Effect of erbium, chromium-doped: yttrium, scandium, gallium, and garnet laser-assisted periodontal therapy using radial firing tip during early healing period: a randomized controlled split-mouth clinical trial.

BACKGROUND: This study aimed to demonstrate the efficacy of erbium, chromium-doped:yttrium, scandium, gallium, and garnet (Er,Cr:YSGG) laser-assisted nonsurgical periodontal therapy in periodontitis patients during 8 weeks of healing. METHODS: A split-mouth, single-blinded, randomized controlled clinical trial was conducted on 12 patients diagnosed with stage III/IV periodontitis and had a minimum of two teeth with probing pocket depth (PPD) > 5 mm in at least two quadrants. Upon randomization, each quadrant was assigned for conventional scaling and root planing (SRP) procedure or laser-assisted therapy (SRP + laser) using radial firing tip (RFPT 5, Biolase). Clinical measurements and gingival crevicular fluid collection were performed for statistical analysis. RESULTS: In the initial statistical analysis on the whole subject teeth, modified gingival index (MGI) reduction was greater in test group at 1(P = 0.0153), 4 (P = 0.0318), and 8 weeks (P = 0.0047) compared to the control in the same period. PPD reduction at 4 weeks in test group was -1.67 ± 0.59 showing significant difference compared to the control (-1.37 ± 0.63, P = 0.0253). When teeth with mean PPD ≥5 mm were sorted, MGI decrease was significantly greater in test group at 1 (P=0.003) and 8 week (P=0.0102) follow-ups. PPD reduction was also significantly greater in test group at 4 week period (-1.98 ± 0.55 vs -1.58 ± 0.56, test vs control, P=0.0224). CONCLUSIONS: Er,Cr:YSGG-assisted periodontal therapy is beneficial in MGI and PPD reductions during early healing period.

"Outcome of non-surgical periodontal treatment on Gal-1 and Gal-3 GCF levels in periodontitis patients: a case-control study".

OBJECTIVES: This study aimed to explore the effect of nonsurgical periodontal treatment on Galectin-1 and -3 GCF levels in gingivitis and periodontitis stage III compared to periodontally healthy individuals, to determine whether they could serve as diagnostic markers / therapeutic targets for periodontitis and revealing their possible role in periodontal disease. MATERIALS AND METHODS: Forty-five systemically healthy participants were included and equally subdivided into three groups: gingivitis, periodontitis (stage III), and a periodontally healthy control group. The clinical parameters were recorded. Galectin-1 and -3 GCF levels were evaluated (before and after non-surgical treatment for periodontitis) using an enzyme linked immune-sorbent assay (ELISA) kit. Receiver operating characteristic (ROC) curve was performed to reveal sensitivity, specificity, predictive value, and diagnostic accuracy of both markers. RESULTS: The study showed statistical significance between different groups regarding Galectin-3 with higher values in periodontitis and the lowest values in healthy control. Also, Galectin-1 was significantly higher in the periodontitis/gingivitis groups than in the control group. Moreover, non-surgical periodontal treatment in periodontitis patients caused a statistical reduction in clinical parameters and biomarkers. ROC analysis revealed excellent diagnostic ability of both biomarkers in discriminating periodontitis/gingivitis against healthy individuals (100% diagnostic accuracy for Galectin-1 and 93% for Galectin-3, AUC > 0.9) and acceptable diagnostic ability between periodontitis participants against gingivitis (73% diagnostic accuracy for Gal-1 and 80% for Gal-3, AUC > 0.7). CONCLUSIONS: Both Galectin-1 and Galectin-3 seem to have outstanding diagnostic accuracy for the identification of periodontal disease, an acceptable ability to measure periodontal disease activity and the severity of inflammatory status. Additionally, they could serve as therapeutic targets to monitor treatment efficiency. CLINICALTRIAL: GOV REGISTRATION NUMBER: (NCT06038812).

Expression of visfatin in gingival crevicular fluid and gingival tissues in different periodontal conditions: a cross-sectional study.

