Progression from healthy periodontium to gingivitis and periodontitis: Insights from bioinformatics-driven proteomics - A systematic review with meta-analysis.

AIM: The current study aimed to: (1) systematically review the published literature regarding the proteomics analyses of saliva and gingival crevicular fluid (GCF) in healthy humans and gingivitis and/or periodontitis patients; and (2) to identify the differentially expressed proteins (DEPs) based on the systematic review, and comprehensively conduct meta-analyses and bioinformatics analyses. METHODS: An online search of Web of Science, Scopus, and PubMed was performed without any restriction on the year and language of publication. After the identification of the DEPs reported by the included human primary studies, gene ontology (GO), the Kyoto encyclopedia of genes and genomes pathway (KEGG), protein-protein interaction (PPI), and meta-analyses were conducted. The risk of bias among the included studies was evaluated using the modified Newcastle-Ottawa quality assessment scale. RESULTS: The review identified significant differences in protein expression between healthy individuals and those with gingivitis and periodontitis. In GCF, 247 proteins were upregulated and 128 downregulated in periodontal diseases. Saliva analysis revealed 79 upregulated and 70 downregulated proteins. There were distinct protein profiles between gingivitis and periodontitis, with 159 and 31 unique upregulated proteins in GCF, respectively. Meta-analyses confirmed significant upregulation of various proteins in periodontitis, including ALB and MMP9, while CSTB and GSTP1 were downregulated. AMY1A and SERPINA1 were upregulated in periodontitis saliva. HBD was upregulated in gingivitis GCF, while DEFA3 was downregulated. PPI analysis revealed complex networks of interactions among DEPs. GO and KEGG pathway analyses provided insights into biological processes and pathways associated with periodontal diseases. CONCLUSION: The ongoing MS-based proteomics studies emphasize the need for a highly sensitive and specific diagnostic tool for periodontal diseases. Clinician acceptance of the eventual diagnostic method relies on its ability to provide superior or complementary information to current clinical assessment procedures. Future research should prioritize the multiplex measurement of multiple biomarkers simultaneously to enhance diagnostic accuracy and large study cohorts are necessary to ensure the validity and reliability of research findings.

Metabolomics for dental caries diagnosis: Past, present, and future.

Dental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.

Proteomic Analysis of Human Saliva via Solid-Phase Microextraction Coupled with Liquid Chromatography-Mass Spectrometry.

Proteomics of human saliva samples was achieved for the first time via biocompatible solid-phase microextraction (bio-SPME) devices. Upon introduction of a porogen to a conventional C18 coating, porous C18/polyacrylonitrile (PAN) SPME blades were able to extract peptides up to 3.0 kDa and more peptides than commercial SPME blades. Following Trypsin digestion, salivary proteomic analysis was achieved via SPME-LC-MS/MS. Seven endogenous proteins were consistently identified in all saliva samples via bio-SPME. Taking advantage of this strategy, untargeted peptidomics was applied for the comparison of saliva samples between healthy and SARS-CoV-2 positive individuals. The results showed clear peptidomic differences between the viral and healthy saliva samples. This proof-of-concept study demonstrates the potential of bio-SPME-LC-MS/MS for peptidomics and proteomics in biomedical applications.

Mass spectrometry-based proteomics profiling of dogs with and without oral diseases: a systematic review.

