapeutic targets, emphasizing the complex genetics-periodontal health interplay. CLINICAL SIGNIFICANCE: This study unveils salivary protein polymorphisms as pivotal factors in PD. Protective genes including CFH and TLR9, and risk-associated genes including CRP and TLR4, indicate a genetic basis for PD susceptibility.

Comparative 3D study of dental arches in children with microcephaly associated with congenital Zika syndrome, orofacial cleft, and without craniofacial anomalies.

INTRODUCTION: The dentist participates in the treatment protocol for craniofacial anomalies in individuals from the first months of life. OBJECTIVE: to compare in a retrospective cohort study the morphometry of the edentulous palate of children microcephaly associated with congenital Zika syndrome (CZS), unilateral complete cleft lip and alveolus (UCL), and without craniofacial anomalies. METHODS: Forty-five digitized dental molds composed the sample divided into three groups: CZS; UCL; and without craniofacial anomalies (control group). The following measurements were evaluated: intercanine and intertuberosity distances; dental arch length, area, volume, and mismatch superimposition. Parametric and non-parametric tests were applied (α = 5%). RESULTS: CZS group showed the smallest means of intercanine distance and area than those of the other groups (p = .001 and p = .010, respectively). The dental arch length was greater in the CZS group than in the control group (p = .020). The evaluation of the mismatch superimposition showed that the CZS group had the lowest means of maximum distance and root mean square than that of the UCL group (p = .025 and p = .005, respectively). CONCLUSION: CZS participants tended to palatal narrowing, while UCL individuals had parameters similar to those of the control group, despite the alveolus defect.

A critical review on the association of hyposalivation and dental caries in children and adolescents.

OBJECTIVE: The purpose of this critical review is to assess if children and adolescents with hyposalivation are more affected by dental caries than those with normal flow rate. DESIGN: A literature search was performed using keywords and MeSH terms related to hyposalivation and dental caries in the Medline/PubMed, Web of Science, Cochrane Library, Scopus, LILACS/BBO databases and in gray literature without language or date restrictions until March 2022. Observational studies that accessed the presence of dental caries in patients up to 18 years-old with hyposalivation and compared with a control group (normal salivation rate) were considered eligible. The results from search were imported to EndNote Web, where duplicates were removed followed by title/abstract and full text analysis. RESULTS: A total of 12,236 non-duplicated studies were found and 14 fulfilled the criteria and were included in the present review, 9 cross-sectional and 5 cohorts. Stimulated salivary flow rates were assessed in 3644 participants, aged 3-17 years. Three cohort and three cross-sectional studies observed association between low salivary flow rates and the presence of dental caries, while the other 9 included articles did not verify this association. However, the absence of a standard criteria for the hyposalivation classification in young patients was observed and brough light to this important limitation among the studies. CONCLUSION: The salivary flow rate estimation for caries risk assessment must be the target of further studies to make possible and reliable, homogeneous, and unbiasedly assessment of the association between hyposalivation and dental caries in young patients.

Engineered Salivary Peptides Reduce Enamel Demineralization Provoked by Cariogenic S. mutans Biofilm.

Engineering of the acquired enamel pellicle using salivary peptides has been shown to be a promising anticaries strategy. However, the mechanisms by which these peptides protect teeth against tooth decay are not fully understood. In this study, we evaluated the effect of the engineered salivary peptides DR9-DR9 and DR9-RR14 on enamel demineralization in two experimental conditions: (1) adsorbed onto the enamel surface forming the AEP, and (2) forming the AEP combined with their use to treat the biofilms 2×/day, using a validated cariogenic Streptococcus mutans in vitro biofilm model. Biofilms were grown for 144 h on enamel slabs and then collected to determine the bacterial viability (CFU/biofilm) and biofilm mass (mg protein/biofilm), and to extract cellular/extracellular proteins, which were characterized by mass spectrometry. The culture medium was changed 2×/day to fresh medium, and pH (indicator of biofilm acidogenicity) and calcium concentration (indicator of demineralization) was determined in used medium. DR9-RR14 peptide significantly reduced enamel demineralization (p < 0.0001) in both experimental conditions. However, this peptide did not have a significant effect on biofilm biomass (p > 0.05) nor did it modulate the expression of cellular and extracellular bacterial proteins involved in biofilm cariogenicity. These findings suggest that DR9-RR14 may control caries development mainly by a physicochemical mechanism.