BACKGROUND: Studies have shown that visfatin is an inflammatory factor closely related to periodontitis. We examined the levels of visfatin in gingival crevicular fluid (GCF) and gingival tissues under different periodontal conditions, in order to provide more theoretical basis for exploring the role of visfatin in the pathogenesis of periodontitis. METHODS: We enrolled 87 subjects, with 43 in the chronic periodontitis (CP) group, 21 in the chronic gingivitis (CG) group, and 23 in the periodontal health (PH) group. Periodontal indexes (PD, AL, PLI, and BI) were recorded. GCF samples were collected for visfatin quantification, and gingival tissues were assessed via immunohistochemical staining. RESULTS: Visfatin levels in GCF decreased sequentially from CP to CG and PH groups, with statistically significant differences (P < 0.05). The CP group exhibited the highest visfatin levels, while the PH group had the lowest. Gingival tissues showed a similar trend, with significant differences between groups (P < 0.001). Periodontal indexes were positively correlated with visfatin levels in both GCF and gingival tissues (P < 0.001). A strong positive correlation was observed between visfatin levels in GCF and gingival tissues (rs = 0.772, P < 0.001). CONCLUSION: Greater periodontal destruction corresponded to higher visfatin levels in GCF and gingival tissues, indicating their potential collaboration in damaging periodontal tissues. Visfatin emerges as a promising biomarker for periodontitis and may play a role in its pathogenesis.

The reliability of using gingival crevicular blood to measure blood glucose and hba1c levels in the dental setting: a systematic review and meta-analysis.

OBJECTIVE: There are 500 million patients living with diabetes mellitus worldwide and 50% of them remain undiagnosed. Routine periodontal probing provides gingival crevicular blood in patients with gingivitis. Gingival blood may be useful for diabetes screening without the need for any expensive, painful or time-consuming method by using convenient glucometers. Therefore, the objective of this systematic review and meta-analysis is to answer the question to "is there a difference in glucose or HbA1c levels (O) in patients with positive gingival bleeding (P) measured on gingival crevicular blood (GCB) (I) compared to finger prick capillary blood (CB) (C). MATERIALS AND METHODS: The authors performed an electronic search of six databases using identical MeSH phrases. Only human clinical studies without limitations on the year of publication were considered. Data extraction was done by using standardized data collection sheets. Risk of bias assessment were conducted using QUADAS-2 and QUADAS-C. Meta-analyses were carried out with the random effects model to aggregate the correlation coefficients and the difference between the means between gingival and capillary blood reading, using 95% confidence intervals. RESULTS: The database and manual search yielded 268 articles, from which the selection procedure provided 36 articles for full-text screening, and the final pool of eligible articles composed of 23 studies with 1680 patients. Meta-analysis results on glycemic levels showed differences between the GCB and CB procedures in patients with and without diabetes with values of -6.80 [-17.35; 3.76] and - 4.36 [-9.89; 1.18], respectively. Statistically significant correlations were found (p = 0.001) between GCB and CB measurements in patients with (0.97 [0.927; 0.987]) and without diabetes (0.927 [0.873; 0.958]). CONCLUSION: Gingival blood could prove to be useful to identify patients with undiagnosed diabetes when the necessary amount of uncontaminated blood is present. However, this technique is limited by the possibility of contamination, prandial status and inaccuracies, so it is unsuited to address the patient's glycemic control accurately.

Serum biomarker levels in smokers and non-smokers following periodontal therapy. A prospective cohort study.

BACKGROUND: To compare presence and levels of serum cytokines in smokers and non-smokers with periodontitis following periodontal therapy. METHODS: Thirty heavy smokers and 30 non-smokers with stage III or IV periodontitis were included in this prospective cohort study. Clinical data and blood serum were collected at baseline (T0), after step I-III (T1), and after 12 months step IV periodontal therapy (T2). Cytokine IL-1ß, IL-6, IL-8, TNF-α, IL-10, and IP-10 levels were measured using multiplex kit Bio-Plex Human Pro™ Assay. Linear regression models with cluster robust variance estimates to adjust for repeated observations were used to test intra- and intergroup levels for each marker, IL-6 and IL-8 defined as primary outcomes. RESULTS: Clinical outcomes improved in both groups following therapy (p < 0.05). IL-6 levels increased with 75.0% from T0-T2 among smokers (p = 0.004). No significant intra- or intergroup differences were observed for IL-8. Higher levels of TNF-α (44.1%) and IL-10 (50.6%) were detected in smokers compared with non-smokers at T1 (p = 0.007 and p = 0.037, respectively). From T1-T2, differences in mean change over time for levels of TNF-α and IL-10 were observed in smokers compared with non-smokers (p = 0.005 and p = 0.008, respectively). CONCLUSION: Upregulated levels of serum cytokines in smokers indicate a systemic effect of smoking following periodontal therapy. Differences in cytokine levels between smokers and non-smokers demonstrate a smoking induced modulation of specific systemic immunological responses in patients with severe periodontitis.

[Relationship between short-chain fatty acids in the gingival crevicular fluid and periodontitis of stage â ¢ or â £].