BACKGROUND: Understanding the distinct proteomics profiles in dogs' oral biofluids enhances diagnostic and therapeutic insights for canine oral diseases, fostering cross-species translational research in dentistry and medicine. This study aimed to conduct a systematic review to investigate the similarities and differences between the oral biofluids' proteomics profile of dogs with and without oral diseases. METHODS: PubMed, Web of Science, and Scopus were searched with no restrictions on publication language or year to address the following focused question: "What is the proteome signature of healthy versus diseased (oral) dogs' biofluids?" Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analyses of the most abundant proteins were performed. Moreover, protein-protein interaction analysis was conducted. The risk of bias (RoB) among the included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data. RESULTS: In healthy dogs, the proteomic analysis identified 5,451 proteins, with 137 being the most abundant, predominantly associated with 'innate immune response'. Dogs with oral diseases displayed 6,470 proteins, with distinct associations: 'defense response to bacterium' (periodontal diseases), 'negative regulation of transcription' (dental calculus), and 'positive regulation of transcription' (oral tumors). Clustering revealed significant protein clusters in each case, emphasizing the diverse molecular profiles in health and oral diseases. Only six studies were provided to the JBI tool, as they encompassed case-control evaluations that compared healthy dogs to dogs with oral disease(s). All included studies were found to have low RoB (high quality). CONCLUSION: Significant differences in the proteomics profiles of oral biofluids between dogs with and without oral diseases were found. The synergy of animal proteomics and bioinformatics offers a promising avenue for cross-species research, despite persistent challenges in result validation.

Antibiofilm Activity and Biocompatibility of Temporin-SHa: A Promising Antimicrobial Peptide for Control of Fluconazole-Resistant Candida albicans.

The aim of the study was to investigate the effect of antimicrobial peptides (AMPs) Hylin-a1, KR-12-a5, and Temporin-SHa in Candida albicans as well as the biocompatibility of keratinocytes spontaneously immortalized (NOK-si) and human gingival fibroblasts (FGH) cells. Initially, the susceptible (CaS-ATCC 90028) and fluconazole-resistant (CaR-ATCC 96901) C. albicans strains were grown to evaluate the effect of each AMP in planktonic culture, biofilm, and biocompatibility on oral cells. Among the AMPs evaluated, temporin-SHa showed the most promising results. After 24 h of Temporin-SHa exposure, the survival curve results showed that CaS and CaR suspensions reduced 72% and 70% of cell viability compared to the control group. The minimum inhibitory/fungicide concentrations (MIC and MFC) showed that Temporin-SHa was able to reduce ≥50% at ≥256 µg/mL for both strains. The inhibition of biofilm formation, efficacy against biofilm formation, and total biomass assays were performed until 48 h of biofilm maturation, and Temporin-SHa was able to reduce ≥50% of CaS and CaR growth. Furthermore, Temporin-SHa (512 µg/mL) was classified as non-cytotoxic and slightly cytotoxic for NOK-si and FGH, respectively. Temporin-SHa demonstrated an anti-biofilm effect against CaS and CaR and was biocompatible with NOK-si and FGH oral cells in monolayer.

Salivary protein homology between humans and dogs: Mass spectrometry-based proteomics analysis.

OBJECTIVE: This benchmark study aimed to investigate sex-related differences based on the identification and characterization of the salivary proteome of healthy male and female dogs using mass spectrometry (MS) technique and a homology-driven approach to analyze salivary proteins in both human and dog species utilizing protein sequence alignment technique. METHODS: Unstimulated whole saliva was collected from 10 healthy Beagles. After processing the samples and determining the total protein content, in-solution protein digestion was performed involving denaturation, reduction of disulfide bonds, alkylation, and removal of interfering compounds. Samples were analyzed using LC-ESI-MS/MS. RESULTS: LC-ESI-MS/MS analysis identified 327 and 341 unique proteins in male and female dog saliva, respectively, of which 318 (97.25 %) in male dogs and 326 (95.60 %) in female dogs were characterized. Abundant shared proteins included albumin, BPI fold-containing family A member 2, and VWFD domain-containing protein. A notable uncharacterized protein, VWFD domain-containing protein, was among the most abundant in both sexes. Comparative analysis of 69 abundant shared proteins indicated an upregulation of CES5A, EFHD, GC, IGHM, LOC100653049, KRT10, LCP1, PGD, TPI1 in male dogs, while LOC100855593 was upregulated in female dogs. In total, 84 % (n = 229/274) and 86 % (n = 235/275) salivary proteins identified in male and female dogs, respectively, were homologous to human proteins, with an overall homology of 86 % (n = 364/423), including 15 with 100 % homology. CONCLUSION: The study revealed clear differences in the salivary proteomics profile of healthy male and female dogs. However, most of the salivary proteins in both male and female dogs showed homology with human salivary proteins. CLINICAL RELEVANCE: The identification of unique salivary proteome profiles in male and female dogs, coupled with substantial homology to human proteins, provides promising biomarkers for health assessment, highlighting its clinical significance for diagnostics and therapeutic exploration not only in veterinary and human dentistry, but across mammalian species.