Oral pigmentation as an adverse effect of chloroquine and hydroxychloroquine use: A scoping review.

BACKGROUND: Chloroquine and hydroxychloroquine are 2 medications used to treat some systemic diseases. OBJECTIVE: The aim of this scoping review was to assess the occurrence of oral pigmentation induced by chloroquine or hydroxychloroquine and to understand the pathogenic mechanism behind this phenomenon. METHODS: The review was performed according to the list of PRISMA SrC recommendations and the JBI Manual for Evidence Synthesis for Scoping Reviews. MEDLINE (PubMed), Scopus, EMBASE, SciELO, Web of Science, Lilacs, and LIVIVO were primary sources, and "gray literature" was searched in OpenThesis and Open Access Thesis and Dissertations (OATD). Studies that screened the occurrence of oral pigmentation associated to the use of chloroquine or hydroxychloroquine were considered eligible. No restrictions of year and language of publication were applied. Study selection and data extraction were performed by 2 independent reviewers. The risk of bias was assessed through the JBI tool, depending on the design of the selected studies. RESULTS: The initial search resulted in 2238 studies, of which 19 were eligible. Sixteen studies were case reports, 2 had case-control design and 1 was cross-sectional. Throughout the studies, 44 cases of oral pigmentation were reported. The hard palate was the anatomic region most affected with pigmentation (66%). According to the case reports, most of the lesions (44%) were bluish-gray. The minimum time from the beginning of treatment (chloroquine or hydroxychloroquine) to the occurrence of pigmentation was 6 months. The mean treatment time with the medications was 4.9 years, and the mean drug dosage was 244 mg. Most of the studies (63.1%) had low risk of bias (high methodological quality). CONCLUSIONS: The outcomes of this study suggest that hyperpigmentation depend on drug dosage and treatment length. Hyperpigmentation was detected after a long period of treatment with chloroquine or hydroxychloroquine.

Modulation of Streptococcus mutans Adherence to Hydroxyapatite by Engineered Salivary Peptides.

Since the modification of the proteinaceous components of the Acquired Enamel Pellicle (AEP) could influence the adhesion of Streptococcus mutans, the most cariogenic bacteria, to dental surfaces, we assessed if engineered salivary peptides would affect the adherence and modulate the bacterial proteome upon adherence. Single-component AEPs were formed onto hydroxyapatite (HAp) discs by incubating them with statherin, histatin-3, DR9, DR9-DR9, DR9-RR14, RR14, and parotid saliva. Then, the discs were inoculated with S. mutans UA159 and the bacteria were allowed to adhere for 2 h, 4 h, and 8 h (n = 12/treatment/time point). The number of bacteria adhered to the HAp discs was determined at each time point and analyzed by two-way ANOVA and Bonferroni tests. Cell-wall proteins were extracted from adhered, planktonic, and inoculum (baseline) bacteria and proteome profiles were obtained after a bottom-up proteomics approach. The number of adhered bacteria significantly increased over time, being the mean values obtained at 8 h, from highest to lowest, as follows: DR9-RR14 > statherin > RR14 = DR9-DR9 > DR9 = histatin3 > saliva (p < 0.05). Treatments modulated the bacterial proteome upon adherence. The findings suggested a potential use of our engineered peptide DR9-DR9 to control S. mutans biofilm development by reducing bacterial colonization.

Analysis of salivary parameters of mucopolysaccharidosis individuals.

Mucopolysaccharidosis (MPS) is a heterogeneous group of rare, chronic, progressive and systemic inherited disorders resulting from deficiency or lack of lysosomal enzymes responsible for the degradation of glycosaminoglycans. Products of nitrosative stress have been previously detected in blood and urine samples of patients with MPS. However, it is unclear whether they are present in the saliva of MPS patients and also if they correlate with salivary parameters such as flow and pH. This study compared the salivary levels of NOX (NO2- + NO3-), nitrite (NO2-), protein (albumin), erythrocyte and leukocyte numbers, as well as the salivary flow rate and pH values of samples obtained from 10 MPS patients and 10 healthy subjects. MPS patients exhibited higher salivary levels of NOX and NO2- when compared to healthy subjects (p < 0.05). Albumin was only detected in six saliva samples of MPS patients and, erythrocytes and leukocytes were detected in 60% and 40% of the MPS patients, respectively. In addition, salivary flow rate and pH averages were statistically lower in this group when compared to healthy samples (p < 0.05). Overall, the data indicates that the salivary levels of NO products can be used in combination with other heath indicators to monitor MPS disorders.

