Publications by authors named "Nagihan Bostanci"

103 Publications

OralDisk: A Chair-Side Compatible Molecular Platform Using Whole Saliva for Monitoring Oral Health at the Dental Practice.

Biosensors (Basel) 2021 Oct 28;11(11). Epub 2021 Oct 28.

Hahn-Schickard, Georges-Koehler-Allee 103, 79110 Freiburg, Germany.

Periodontitis and dental caries are two major bacterially induced, non-communicable diseases that cause the deterioration of oral health, with implications in patients' general health. Early, precise diagnosis and personalized monitoring are essential for the efficient prevention and management of these diseases. Here, we present a disk-shaped microfluidic platform (OralDisk) compatible with chair-side use that enables analysis of non-invasively collected whole saliva samples and molecular-based detection of ten bacteria: seven periodontitis-associated (, , , , , , ) and three caries-associated (oral , , ). Each OralDisk test required 400 µL of homogenized whole saliva. The automated workflow included bacterial DNA extraction, purification and hydrolysis probe real-time PCR detection of the target pathogens. All reagents were pre-stored within the disk and sample-to-answer processing took < 3 h using a compact, customized processing device. A technical feasibility study (25 OralDisks) was conducted using samples from healthy, periodontitis and caries patients. The comparison of the OralDisk with a lab-based reference method revealed a ~90% agreement amongst targets detected as positive and negative. This shows the OralDisk's potential and suitability for inclusion in larger prospective implementation studies in dental care settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/bios11110423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8615610PMC
October 2021

Lectin-Functionalized Polyethylene Glycol for Relief of Mucosal Dryness.

Adv Healthc Mater 2021 Oct 28:e2101719. Epub 2021 Oct 28.

Division of Glycoscience, Department of Chemistry, School of Engineering Sciences in Chemistry, Biotechnology and Health, KTH - Royal Institute of Technology, AlbaNova University Centre, Stockholm, 106 91, Sweden.

The importance of lubrication between oral surfaces provided by the salivary film is most acutely apparent when it is disrupted, a prevalent consequence of salivary gland hypofunction experienced with aging, a symptom of certain diseases, or a side effect of some medical interventions. Sufferers report difficulty with speech and oral food processing and collectively is detrimental to quality of life. Polyethylene glycol (PEG) is widely employed as a successful biocompatible boundary lubricant in engineering and biomedical applications. It is hypothesized that the immobilization of PEG to biological materials such as oral epithelial cells and tissue can mimic the salivary film and provide durable relief from the symptoms of mucosal dryness. To do so, PEG is functionalized with a sugar binding lectin (wheat germ agglutinin) to enhance epithelial adhesion through lectin-sugar interactions. Retention and lubricity are characterized on an ex vivo oral tissue tribology rig. WGA-PEG coats and retains on mucin films, oral epithelial cells, and porcine tongue tissue, and offers sustained reduction in coefficient of friction (COF). WGA-PEG could be developed into a useful topical treatment for reducing oral friction and the perception of dry mouth.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adhm.202101719DOI Listing
October 2021

Cytokine profiles and the dynamic of gingivitis development in humans.

J Clin Periodontol 2021 Oct 19. Epub 2021 Oct 19.

Section for Periodontology, Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark.

Aim: To investigate the relationship between cytokine profiles and "fast" and "slow" patterns of gingival inflammation development.

Materials And Methods: Forty-two adults participated in an experimental gingivitis study, comprising a 2-week hygiene phase (clinical examination and professional cleaning); a 3-week induction phase (absence of oral hygiene); and a 2-week resolution phase (re-establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumour necrosis factor-alpha (TNF-α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group-based-trajectory-modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed-effects modelling.

Results: GBTM analysis revealed two cytokine profiles, "non-organized response" (IL-4, IL-6, IL-8, IL-12, and IL-13) and "organized response" (IL-2, IL-10, and TNF-α). Among the "slow" responders, neither cytokine profile was associated with gingivitis. In contrast, a "fast" response was associated with a higher "non-organized response" factor (coef. 0.14) and a lower "organized response" factor (coef. -0.03).

Conclusion: A "fast" gingivitis development was associated with a higher "non-organized response" and a lower "organized response", which may elucidate the role of individual variability in gingivitis susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpe.13565DOI Listing
October 2021

Oral health and emotional well-being in premenopausal and postmenopausal women: a cross-sectional cohort study.

BMC Womens Health 2021 09 23;21(1):338. Epub 2021 Sep 23.

Section of Oral Health and Periodontology, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Alfred Nobels Allé 8, 14152, Huddinge, Sweden.

Background: Menopause, the absence of ovarian sex steroids, is frequently accompanied by emotional and physiological changes in a woman´s body, as well as oral health changes. The present study aimed to evaluate the association between the periodontal health status and emotional and physical well-being among postmenopausal women (PMW) in comparison with regularly menstruating premenopausal women (RMPW).

Methods: A total of 115 women (PMW, n = 56, mean age ± SD: 54 ± 5; RMPW, n = 59, mean age ± SD: 41 ± 4) received a comprehensive medical assessment and a full-mouth oral examination. All completed the Women's Health Questionnaire (WHQ) to measure emotional and physical well-being. The corresponding bone mineral density (BMD) scores were obtained from participants´ medical records.

Results: Tooth loss was significantly higher in PMW than RMPW after adjusting for age (3.88 ± 2.41 vs 2.14 ± 2.43, p < 0.05). No significant difference was found in the prevalence of periodontitis between the two groups (PMW: 39.2%, RMPW: 32.2%, p > 0.05). The prevalence of periodontitis was associated with fewer daily brushing sessions in PMW (p = 0.021). Based on the WHQ, both PMW and RMPW with periodontitis had higher ''depressed mood'' scores compared to periodontally healthy women (p = 0.06 and p = 0.038, respectively). The women who reported fewer daily toothbrushing sessions found to have higher depressive mood scores (p = 0.043).

Conclusions: Presence of periodontitis is associated with the emotional and physical well-being of women and reinforcement of oral healtcare is recommended at different stages of a woman's life including menopause to reduce the risk for early tooth loss in women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-021-01480-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459505PMC
September 2021

Active matrix metalloproteinase-8 (aMMP-8) point-of-care test (POCT) in the COVID-19 pandemic.