Investigating the perceptions and experiences of Canadian dentists on dental regulatory bodies' communications and guidelines during the COVID-19 pandemic.

OBJECTIVE: Dental regulatory bodies aim to ensure the health and safety of dentists, dental staff patients and the public. An important responsibility during a pandemic is to communicate risk and guidelines for patient care. Limited data exist on the perceptions and experiences of dentists navigating new guidelines for mitigating risk in dental care during the pandemic. The objective of this study was to use a qualitative approach to explore how dentists in Canada experienced and perceived their regulatory bodies' communication about COVID-19 risks and guidelines during the pandemic. METHODS: Participants were Canadian dentists (N = 644) recruited through the email roster of nine provincial dental associations or regulatory bodies. This qualitative analysis was nested within a prospective longitudinal cohort study in which data were collected using online questionnaires at regular intervals from August 2020 to November 2021. To address the objective reported in this paper, a conventional qualitative content analysis method was applied to responses to three open-ended questions included in the final questionnaire. RESULTS: Participants encountered challenges and frustrations amid the COVID-19 pandemic, grappling with diverse regulations and communications from dental bodies. While some bodies offered helpful guidance, many participants felt the need for improved communication on guidelines. Dentists urged for expedited, clearer and more frequent updates, expressing difficulty in navigating overwhelming information. Negative views emerged on the vague and unclear communication of COVID-19 guidelines, contributing to confusion and frustration among participants. CONCLUSION: As COVID-19 persists and in planning for future pandemics, these experiential findings will help guide regulatory bodies in providing clear, timely and practical guidelines to protect the health and safety of dentists, dental staff, patients and the public.

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.

Personal protective equipment during COVID-19: A natural history of dental and dental hygiene regulatory guidance in Canada.

BACKGROUND: Due to the evolving nature of COVID-19, there is evidence that COVID-19-specific infection prevention and control guideline (IPCG) documents formulated for oral health care settings are also changing rapidly. To better inform future policies, a comprehensive review of all IPCG documents across different phases of restrictions for oral health care practitioners is required. TYPES OF STUDIES REVIEWED: A search was performed for documents shared from March 2020 through January 2022 on websites of oral health regulatory authorities in Canada's 10 provinces and 3 territories. The authors performed a narrative review of the identified IPCG documents for dentists (n = 78) and dental hygienists (n = 57). RESULTS: Overall findings from more than 100 IPCG documents distributed during a period of 23 months revealed that the frequency of these updates differed among jurisdictions and between the 2 oral health care practitioners (ie, dentists and dental hygienists) within the same jurisdiction. The most notable observation was the different face-covering recommendations for dentists and dental hygienists within the same jurisdiction during the same timeframe. A common document was sometimes observed for dentists and dental hygienists, however, most jurisdictions had separate IPCG documents. CONCLUSIONS AND PRACTICAL IMPLICATIONS: The different approaches could have been justified on the basis of prevalence of COVID-19 and availability of personal protective equipment; however, there was a risk of creating confusion about IPCG best practices. The findings of this review will support decision makers when planning future development and dissemination of regulations for all oral health care practitioners.

Identification of SARS-CoV-2 biomarkers in saliva by transcriptomic and proteomics analysis.