OBJECTIVE: To analyze the concentration of formic acid, propionic acid and butyric acid in gingival crevicular fluid (GCF) of patients with stages Ⅲ and Ⅳ periodontitis, and their relationship with periodontitis. METHODS: The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology, Peking University School and Hospital of Stomatology from February 2008 to May 2011. Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant. Periodontal clinical parameters, including plaque index(PLI), probing depth(PD), bleeding index(BI), and attachment loss(AL). Concentrations of formic acid, propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capillary electrophoresis (HPCE). The prediction ability of formic acid, propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed. RESULTS: In this study, 32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled, including 9 patients with grade B and 28 patients with grade C. Clinical periodontal variables in the patients with periodontitis were significantly higher than those in the control group (P<0.001). Formic acid was significantly lower in periodontitis than that in the control group [5.37 (3.39, 8.49) mmol/L vs. 12.29 (8.35, 16.57) mmol/L, P<0.001]. Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group: Propionic acid, 10.23 (4.28, 14.90) mmol/L vs. 2.71 (0.00, 4.25) mmol/L, P < 0.001; butyric acid, 2.63 (0.47, 3.81) mmol/L vs. 0.00 (0.00, 0.24) mmol/L, P<0.001. There was no significant difference in formic acid, propionic acid and butyric acid concentrations between grade B and grade C periodontitis (P>0.05). Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket, while the concentration of formic acid decreased with the increase of PD. Propionic acid (OR=1.51, 95%CI: 1.29-1.75) and butyric acid (OR=3.72, 95%CI: 1.93-7.17) were risk factors for periodontitis, while formic acid (OR=0.87, 95%CI: 0.81-0.93) might be a protective factor for periodontitis. Propionic acid (AUC=0.852, 95%CI: 0.805－0.900), butyric acid (AUC=0.889, 95%CI: 0.841－0.937), f (formic acid, AUC=0.844, 95%CI: 0.793－0.895) demonstrated a good predictive capacity for the risk of periodontitis. CONCLUSION: The concentration of formic acid decrease in the GCF of periodontitis patients, which is a protective factor for periodontitis, its reciprocal have good predictive capacity. However, propionic acid and butyric acid increase, which are risk factors for periodontitis and have good predictive capacity. The concentration of formic acid, propionic acid, and butyric acid vary with probing depth, but there is no significant difference between grade B and grade C periodontitis.

A newly developed kit for dental apical root resorption detection: efficacy and acceptability.

OBJECTIVES: To determine the efficacy of a newly developed kit in dentine sialophosphoprotein (DSPP) detection and compare it with enzyme-linked immunosorbent assay (ELISA). User acceptance was also determined. MATERIALS AND METHODS: This cross-sectional study consisted of 45 subjects who were divided into 3 groups based on the severity of root resorption using radiographs: normal (RO), mild (RM), and severe (RS). DSPP in GCF samples was analyzed using both methods. Questionnaires were distributed to 30 orthodontists to evaluate future user acceptance. RESULTS: The sensitivity and specificity of the kit were 0.98 and 0.8 respectively. The DSPP concentrations measured using ELISA were the highest in the RS group (6.33 ± 0.85 ng/mL) followed by RM group (3.77 ± 0.36 ng/mL) and the RO group had the lowest concentration (2.23 ± 0.55 ng/mL). The new kit portrayed similar results as the ELISA, the optical density (OD) values were the highest in the RS group (0.62 ± 0.10) followed by RM group (0.33 ± 0.03) and the RO group (0.19 ± 0.06). The differences among all the groups were statistically significant (p < 0.05) for both methods. The Pearson correlation coefficient showed a statistically significant (p < 0.001) strong and positive correlation between DSPP concentrations and OD values. CONCLUSIONS: The new kit was validated to detect the colour intensities of different severity of root resorptions. Most of the responses to the survey were positive towards the new kit for being a safer and simpler method to detect apical root resorption.

Investigating the diagnostic potential of IL-1ß, IL-10, and IL-36γ in gingival crevicular fluid in patients with different periodontal conditions.

BACKGROUND: The study aimed to analyze cytokine levels, including interleukin (IL)-1ß, IL-10, and IL-36γ, to investigate the link between pro- and anti-inflammatory responses in periodontal conditions and assess their potential as diagnostic biomarkers for distinguishing between different types of periodontal conditions. METHODS: 80 systemically healthy non-smokers (25 periodontally healthy, 25 with gingivitis, 30 with periodontitis) were included. Clinical periodontal parameters were recorded, and gingival crevicular fluid (GCF) samples were obtained. Receiver operating characteristic (ROC) curve analysis was applied to determine the diagnostic value of cytokines. RESULTS: IL-36γ had the highest sensitivity for diagnosing periodontitis, although its specificity for identifying those without periodontitis was relatively low. The combination of IL-1ß and IL-36γ was the most effective in differentiating periodontitis from periodontal health. IL-10 was found to be an acceptable discriminator for distinguishing gingivitis from healthy conditions. However, its sensitivity and specificity for identifying gingivitis were lower. The combination of the three cytokines showed the highest ability to distinguish between periodontitis and gingivitis. CONCLUSION: The levels of IL-1ß, IL-10, and IL-36γ in GCF may provide insights into periodontal health and disease status. Further studies are needed to validate these results and explore the potential of these cytokines in periodontal disease management.