Expert Rev Proteomics 2021 08 11;18(8):707-717. Epub 2021 Sep 11.

Unit of Pedodontics and Preventive Dentistry, Oral Health Sciences Centre, Post Graduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

Introduction: Active matrix metalloproteinase (aMMP)-8 utilized in point-of-care testing (POCT) is regarded as a potential biomarker for periodontal and peri-implant diseases. Various host and microbial factors eventually influence the expression, degranulation, levels and activation of aMMP-8. The type of oral fluids (saliva, mouthrinse, gingival crevicular, and peri-implant sulcular fluids [GCF/PISF], respectively) affect the analysis.

Areas Covered: With this background, we aimed to review here the recent studies on practical, inexpensive, noninvasive and quantitative mouthrinse and GCF/PISF chair-side POCT lateral flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyzer) and how they help to detect, predict, monitor the course, treatment and prevention of periodontitis and peri-implantitis. The correlations of aMMP-8 POCT to other independent and catalytic activity assays of MMP-8 are also addressed.

Expert Opinion: The mouthrinse aMMP-8 POCT can also detect prediabetes/diabetes and tissue destructive oral side-effects due to the head and neck cancers' radiotherapy. Chlorhexidine and doxycycline can inhibit collagenolytic human neutrophil and GCF aMMP-8. Furthermore, by a set of case-series we demonstrate the potential of mouthrinse aMMP-8 POCT to real-time/online detect periodontitis as a potential risk disease for coronavirus disease 2019 (COVID-19). The clinical interdisciplinary utilization of aMMP-8 POCT requires additional oral, medical, and interdisciplinary studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14789450.2021.1976151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8442753PMC
August 2021

Dysbiosis of the Human Oral Microbiome During the Menstrual Cycle and Vulnerability to the External Exposures of Smoking and Dietary Sugar.

Front Cell Infect Microbiol 2021 19;11:625229. Epub 2021 Mar 19.

Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Physiological hormonal fluctuations exert endogenous pressures on the structure and function of the human microbiome. As such, the menstrual cycle may selectively disrupt the homeostasis of the resident oral microbiome, thus compromising oral health. Hence, the aim of the present study was to structurally and functionally profile the salivary microbiome of 103 women in reproductive age with regular menstrual cycle, while evaluating the modifying influences of hormonal contraceptives, sex hormones, diet, and smoking. Whole saliva was sampled during the menstrual, follicular, and luteal phases (n = 309) of the cycle, and the participants reported questionnaire-based data concerning their life habits and oral or systemic health. No significant differences in alpha-diversity or phase-specific clustering of the overall microbiome were observed. Nevertheless, the salivary abundances of genera , , , and varied throughout the cycle, and a higher species-richness was observed during the luteal phase. While the overall community structure maintained relatively intact, its functional properties were drastically affected. In particular, 11 functional modules were differentially abundant throughout the menstrual cycle, including pentose phosphate metabolism, and biosynthesis of cobalamin and neurotransmitter gamma-aminobutyric acid. The menstrual cycle phase, but not oral contraceptive usage, was accountable for greater variations in the metabolic pathways of the salivary microbiome. Further co-risk factor analysis demonstrated that and were increased in current smokers, whereas high dietary sugar consumption modified the richness and diversity of the microbiome during the cycle. This is the first large study to systematically address dysbiotic variations of the oral microbiome during the course of menstrual cycle, and document the additive effect of smoking and sugar consumption as environmental risk factors. It reveals the structural resilience and functional adaptability of the oral microbiome to the endogenous hormonal pressures of the menstrual cycle, while revealing its vulnerability to the exogenous exposures of diet and smoking.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.625229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018275PMC
July 2021

Salivary Biomarkers for Dental Caries Detection and Personalized Monitoring.

J Pers Med 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Dental Medicine, Division of Oral Diseases, Karolinska Institutet, 141 04 Huddinge, Sweden.

This study investigated the potential of salivary bacterial and protein markers for evaluating the disease status in healthy individuals or patients with gingivitis or caries. Saliva samples from caries- and gingivitis-free individuals ( = 18), patients with gingivitis ( = 17), or patients with deep caries lesions ( = 38) were collected and analyzed for 44 candidate biomarkers (cytokines, chemokines, growth factors, matrix metalloproteinases, a metallopeptidase inhibitor, proteolytic enzymes, and selected oral bacteria). The resulting data were subjected to principal component analysis and used as a training set for random forest (RF) modeling. This computational analysis revealed four biomarkers (IL-4, IL-13, IL-2-RA, and eotaxin/CCL11) to be of high importance for the correct depiction of caries in 37 of 38 patients. The RF model was then used to classify 10 subjects (five caries-/gingivitis-free and five with caries), who were followed over a period of six months. The results were compared to the clinical assessments of dental specialists, revealing a high correlation between the RF prediction and the clinical classification. Due to the superior sensitivity of the RF model, there was a divergence in the prediction of two caries and four caries-/gingivitis-free subjects. These findings suggest IL-4, IL-13, IL-2-RA, and eotaxin/CCL11 as potential salivary biomarkers for identifying noninvasive caries. Furthermore, we suggest a potential association between JAK/STAT signaling and dental caries onset and progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jpm11030235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004821PMC
March 2021

Validation and verification of predictive salivary biomarkers for oral health.

Sci Rep 2021 03 19;11(1):6406. Epub 2021 Mar 19.

Faculty of Pharmacy, Masaryk University, Palackeho trida 1946/1, 61242, Brno, Czech Republic.