The detection of SARS-CoV-2 biomarkers by real time PCR (rRT-PCR) has shown that the sensitivity of the test is negatively affected by low viral loads and the severity of the disease. This limitation can be overcome by the use of more sensitive approaches such as mass spectrometry (MS), which has not been explored for the detection of SARS-CoV-2 proteins in saliva. Thus, this study aimed at assessing the translational applicability of mass spectrometry-based proteomics approaches to identify viral proteins in saliva from people diagnosed with COVID-19 within fourteen days after the initial diagnosis, and to compare its performance with rRT-PCR. After ethics approval, saliva samples were self-collected by 42 COVID-19 positive and 16 healthy individuals. Samples from people positive for COVID-19 were collected on average on the sixth day (± 4 days) after initial diagnosis. Viable viral particles in saliva were heat-inactivated followed by the extraction of total proteins and viral RNA. Proteins were digested and then subjected to tandem MS analysis (LC-QTOF-MS/MS) using a data-dependent MS/MS acquisition qualitative shotgun proteomics approach. The acquired spectra were queried against a combined SARS-CoV-2 and human database. The qualitative detection of SARS-CoV-2 specific RNA was done by rRT-PCR. SARS-CoV-2 proteins were identified in all COVID-19 samples (100%), while viral RNA was detected in only 24 out of 42 COVID-19 samples (57.1%). Seven out of 18 SARS-CoV-2 proteins were identified in saliva from COVID-19 positive individuals, from which the most frequent were replicase polyproteins 1ab (100%) and 1a (91.3%), and nucleocapsid (45.2%). Neither viral proteins nor RNA were detected in healthy individuals. Our mass spectrometry approach appears to be more sensitive than rRT-PCR for the detection of SARS-CoV-2 biomarkers in saliva collected from COVID-19 positive individuals up to 14 days after the initial diagnostic test. Based on the novel data presented here, our MS technology can be used as an effective diagnostic test of COVID-19 for initial diagnosis or follow-up of symptomatic cases, especially in patients with reduced viral load.

Brewing better connections: Coffee with the dean to enhance admin-student communication.

Effective communication is pivotal in nurturing a supportive learning atmosphere. At the University of Saskatchewan's College of Dentistry, traditional methods like emails and meetings seemed inadequate in engaging all students. Concerns stemmed from power dynamics and limited dialogue avenues. To bridge this gap, an innovative solution emerged. Introducing "Coffee with the Dean": A bi-weekly event fostering informal discussions between students and the dean. Set in a relaxed ambiance, students openly covered diverse topics. The project aimed to foster transparent communication and bolster a sense of unity. Implemented over six months, the initiative saw significant outcomes. Assessment involved an anonymous survey to DMD students, garnering a 34% response rate. Impressively, 89% acknowledged enhanced communication, with 53% and 23% expressing high and moderate satisfaction in asking questions and providing feedback. Moreover, 67% displayed a likelihood to attend future sessions. A notable 89% appreciated the project's community-building impact. Although challenges emerged, including scheduling and participation constraints, the project achieved its goal. The casual setup facilitated student expression and prompted insightful exchanges. The experience emphasizes the importance of secure dialogue spaces and consistent communication channels. "Coffee with the Dean" stands as a potent tool for heightened student-administration interaction. Its role in elevating communication aligns with the quest for educational excellence, ensuring holistic student growth.

Validity and reliability of the COVID-19 Anxiety Syndrome Scale in Canadian dentists.

BACKGROUND: The COVID-19 pandemic has resulted in a high level of mental health problems for the population worldwide including healthcare workers. Several studies have assessed these using measurements for anxiety for general populations. The COVID-19 Anxiety Syndrome Scale (C-19ASS) is a self-report measure developed to assess maladaptive forms of coping with COVID-19 (avoidance, threat monitoring and worry) among a general adult population in the United States. We used it in a prospective cohort study of COVID-19 incidence rates in practising Canadian dentists. We therefore need to ensure that it is valid for dentists in French and English languages. This study aimed to evaluate the validity of the C-19ASS in that population. METHODS: Cross-sectional data from the January 2021 monthly follow-up in our prospective cohort study were used. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed. RESULTS: The results of EFA revealed a 2-factor structure solution that explained 47% of the total variance. The CFA showed a good model fit on the data in both English and French languages. The Cronbach's alpha indicated acceptable levels of reliability. Furthermore, the C-19ASS showed excellent divergent validity from the Generalized Anxiety Disorder-7 (GAD-7) scale. CONCLUSIONS: The C-19ASS is valid and reliable instrument to measure COVID-19-related anxiety in English and French among Canadian dentists. PRACTICAL IMPLICATIONS: This validated measure will contribute to understanding of the mental health impact of the pandemic on dentists in Canada and enable the dental regulatory authorities and organizations to intervene to help dentists.