All three of these cytokines exhibit exceptional diagnostic accuracy, particularly in distinguishing between chronic periodontitis and periodontal health.Moreover, the combination of IL-1ß and IL-36γ stands out as the most accurate diagnostic indicator for periodontitis. This combination could serve as a robust biomarker panel for the early detection and monitoring of periodontal disease, potentially allowing for timely interventions to prevent disease progression.

A simplified protocol for deep quantitative proteomic analysis of gingival crevicular fluid for skeletal maturity indicators.

Assessment of craniofacial skeletal maturity is of great importance in orthodontic diagnosis and treatment planning. Traditional radiographic methods suffer from clinician subjectivity and low reproducibility. Recent biochemical methods, such as the use of gingival crevicular fluid (GCF) protein biomarkers involved in bone metabolism, have provided new opportunities to assess skeletal maturity. However, mass spectrometry (MS)-based GCF proteomic analysis still faces significant challenges, including the interference of high abundance proteins, laborious sample prefractionation and relatively limited coverage of GCF proteome. To improve GCF sample processing and further discover novel biomarkers, we herein developed a single-pot, solid-phase-enhanced sample-preparation (SP3)-based high-field asymmetric waveform ion mobility spectrometry (FAIMS)-MS protocol for deep quantitative analysis of the GCF proteome for skeletal maturity indicators. SP3 combined with FAIMS could minimize sample loss and eliminate tedious and time-consuming offline fractionation, thereby simplifying GCF sample preparation and improving analytical coverage and reproducibility of the GCF proteome. A total of 5407 proteins were identified in GCF samples from prepubertal and circumpubertal groups, representing the largest dataset of human GCF proteome to date. Compared to the prepubertal group, 61 proteins were differentially expressed (31 up-regulated, 30 down-regulated) in the circumpubertal group. The six-protein marker panel, including ATP5D, CLTA, CLTB, DNM2, HSPA8 and NCK1, showed great potential to predict the circumpubertal stage (ROC-AUC 0.937), which provided new insights into skeletal maturity assessment.

Granzyme B promotes matrix metalloproteinase-1 (MMP-1) release from gingival fibroblasts in a PAR1- and Erk1/2-dependent manner: A novel role in periodontal inflammation.

OBJECTIVE: To gain insights into how proteases signal to connective tissues cells in the periodontium. BACKGROUND: The connective tissue degradation observed in periodontitis is largely due to matrix metalloproteinase (MMP) release by gingival fibroblasts. Granzyme B (GzmB) is a serine protease whose role in periodontitis is undefined. METHODS: Human gingival crevicular fluid (GCF) samples were obtained from sites with periodontal disease and healthy control sites. GzmB was quantified in the GCF ([GzmB]GCF ) by ELISA. Gingival fibroblasts (GF) were cultured in the presence or absence of recombinant GzmB. Culture supernatants were analyzed by ELISA to quantify GzmB-induced release of interstitial collagenase (MMP-1). In some experiments, cells were pre-treated with the inhibitor PD98059 to block MEK/ERK signaling. The protease-activated receptor-1 (PAR-1) was blocked with ATAP-2 neutralizing antibody prior to GzmB stimulation. Systemic MMP-1 levels were measured in plasma from wild-type (WT) and granzyme-B-knockout (GzmB-/- ) mice. RESULTS: The [GzmB]GCF in human samples was ~4-5 fold higher at sites of periodontal disease (gingivitis/periodontitis) compared to healthy control sites, suggesting an association between GzmB and localized matrix degradation. GzmB induced a ~4-5-fold increase in MMP-1 secretion by cultured fibroblasts. GzmB induced phosphorylation of Erk1/2, which was abrogated by PD98059. GzmB-induced upregulation of MMP-1 secretion was also reduced by PD98059. Blockade of PAR-1 function by ATAP-2 abrogated the increase in MMP-1 secretion by GF. Circulating MMP-1 was similar in WT and GzmB-/- mice, suggesting that GzmB's effects on MMP-1 release are not reflected systemically. CONCLUSION: These data point to a novel GzmB-driven signaling pathway in fibroblasts in which MMP-1 secretion is upregulated in a PAR1- and Erk1/2-dependent manner.