Oral health is important not only due to the diseases emerging in the oral cavity but also due to the direct relation to systemic health. Thus, early and accurate characterization of the oral health status is of utmost importance. There are several salivary biomarkers as candidates for gingivitis and periodontitis, which are major oral health threats, affecting the gums. These need to be verified and validated for their potential use as differentiators of health, gingivitis and periodontitis status, before they are translated to chair-side for diagnostics and personalized monitoring. We aimed to measure 10 candidates using high sensitivity ELISAs in a well-controlled cohort of 127 individuals from three groups: periodontitis (60), gingivitis (31) and healthy (36). The statistical approaches included univariate statistical tests, receiver operating characteristic curves (ROC) with the corresponding Area Under the Curve (AUC) and Classification and Regression Tree (CART) analysis. The main outcomes were that the combination of multiple biomarker assays, rather than the use of single ones, can offer a predictive accuracy of > 90% for gingivitis versus health groups; and 100% for periodontitis versus health and periodontitis versus gingivitis groups. Furthermore, ratios of biomarkers MMP-8, MMP-9 and TIMP-1 were also proven to be powerful differentiating values compared to the single biomarkers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85120-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979790PMC
March 2021

One-step, wash-free, bead-based immunoassay employing bound-free phase detection.

Anal Chim Acta 2021 Apr 5;1153:338280. Epub 2021 Feb 5.

Hahn-Schickard, Georges-Koehler-Allee 103, 79110 Freiburg, Germany; Laboratory for MEMS Applications, IMTEK-Department of Microsystems Engineering, University of Freiburg, Georges-Koehler-Allee 103, 79110, Freiburg, Germany. Electronic address:

We present a simple and fast one-step heterogeneous immunoassay, with performance characteristics that can enable easy and versatile adaptation to miniaturized, automated point-of-care systems. This novel analytical method uses magnetic and fluorescent beads as capture and detection agents respectively. Its main feature is the measurement of the fluorescent signal in the bound-free phase for (semi-)quantitative detection of analytes. Thus, no washing is required and the workflow consists only of sample and reagent supply, incubation, separation and detection. The immunoassay concept is demonstrated with C-reactive protein (CRP), a systemic inflammation marker. CRP in only 5 μL of undiluted serum was measured in the range 20-140 mg L (includes clinically relevant cut-off values). The limit of detection (LOD) was 22.1 ± 6.3 mg L (incubation 15 min). A CRP certified reference material was measured on five different days. Intra- and inter-assay coefficients of variation were 4.6 ± 1.9% and 5.6% respectively. To demonstrate the compatibility of the assay concept with additional matrices and concentration ranges, three oral inflammation markers, namely matrix metalloproteinases 8 and 9 (MMP-8, MMP-9) and tissue inhibitor of metalloproteinases 1 (TIMP-1), were measured in saliva in the ranges 0.47-30 ng mL for MMP-8 and MMP-9, and 0.69-44 ng mL for TIMP-1. LODs were 0.24 ng mL, 0.38 ng mL and 0.39 ng mL respectively (incubation 20 min). Multiplexing capacity of the assay concept was also shown with these markers. The demonstrated excellent reproducibility of the results, combined with the versatility and low complexity of the introduced immunoassay concept, make it an attractive candidate for applied analytical chemistry and automated point-of-care testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.aca.2021.338280DOI Listing
April 2021

Regulation of matrix metalloproteinases-8, -9 and endogenous tissue inhibitor-1 in oral biofluids during pregnancy and postpartum.

Arch Oral Biol 2021 Apr 23;124:105065. Epub 2021 Jan 23.

Department of Periodontology, School of Dentistry, Ege University, İzmir, Turkey.

Objective: During pregnancy, mothers undergoe considerable physiological changes affecting the whole body including periodontal tissues. Susceptibility to gingival inflammation during pregnancy could be mediated by modulation of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). Therefore, the aim of this study was to investigate salivary and gingival crevicular fluid (GCF) levels of MMPs and TIMPs during the second and third trimester of pregnancy and postpartum.

Design: Saliva and GCF samples were collected from 96 pregnant women (PW) before and after giving birth. The sixty matched non-pregnant women (N-PW) were recruited as a control group and full-mouth periodontal examination was performed. The levels of MMP-8, MMP-9 and TIMP-1 were determined by immunofluorometric and enzyme-linked immunosorbent assays.

Results: The PW group exhibited significantly higher levels of MMP-8 and MMP-9 in their saliva than the N-PW group while corresponding salivary TIMP-1 levels were significantly lower in NPW compared to the postpartum stage. This resulted in significantly higher MMP-8/TIMP-1 and MMP-9/TIMP-1ratio in the saliva from PW before and after birth than in that from N-PW. MMP-8, MMP-9 and TIMP-1 levels were higher in GCF from PW and postpartum than in that from N-PW.

Conclusions: MMP-8 and MMP-9 levels in saliva and GCF reflect inflammatory burden during pregnancy. They could be used for monitoring the inflammatory state of gingival tissues during pregnancy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.archoralbio.2021.105065DOI Listing
April 2021

Elevated serum TREM-1 is associated with periodontitis and disease activity in rheumatoid arthritis.

Sci Rep 2021 02 3;11(1):2888. Epub 2021 Feb 3.

Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Alfred Nobels alle 8, 14104, Huddinge, Stockholm, Sweden.

The triggering receptor expressed on myeloid cells 1 (TREM-1) and peptidoglycan recognition protein 1 (PGLYRP1) are involved in the propagation of inflammatory responses. This study investigated whether serum levels of TREM-1 and PGLYRP1 correlate with periodontitis in rheumatoid arthritis (RA) patients. A total of 154 non-smoking participants with RA (n = 55, F/M: 41/14), Behçet´s disease (BD, n = 41, F/M: 30/11) and healthy controls (HC, n = 58, F/M: 40/18) were recruited. Serum and saliva were collected, the 28-joint disease activity score (DAS-28) was calculated and dental/periodontal measurements were recorded. Serum TREM-1 and PGLYRP1 levels were measured by ELISA and salivary bacterial DNA counts by quantitative polymerase chain reaction. TREM-1 and PGLYRP1 levels were higher in RA (166.3 ± 94.3; 155.5 ± 226.9 pg/ml) than BD (102.3 ± 42.8; 52.5 ± 26.3 pg/ml) and HCs (89.8 ± 55.7; 67.4 ± 37.3 pg/ml) (p < 0.05). In RA, periodontitis was associated with increased TREM-1 and PGLYRP1 levels (p < 0.05), yet in patients under methotrexate TREM-1 levels were lower. TREM-1 correlated with C-reactive protein (CRP) levels, DAS-28 and erythrocyte sedimentation rate, whereas PGLYRP1 positively correlated with CRP. RA patients displayed 3.5-fold higher salivary bacterial DNA counts than HCs. Increased serum TREM-1 levels correlated with PGLYRP1, CRP and DAS-28-ESR in RA patients with periodontitis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-82335-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859204PMC
February 2021

Associations between serum antibodies to periodontal pathogens and preclinical phases of rheumatoid arthritis.