Comparative analysis indicates a simple protocol for DNA extraction of the aromatic plant Lippia alba.

An efficient method of genomic DNA extraction that provides high quality and yield is a crucial pre-requisite and limiting factor in plant genetic analysis. However, pure genomic DNA can be challenging to obtain from some plant species due to their sugar and secondary metabolite contents. Lippia alba is an important aromatic and medicinal plant, chemically characterized by the presence of tannins, flavonoids, anthocyanins, and essential oils, which interfere with the extraction of pure genomic DNA. In this scenario, optimizing the extraction methods and minimizing the effects of these compounds are necessary. This study compares six plant DNA extraction protocols based on the CTAB method. The quality and quantity of DNA samples obtained were determined by physical appearance by electrophoresis in agarose gels and spectrophotometry. The results highlight the difficulty in obtaining pure and clear bands for all tested methods, except for the polyvinylpyrrolidone (PVP)-based protocol created by our team, which was the better option for obtaining high-quality genomic DNA of L. alba. We conclude that adding PVP-40 into DNA extraction buffers can optimize the DNA extraction of L. alba and indicate this protocol for DNA extraction from other aromatic plants.

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.

Mass spectrometry-based proteomic approaches for salivary protein biomarkers discovery and dental caries diagnosis: A critical review.

Dental caries is a multifactorial chronic disease resulting from the intricate interplay among acid-generating bacteria, fermentable carbohydrates, and several host factors such as saliva. Saliva comprises several proteins which could be utilized as biomarkers for caries prevention, diagnosis, and prognosis. Mass spectrometry-based salivary proteomics approaches, owing to their sensitivity, provide the opportunity to investigate and unveil crucial cariogenic pathogen activity and host indicators and may demonstrate clinically relevant biomarkers to improve caries diagnosis and management. The present review outlines the published literature of human clinical proteomics investigations on caries and extensively elucidates frequently reported salivary proteins as biomarkers. This review also discusses important aspects while designing an experimental proteomics workflow. The protein-protein interactions and the clinical relevance of salivary proteins as biomarkers for caries, together with uninvestigated domains of the discipline are also discussed critically.

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.

Salivary Proteins as Dental Caries Biomarkers: A Systematic Review.

Salivary proteins play an important role in repairing mechanisms of damaged tissues and the maintenance of oral health. However, there is a dearth of information in the literature regarding the concentrations of salivary proteins in caries-free (CF) and caries-active (CA) subjects. Hence, this systematic review was conducted to update our previous systematic review published in 2013 that aimed to assess the association between caries and salivary proteins by comparing CF and CA individuals. Thereby, evaluating the possibility of whether salivary proteins can be regarded as biomarkers for caries. An extensive search of studies was conducted using PubMed, EMBASE, Clarivate Analytics' Web of Science, and Elsevier's Scopus between July 2012 and January 2022, without any language restriction. Manual searching in Google Scholar and evaluation of bibliographies of the included studies were also undertaken. The Newcastle-Ottawa Scale was used to assess the risk of bias (RoB) within the included studies. Of 22 included studies, 1,551 human subjects (range: 30-213 participants) were recruited, of which 848 individuals (54.7%) were CA and 703 (45.3%) were CF. Regarding the utilization of DMFT as the caries index, high variability was observed across different articles. A statistically significant increase in the salivary levels of alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, and mucin-1 was found in CA patients, while the salivary levels of carbonic anhydrase 6, proteinase-3, and statherin were observed to be significantly increased in CF subjects. Conflicting results were found regarding the salivary levels of immunoglobulin A and total proteins among CA and CF subjects. The included studies were categorized as low RoB (n = 15), medium RoB (n = 4), and high RoB (n = 3). Due to significant heterogeneity among the included studies, no meta-analysis could be performed. In conclusion, the salivary levels of protein(s) might be a useful biomarker for caries diagnosis, especially alpha-amylase, acidic proline-rich protein-1, histatin-5, lactoperoxidase, mucin-1, carbonic anhydrase 6, proteinase-3, and statherin. However, their diagnostic value must be verified by large-scale prospective studies.