Association of active oxygen-releasing gel and photodynamic therapy in the treatment of residual periodontal pockets in type 2 diabetic patients: A randomized controlled clinical study.

BACKGROUND: The aim of this study was to evaluate the effect of active oxygen-releasing gel as an adjuvant, with and without antimicrobial photodynamic therapy (aPDT), in the treatment of residual pockets in periodontal patients with type 2 diabetes mellitus (DM2). METHODS: Patients with residual pockets with probing depth (PD) ≥4 mm and bleeding on probing (BOP) were divided into the following groups: SI (n = 17)-subgingival instrumentation in a single session; BM (n = 17)-SI followed by local application of active oxygen-releasing gel inside the periodontal pocket for 3 min; BM + aPDT (n = 17)-SI followed by application of BM for 3 min and pocket irrigation with methylene blue, and 660-nm diode laser irradiation at 100 mW for 50 s. The periodontal clinical parameters, serum levels of glycated hemoglobin, and immunological analysis of crevicular fluid were evaluated. All data were submitted to statistical analysis (α = 5%). RESULTS: A significant reduction in BOP was verified at 90 and 180 days in the BM + aPDT group. The percentage of sites with PD ≥ 4 mm was significantly reduced at 90 days in BM + aPDT and BM, whereas after 180 days only BM showed a significant reduction. In the BM + aPDT group, there was a significant reduction in tumor necrosis factor α levels at 90 days. There were no differences between the treatments. CONCLUSION: The use of adjuvant active oxygen-releasing gel, with or without aPDT, resulted in the same clinical benefits as SI in the treatment of residual pockets in poorly controlled DM2 patients.

Peri-implantitis Diagnosis and Prognosis Using Biomarkers: A Systematic Literature Review.

PURPOSE: To summarize the latest scientific literature regarding the concentrations of biomarkers in saliva and peri-implant crevicular fluid (PICF) of healthy implant (HI) patients and patients with peri-implant mucositis (PIM) and peri-implantitis (PI). MATERIALS AND METHODS: The literature review was performed according to PRISMA guidelines. The databases used were PubMed MEDLINE, ScienceDirect, and Cochrane Library. A combination of keywords was used, and selection criteria were applied. Selected articles were published between February 1, 2017, and February 1, 2022, written in English, conducted in humans, and examined the levels of saliva and PICF biomarkers in PI patients and compared them to HI/PIM patients. RESULTS: A total of 16 publications were selected, involving a total of 1,117 patients with 1,346 implants. Qualitative analysis revealed 49 different biomarkers, the levels of which were compared between groups. After evaluating the most frequently studied biomarkers, significantly higher values of IL-1ß, RANKL, sRANKL, IL-6, TNF-α, TNFSF12, MMP2, and MMP8 levels were observed in the PI group than in the HI group. CONCLUSIONS: Of all 49 biomarkers evaluated, IL-1ß and RANKL have potentially the highest diagnostic significance in the assessment of peri-implant inflammatory conditions, as differences were observed between all three groups (HI < PIM < PI), but data from current publications were not fully sufficient to provide strong evidence.

Soluble Receptor Activator of Nuclear Factor Ligand and Osteoprotegerin Levels in Gingival Crevicular Fluid among Cigarette Smokers and Non-smokers with and without Periodontitis.

AIM: This study aimed to measure and compare the levels of soluble receptor activator of nuclear factor ligand (RANKL) and osteoprotegerin (OPG) in the gingival crevicular fluid (GCF), as well as their ratio, in smokers and nonsmokers with periodontitis. MATERIALS AND METHODS: Gingival crevicular fluid samples were collected using PerioPaper strips, from 150 individuals, who were categorized into three groups: current smokers with periodontitis stage III grades C and B (n = 50), nonsmokers with periodontitis stages I and II grade A (n = 50), and control healthy individuals (n = 50). The concentrations (pg/mL) of sRANKL and OPG in the GCF were measured by enzyme-linked immunesorbent assays (ELISA). RESULT: The smokers' group exhibited the highest sRANKL (pg/mL) concentration as a subsequent lead to a higher sRANKL/OPG ratio. The healthy control group exhibited higher OPG and lower sRANKL concentration, subsequently, the sRANKL/OPG ratio was reduced compared with the other study groups. However, there was no statistical significance of sRANKL and its relative ratio between periodontitis stage III grades C and B, periodontitis stages I and II grade A, and healthy control individuals. There was a statistically significant positive moderate correlation between smoking duration (years) and the sRANKL (pg/mL) concentration and a statistically significant negative moderate correlation between OPG (pg/mL) concentration and cigarettes smoked per day. CONCLUSION: As a result, compared to the other research groups, smokers with periodontitis stage III grades C and B had greater GCF concentrations of sRANKL, lower OPG, and a higher sRANKL/OPG ratio. The difference in OPG (pg/mL) level was statistically significant. However, there was no statistically significant difference in sRANKL (pg/mL) or its relative ratio, sRANKL/OPG, across the groups. CLINICAL SIGNIFICANCE: A characteristic that sets periodontitis apart is alveolar bone loss. Resorption is induced by RANKL and inhibited by OPG, resulting in a relative ratio. In light of this, the levels of RANKL and OPG may be helpful indicators for monitoring the activity of periodontal disease in both smokers and nonsmokers with and without periodontitis.