Rheumatology (Oxford) 2021 Oct;60(10):4755-4764

Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

Objectives: To examine whether serum antibodies against selected periodontal pathogens are associated with early symptoms of RA development in healthy individuals at risk of developing the disease.

Methods: Within an ongoing study cohort of first-degree relatives of patients with RA (RA-FDRs), we selected four groups corresponding to specific preclinical phases of RA development (n = 201). (i) RA-FDR controls without signs and symptoms of arthritis nor RA-related autoimmunity (n = 51); (ii) RA-FDRs with RA-related autoimmunity (n = 51); (iii) RA-FDRs with inflammatory arthralgias without clinical arthritis (n = 51); and (iv) RA-FDRs who have presented at least one swollen joint ('unclassified arthritis') (n = 48). Groups were matched for smoking, age, sex and shared epitope status. The primary outcome was IgG serum levels against five selected periodontal pathogens and one commensal oral species assessed using validated-in-house ELISA assays. Associations between IgG measurements and preclinical phases of RA development were examined using Kruskal-Wallis or Mann-Whitney tests (α = 0.05).

Results: None of the IgGs directed against individual periodontal pathogens significantly differed between the four groups of RA-FDRs. Further analyses of cumulated IgG levels into bacterial clusters representative of periodontal infections revealed significantly higher IgG titres against periodontopathogens in anti-citrullinated protein antibodies (ACPA)-positive RA-FDRs (P = 0.015). Current smoking displayed a marked trend towards reduced IgG titres against periodontopathogens.

Conclusion: Our results do not suggest an association between serum IgG titres against individual periodontal pathogens and specific preclinical phases of RA development. However, associations between cumulative IgG titres against periodontopathogens and the presence of ACPAs suggest a synergistic contribution of periodontopathogens to ACPA development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keab097DOI Listing
October 2021

Metagenomic sequencing provides new insights into the subgingival bacteriome and aetiopathology of periodontitis.

J Periodontal Res 2021 Apr 6;56(2):205-218. Epub 2021 Jan 6.

Singapore Oral Microbiomics Initiative, National Dental Research Institute Singapore, SingHealth, Singapore, Singapore.

"Open-ended" molecular techniques such as 16S rRNA sequencing have revealed that the oral bacteriome of subgingival plaque is more diverse than originally thought. 16S rRNA analysis has demonstrated that constituents of the overall bacterial community are qualitatively similar in health and disease, differing mainly in their relative proportions with respect to each other. Species in low abundance can also act as critical species, leading to the concept of global community dysbiosis which relates to shifts in community structure, rather than shifts in membership. Correlation analysis suggests that coordinated interactions in the community are essential for incipient dysbiosis and disease pathogenesis. The subgingival bacteriome also provides biomarkers that are useful for disease detection and management. Combined with clinical and biological parameters, these may assist clinicians in developing and implementing effective treatment strategies to restore microbial homeostasis and monitor disease. Identification of higher risk groups or poor responders to treatment using unique subgingival bacteriome signatures may also lead to early intervention.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jre.12811DOI Listing
April 2021

Active matrix metalloproteinase-8 and interleukin-6 detect periodontal degeneration caused by radiotherapy of head and neck cancer: a pilot study.

Expert Rev Proteomics 2020 10 7;17(10):777-784. Epub 2021 Jan 7.

Department of Oral and Maxillofacial Diseases, University of Helsinki, Helsinki University Hospital , Helsinki, Finland.

: This cohort study investigated the role of the active matrix metalloproteinase-8 (aMMP-8) and interleukin-6 (IL-6) as oral fluid biomarkers for monitoring the periodontal degeneration occurring in head and neck cancer (HNC) patients treated by radiotherapy. : Eleven patients, aged 28-74, diagnosed with HNC were included in the study. Complete periodontal and oral examinations were performed pre-radiotherapy and 1 month after radiotherapy. Mouthrinse samples (pre-radiotherapy, after 6 weeks of radiotherapy and 1 month after radiotherapy) were assayed by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) for aMMP-8 and ELISA for IL-6. : HNC radiotherapy had a deteriorating impact on the periodontium and a significant impact on periodontal biomarkers aMMP-8 and IL-6 and increased their levels in mouthrinse. Clinical-attachment-loss (CAL) (site of greatest loss: mean = 1.7 mm, range = 1-3 mm) corresponding to rapid progression of periodontitis. There was a positive repeated measures correlation (rmcorr = 0.667) between the aMMP-8 and IL-6 levels. : Elevated aMMP-8 levels were observed 1 month after radiotherapy among some HNC patients suggesting a prolonged increased susceptibility to further periodontal tissue destruction. Currently available aMMP-8 point-of-care testing could be useful to monitor and assess quantitatively online and real-time the risk of deterioration of periodontal health during HNC radiotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14789450.2020.1858056DOI Listing
October 2020

Metaproteome and metabolome of oral microbial communities.

Periodontol 2000 2021 02 23;85(1):46-81. Epub 2020 Nov 23.

Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

The emergence of high-throughput technologies for the comprehensive measurement of biomolecules, also referred to as "omics" technologies, has helped us gather "big data" and characterize microbial communities. In this article, we focus on metaproteomic and metabolomic approaches that support hypothesis-driven investigations on various oral biologic samples. Proteomics reveals the working units of the oral milieu and metabolomics unveils the reactions taking place; and so these complementary techniques can unravel the functionality and underlying regulatory processes within various oral microbial communities. Current knowledge of the proteomic interplay and metabolic interactions of microorganisms within oral biofilm and salivary microbiome communities is presented and discussed, from both clinical and basic research perspectives. Communities indicative of, or from, health, caries, periodontal diseases, and endodontic lesions are represented. Challenges, future prospects, and examples of best practice are given.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/prd.12351DOI Listing
February 2021

Proteome and Microbiome Mapping of Human Gingival Tissue in Health and Disease.