Detection of periodontal disease activity based on histatin degradation in individuals with cerebral palsy.

Objectives: This proof-of-concept study aimed at evaluating the proteolytic profile of histatin 1 and 5 in saliva of adolescents with spastic cerebral palsy (CP) with gingivitis. Methods: This cross-sectional study included 24 individuals allocated into three groups: G1 (CP with gingivitis; n = 8), G2 (without CP and without gingivitis; n = 8), and G3 (without CP and with gingivitis; n = 8). The gingival index (GI) and simplified oral hygiene index (OHI-S) were evaluated. Whole saliva was collected and used to assess the rate and mode of histatin 1 and 5 at different times. The degradation products were visualized after cationic PAGE and the protein band densities (BDs) were compared with a protein standard. Fragmentation products were collected from the gel, pooled by group and characterized by mass spectrometry. BDs and gingival health parameters were analyzed by One-Way ANOVA or Kruskal Wallis tests, whereas poisson multilevel regression was used to the factors that influenced histatin degradation (α = 5%). Results: Groups G1 and G3 differed significantly on OHI-S, visible biofilm, oral calculus and GI (p < 0.001). Poisson Regression showed that: 1) CP and gingivitis influenced the degradation of histatin 1 and 5 (p < 0.05); 2) The degradation of histatin 5 was influenced by age and male sex (p < 0.05); and 3) GI influenced significantly the degradation of histatin 1 (p < 0.001). Unique histatin degradation peptides were identified in individuals with gingivitis. Conslusions: These data demonstrated that both the kinetics and pattern of histatins degradation differ according to the gingival health or disease conditions.

Current State and Challenges of the Global Outcomes of Dental Caries Research in the Meta-Omics Era.

Despite significant healthcare advances in the 21st century, the exact etiology of dental caries remains unsolved. The past two decades have witnessed a tremendous growth in our understanding of dental caries amid the advent of revolutionary omics technologies. Accordingly, a consensus has been reached that dental caries is a community-scale metabolic disorder, and its etiology is beyond a single causative organism. This conclusion was based on a variety of microbiome studies following the flow of information along the central dogma of biology from genomic data to the end products of metabolism. These studies were facilitated by the unprecedented growth of the next- generation sequencing tools and omics techniques, such as metagenomics and metatranscriptomics, to estimate the community composition of oral microbiome and its functional potential. Furthermore, the rapidly evolving proteomics and metabolomics platforms, including nuclear magnetic resonance spectroscopy and/or mass spectrometry coupled with chromatography, have enabled precise quantification of the translational outcomes. Although the majority supports 'conserved functional changes' as indicators of dysbiosis, it remains unclear how caries dynamics impact the microbiota functions and vice versa, over the course of disease onset and progression. What compounds the situation is the host-microbiota crosstalk. Genome-wide association studies have been undertaken to elucidate the interaction of host genetic variation with the microbiome. However, these studies are challenged by the complex interaction of host genetics and environmental factors. All these complementary approaches need to be orchestrated to capture the key players in this multifactorial disease. Herein, we critically review the milestones in caries research focusing on the state-of-art singular and integrative omics studies, supplemented with a bibliographic network analysis to address the oral microbiome, the host factors, and their interactions. Additionally, we highlight gaps in the dental literature and shed light on critical future research questions and study designs that could unravel the complexities of dental caries, the most globally widespread disease.