Analysis of salivary parameters of mucopolysaccharidosis individuals

Abstract Mucopolysaccharidosis (MPS) is a heterogeneous group of rare, chronic, progressive and systemic inherited disorders resulting from deficiency or lack of lysosomal enzymes responsible for the degradation of glycosaminoglycans. Products of nitrosative stress have been previously detected in blood and urine samples of patients with MPS. However, it is unclear whether they are present in the saliva of MPS patients and also if they correlate with salivary parameters such as flow and pH. This study compared the salivary levels of NOX (NO2- + NO3-), nitrite (NO2-), protein (albumin), erythrocyte and leukocyte numbers, as well as the salivary flow rate and pH values of samples obtained from 10 MPS patients and 10 healthy subjects. MPS patients exhibited higher salivary levels of NOX and NO2- when compared to healthy subjects (p < 0.05). Albumin was only detected in six saliva samples of MPS patients and, erythrocytes and leukocytes were detected in 60% and 40% of the MPS patients, respectively. In addition, salivary flow rate and pH averages were statistically lower in this group when compared to healthy samples (p < 0.05). Overall, the data indicates that the salivary levels of NO products can be used in combination with other heath indicators to monitor MPS disorders.

Proteome difference among the salivary proteins adsorbed onto metallic orthodontic brackets and hydroxyapatite discs.

The aim of this study was to investigate the atomic composition and the proteome of the salivary proteins adsorbed on the surface of orthodontic metallic bracket. For this, the atomic composition of orthodontic metallic brackets was analyzed with X-ray Photoelectron Spectroscopy (XPS). The acquired bracket pellicle was characterized after brackets were immersed in human whole saliva supernatant for 2 hours at 37°C. Hydroxyapatite (HA) discs were used as a control. Acquired pellicle was harvested from the HA discs (n = 12) and from the metallic brackets (n = 12). Proteomics based on mass spectrometry technology was used for salivary protein identification and characterization. Results showed that most of the proteins adsorbed on the surface of orthodontic metallic brackets and on the HA discs were identified specifically to each group, indicating a small overlapping between the salivary proteins on each study group. A total of 311 proteins present on the HA discs were unique to this group while 253 proteins were unique to metallic brackets, and only 45 proteins were common to the two groups. Even though most proteins were unique to each study group, proteins related to antimicrobial activity, lubrication, and remineralization were present in both groups. These findings demonstrate that the salivary proteins adsorbed on the bracket surface are dependent on the material molecular composition.

One-Year Update on Salivary Diagnostic of COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is a global health problem, which is challenging healthcare worldwide. In this critical review, we discussed the advantages and limitations in the implementation of salivary diagnostic platforms of COVID-19. The diagnostic test of COVID-19 by invasive nasopharyngeal collection is uncomfortable for patients and requires specialized training of healthcare professionals in order to obtain an appropriate collection of samples. Additionally, these professionals are in close contact with infected patients or suspected cases of COVID-19, leading to an increased contamination risk for frontline healthcare workers. Although there is a colossal demand for novel diagnostic platforms with non-invasive and self-collection samples of COVID-19, the implementation of the salivary platforms has not been implemented for extensive scale testing. Up to date, several cross-section and clinical trial studies published in the last 12 months support the potential of detecting SARS-CoV-2 RNA in saliva as a biomarker for COVID-19, providing a self-collection, non-invasive, safe, and comfortable procedure. Therefore, the salivary diagnosis is suitable to protect healthcare professionals and other frontline workers and may encourage patients to get tested due to its advantages over the current invasive methods. The detection of SARS-CoV-2 in saliva was substantial also in patients with a negative nasopharyngeal swab, indicating the presence of false negative results. Furthermore, we expect that salivary diagnostic devices for COVID-19 will continue to be used with austerity without excluding traditional gold standard specimens to detect SARS-CoV-2.

RANK, RANKL, and OPG in Dentigerous Cyst, Odontogenic Keratocyst, and Ameloblastoma: A Meta-Analysis.