Front Cell Infect Microbiol 2020 2;10:588155. Epub 2020 Oct 2.

Division of Oral Diseases, Department of Dental Medicine, Karolinska Insitutet, Huddinge, Sweden.

Efforts to map gingival tissue proteomes and microbiomes have been hampered by lack of sufficient tissue extraction methods. The pressure cycling technology (PCT) is an emerging platform for reproducible tissue homogenisation and improved sequence retrieval coverage. Therefore, we employed PCT to characterise the proteome and microbiome profiles in healthy and diseased gingival tissue. Healthy and diseased contralateral gingival tissue samples (total = 10) were collected from five systemically healthy individuals (51.6 ± 4.3 years) with generalised chronic periodontitis. The tissues were then lysed and digested using a Barocycler, proteins were prepared and submitted for mass spectrometric analysis and microbiome DNA for 16S rRNA profiling analysis. Overall, 1,366 human proteins were quantified (false discovery rate 0.22%), of which 69 proteins were differentially expressed (≥2 peptides and < 0.05, 62 up, 7 down) in periodontally diseased sites, compared to healthy sites. These were primarily extracellular or vesicle-associated proteins, with functions in molecular transport. On the microbiome level, 362 species-level operational taxonomic units were identified. Of those, 14 predominant species accounted for >80% of the total relative abundance, whereas 11 proved to be significantly different between healthy and diseased sites. Among them, sp. HMT253 and and were associated with disease sites and strongly interacted ( > 0.7) with 30 and 6 up-regulated proteins, respectively. Healthy-site associated strains sp. HMT478 and sp. HMT417 showed strong negative interactions ( < -0.7) with 31, 21, 9, and 18 up-regulated proteins, respectively. In contrast the down-regulated proteins did not show strong interactions with the regulated bacteria. The present study identified the proteomic and intra-tissue microbiome profile of human gingiva by employing a PCT-assisted workflow. This is the first report demonstrating the feasibility to analyse full proteome profiles of gingival tissues in both healthy and disease sites, while deciphering the tissue site-specific microbiome signatures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2020.588155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566166PMC
June 2021

Microbial Analysis of Saliva to Identify Oral Diseases Using a Point-of-Care Compatible qPCR Assay.

J Clin Med 2020 Sep 11;9(9). Epub 2020 Sep 11.

Austrian Institute of Technology, Molecular Diagnostics, Giefinggasse 4, 1210 Wien, Austria.

Oral health is maintained by a healthy microbiome, which can be monitored by state-of-the art diagnostics. Therefore, this study evaluated the presence and quantity of ten oral disease-associated taxa (, , , , , , , , oral associated ) in saliva and their clinical status association in 214 individuals. Upon clinical examination, study subjects were grouped into healthy, caries and periodontitis and their saliva was collected. A highly specific point-of-care compatible dual color qPCR assay was developed and used to study the above-mentioned bacteria of interest in the collected saliva. Assay performance was compared to a commercially available microbial reference test. Eight out of ten taxa that were investigated during this study were strong discriminators between the periodontitis and healthy groups: , , , , , and oral ( < 0.05). Significant differentiation between the periodontitis and caries group microbiome was only shown for ( < 0.05). A clear distinction between oral health and disease was enabled by the analysis of quantitative qPCR data of target taxa levels in saliva.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9092945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565348PMC
September 2020

Salivary proteotypes of gingivitis tolerance and resilience.

J Clin Periodontol 2020 11 16;47(11):1304-1316. Epub 2020 Sep 16.

Section of Periodontology, Department of Dentistry and Oral Health, Aarhus University, Aarhus, Denmark.

Aim: This study aimed to characterize the salivary proteome during the induction and resolution of gingival inflammation in the course of human experimental gingivitis (EG), and to cluster the proteomic profiles based on the clinically defined "slow" and "fast" response patterns.

Materials And Methods: A total of 50 unstimulated whole saliva were obtained from the EG model which was induced over 21 days (days 0, 7, 14 and 21), followed by a two-week resolution phase (day 35). Label-free quantitative proteomics using liquid chromatography-tandem mass spectrometry was applied. Regulated proteins were subject to Gene Ontology enrichment analysis.

Results: A total of 804 human proteins were quantified by ≥ 2 peptides. Principal component analysis depicted significant differences between "fast" and "slow" responders. Despite gingival and plaque scores being similar at baseline among the two groups, "fast" responders presented with 48 proteins that were at > 4-fold higher levels than "slow" responders. These up-regulated proteins showed enrichment in "antigen presentation" and "proteolysis."

Conclusions: Together, these findings highlight the utility of integrative systems-level quantitative proteomic approaches to unravel the molecular basis of "salivary proteotypes" associated with gingivitis dubbed as "fast" and "slow" responders. Hence, these differential responses may help prognosticate individual susceptibility to gingival inflammation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpe.13358DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692908PMC
November 2020

Salivary Biomarkers of Oral Inflammation Are Associated With Cardiovascular Events and Death Among Kidney Transplant Patients.

Transplant Proc 2020 Dec 4;52(10):3231-3235. Epub 2020 Aug 4.

Department of Oral and Maxillofacial Diseases, Head and Neck Center, Helsinki University Hospital, Helsinki, Finland; Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Huddinge, Sweden.

Background: Triggering receptors expressed on myeloid cells (TREMs) and their ligand, peptidoglycan recognition protein 1 (PGLYRP-1), have been detected in secretions from patients with inflammatory diseases, which may lead to the formation of atherosclerotic plaques. Here, we aimed to analyze the association between salivary concentrations of soluble (s)TREM-1 and PGLYRP-1 with death and cardiovascular disease before and after kidney transplantation.