Obesity Is Associated with a Weakened Gingival Inflammatory Cytokine Response.

Background and Objectives: An obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and to examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis-resistant obese individuals. Materials and Methods: Thirty-nine participants in good periodontal health were recruited. Twenty patients were classified as lean and nineteen as obese based on their BMI levels. A thorough periodontal assessment was carried out. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were analyzed for interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A), and CRP. Results: GCF CRP levels were significantly higher in the obese than in the lean individuals. No statistically significant differences were noted between the two groups in either GCF or blood in terms of any of the inflammatory cytokine levels. IL-17A was not detected in the GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, and the association tended to be stronger in the obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels were positively associated with multiple GCF inflammatory cytokines (e.g., IL-1ß, IL-6, IL-8, and TNF-α) in all subjects, the associations tended to be weaker in the obese individuals (e.g., IL-1ß, IL-6, and TNF-α). Furthermore, the levels of the GCF inflammatory cytokines IL-6 and TNF-α were decreased in the obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a weakened inflammatory cytokine response in the gingival tissues of obese individuals.

Periodontal disease and visfatin level: A systematic review and meta-analysis.

Visfatin is considered an inflammatory biomarker in periodontal disease (PD). In this meta-analysis, we aimed to evaluate the relationship between Visfatin biomarker level with PD. In this study, Medline, Scopus, Web of Science, and Google Scholar were searched. We included studies that examined visfatin levels in samples from healthy people and periodontal disease until March 2023. The quality of the selected articles was evaluated using the Newcastle-Ottawa assessment scale. Depending on heterogeneity of studies, random-effects or fixed-effect models were used to pool results and report the standardized mean difference (SMD). After screening the retrieved papers, the related data were extracted. A total of 159 studies were identified, and 16 studies were included in the meta-analysis. In 9 studies, the SMD of visfatin level of gingival crevicular fluid (GCF) in patients with chronic periodontitis (CP) and healthy individuals was 4.32 (p<0.001). In 6 studies, the SMD of salivary visfatin level in patients with CP and healthy individuals was 2.95 (p = 0.004). In addition, in five studies, the SMD of serum visfatin level in patients with CP and healthy individuals was 7.87 (p<0.001). Therefore, Visfatin levels in serum, saliva, and GCF of patients with CP were increased in comparison to healthy individuals. Comparison of visfatin levels in saliva of gingivitis patients and healthy individuals showed a significant increase of visfatin in gingivitis patients (SMD:0.57, P = 0.018), but no significant difference was observed in the mean GCF visfatin level of gingivitis patients and healthy individuals (SMD:2.60, P = 0.090). In addition, the results suggested that there is no difference between gingivitis cases compared to CP patients (SMD:3.59, P = 0.217). Visfatin levels in GCF, serum, and saliva have the potential to be used as a diagnostic biomarker of periodontitis.

Periodontitis is associated with the increased levels of visfatin: a meta-analysis.