The aim of this study was to assess and compare RANK, RANKL, and OPG immunoexpression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma. The protocol was registered in PROSPERO (CRD42018105543). Seven databases (Embase, Lilacs, LIVIVO, PubMed, Scopus, SciELO, and Web of Science) were the primary search sources and two databases (Open Grey and Open Thesis) partially captured the "grey literature". Only cross sectional studies were included. The JBI Checklist assessed the risk of bias. A meta-analysis with random effects model estimated the values from the OPG and RANKL ratio reported by the individual studies and respective 95% confidence intervals. The heterogeneity among studies was assessed with I2 statistics. Only nine studies met the inclusion criteria and were considered in the analyses. The studies were published from 2008 to 2018. Two studies presented low risk of bias, while seven studies presented moderate risk. The meta-analysis showed the highest OPG>RANKL ratio for dentigerous cyst (ES=43.3%; 95% CI=14.3-74.8) and odontogenic keratocyst (ES=36.8%; 95% CI=18.8-56.7). In contrast, the highest OPG

Statherin-derived peptides as antifungal strategy against Candida albicans.

OBJECTIVE: The aim of this in vitro study was to evaluate the effect of statherin and its naturally occurring peptides (DR9-2, DR9, GE-12, IT-32, GQ-19, IP-18) on Candida albicans metabolism and biofilm development. DESIGN: After the killing assay, a peptide pellicle was formed on the bottom of a polystyrene plate at the IC50 of each peptide. Over the peptide pellicle, Candida albicans biofilm (48 h) was grown. The peptides antimicrobial activity after the peptides treatment was evaluated by alamarBlue, total biofilm biomass and colony forming units (CFU) counting. RESULTS: The pellicle with statherin and the peptides (DR9-2, DR9, GE-12, IP-18, GQ-19) was able to reduce he viability of Candida albicans compared to the negative control. They also decreased cell proliferation by 20 % and total biomass. IT-32 showed the highest reduction in cell proliferation and biomass, which was similar to the positive control, histatin 5. CONCLUSIONS: These results suggest that the naturally occuring peptides from statherin are able to decrease Candida albicans colonization and biofilm proliferation.

Rank, rankl, and opg in dentigerous cyst, odontogenic keratocyst, and ameloblastoma: a meta-analysis

Abstract The aim of this study was to assess and compare RANK, RANKL, and OPG immunoexpression in dentigerous cyst, odontogenic keratocyst, and ameloblastoma. The protocol was registered in PROSPERO (CRD42018105543). Seven databases (Embase, Lilacs, LIVIVO, PubMed, Scopus, SciELO, and Web of Science) were the primary search sources and two databases (Open Grey and Open Thesis) partially captured the "grey literature". Only cross sectional studies were included. The JBI Checklist assessed the risk of bias. A meta-analysis with random effects model estimated the values from the OPG and RANKL ratio reported by the individual studies and respective 95% confidence intervals. The heterogeneity among studies was assessed with I2 statistics. Only nine studies met the inclusion criteria and were considered in the analyses. The studies were published from 2008 to 2018. Two studies presented low risk of bias, while seven studies presented moderate risk. The meta-analysis showed the highest OPG>RANKL ratio for dentigerous cyst (ES=43.3%; 95% CI=14.3-74.8) and odontogenic keratocyst (ES=36.8%; 95% CI=18.8-56.7). In contrast, the highest OPG<RANKL ratio was found for ameloblastoma (ES=73.4%; 95% CI=55.4-88.4) and it was higher in the stromal region compared to the odontogenic epithelial region. The results may explain the aggressive potential of ameloblastoma from the higher OPG<RANKL ratio in this tumor, while it was lower for dentigerous cyst and odontogenic keratocyst.

Resumo O objetivo deste estudo foi avaliar e comparar a imunoexpressão de RANK, RANKL e OPG em cisto dentígero, ceratocisto odontogênico e ameloblastoma. O protocolo foi registrado no PROSPERO (CRD [Oculto]). Sete bancos de dados (Embase, Lilacs, LIVIVO, PubMed, Scopus, SciELO e Web of Science) foram as principais fontes de pesquisa e duas bases de dados (Open Grey e Open Thesis) capturaram parcialmente a "literatura cinza". Apenas estudos transversais foram incluídos. A ferramenta JBI avaliou o risco de viés. Uma metanálise com modelo de efeitos aleatórios estimou os valores da razão OPG e RANKL relatados pelos estudos individuais e seus respectivos intervalos de confiança de 95%. A heterogeneidade entre os estudos foi avaliada por meio do teste I2. Apenas nove estudos preencheram os critérios de inclusão e foram considerados nas análises. Os estudos foram publicados entre 2008 e 2018. Dois estudos apresentaram baixo risco de viés, enquanto sete estudos apresentaram risco moderado. A meta-análise mostrou a maior razão OPG> RANKL para cisto dentígero (ES=43,3%; IC95%=14,3-74,8) e ceratocisto odontogênico (ES=36,8%; IC95%=18,8-56,7). Por outro lado, a maior razão OPG <RANKL foi encontrada para ameloblastoma (ES=73,4%; IC95%=55,4-88,4) e foi maior na região estromal em comparação com a região epitelial odontogênica. Os resultados podem explicar o potencial agressivo do ameloblastoma devido a uma maior proporção OPG <RANKL nesse tumor, enquanto tal proporção foi menor no cisto dentígero e no ceratocisto odontogênico.