Materials And Methods: Saliva samples from 53 patients on dialysis were collected during their regular dental evaluation before treatment and after kidney transplantation. Oral inflammatory burden was assessed from panoramic radiographs and full-mouth dental examination. Demographic data, graft function, patient survival, and history of major cardiovascular events (MACEs) were retrieved from hospital records.

Results: Salivary sTREM-1 before transplantation increased the odds for death and MACE. In addition, PGLYRP-1 increased the odds for MACE before transplantation. After transplantation, neither salivary sTREM-1 nor PGLYRP-1 increased the odds for death or MACE, probably because of the previous eradication of oral inflammatory foci. None of the studied biomarkers correlated with kidney transplant function.

Conclusions: Salivary sTREM-1 and PGLYRP-1 before transplantation were associated with MACE and death. The utility of salivary proinflammatory biomarkers for risk stratification in kidney transplant candidates requires further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.transproceed.2020.07.007DOI Listing
December 2020

Novel and known periodontal pathogens residing in gingival crevicular fluid are associated with rheumatoid arthritis.

J Periodontol 2021 03 27;92(3):359-370. Epub 2020 Aug 27.

Department of Dental Medicine, Division of Oral Diseases, Karolinska Institutet, Stockholm, Sweden.

Background: Periodontitis is a suspected environmental risk factor for the development of rheumatoid arthritis (RA). However, correlation mechanisms between the two pathologies remain elusive. This study examined potential correlations between detached subgingival bacteria collected in gingival crevicular fluid (GCF) and RA parameters.

Methods: RA patients (n = 52, F:M = 40:12), patients with Behcet's disease (BD, n = 40, F:M = 29:11) as another systemic inflammatory disease were studied along with a systemically healthy control group (HC, n = 57, F:M = 40:17). All participants were non-smokers. Full mouth periodontal parameters were recorded. RA activity was assessed using the 28-joint Disease Activity Score (DAS-28). Rheumatoid factors (RFs)-IgM and -IgA were measured by ELISA. GCF samples were investigated by means of fluorescent in situ hybridization for 10 different bacterial taxa.

Results: The taxa TM7, Synergistetes cluster B, Leptotrichia, Megasphaera, Anaeroglobus geminatus, and Tannerella forsythia displayed significantly differential abundances between the groups. Whereas abundances of Megasphaera and A. geminatus were significantly increased in the RA group, only Porphyromonas gingivalis displayed significant correlations with plaque scores, bleeding on probing, and RF-IgA. RA patients displaying RF-IgA levels >75 IU/mL exhibited five-fold more abundant P. gingivalis levels than patients below the threshold. This association with RF-IgA levels appeared even more pronounced, by six-fold more P. gingivalis (P = 0.025), in patients with a DAS-28 score >3.2, indicative of moderate/very active RA.

Conclusions: Unattached GCF bacteria may mediate the association between periodontitis and RA, and monitoring the bacterial composition of GCF might inform on RA activity. The role of newly identified bacterial taxa in RA warrants further investigations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/JPER.20-0295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048861PMC
March 2021

Revisiting "-omics" in Oral Health and Disease.

Authors:
Nagihan Bostanci

Proteomics Clin Appl 2020 05;14(3):e1900022

Division of Oral Disease, Department of Dental Medicine, Karolinska Institutet, Huddinge, 14104, Sweden.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201900022DOI Listing
May 2020

Salivary Microbiome Shifts in Response to Periodontal Treatment Outcome.

Proteomics Clin Appl 2020 05 27;14(3):e2000011. Epub 2020 Apr 27.

Division of Oral Diseases, Department of Dental Medicine , Karolinska Institutet, Huddinge, 14104, Sweden.

Purpose: Periodontitis is linked to a localized dysbiotic microbial shift. This trending may often not be evident due to deep taxonomic changes of low abundance organisms and lack of consideration of variations in the treatment response. By using next generation sequencing this study aims to evaluate the salivary microbiome dynamics of periodontal treatment and the implication of treatment outcome EXPERIMENTAL DESIGN: Patients with generalized aggressive periodontitis are treated non-surgically and followed up for 6 months. Saliva is collected for microbiome profiling by next generation sequencing and diversity analysis, as well as quantitative real-time polymerase chain reaction (qPCR). The treatment outcome on the first follow-up is also considered.

Results: Clinical parameters are significantly improved following treatment, but with no accompanying relative abundance changes on the phylum, genus and species levels, or diversity indices. Distinctive differences are observed on species level when the sensitive qPCR is used. Patients responding poorly to treatment display a marginally lower microbiome profile distance from baseline, compared to those responding favorably.

Conclusion And Clinical Relevance: Periodontal treatment does not alter the broader salivary microbiome profile, but may have selective implications on the species level. Treatment outcome can be impactful in the microbiome profile, as reduced microbiome changes may be associated with poorer clinical responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.202000011DOI Listing
May 2020

Salivary biomarkers in the context of gingival inflammation in children with cystic fibrosis.

J Periodontol 2020 10 14;91(10):1339-1347. Epub 2020 Apr 14.

Department of Dental Medicine, Section of Periodontology and Dental Prevention, Division of Oral Diseases, Karolinska Institutet, Stockholm, Sweden.

Background: Cystic fibrosis (CF) is a life-threatening chronic inflammatory disease in children due to respiratory complications. Saliva could serve as a reservoir of bacterial colonization and potentially reflect systemic inflammation. This study investigated whether salivary triggering receptor expressed on myeloid cells 1 (TREM-1), peptidoglycan recognition protein 1 (PGLYRP1), interleukin (IL)-1β, and calprotectin are associated with CF or reflect concomitant gingival inflammation.

Methods: Ten CF (aged 3 to 12 years) and 10 systemically healthy (SH) age- and sex-matched children (C) were enrolled in the study. Individuals with CF underwent routine laboratory determinations. Probing depth, gingival index (GI), plaque index (PI), and bleeding on probing (BOP) were recorded on fully erupted teeth and saliva samples collected. Salivary TREM-1, PGLYRP1, IL-1β, and calprotectin were analyzed by enzyme-linked immunosorbent assay.