OBJECTIVE: Periodontitis is a common inflammatory disease associated with systemic factors. Visfatin is a pleiotropic adipokine that exerts metabolic and immune functions. Studies have shown visfatin played roles in the development of periodontitis. The present study aims to compare the levels of visfatin in body fluids including serum, saliva, and gingival crevicular fluid (GCF) between periodontitis patients and healthy individuals, and to elucidate the alteration of visfatin levels after periodontal treatments. MATERIALS AND METHODS: The database searched included Pubmed, Embase, Web of Science, and Cochrane Library. According to the Eligibility criteria, the records were screened and the eligible studies were included. The methodological qualities of the included case-controlled studies were assessed according to the Newcastle-Ottawa scale (NOS). The Methodological Index for Nonrandomized Studies (MINORS) was applied for assessing the qualities of the included clinical trials. The statistical analyses were processed using STATA 15.0. RESULTS: Twenty-three studies were included in the statistical analyses. The meta-analysis showed significantly elevated visfatin levels of GCF, serum, and saliva in the periodontitis population compared with the controls (GCF: SMD = 5.201, 95% CI: 3.886-6.516, Z = 7.75, P < 0.05; Serum: SMD = 7.417, 95% CI: 3.068-11.767, Z = 3.34, P = P < 0.05; Saliva: SMD = 2.683, 95% CI: 1.202-4.163, Z = 3.34, P < 0.05). Visfatin levels of saliva serum and GCF were significantly decreased after periodontal treatment. (Saliva: SMD = -1.338, 95% CI: -2.289-0.487, Z = 39.77, P < 0.05; Serum: SMD = -2.890, 95% CI: -5.300-0.480, Z = 2.35, P < 0.05; GCF: SMD = -6.075, 95% CI: -11.032-1.117, Z = 2.40, P = 0.016; I 2 = 95.9%, P < 0.05). CONCLUSIONS: Periodontitis elevated the visfatin levels in GCF, serum, and saliva. Additionally, GCF, serum, and saliva visfatin levels could be reduced after periodontal treatment.

Effect of non-surgical periodontal treatment on cytokines/adipocytokines levels among periodontitis patients with or without obesity: a systematic review and meta-analysis.

BACKGROUND: The objective of this systematic review and meta-analysis was to evaluate the effects of non-surgical periodontal therapy (NSPT) on inflammatory-related cytokines/adipocytokines in periodontitis patients with or without obesity. METHODS: We followed the preferred reporting items for systematic reviews and meta-analyses statement and registered the study (CRD42022375331) in the Prospective International Register of Systematic Reviews. We screened randomized-controlled trials and controlled clinical trials from six databases up to December 2022. Quality assessment was performed with RoB-2 and ROBINS-I tools for randomized trials and non-randomized trials, respectively. Meta-analysis was carried out using a random-effect model. RESULTS: We included seventeen references in the systematic analysis, and sixteen in the meta-analysis. Baseline results of pro-inflammatory biomarkers, including serum interleukin (IL)-6, serum and gingival crevicular fluid (GCF), tumor necrosis factor (TNF)-a, serum C-reactive protein (CRP)/hs-CRP, and serum and GCF resistin, were higher in obesity subjects than in normal weight subjects. The effect of NSPT with respect to levels of cytokines/adipocytokines, including IL-6, TNF-a, CRP/hs-CRP, resistin, adiponectin, leptin and retinol binding protein 4 (RBP4), were then analyzed in the systematic and meta-analysis. After three months of NSPT, serum (MD = -0.54, CI = -0.62 - -0.46), and GCF (MD = -2.70, CI = -4.77 - -0.63) levels of IL-6, along with the serum RBP4 (MD = -0.39, CI = -0.68-0.10) decreased in periodontitis individuals with obesity. NSPT also improved GCF adiponectin levels after three months (MD = 2.37, CI = 0.29 - 4.45) in periodontitis individuals without obesity. CONCLUSIONS: Obese status altered the baseline levels of cytokines/adipocytokines (serum IL-6, serum and GCF TNF-a, serum CRP/hs-CRP, and serum and GCF resistin). Then NSPT can shift the levels of specific pro-inflammatory mediators and anti-inflammatory mediators in biological fluids, both in obesity and non-obesity individuals. NSPT can reduce serum and GCF IL-6 levels together with serum RBP4 level in individuals with obesity after 3 months, besides, there is no sufficient evidence to prove that obese patients have a statistically significant decrease in the levels of other cytokines compared to patients with normal weight. NSPT can also increase GCF adiponectin level in normal weight individuals after 3 months. Our findings imply the potential ideal follow-up intervals and sensitive biomarkers for clinical bioanalysis in personalized decision-making of effect of NSPT due to patients' BMI value.

Impact of low-level laser therapy as an adjunct to non-surgical periodontal treatment on the levels of tissue plasminogen activator and plasminogen activator inhibitor 1 in Stage 3-4, Grade C periodontitis patients: a split-mouth, randomized control study.