Effectiveness of anesthetic solutions for pain control in lower third molar extraction surgeries: a systematic review of randomized clinical trials with network meta-analysis.

OBJECTIVE: To assess the effectiveness of different anesthetic solutions for pain control immediately after the extraction of lower third molars. METHODS: Nine databases were used to identify randomized clinical trials, without restriction of language or year of publication. The "JBI Critical Appraisal Tools for Systematic Reviews" was used to assess the risk of bias in the studies. The network meta-analysis was performed to compare the effectiveness of different anesthetics to control the pain immediately after the surgery of lower third molars, using the standardized mean difference (SMD) as the effect estimate. The GRADE approach was used to assess the certainty of evidence. RESULTS: The search presented 13,739 initial results, from which 45 met the eligibility criteria and presented low to moderate risk of bias. Thirteen studies were included in the meta-analysis. The 2% lidocaine + clonidine presented the lowest pain scores (SMD = - 1.44; - 2.72 to - 0.16) compared to 4% articaine + adrenaline, followed by 0.5% bupivacaine + adrenaline (SMD = - 1.36; - 2.13 to - 0.59). The certainty of evidence varied between very low to moderate. CONCLUSION: 2% lidocaine + clonidine and 0.5% bupivacaine + adrenaline were the anesthetics with the highest probability for pain control immediately after the surgical procedure of removing impacted lower third molars. CLINICAL SIGNIFICANCE: The use of an adequate anesthetic with effective pain control can contribute to a more comfortable postoperative period.

Saliva as a tool for monitoring hemodialysis: a systematic review and meta-analysis

Abstract This study aimed to assess whether the reductions in serum urea and creatinine levels are different from the reductions in salivary urea and creatinine levels that occur after hemodialysis in chronic renal patients. The systematic review protocol was registered in the PROSPERO database. Eight databases were searched to identify pretest-posttest studies of chronic kidney disease patients undergoing hemodialysis, with no language or year restrictions. The JBI Critical Appraisal Tool was used to assess the risk of bias. Meta-analyses using random-effect models were conducted to compare salivary and serum correlations and to pooled mean and proportion differences from pre- to posthemodialysis urea and creatinine levels by subgroup analysis. The I2 test was used to assess heterogeneity, and a meta-regression was performed to statistically assess correlations and differences in the pooled effects pre- and postdialysis. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. The search resulted in 1404 records, and only six studies (n = 252 participants) fulfilled the eligibility criteria and were included. The studies were published between 2013 and 2018. All studies showed a significant reduction in both salivary and serum urea/creatinine levels. All eligible studies presented a low risk of bias. The meta-analysis shows a moderate to high correlation between salivary and blood levels of urea (r: 0.79; 95% CI: 0.56-1.00) and creatinine (r: 0.64; 95%CI: 0.16-1.00), with a very low level of certainty. The reductions in salivary urea and creatinine levels are similar to and correlated with the reductions in blood urea and creatine levels after hemodialysis among chronic kidney disease patients.

Saliva as a tool for monitoring hemodialysis: a systematic review and meta-analysis.

This study aimed to assess whether the reductions in serum urea and creatinine levels are different from the reductions in salivary urea and creatinine levels that occur after hemodialysis in chronic renal patients. The systematic review protocol was registered in the PROSPERO database. Eight databases were searched to identify pretest-posttest studies of chronic kidney disease patients undergoing hemodialysis, with no language or year restrictions. The JBI Critical Appraisal Tool was used to assess the risk of bias. Meta-analyses using random-effect models were conducted to compare salivary and serum correlations and to pooled mean and proportion differences from pre- to posthemodialysis urea and creatinine levels by subgroup analysis. The I2 test was used to assess heterogeneity, and a meta-regression was performed to statistically assess correlations and differences in the pooled effects pre- and postdialysis. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of evidence. The search resulted in 1404 records, and only six studies (n = 252 participants) fulfilled the eligibility criteria and were included. The studies were published between 2013 and 2018. All studies showed a significant reduction in both salivary and serum urea/creatinine levels. All eligible studies presented a low risk of bias. The meta-analysis shows a moderate to high correlation between salivary and blood levels of urea (r: 0.79; 95% CI: 0.56-1.00) and creatinine (r: 0.64; 95%CI: 0.16-1.00), with a very low level of certainty. The reductions in salivary urea and creatinine levels are similar to and correlated with the reductions in blood urea and creatine levels after hemodialysis among chronic kidney disease patients.