Results: Children with CF had significantly higher BOP scores (P = 0.001) and calprotectin levels (P = 0.017) compared with the C group. TREM-1, PGLYRP1, and IL-1β could not distinguish between CF and SH but showed positive correlation with GI, PI, and BOP in both groups. Calprotectin levels positively correlated with procalcitonin (P = 0.014), thrombocyte counts (P = 0.001), mean platelet volume (P = 0.030), and with PGLYRP1 (P = 0.019) and IL-1β (P = 0.013) in CF children. Receiver operating characteristic curve analysis for calprotectin (CFvsC) showed an area under the curve of 0.79 (95% CI 0.58 to 0.99, P = 0.034).

Conclusions: CF children presented with higher gingival inflammation scores and salivary calprotectin levels, that correlated with systemic inflammatory markers. Salivary calprotectin levels were not associated with periodontal parameters. Hence, preliminary data demonstrate that salivary calprotectin might have a chairside diagnostic potential for CF in children.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/JPER.19-0415DOI Listing
October 2020

Dysbiosis of the Oral Ecosystem in Severe Congenital Neutropenia Patients.

Proteomics Clin Appl 2020 05 3;14(3):e1900058. Epub 2020 Mar 3.

Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Huddinge, 14104, Sweden.

Purpose: To decipher the underlying immunological mechanisms in predisposition to oral microbial dysbiosis in severe congenital neutropenia (SCN) patients.

Experimental Design: Ten SCN patients (5-23 years old) and 12 healthy controls (5-22 years old) are periodontally examined and provided saliva, subgingival plaque, and gingival crevicular fluid (GCF) samples. The SCN patients received oral hygiene therapy and are re-evaluated after 6 months. Antimicrobial peptides HPN1-3 and LL-37 are assessed in saliva by ELISA. Concentration of 30 cytokines is measured in saliva and GCF by human 30-plex panel, while bacterial profiles of saliva and subgingival plaque are assessed using 16S rDNA amplicon sequencing.

Results: There is no significant difference in salivary HPN1-3 and LL-37 concentration between the SCN patients and controls. At baseline, clinical, immunological, and microbiological parameters of the patients are indicative of oral ecological dysbiosis. The SCN patients have significantly higher bleeding on probing (BOP)%, GCF volume, and cytokine levels, high bacterial load with low bacterial diversity in saliva. The associations between the microbiome and immunological parameters in the SCN patients differ from those in the healthy individuals.

Conclusions And Clinical Relevance: SCN patients have a dysregulated immune response toward commensal oral microbiota, which could be responsible for the observed clinical and microbiological signs of dysbiosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201900058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317524PMC
May 2020

The relationship between oral diseases and infectious complications in patients under dialysis.

Oral Dis 2020 Jul 19;26(5):1045-1052. Epub 2020 Feb 19.

Department of Oral and Maxillofacial Diseases, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.

Objectives: Association was investigated between oral health before dialysis and the incidence of systemic infections during dialysis. We hypothesized that low-grade systemic inflammation caused by poor oral health associates with infectious episodes in patients on dialysis, despite earlier eradication of oral infection foci.

Subjects And Methods: A total of 117 patients (46 with peritoneal and 71 with hemodialysis) were examined and treated at predialysis stage and followed up during dialysis. Number of infection episodes and microorganisms cultured from blood and peritoneal fluid were analyzed. Number of teeth, periodontal inflammatory burden, and total dental index scores were assessed, and salivary matrix metalloproteinase 8, triggering receptor on myeloid cells 1, peptidoglycan recognition protein 1 (PGLYRP1), and interleukin-1β were measured.

Results: In hemodialysis, 134 infection episodes were recorded, while peritoneal dialysis group had 77 peritonitis episodes. Culture-negative samples were 69% in hemodialysis and 23% in peritoneal dialysis group. Staphylococci were the most frequently associated microorganisms. Infections during dialysis did neither associate with oral health parameters nor associate with salivary inflammatory biomarkers, except for PGLYRP1, which associated with number of infection episodes during hemodialysis (p = .046).

Conclusions: A number of infection episodes during hemodialysis were associated with salivary PGLYRP1 but not the other salivary markers or oral infection markers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/odi.13296DOI Listing
July 2020

Salivary Fingerprinting of Periodontal Disease by Infrared-ATR Spectroscopy.

Proteomics Clin Appl 2020 05 1;14(3):e1900092. Epub 2020 Mar 1.

Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Huddinge, 14152, Stockholm, Sweden.

Purpose: Periodontal diseases, the most common chronic inflammatory diseases in humans, do not only affect tooth-supporting tissues but also other body parts by contributing to the development of life-threatening conditions. Since currently available diagnostic methods in periodontics lack the ability to identify patients at high risk for periodontal disease progression, development of innovative, non-invasive, rapid detection methods for diagnosing periodontal diseases is needed. This study aims to assess the potential of infrared attenuated total reflection (IR-ATR) spectroscopy to detect differences in composition of saliva supernatant in non-periodontitis individuals (control) and patients with generalized aggressive periodontitis (G-AgP).

Experimental Design: IR-ATR is performed with a wavelength interval from 1230 to 1180 cm , analyzed with a simple subtraction in absorbance data.

Results: Ten samples show in the analysis of variance of the two data sets a true difference (99.8%). A principal component analysis (PCA) is able to discriminate between G-AgP and control groups.

Conclusion And Clinical Relevance: This study demonstrates for the first time that IR-ATR spectroscopy is a promising tool for the analysis of saliva supernatant for the diagnosis of periodontitis, and potentially other periodontal conditions. IR-ATR spectroscopy holds the potential to be miniaturized and utilized as a non-invasive screening test.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201900092DOI Listing
May 2020

Pressure Cycling Technology Assisted Mass Spectrometric Quantification of Gingival Tissue Reveals Proteome Dynamics during the Initiation and Progression of Inflammatory Periodontal Disease.

Proteomics 2020 02 15;20(3-4):e1900253. Epub 2020 Jan 15.

Section of Peridontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Kartolinska Insitutet, Alfred Nobels alle 8, 14104, Huddinge, Sweden.