AIM: To investigate the effects of low-level laser therapy (LLLT) as an adjunct to non-surgical periodontal treatment (NSPT) on the plasminogen-activating system. MATERIALS AND METHODS: Stage 3-4 Grade C periodontitis and age-gender-matched healthy individuals participated in the split-mouth study (ClinicalTrials.gov identifier, NCT05233501). The study groups were Periodontitis/NSPT (Sham); Periodontitis/NSPT + LLLT (LLLT); Healthy (Control). Following NSPT, LLLT was applied on Days 0, 2 and 7. Clinical parameters were recorded at baseline and on Day 30. Gingival crevicular fluid (GCF) was collected at baseline, on days 7, 14, and 30; tissue-type plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) levels were measured with ELISA. RESULTS: Clinical parameters, total GCF tPA (tPAt) and PAI-1 (PAI-1t) levels significantly reduced in LLLT and Sham groups (< 0.001). GCF tPAt levels in LLLT were significantly lower (< 0.05) than Sham on Day 7. GCF tPAt levels in periodontitis groups were significantly higher than the Control at baseline, on Days 7 and 14 (< 0.01). By Day 30, both groups decreased to control levels (> 0.05). GCF PAI-1t levels were significantly lower in LLLT than the Sham on day 30 (< 0.01), comparable to healthy controls (> 0.05). CONCLUSION: Adjunctive LLLT modulates the plasminogen activating system in severe periodontitis by altering GCF tPA and PAI-1 levels. CLINICAL RELEVANCE: LLLT as an adjunct to non-surgical periodontal treatment in patients with Stage 3-4 Grade C leads to reduced plasminogen activation.

Expression of tight junction proteins in smokers and non-smokers with generalized Stage III periodontitis.

OBJECTIVE: This study aims to evaluate the gingival crevicular fluid (GCF) levels of tumor necrosis factor-α (TNF-α), zonula occludens-1 (ZO-1), occludin (Occ), and tricellulin (Tric) in periodontitis, as well as their alterations due to smoking. BACKGROUND: Tight junctions (TJ), which consist of transmembrane and cytoplasmic scaffolding proteins, connect the epithelial cells of the periodontium. Occ, claudins, junctional adhesion molecules, and Tric are transmembrane TJ proteins found at the cell membrane. The transmembrane TJ proteins and the intracellular cytoskeleton are directly linked by cytoplasmic scaffolding proteins such as ZO-1. Although the functions and locations of these molecules have been defined, their behavior in periodontal inflammation is unknown. METHODS: The study included four groups: individuals with periodontal health without smoking (C; n = 31), individuals with generalized Stage III periodontitis without smoking (P; n = 28), individuals with periodontal health while smoking (CS; n = 22), and individuals with generalized Stage III periodontitis while smoking (PS; n = 18). Clinical periodontal parameters were recorded, and enzyme-linked immunosorbent assay (ELISA) was used to examine ZO-1, Occ, Tric, and TNF-α levels in GCF. RESULTS: In the periodontitis groups, clinical parameters were significantly higher (p < .001). The site-specific levels of TNF-α, ZO-1, Tric, and Occ in the P group were statistically higher than those in the other groups (p < .05). TNF-α, probing pocket depth (PPD), and bleeding on probing (BOP) exhibited positive correlations with all TJ proteins (p < .005). CONCLUSIONS: Smoking could potentially affect the levels of epithelial TJ proteins in the GCF, thereby potentially playing a significant role in the pathogenesis of the periodontal disease.

Accuracy of periodontitis diagnosis obtained using multiple molecular biomarkers in oral fluids: A systematic review and meta-analysis.

AIM: To determine the accuracy of biomarker combinations in gingival crevicular fluid (GCF) and saliva through meta-analysis to diagnose periodontitis in systemically healthy subjects. METHODS: Studies on combining two or more biomarkers providing a binary classification table, sensitivity/specificity values or group sizes in subjects diagnosed with periodontitis were included. The search was performed in August 2022 through PUBMED, EMBASE, Cochrane, LILACS, SCOPUS and Web of Science. The methodological quality of the articles selected was evaluated using the QUADAS-2 checklist. Hierarchical summary receiver operating characteristic modelling was employed to perform the meta-analyses (CRD42020175021). RESULTS: Twenty-one combinations in GCF and 47 in saliva were evaluated. Meta-analyses were possible for six salivary combinations (median sensitivity/specificity values): IL-6 with MMP-8 (86.2%/80.5%); IL-1ß with IL-6 (83.0%/83.7%); IL-1ß with MMP-8 (82.7%/80.8%); MIP-1α with MMP-8 (71.0%/75.6%); IL-1ß, IL-6 and MMP-8 (81.8%/84.3%); and IL-1ß, IL-6, MIP-1α and MMP-8 (76.6%/79.7%). CONCLUSIONS: Two-biomarker combinations in oral fluids show high diagnostic accuracy for periodontitis, which is not substantially improved by incorporating more biomarkers. In saliva, the dual combinations of IL-1ß, IL-6 and MMP-8 have an excellent ability to detect periodontitis and a good capacity to detect non-periodontitis. Because of the limited number of biomarker combinations evaluated, further research is required to corroborate these observations.