Salivary proteomic profile of dogs with and without dental calculus.

BACKGROUND: Dogs' saliva is a complex mixture of inorganic and organic constituents, rich in proteins. Therefore, knowing the saliva composition of these animals is extremely important to identify the presence of proteins that may be involved in physiological and pathological mechanisms of their oral cavity. The present study aimed to characterize the proteomic profile of saliva from dogs with and without dental calculus. RESULTS: Saliva samples were collected from 20 dogs. Before the collection, a visual clinical examination was performed and 8 subjects (40%) did not present any signs of dental calculus, while 12 (60%) presented dental calculus. After saliva collection, the samples were submitted to protein quantification (mBCA), and then they were prepared for analysis by nLC-ESI-MS/MS. A total of 658 unique proteins were identified, of which 225 were specific to dogs without dental calculus, 300 were specific to dogs with dental calculus, and 133 were common to all subjects. These proteins presented functions including transportation, immune response, structural, enzymatic regulation, signal transduction, transcription, metabolism, and some proteins perform functions as yet unknown. Several salivary proteins in dogs with dental calculus differed from those found in the group without dental calculus. Among the abundant proteins detected in periodontal affected cases, can be highlighting calcium-sensing receptor and transforming growth factor beta. Enrichment analysis reveled the presence of Rho GTPases signaling pathway. CONCLUSIONS: This research identified salivary proteins, that should be further investigated as potencial biomarkers of chronic periodontits with dental calculus formation in dogs.

Saliva as an alternative to blood in the determination of uremic state in adult patients with chronic kidney disease: a systematic review and meta-analysis.

OBJECTIVES: To assess whether salivary urea and creatinine levels accurately reflect their serum levels in blood samples of adults to detect chronic kidney disease. MATERIALS AND METHODS: A systematic review was conducted in eight electronic databases. The protocol was registered in PROSPERO. Only diagnostic test studies were included. The JBI critical appraisal tools assessed the risk of bias. A meta-analysis of proportions was performed. The GRADE tool assessed the quality of evidence and strength of recommendation across the studies included. RESULTS: Eight studies met the eligibility criteria and were included. Six studies assessed salivary urea, and six studies assessed salivary creatinine. All studies presented moderate risk of bias. The meta-analysis depicted an overall sensitivity of 93.3% (95% CI = 88.6; 97.9) for salivary creatinine levels and 87.5% (95% CI = 83.2; 91.8) for salivary urea levels, while the overall specificity was 87.1% (95% CI = 82.8; 91.3) and 83.2% (95% CI = 65.0; 101.4) for salivary creatinine and urea levels, respectively. The overall accuracy of salivary creatinine was 5.2 percentage points higher compared with salivary urea levels (90.8% vs. 85.6%). According to the GRADE tool, the analysed outcomes were classified as having low to moderate level of certainty. CONCLUSION: Compared with blood samples, salivary urea and creatinine levels presented high diagnostic values for chronic kidney disease screening, but should not be considered equivalent to levels obtained from blood at stages three, four, or five of the disease. CLINICAL SIGNIFICANCE: Chronic kidney disease patients could receive a clinically significant benefit from replacing blood with saliva for potentially monitoring renal function. Saliva collection presents greater simplicity, comfort, safety, and lower collection cost.

Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice.

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

Diagnostic potential of saliva proteome analysis: a review and guide to clinical practice.

Proteomic techniques have become popular in medicine and dentistry because of their widespread use in analyzing bodily fluids such as blood, saliva, urine, and gingival crevicular fluids as well as hard tissues such as enamel, dentine, and cementum. This review is a guide to proteomic techniques in general dentistry, summarizing techniques and their clinical application in understanding and diagnosing diseases and their use in identifying biomarkers of various diseases.