Understanding the progression of periodontal tissue destruction is at the forefront of periodontal research. The authors aimed to capture the dynamics of gingival tissue proteome during the initiation and progression of experimental (ligature-induced) periodontitis in mice. Pressure cycling technology (PCT), a recently developed platform that uses ultra-high pressure to disrupt tissues, is utilized to achieve efficient and reproducible protein extraction from ultra-small amounts of gingival tissues in combination with liquid chromatography-tandem mass spectrometry (MS). The MS data are processed using Progenesis QI and the regulated proteins are subjected to METACORE, STRING, and WebGestalt for functional enrichment analysis. A total of 1614 proteins with ≥2 peptides are quantified with an estimated protein false discovery rate of 0.06%. Unsupervised clustering analysis shows that the gingival tissue protein abundance is mainly dependent on the periodontitis progression stage. Gene ontology enrichment analysis reveals an overrepresentation in innate immune regulation (e.g., neutrophil-mediated immunity and antimicrobial peptides), signal transduction (e.g., integrin signaling), and homeostasis processes (e.g., platelet activation and aggregation). In conclusion, a PCT-assisted label-free quantitative proteomics workflow that allowed cataloging the deepest gingival tissue proteome on a rapid timescale and provided novel mechanistic insights into host perturbation during periodontitis progression is applied.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pmic.201900253DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033018PMC
February 2020

Effect of Chewing on the Expression of Salivary Protein Composition: A Systematic Review.

Proteomics Clin Appl 2020 05 17;14(3):e1900039. Epub 2020 Jan 17.

Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Huddinge, 14104, Sweden.

Salivary proteins have an imperative role in the maintenance of oral health and repairing mechanisms of injured tissues. However, there is paucity of information reported in the literature about the influence of chewing activities on the secretion or expression of salivary proteins. The purpose of this systematic review is to evaluate the effect of chewing on the expression of salivary proteins composition in healthy individuals. A thorough systematic search shows 14 eligible studies for the review. The results of the systematic review show the effect of chewing on total protein concentration, alpha-amylase (α-amylase), peroxidase, lysozyme, immunoglobulin A (IgA), and mucin. Six papers concluded that chewing has a little or no effect on total protein concentration, α-amylase, peroxidase, lysozyme, and IgA activities. Five papers reported a negative (decreasing) effect of chewing on the function of total protein, α-amylase, IgA, and mucin. Only two papers showed an increase in total protein and IgA function upon chewing stimulation. The results of this systematic review indicate that more standardized evidence-based research is required for better assessment of chewing effects on salivary proteins. Within the limitations of this review, the existing evidence suggests that chewing in healthy people has minimum effect on the expression and activities of salivary proteins.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201900039DOI Listing
May 2020

Label-Free Quantitative Proteomics versus Antibody-Based Assays to Measure Neutrophil-Derived Enzymes in Saliva.

Proteomics Clin Appl 2020 05 7;14(3):e1900050. Epub 2020 Jan 7.

Section of Periodontology and Dental Prevention, Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Alfred Nobels allé 8, 14152, Huddinge, Stockholm, Sweden.

Purpose: This study aims to validate label-free quantitative proteomics (LFQ) against antibody-based methods for quantifying established periodontal disease biomarkers in saliva.

Experimental Design: In an experimental gingivitis model, healthy volunteers (n = 10) provide saliva at baseline (d0), during the induction (d7, d14, d21) and resolution (d35) of gingival inflammation (total n = 50). Biomarker levels are analyzed by LFQ and time-resolved immunofluorometric assay (IFMA) or enzyme-linked immunosorbent assay (ELISA). Molecular matrix metalloproteinase (MMP)-8 forms are assessed by Western blot (WB) analysis.

Results: LFQ detects significantly (p < 0.05) elevated MMP-8 (d21vsd7, d35vsd7) and tissue inhibitor of matrix metalloproteinases (TIMP)-1 (d35vsd7). Latent MMP-8 (70-80 kDa) is present (d0-d35), but not active MMP-8 (50-60 kDa). LFQ and immunoassay data significantly correlate for MMP-8 (r = 0.36), myeloperoxidase (r = 0.39), polymorphonuclear leukocyte elastase (r = 0.33), and TIMP-1 (r = -0.24).

Conclusion And Clinical Relevance: LFQ can quantify enzyme levels in saliva, however lacks the ability to measure enzymatic activity. WB analysis reveals that MMP-8 may not be activated during induction of gingival inflammation. Significant but weak correlations between IFMA or ELISA and LFQ suggest a limited capacity of available antibodies to reliably quantify salivary biomarkers for periodontal diseases. Novel "anti-peptide" antibodies designed by newer targeted mass spectrometry-based approaches can help to overcome these drawbacks.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/prca.201900050DOI Listing
May 2020

The adjunctive use of host modulators in non-surgical periodontal therapy. A systematic review of randomized, placebo-controlled clinical studies.

J Clin Periodontol 2020 07;47 Suppl 22:199-238

Division of Oral Diseases, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.

Background: Considering the role of the inflammatory host response in the pathogenesis of periodontitis, different host modulators have been proposed to enhance the outcomes of non-surgical periodontal therapy (NSPT), but their efficacy has not been fully clarified.

Objectives: This systematic review investigated the efficacy of host modulators combined with NSPT in reducing probing pocket depth (PPD) in periodontitis patients.

Materials And Methods: Placebo-controlled RCTs with ≥6 months follow-up were searched. Meta-analysis was conducted when ≥5 studies using the same host modulator were identified.

Results: Fifty eight studies met the inclusion criteria. After 6 months, local administration of 1.2% statin gels as adjuncts to NSPT significantly improved PPD reduction (1.83 mm) in infrabony defects and systemic administration of sub-antimicrobial dose doxycycline (SDD) in addition to NSPT improved PPD reduction of deep pockets. Administration of probiotics conferred limited clinical benefits. Local bisphosphonate and metformin gels showed potential for clinical use in infrabony defects, which needs to be confirmed.

Conclusions: Local delivery of statins in infrabony defects and systemic SDD for deep pockets may confer additional clinical benefits to NSPT. Their long-term effectiveness and safety need to be confirmed in independent multi-centred studies. Further studies are needed to confirm the benefit of other host modulators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcpe.13232DOI Listing
July 2020
-->